Skyla® is indicated to prevent pregnancy for up to 3 years.

{ "type": "p", "children": [], "text": "Skyla® is indicated to prevent pregnancy for up to 3 years. " }

Replace the system after 3 years if continued use is desired.

{ "type": "p", "children": [], "text": "Replace the system after 3 years if continued use is desired." }

Skyla contains 13.5 mg of levonorgestrel (LNG) released in vivo at a rate of approximately 14 mcg/day after 24 days. This rate decreases progressively to approximately 6 mcg/day after 1 year and to 5 mcg/day after 3 years. The average in vivo release rate of LNG is approximately 8 mcg/day over the first year of use and 6 mcg/day over a period of 3 years. [See Clinical Pharmacology (12.3).]

Skyla must be removed by the end of the third year and can be replaced at the time of removal with a new Skyla if continued contraceptive protection is desired.

Skyla can be physically distinguished from other intrauterine systems (IUSs) by the combination of the visibility of the silver ring on ultrasound and the brown color of the removal threads.

Skyla is supplied in a sterile package within an inserter that enables single-handed loading (see Figure 1). Do not open the package until required for insertion [see Description (11.2)]. Do not use if the seal of the sterile package is broken or appears compromised. Use strict aseptic techniques throughout the insertion procedure [see Warnings and Precautions (5.3)].

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1: When to Insert Skyla</span> </caption> <col width="32%"/> <col width="68%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Starting Skyla in women not currently using hormonal or intrauterine contraception</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt>•</dt> <dd>Insert Skyla any time there is reasonable certainty that the woman is not pregnant. Consider the possibility of ovulation and conception prior to initiation of this product <span class="Italics">[see Contraindications (<a href="#ID_41ab7112-df4d-468d-aae5-cbf9a0bf6be5">4</a>)].</span> </dd> <dt>•</dt> <dd>If Skyla is inserted during the first seven days of the menstrual cycle or immediately after a first trimester abortion, back-up contraception is not needed.</dd> <dt>•</dt> <dd>If Skyla is not inserted during the first seven days of the menstrual cycle, a barrier method of contraception should be used, or the patient should abstain from vaginal intercourse for seven days to prevent pregnancy.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Switching to Skyla from an oral, transdermal or vaginal hormonal contraceptive</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt>•</dt> <dd>Insert Skyla at any time, including during the hormone-free interval of the previous method.</dd> <dt>•</dt> <dd>If inserted during active use of the previous method, continue that method for 7 days after Skyla insertion or until the end of the current treatment cycle.</dd> <dt>•</dt> <dd>If the woman was using continuous hormonal contraception, discontinue that method seven days after Skyla insertion.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Switching to Skyla from an injectable progestin contraceptive</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt>•</dt> <dd>Insert Skyla at any time; a non-hormonal back-up birth control (such as condoms or spermicide) should also be used for 7 days if Skyla is inserted more than 3 months (13 weeks) after the last injection.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Switching to Skyla from a contraceptive implant or another IUS </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt>•</dt> <dd>Insert Skyla on the same day the implant or IUS is removed. </dd> <dt>•</dt> <dd>Insert Skyla at any time during the menstrual cycle.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Inserting Skyla after first trimester abortion or miscarriage </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt>•</dt> <dd>Insert Skyla immediately after a first-trimester abortion or miscarriage, unless it is a septic abortion <span class="Italics">[see Contraindications (<a href="#ID_41ab7112-df4d-468d-aae5-cbf9a0bf6be5">4</a>)].</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Inserting Skyla after childbirth or second-trimester abortion or miscarriage</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Immediate insertion after childbirth or second-trimester abortion or miscarriage</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt>•</dt> <dd>Insert Skyla after removal of the placenta. Back-up contraception is not needed. <span class="Italics">[See Contraindications (<a href="#ID_41ab7112-df4d-468d-aae5-cbf9a0bf6be5">4</a>), Warnings and Precautions (<a href="#ID_6fd0d21d-a70b-451d-81f3-643de5b7427d">5.5</a>, <a href="#ID_918495c6-212c-432d-ae8b-8bd685d1f80b">5.6</a>), Adverse Reactions (<a href="#ID_b4dbb721-5e05-47b3-b789-e62fc27a440a">6.2</a>)].</span> </dd> </dl> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Interval insertion following complete involution of the uterus</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <dl> <dt>•</dt> <dd>Wait a minimum of 6 weeks or until the uterus is fully involuted before inserting Skyla [see <span class="Italics">Warnings and Precautions (<a href="#ID_6fd0d21d-a70b-451d-81f3-643de5b7427d">5.5</a>, <a href="#ID_918495c6-212c-432d-ae8b-8bd685d1f80b">5.6</a>), Adverse Reactions (<a href="#ID_b4dbb721-5e05-47b3-b789-e62fc27a440a">6.2</a>)].</span> </dd> <dt>•</dt> <dd>Insert Skyla any time there is reasonable certainty the woman is not pregnant.</dd> <dt>•</dt> <dd>If Skyla is not inserted during the first 7 days of the menstrual cycle, a back-up method of contraception should be used, or the woman should abstain from vaginal intercourse for 7 days to prevent pregnancy <span class="Italics">[see Contraindications (<a href="#ID_41ab7112-df4d-468d-aae5-cbf9a0bf6be5">4</a>), Warnings and Precautions (<a href="#ID_f19ba4a2-53a7-4218-a9e4-88640f02eaa8">5.2</a>)].</span> </dd> </dl> </td> </tr> </tbody> </table></div>

Note: The inserter provided with Skyla (see Figure 1) and the Insertion Procedure described in this section are not applicable for immediate insertion after childbirth or second-trimester abortion or miscarriage. For immediate insertion, remove Skyla from the inserter by first loading (see Figure 2) and then releasing (see Figure 7) Skyla from the inserter, and insert according to accepted practice.

Proceed with insertion only after completing the above steps and ascertaining that the patient is appropriate for Skyla. Ensure use of aseptic technique throughout the entire procedure.

Do not force the inserter. If necessary, dilate the cervical canal.

Advance the inserter gently towards the fundus of the uterus until the flange touches the cervix. If you encounter fundal resistance do not continue to advance. Skyla is now in the fundal position (Figure 6). Fundal positioning of Skyla is important to prevent expulsion.

Reexamine and evaluate patients 4 to 6 weeks after insertion and once a year thereafter, or more frequently if clinically indicated.

If a patient with irregular cycles or amenorrhea wants to start a different contraceptive method, start the new method at least 7 days before removal.

Skyla is a LNG-releasing IUS (a type of intrauterine device, or IUD) consisting of a T-shaped polyethylene frame with a steroid reservoir containing a total of 13.5 mg LNG.

{ "type": "p", "children": [], "text": "Skyla is a LNG-releasing IUS (a type of intrauterine device, or IUD) consisting of a T-shaped polyethylene frame with a steroid reservoir containing a total of 13.5 mg LNG. " }

The use of Skyla is contraindicated when one or more of the following conditions exist:

{ "type": "p", "children": [], "text": "The use of Skyla is contraindicated when one or more of the following conditions exist:" }

{ "type": "", "children": [], "text": "" }

Evaluate women for ectopic pregnancy if they become pregnant with Skyla in place because the likelihood of a pregnancy being ectopic is increased with Skyla. Approximately one-half of pregnancies that occur with Skyla in place are likely to be ectopic. Also consider the possibility of ectopic pregnancy in the case of lower abdominal pain, especially in association with missed menses or if an amenorrheic woman starts bleeding.

The incidence of ectopic pregnancy in clinical trials with Skyla, which excluded women with a history of ectopic pregnancy, was approximately 0.1% per year. The risk of ectopic pregnancy in women who have a history of ectopic pregnancy and use Skyla is unknown. Women with a previous history of ectopic pregnancy, tubal surgery or pelvic infection carry a higher risk of ectopic pregnancy. Ectopic pregnancy may result in loss of fertility.

If pregnancy occurs while using Skyla, remove Skyla because leaving it in place may increase the risk of spontaneous abortion and preterm labor. Removal of Skyla or probing of the uterus may also result in spontaneous abortion. In the event of an intrauterine pregnancy with Skyla, consider the following:

In patients becoming pregnant with an IUS in place, septic abortion—with septicemia, septic shock, and death—may occur.

If a woman becomes pregnant with Skyla in place and if Skyla cannot be removed or the woman chooses not to have it removed, warn her that failure to remove Skyla increases the risk of miscarriage, sepsis, premature labor and premature delivery. Advise her of isolated reports of virilization of the female fetus following local exposure to LNG during pregnancy with an LNG IUS in place [see Use in Specific Populations (8.1)]. Follow her pregnancy closely and advise her to report immediately any symptom that suggests complications of the pregnancy.

Severe infection or sepsis, including Group A streptococcal sepsis (GAS), have been reported following insertion of a LNG-releasing IUS. In some cases, severe pain occurred within hours of insertion followed by sepsis within days. Because death from GAS is more likely if treatment is delayed, it is important to be aware of these rare but serious infections. Aseptic technique during insertion of Skyla is essential in order to minimize serious infections such as GAS.

Skyla is contraindicated in the presence of known or suspected PID or in women with a history of PID unless there has been a subsequent intrauterine pregnancy [see Contraindications (4)]. IUDs have been associated with an increased risk of PID, most likely due to organisms being introduced into the uterus during insertion. In clinical trials, PID was observed in 0.4% of women overall and occurred more frequently within the first year and most often within the first month after insertion of Skyla.

Promptly examine users with complaints of lower abdominal or pelvic pain, odorous discharge, unexplained bleeding, fever, genital lesions or sores. Remove Skyla in cases of recurrent endometritis or pelvic inflammatory disease, or if an acute pelvic infection is severe or does not respond to treatment.

PID is often associated with a sexually transmitted infection (STI), and Skyla does not protect against STI. The risk of PID is greater for women who have multiple sexual partners, and also for women whose sexual partner(s) have multiple sexual partners. Women who have had PID are at increased risk for a recurrence or re-infection. In particular, ascertain whether the woman is at increased risk of infection (for example, leukemia, acquired immune deficiency syndrome [AIDS], intravenous drug abuse).

PID may be asymptomatic but still result in tubal damage and its sequelae.

Following a diagnosis of PID, or suspected PID, bacteriologic specimens should be obtained, and antibiotic therapy should be initiated promptly. Removal of Skyla after initiation of antibiotic therapy is usually appropriate.

Actinomycosis has been associated with IUDs. Remove Skyla from symptomatic women and treat with antibiotics. The significance of actinomyces-like organisms on Pap smear in an asymptomatic IUD user is unknown, and so this finding alone does not always require Skyla removal and treatment. When possible, confirm a Pap smear diagnosis with cultures.

Perforation (total or partial, including penetration/embedment of Skyla in the uterine wall or cervix) may occur most often during insertion, although the perforation may not be detected until sometime later. The incidence of perforation during clinical trials was < 0.1%.

The risk of uterine perforation is increased in women who have recently given birth, and in women who are breastfeeding at the time of insertion. In a large postmarketing safety study conducted in the US, the risk of uterine perforation was highest when insertion occurred within ≤ 6 weeks postpartum, and also higher with breastfeeding at the time of insertion [see Adverse Reactions (6.2)].

The risk of perforation may be increased if Skyla is inserted when the uterus is fixed, retroverted or not completely involuted.

If perforation occurs, locate and remove Skyla. Surgery may be required. Delayed detection or removal of Skyla in case of perforation may result in migration outside the uterine cavity, adhesions, peritonitis, intestinal perforations, intestinal obstruction, abscesses and erosion of adjacent viscera. In addition, perforation may reduce contraceptive efficacy and result in pregnancy.

Partial or complete expulsion of Skyla may occur resulting in the loss of efficacy. Expulsion may be associated with symptoms of bleeding or pain, or it may be asymptomatic and go unnoticed. Skyla typically decreases menstrual bleeding over time; therefore, an increase of menstrual bleeding may be indicative of an expulsion. Consider further diagnostic imaging, such as x-ray, if expulsion is suspected based on ultrasound [see Warnings and Precautions (5.10)]. In clinical trials, a 3-year expulsion rate of 3.2% (54 out of 1,665 subjects) was reported.

The risk of expulsion is increased with insertions immediately after delivery and appears to be increased with insertion after second-trimester abortion based on limited data. In a large postmarketing safety study conducted in the US, the risk of expulsion was lower with breastfeeding status [see Adverse Reactions (6.2)].

Remove a partially expelled Skyla. If expulsion has occurred, a new Skyla can be inserted any time the provider can be reasonably certain the woman is not pregnant.

Because the contraceptive effect of Skyla is mainly due to its local effects within the uterus, ovulatory cycles with follicular rupture usually occur in women of fertile age using Skyla. Ovarian cysts (reported as adverse reactions if they were abnormal, non-functional cysts and/or had a diameter >3 cm on ultrasound examination) were reported at least once over the course of clinical trials in 13.2% of women using Skyla, and 0.3% of subjects discontinued because of an ovarian cyst. Most ovarian cysts are asymptomatic, although some may be accompanied by pelvic pain or dyspareunia. In most cases the ovarian cysts disappear spontaneously during two to three months observation. Evaluate persistent ovarian cysts. Surgical intervention is not usually required.

Skyla can alter the bleeding pattern and result in spotting, irregular bleeding, heavy bleeding, oligomenorrhea and amenorrhea. During the first 3–6 months of Skyla use, the number of bleeding and spotting days may be higher and bleeding patterns may be irregular. Thereafter, the number of bleeding and spotting days usually decreases but bleeding may remain irregular.

In Skyla clinical trials, amenorrhea developed by the end of the first year of use in approximately 6% of Skyla users. A total of 77 subjects out of 1,672 (4.6%) discontinued due to uterine bleeding complaints. Table 2 shows the bleeding patterns as documented in the Skyla clinical trials based on 90-day reference periods. Table 3 shows the number of bleeding and spotting days based on 28-day cycle equivalents.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 2: Bleeding Patterns Reported with Skyla in Contraception Studies (by 90-day reference periods)</span> </caption> <col width="21%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Skyla</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">First 90 days</span> <br/> <span class="Bold">N=1,531</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Second 90 days</span> <br/> <span class="Bold">N=1,475</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">End of year 1</span> <br/> <span class="Bold">N=1,329</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">End of year 3</span> <br/> <span class="Bold">N=903</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Amenorrhea<span class="Sup">1</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">&lt;1%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">6%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Infrequent bleeding<span class="Sup">2</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">8%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">19%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">20%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">22%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Frequent bleeding<span class="Sup">3</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">31%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">8%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Prolonged bleeding<span class="Sup">4</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">55%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">14%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">6%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2%</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Irregular bleeding<span class="Sup">5</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">39%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">25%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">18%</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">15%</p> </td> </tr> </tbody> </table></div>

1Defined as subjects with no bleeding/spotting throughout the 90-day reference period

2Defined as subjects with 1 or 2 bleeding/spotting episodes in the 90-day reference period

3Defined as subjects with more than 5 bleeding/spotting episodes in the 90-day reference period

4Defined as subjects with bleeding/spotting episodes lasting more than 14 days in the 90-day reference period. Subjects with prolonged bleeding may also be included in one of the other categories (excluding amenorrhea)

5Defined as subjects with 3 to 5 bleeding/spotting episodes and less than 3 bleeding/spotting-free intervals of 14 or more days.

<div class="scrollingtable"><table cellpadding="0pt" width="100%"> <caption> <span>Table 3: Mean number of Bleeding and Spotting Days per 28-day Cycle Equivalent</span> </caption> <col width="16%"/> <col width="17%"/> <col width="17%"/> <col width="17%"/> <col width="17%"/> <col width="17%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">28-day Cycle Equivalent</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Cycle 1</span> </p> <p> <span class="Bold">N=1,588</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Cycle 4</span> </p> <p> <span class="Bold">N=1,535</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Cycle 7</span> </p> <p> <span class="Bold">N=1,468</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Cycle 13</span> </p> <p> <span class="Bold">N=1,345</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First"> <span class="Bold">Cycle 39</span> </p> <p> <span class="Bold">N=781</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Days on treatment</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1–28</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">85–112</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">169–196</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">337–364</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1065–1092</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="middle"></td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">Mean</p> <p>(SD)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">Mean</p> <p>(SD)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">Mean</p> <p>(SD)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">Mean</p> <p>(SD)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">Mean</p> <p>(SD)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Number of bleeding days</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">7.3</p> <p>(5.6)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">3.5</p> <p>(3.4)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2.8</p> <p>(3.1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2.1</p> <p>(2.7)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">1.4</p> <p>(2.1)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="middle"> <p class="First"> <span class="Bold">Number of spotting days</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">9.2</p> <p>(6.1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">4.8</p> <p>(4.4)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">3.8</p> <p>(3.6)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">3.3</p> <p>(3.1)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="middle"> <p class="First">2.7</p> <p>(2.7)</p> </td> </tr> </tbody> </table></div>

If a significant change in bleeding develops during prolonged use, take appropriate diagnostic measures to rule out endometrial pathology. Consider the possibility of pregnancy if menstruation does not occur within six weeks of the onset of a previous menstruation. Once pregnancy has been excluded, repeated pregnancy tests are generally not necessary in amenorrheic women unless indicated, for example, by other signs of pregnancy or by pelvic pain.

Women who currently have or have had breast cancer, or have a suspicion of breast cancer, should not use hormonal contraception, including Skyla because some breast cancers are hormone-sensitive [see Contraindications (4)].

Spontaneous reports of breast cancer have been received during postmarketing experience with a LNG-releasing IUS. Observational studies of the risk of breast cancer with use of a LNG-releasing IUS do not provide conclusive evidence of increased risk.

Use Skyla with caution after careful assessment if any of the following conditions exist, and consider removal of the system if any of them arise during use:

In addition, consider removing Skyla if any of the following conditions arise during use:

Non-clinical testing has demonstrated that Skyla is MR Conditional. A patient with Skyla can be safely scanned in an MR system meeting the following conditions:

Under the scan conditions defined above, the Skyla IUS is expected to produce a maximum temperature rise of less than 2°C after 15 minutes of continuous scanning.

In non-clinical testing, the image artifact caused by the IUS extended up to 5 mm from the IUS when imaged with a gradient echo pulse sequence and a 3.0 T MRI system.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The data described below reflect exposure to Skyla in 1,672 patients in two contraception studies, including 1,383 exposed for one year and 993 who completed the three year studies. The population was generally healthy, 18 to 40-year old females requesting contraception and predominately Caucasian (82.6%). The data cover more than 40,000 cycles of exposure. The frequencies of reported adverse drug reactions represent crude incidences.

Most common adverse reactions (occurring in ≥ 5% users) were increased bleeding (7.8%), vulvovaginitis (20.2%), abdominal/pelvic pain (18.9%), acne/seborrhea (15.0%), ovarian cyst (13.2%), headache (12.4%), dysmenorrhea (8.6%), breast pain/discomfort (8.6%) and nausea (5.5%).

In the contraception studies, 18% discontinued prematurely due to an adverse reaction. The most common adverse reactions leading to discontinuation (in >1% of users) were uterine bleeding complaints (4.6%), device expulsion (3.2%), acne/seborrhea (2.9%), abdominal pain (2.5%) dysmenorrhea/uterine spasms (2.0%) and pelvic pain (1.8%).

Other common adverse reactions (occurring in ≥ 1% users) by System Organ Class (SOC): The frequencies of adverse reactions observed in clinical trials are summarized in Table 4 by SOC (presented as crude incidences).

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 4: Adverse reactions that occurred in at least 1% of Skyla users in clinical trials by SOC </span> </caption> <col width="33%"/> <col width="37%"/> <col width="29%"/> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd> <span class="Sup">Ovarian cysts were reported as adverse events if they were abnormal, non-functional cysts and/or had a diameter &gt;3 cm on ultrasound examination</span> </dd> <dt> <a href="#footnote-reference-2" name="footnote-2">†</a> </dt> <dd> <span class="Sup">Not all bleeding alterations were captured as adverse reactions [see Warnings and Precautions (5.8)].</span> </dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">System Organ Class</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Adverse Reaction</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Incidence (%)</span> <br/> <span class="Bold">(N=1,672)</span> </p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Reproductive System and Breast Disorders</p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Vulvovaginitis</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>20.2</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Ovarian cyst<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> </dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>13.2</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Dysmenorrhea</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>8.6</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Increased bleeding<a class="Sup" href="#footnote-2" name="footnote-reference-2">†</a> </dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>7.8</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Breast pain/discomfort</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>5.3/3.3</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Genital discharge</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>4.2</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Device expulsion (complete and partial)</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>3.2</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Upper genital tract infection</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>1.4</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Gastrointestinal Disorders</p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Abdominal pain/pelvic pain</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>12.7/6.2</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Nausea</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>5.5</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Skin and Subcutaneous<br/>Tissue Disorders</p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Acne/Seborrhea</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>13.6/1.4</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Alopecia</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>1.2</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Nervous System Disorders</p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Headache</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>12.4</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Migraine</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>2.3</dd> </dl> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Psychiatric Disorders</p> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>Depression/Depressed mood</dd> </dl> </td><td class="Botrule Lrule Rrule" valign="top"> <dl> <dt> </dt> <dd>3.8/0.5</dd> </dl> </td> </tr> </tbody> </table></div>

The following adverse reactions have been identified during post-approval use of LNG-releasing IUSs. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

APEX IUD was a large US retrospective cohort study to assess the impact of breastfeeding and timing of postpartum IUD insertion on uterine perforation and IUD expulsion. The analyses included a total of 326,658 insertions, 30% (97,824 insertions) of which were performed in women with a delivery in the previous 12 months. For insertions performed in women who had delivered ≤ 52 weeks before IUD insertion, the majority of postpartum insertions, 57.3% (56,047 insertions) occurred between 6 and 14 weeks postpartum. Breastfeeding data were available in 94,817 insertions performed in women 52 weeks or less after delivery.

The study results indicated that the risk of uterine perforation was highest in women with IUD insertion ≤ 6 weeks postpartum. Immediate postpartum insertion (0–3 days) findings are limited due to the relatively small number of insertions occurring within this time interval. Women who were breastfeeding at the time of insertion were at 33% higher risk of perforation (adjusted hazard ratio [HR]=1.33, 95% confidence interval [CI]: 1.07–1.64) compared to women who were not breastfeeding at the time of insertion. Progressively lower risk of uterine perforation was observed in postpartum time windows beyond 6 weeks, in both breastfeeding and not breastfeeding women. Table 5 presents the uterine perforation rates for LNG IUS stratified by breastfeeding status and postpartum interval.

<div class="scrollingtable"><table cellpadding="0pt" width="100%"> <caption> <span>Table 5: Uterine Perforation1 rates for LNG IUS, by Breastfeeding Status and Postpartum Interval</span> </caption> <col width="20%"/> <col width="18%"/> <col width="22%"/> <col width="17%"/> <col width="23%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="middle"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">Breastfeeding at time of insertion</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">Not breastfeeding at time of insertion</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Postpartum interval at time of insertion</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">Number of events/ insertions</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">Uterine perforation rate per 1,000 insertions</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">Number of events/ insertions</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">Uterine perforation rate <br/>per 1,000 insertions</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">0 to 3 days</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">8/1,896</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">4.22</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">0/277</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">0.00</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">4 days to ≤ 6 weeks</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">120/10,735</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">11.18</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">28/2,377</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">11.78</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">&gt; 6 to ≤ 14 weeks</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">268/29,677</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">9.03</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">80/12,011</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">6.66</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">&gt; 14 to ≤ 52 weeks</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">43/6,139</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">7.00</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">22/9,089</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">2.42</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">&gt; 52 weeks or no delivery </span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"> <p class="First">no data available</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">243/184,733</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">1.32</p> </td> </tr> </tbody> </table></div>

1Uterine perforation includes both complete and partialperforation

Risk of expulsion was variable over the postpartum intervals through 52 weeks. Women who were breastfeeding were at 28% lower risk of IUD expulsion (adjusted HR=0.72, 95% CI: 0.64-0.80) compared to women who were not breastfeeding at time of insertion. Table 6 presents the IUD expulsion rates for LNG IUS stratified by breastfeeding status and postpartum interval.

<div class="scrollingtable"><table cellpadding="0pt" width="100%"> <caption> <span>Table 6: Expulsion1 Rates for LNG IUS, by Breastfeeding Status and Postpartum Interval </span> </caption> <col width="20%"/> <col width="18%"/> <col width="22%"/> <col width="17%"/> <col width="23%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="middle"></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">Breastfeeding at time of insertion</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"> <p class="First"> <span class="Bold">Not breastfeeding at time of insertion</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Postpartum interval at time of insertion</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">Number of events/ insertions</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">Expulsion rate <br/>per 1,000 insertions</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">Number of events/ insertions</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">Expulsion rate <br/>per 1,000 insertions</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">0 to 3 days</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">187/1,896</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">98.63</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">12/277</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">43.32</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">4 days to ≤ 6 weeks</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">185/10,735</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">17.23</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">52/2,377</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">21.88</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">&gt; 6 to ≤ 14 weeks</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">421/29,677</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">14.19</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">306/12,011</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">25.48</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">&gt; 14 to ≤ 52 weeks</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">120/6,139</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">19.55</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">273/9,089</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">30.04</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">&gt; 52 weeks or no delivery </span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="middle"> <p class="First">no data available</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">5,481/184,733</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle"> <p class="First">29.67</p> </td> </tr> </tbody> </table></div>

1Expulsion includes both complete and partial expulsion

No drug-drug interaction studies have been conducted with Skyla.

{ "type": "p", "children": [], "text": "No drug-drug interaction studies have been conducted with Skyla." }

Drugs or herbal products that induce or inhibit LNG metabolizing enzymes, including CYP3A4, may decrease or increase, respectively, the serum concentrations of LNG during the use of Skyla. However, the contraceptive effect of Skyla is mediated via the direct release of LNG into the uterine cavity and is unlikely to be affected by drug interactions via enzyme induction or inhibition.

{ "type": "p", "children": [], "text": "Drugs or herbal products that induce or inhibit LNG metabolizing enzymes, including CYP3A4, may decrease or increase, respectively, the serum concentrations of LNG during the use of Skyla. However, the contraceptive effect of Skyla is mediated via the direct release of LNG into the uterine cavity and is unlikely to be affected by drug interactions via enzyme induction or inhibition." }

The use of Skyla is contraindicated in pregnancy or with a suspected pregnancy and Skyla may cause adverse pregnancy outcomes [see Contraindications (4), Warnings and Precautions (5.1, 5.2)]. If a woman becomes pregnant with Skyla in place, the likelihood of ectopic pregnancy is increased and there is an increased risk of miscarriage, sepsis, premature labor, and premature delivery. Remove Skyla, if possible, if pregnancy occurs in a woman using Skyla. If Skyla cannot be removed, follow the pregnancy closely [see Warnings and Precautions (5.1, 5.2)].

There have been isolated cases of virilization of the external genitalia of the female fetus following local exposure to LNG during pregnancy with an LNG IUS in place. Animal reproduction studies have not been conducted with Skyla.

Published studies report the presence of LNG in human milk. Small amounts of progestins (approximately 0.1% of the total maternal doses) were detected in the breast milk of nursing mothers who used other LNG-releasing IUSs, resulting in exposure of LNG to the breastfed infants. There are no reports of adverse effects in breastfed infants with maternal use of progestin-only contraceptives. Isolated cases of decreased milk production have been reported with a LNG-releasing IUS. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Skyla and any potential adverse effects on the breastfed child from Skyla or from the underlying maternal condition.

About 77% of women who desired pregnancy after study discontinuation and provided follow-up information, conceived within 12 months after removal of Skyla.

Safety and efficacy of Skyla have been established in women of reproductive age. Efficacy is expected to be the same for postpubertal females under the age of 18 as for users 18 years and older. Use of this product before menarche is not indicated.

Skyla has not been studied in women over age 65 and is not approved for use in this population.

Skyla consists of a T-shaped polyethylene frame (T-body) with a steroid reservoir (hormone elastomer core) around the vertical stem. The white T-body has a loop at one end of the vertical stem and two horizontal arms at the other end. The reservoir consists of a whitish or pale yellow cylinder, made of a mixture of LNG and silicone (polydimethylsiloxane), containing a total of 13.5 mg LNG. The reservoir is covered by a semi-opaque silicone membrane, composed of polydimethylsiloxane and colloidal silica. A ring composed of 99.95% pure silver is located at the top of the vertical stem close to the horizontal arms and is visible by ultrasound. The polyethylene of the T-body is compounded with barium sulfate, which makes it radiopaque. A monofilament brown polyethylene removal thread is attached to a loop at the end of the vertical stem of the T-body. The polyethylene of the removal thread contains iron oxide as a colorant (see Figure 10).

The components of Skyla, including its packaging, are not manufactured using natural rubber latex.

Skyla is packaged sterile within an inserter. The inserter (Figure 11), which is used for insertion of Skyla into the uterine cavity, consists of a symmetric two-sided body and slider that are integrated with flange, lock, pre-bent insertion tube and plunger. The outer diameter of the insertion tube is 3.8 mm. The vertical stem of Skyla is loaded in the insertion tube at the tip of the inserter. The arms are pre-aligned in the horizontal position. The removal threads are contained within the insertion tube and handle. Once Skyla has been placed, the inserter is discarded.

The local mechanism by which continuously released LNG contributes to the contraceptive effectiveness of Skyla has not been conclusively demonstrated. Studies of Skyla and similar LNG IUS prototypes have suggested several mechanisms that prevent pregnancy: thickening of cervical mucus preventing passage of sperm into the uterus, inhibition of sperm capacitation or survival, and alteration of the endometrium.

Skyla has mainly local progestogenic effects in the uterine cavity. The local concentrations of LNG lead to morphological changes including stromal pseudodecidualization, glandular atrophy, a leukocytic infiltration and a decrease in glandular and stromal mitoses.

In clinical trials with Skyla, ovulation was assessed based on serum progesterone values >2.5 ng/mL in one study and serum progesterone values >2.5 ng/mL together with serum estradiol levels <27.24 pg/mL in another study. Evidence of ovulation by these criteria was seen in 34 out of 35 women in the first year, in 26 out of 27 women in the second year, and in all 26 women in the third year.

Low doses of LNG are administered into the uterine cavity with the Skyla intrauterine delivery system. The in vivo release rate is approximately 14 mcg/day after 24 days and is reduced to approximately 10 mcg/day after 60 days and then declines progressively to approximately 6 mcg/day after 1 year and 5 mcg/day after 3 years. The average LNG in vivo release rate is approximately 8 mcg/day over the first year of use and 6 mcg/day over the period of 3 years.

In a subset of 7 subjects, the maximum observed serum LNG concentration (mean ±SD) was 192 ± 105 pg/mL, reached after 2 days (median) of Skyla insertion. Thereafter, the LNG serum concentrations (mean ±SD) at year 1, 2, and 3 were 77 ± 21 pg/mL, 62 ± 38 pg/mL, and 72 ± 29 pg/mL, respectively. A population pharmacokinetic evaluation based on a broader database (>1000 patients) showed similar concentration data of 168 ± 46 pg/mL at 7 days after placement. Thereafter, LNG serum concentrations decline slowly to a value 61 ± 19 pg/mL after 3 years.

The apparent volume of distribution of LNG is reported to be approximately 1.8 L/kg. LNG is bound non-specifically to serum albumin and specifically to sex hormone binding globulin (SHBG). Accordingly, changes in the concentration of SHBG in serum result in an increase (at higher SHBG concentration) or a decrease (at lower SHBG concentration) of the total LNG concentration in serum. In a subset of 7 subjects, the concentration of SHBG declined by a mean value of 18% within 2 weeks after insertion of Skyla and remained relatively stable over the 3 year period of use. Less than 2% of the circulating LNG is present as free steroid.

Following intravenous administration of 0.09 mg LNG to healthy volunteers, the total clearance of LNG is approximately 1 mL/min/kg and the elimination half-life is approximately 20 hours. Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for wide individual variations in LNG concentrations seen in individuals using LNG–containing contraceptive products.

LNG and its phase I metabolites are excreted primarily as glucuronide conjugates. About 45% of LNG and its metabolites are excreted in the urine and about 32% are excreted in feces, mostly as glucuronide conjugates.

Pediatric: Safety and efficacy of Skyla have been established in women of reproductive age. Use of this product before menarche is not indicated.

In a one-year phase 3 study in post-menarcheal female adolescents (mean age 16.2, range 12 to 18 years) using Skyla, the population pharmacokinetic analysis of 278 adolescents showed mean estimated LNG serum concentrations slightly higher (approximately 10%) in adolescents compared to prior data in adults. This correlates to the generally lower body weight in adolescents. The ranges estimated for adolescents lie within the ranges estimated for adults.

Geriatric: Skyla has not been studied in women over age 65 and is not approved for use in this population.

Race: A three-year phase 3 study in the Asian-Pacific region (93% Asian women, the majority of whom were Chinese, 7% other ethnicities) using Skyla was performed. The population pharmacokinetic analysis of the Asian (Chinese) population in this study showed that estimated LNG serum concentrations in Asian women were slightly higher (approximately 4 to 16%) than those in another phase 3 study which was performed in mainly Caucasian women (79.7%). This slightly higher exposure might be explained by the lower body weight of Asian women.

Hepatic Impairment: No studies were conducted to evaluate the effect of hepatic disease on the disposition of Skyla.

Renal Impairment: No formal studies were conducted to evaluate the effect of renal disease on the disposition of Skyla.

No drug-drug interaction studies were conducted with Skyla [see Drug Interactions (7)].

[See Warnings and Precautions (5.9).]

The contraceptive efficacy of Skyla was evaluated in a clinical trial that enrolled generally healthy women aged 18–35, 1,432 of whom received Skyla. Of these, 38.8 % (556) were nulliparous women, and 819 women completed 3 years of use. The trial was a multicenter, multi-national, randomized open-label study conducted in 11 countries in Europe, Latin America, the US and Canada. Women less than six weeks postpartum, with a history of ectopic pregnancy, with clinically significant ovarian cysts or with HIV or otherwise at high risk for sexually transmitted infections were excluded. A total of 540 (37.7%) were treated at US sites and 892 (62.3%) were at non-US sites. The racial demographics of enrolled women who received Skyla was: Caucasian (79.7%), Hispanic (11.5%), Black/African Americans (5.2%), Other (2.7%) and Asian (0.8%). The weight range was 38 to 155 kg (mean weight: 68.7 kg) and mean BMI was 25.3 kg/m2 (range 16–55 kg/m2). The clinical trial had no upper or lower weight or BMI limit. Of Skyla-treated women, 21.9% discontinued the study treatment due to an adverse event, 4.4% were lost to follow up, 1.8% withdrew for unspecified reasons, 1.1% discontinued due to protocol deviation, 0.6% discontinued due to pregnancy, and 13.0% discontinued due to other reasons.

{ "type": "p", "children": [], "text": "The contraceptive efficacy of Skyla was evaluated in a clinical trial that enrolled generally healthy women aged 18–35, 1,432 of whom received Skyla. Of these, 38.8 % (556) were nulliparous women, and 819 women completed 3 years of use. The trial was a multicenter, multi-national, randomized open-label study conducted in 11 countries in Europe, Latin America, the US and Canada. Women less than six weeks postpartum, with a history of ectopic pregnancy, with clinically significant ovarian cysts or with HIV or otherwise at high risk for sexually transmitted infections were excluded. A total of 540 (37.7%) were treated at US sites and 892 (62.3%) were at non-US sites. The racial demographics of enrolled women who received Skyla was: Caucasian (79.7%), Hispanic (11.5%), Black/African Americans (5.2%), Other (2.7%) and Asian (0.8%). The weight range was 38 to 155 kg (mean weight: 68.7 kg) and mean BMI was 25.3 kg/m2 (range 16–55 kg/m2). The clinical trial had no upper or lower weight or BMI limit. Of Skyla-treated women, 21.9% discontinued the study treatment due to an adverse event, 4.4% were lost to follow up, 1.8% withdrew for unspecified reasons, 1.1% discontinued due to protocol deviation, 0.6% discontinued due to pregnancy, and 13.0% discontinued due to other reasons. " }

The pregnancy rate calculated as the Pearl Index (PI) in women aged 18–35 years was the primary efficacy endpoint used to assess contraceptive reliability. The PI was calculated based on 28-day equivalent exposure cycles; evaluable cycles excluded those in which back-up contraception was used unless a pregnancy occurred in that cycle. Skyla-treated women provided 15,763 evaluable 28-day cycle equivalents in the first year and 39,368 evaluable cycles over the three year treatment period. The PI estimate for the first year of use based on the 5 pregnancies that occurred after the onset of treatment and within 7 days after Skyla removal or expulsion was 0.41 with a 95% upper confidence limit of 0.96. The cumulative 3-year pregnancy rate, based on 10 pregnancies, estimated by the Kaplan-Meier method was 0.9 per 100 women or 0.9%, with a 95% upper confidence limit of 1.7%.

{ "type": "p", "children": [], "text": "The pregnancy rate calculated as the Pearl Index (PI) in women aged 18–35 years was the primary efficacy endpoint used to assess contraceptive reliability. The PI was calculated based on 28-day equivalent exposure cycles; evaluable cycles excluded those in which back-up contraception was used unless a pregnancy occurred in that cycle. Skyla-treated women provided 15,763 evaluable 28-day cycle equivalents in the first year and 39,368 evaluable cycles over the three year treatment period. The PI estimate for the first year of use based on the 5 pregnancies that occurred after the onset of treatment and within 7 days after Skyla removal or expulsion was 0.41 with a 95% upper confidence limit of 0.96. The cumulative 3-year pregnancy rate, based on 10 pregnancies, estimated by the Kaplan-Meier method was 0.9 per 100 women or 0.9%, with a 95% upper confidence limit of 1.7%." }

1http://www.cdc.gov/std/tg2015/pid.htm. Accessed August 22, 2016.

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Skyla is supplied sterile. Skyla is sterilized with ethylene oxide. Do not resterilize. For single use only. Do not use if the inner package is damaged or open. Insert before the end of the month shown on the label.

{ "type": "p", "children": [], "text": "Skyla is supplied sterile. Skyla is sterilized with ethylene oxide. Do not resterilize. For single use only. Do not use if the inner package is damaged or open. Insert before the end of the month shown on the label." }

Store at 25°C (77°F); with excursions permitted between 15–30°C (59–86°F) [see USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store at 25°C (77°F); with excursions permitted between 15–30°C (59–86°F) [see USP Controlled Room Temperature]. " }

Advise the patient to read the FDA-approved patient labeling (Patient Information)

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Patient Information)" }

{ "type": "", "children": [], "text": "" }

Manufactured for:

{ "type": "p", "children": [], "text": "Manufactured for:" }

Bayer HealthCare Pharmaceuticals Inc.Whippany, NJ 07981

{ "type": "p", "children": [], "text": "Bayer HealthCare Pharmaceuticals Inc.Whippany, NJ 07981" }

© 2013, Bayer HealthCare Pharmaceuticals Inc.All rights reserved.

{ "type": "p", "children": [], "text": "© 2013, Bayer HealthCare Pharmaceuticals Inc.All rights reserved." }

<div class="scrollingtable"><table width="100%"> <col width="51%"/> <col width="49%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Patient Information</span> </p> <p> <span class="Bold">Skyla (sky-lah)</span> </p> <p>(levonorgestrel-releasing intrauterine system)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First">Read this Patient Information carefully before you decide if Skyla is right for you. This information does not take the place of talking with your gynecologist or other healthcare provider who specializes in women’s health. If you have any questions about Skyla, ask your healthcare provider. You should also learn about other birth control methods to choose the one that is best for you.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Skyla does not protect against HIV infection (AIDS) and other sexually transmitted infections (STIs).</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">What is Skyla?</span> </p> <dl> <dt>•</dt> <dd>Skyla is a hormone-releasing system placed in your uterus by your healthcare provider to prevent pregnancy for up to 3 years.</dd> <dt>•</dt> <dd>Skyla can be removed by your healthcare provider at any time.</dd> <dt>•</dt> <dd>Skyla can be used whether or not you have given birth to a child.</dd> </dl> <p>Skyla is a small, flexible plastic T-shaped system that slowly releases a progestin hormone called levonorgestrel (LNG) that is often used in birth control pills. Because Skyla releases LNG into your uterus, only small amounts of the hormone enter your blood. Skyla does not contain estrogen.</p> <p>Two thin threads are attached to the stem (lower end) of Skyla. The threads are the only part of Skyla you can feel when Skyla is in your uterus; however, unlike a tampon string, the threads do not extend outside your body.</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule" valign="top"><a name="id-1428654908"></a><img alt="Skyla is small" src="/dailymed/image.cfm?name=image-03.jpg&amp;setid=9f44ff35-e052-49cd-a1c2-0bfd87d49309"/><p class="First">Skyla is small</p> </td><td align="center" class="Botrule Rrule" valign="top"><a name="id1852380331"></a><img alt="Skyla is Flexible" src="/dailymed/image.cfm?name=image-04.jpg&amp;setid=9f44ff35-e052-49cd-a1c2-0bfd87d49309"/><p class="First">and flexible</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">What if I need birth control for more than 3 years?</span> </p> <p>Skyla must be removed after 3 years. Your healthcare provider can place a new Skyla during the same office visit if you choose to continue using Skyla.</p> <p> <span class="Bold">What if I want to stop using Skyla?</span> </p> <p>Skyla is intended for use up to 3 years but you can stop using Skyla at any time by asking your healthcare provider to remove it. You could become pregnant as soon as Skyla is removed, so you should use another method of birth control if you do not want to become pregnant. Talk to your healthcare provider about the best birth control methods for you, because your new method may need to be started 7 days before Skyla is removed to prevent pregnancy.</p> <p> <span class="Bold">What if I change my mind about birth control and want to become pregnant in less than 3 years?</span> </p> <p>Your healthcare provider can remove Skyla at any time. You may become pregnant as soon as Skyla is removed. About 3 out of 4 women who want to become pregnant will become pregnant sometime in the first year after Skyla is removed.</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">How does Skyla work?</span> </p> <p>Skyla may work in several ways including thickening cervical mucus, inhibiting sperm movement, reducing sperm survival, and thinning the lining of your uterus. It is not known exactly how these actions work together to prevent pregnancy.</p> <a name="id-1360653765"></a><img alt="Uterus" src="/dailymed/image.cfm?name=image-05.jpg&amp;setid=9f44ff35-e052-49cd-a1c2-0bfd87d49309"/></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">How well does Skyla work for contraception?</span> </p> <p>The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant.</p> <p>Skyla, an intrauterine device (IUD) also known as an intrauterine system (IUS),, is in the box at the top of the chart.</p> <a name="id-1627768992"></a><img alt="Pregnancy Chart" src="/dailymed/image.cfm?name=image-06.jpg&amp;setid=9f44ff35-e052-49cd-a1c2-0bfd87d49309"/><p> <span class="Bold">Who might use Skyla? </span> </p> <p>You might choose Skyla if you:</p> <dl> <dt>•</dt> <dd>want long-term birth control that provides a low chance of getting pregnant (less than 1 in 100)</dd> <dt>•</dt> <dd>want birth control that works continuously for up to 3 years </dd> <dt>•</dt> <dd>want birth control that is reversible</dd> <dt>•</dt> <dd>want a birth control method that you do not need to take daily</dd> <dt>•</dt> <dd>are willing to use a birth control method that is placed in the uterus </dd> <dt>•</dt> <dd>want birth control that does not contain estrogen</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Do not use Skyla if you:</span> </p> <dl> <dt>•</dt> <dd>are or might be pregnant; Skyla cannot be used as an emergency contraceptive </dd> <dt>•</dt> <dd>have a serious pelvic infection called pelvic inflammatory disease (PID) or have had PID in the past unless you have had a normal pregnancy after the infection went away</dd> <dt>•</dt> <dd>have an untreated genital infection now</dd> <dt>•</dt> <dd>have had a serious pelvic infection in the past 3 months after a pregnancy</dd> <dt>•</dt> <dd>can get infections easily. For example, if you:</dd> <dt>•</dt> <dd>have multiple sexual partners or your partner has multiple sexual partners</dd> <dt>•</dt> <dd>have problems with your immune system</dd> <dt>•</dt> <dd>use or abuse intravenous drugs</dd> <dt>•</dt> <dd>have or suspect you might have cancer of the uterus or cervix</dd> <dt>•</dt> <dd>have bleeding from the vagina that has not been explained</dd> <dt>•</dt> <dd>have liver disease or a liver tumor</dd> <dt>•</dt> <dd>have breast cancer or any other cancer that is sensitive to progestin (a female hormone), now or in the past</dd> <dt>•</dt> <dd>have an intrauterine device in your uterus already</dd> <dt>•</dt> <dd>have a condition of the uterus that changes the shape of the uterine cavity, such as large fibroid tumors</dd> <dt>•</dt> <dd>are allergic to levonorgestrel, silicone, polyethylene, silver, silica, barium sulfate or iron oxide</dd> </dl> <p> <span class="Bold">Before having Skyla placed, tell your healthcare provider about all of your medical conditions including if you:</span> </p> <dl> <dt>•</dt> <dd>have any of the conditions listed above</dd> <dt>•</dt> <dd>have had a heart attack</dd> <dt>•</dt> <dd>have had a stroke</dd> <dt>•</dt> <dd>were born with heart disease or have problems with your heart valves</dd> <dt>•</dt> <dd>have problems with blood clotting or take medicine to reduce clotting</dd> <dt>•</dt> <dd>have high blood pressure</dd> <dt>•</dt> <dd>recently had a baby or are breastfeeding</dd> <dt>•</dt> <dd>have severe headaches or migraine headaches</dd> <dt>•</dt> <dd>have AIDS, HIV, or any other sexually transmitted infection</dd> </dl> <p>Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">How is Skyla placed?</span> </p> <p>Skyla is placed by your healthcare provider during an in-office visit or immediately after giving birth.</p> <p>First, your healthcare provider will examine your pelvis to find the exact position of your uterus. Your healthcare provider will then clean your vagina and cervix with an antiseptic solution and slide a slim plastic tube containing Skyla through the cervix into your uterus. Your healthcare provider will then remove the plastic tube, and leave Skyla in your uterus. Your healthcare provider will cut the threads to the right length.</p> <p>You may experience pain, bleeding or dizziness during and after placement. If your symptoms do not pass within 30 minutes after placement, Skyla may not have been placed correctly. Your healthcare provider will examine you to see if Skyla needs to be removed or replaced.</p> <p> <span class="Bold">Should I check that Skyla is in place?</span> </p> <p>Yes, you should check that Skyla is in proper position by feeling the removal threads. It is a good habit to do this 1 time a month. Your healthcare provider should teach you how to check that Skyla is in place. First, wash your hands with soap and water. You can check by reaching up to the top of your vagina with clean fingers to feel the removal threads. Do not pull on the threads. If you feel more than just the threads or if you cannot feel the threads, Skyla may not be in the right position and may not prevent pregnancy. Avoid intercourse or use non-hormonal back-up birth control (such as condoms or spermicide) and ask your healthcare provider to check that Skyla is still in the right place.</p> <p> <span class="Bold">How soon after placement of Skyla should I return to my healthcare provider?</span> </p> <p>Call your healthcare provider if you have any questions or concerns (see “When should I call my healthcare provider?”). Otherwise, you should return to your healthcare provider for a follow-up visit 4 to 6 weeks after Skyla is placed to make sure that Skyla is in the right position.</p> <p> <span class="Bold">Can I use tampons or menstrual cups with Skyla?</span> </p> <p>Yes, tampons or menstrual cups may be used with Skyla. Change tampons or menstrual cups with care to avoid pulling the threads of Skyla. If you think you may have pulled Skyla out of place, avoid intercourse or use a non-hormonal back-up birth control (such as condoms or spermicide), and contact your healthcare provider.</p> <p> <span class="Bold">What if I become pregnant while using Skyla?</span> </p> <p>Call your healthcare provider right away if you think you may be pregnant. If possible, also do a urine pregnancy test. If you get pregnant while using Skyla, you may have an ectopic pregnancy. This means that the pregnancy is not in the uterus. Unusual vaginal bleeding or abdominal pain may be a sign of ectopic pregnancy.</p> <p>Ectopic pregnancy is a medical emergency that often requires surgery. Ectopic pregnancy can cause internal bleeding, infertility, and even death.</p> <p>There are also risks if you get pregnant while using Skyla and the pregnancy is in the uterus. Severe infection, miscarriage, premature delivery, and even death can occur with pregnancies that continue with an intrauterine device (IUD). Because of this, your healthcare provider may try to remove Skyla, even though removing it may cause a miscarriage. If Skyla cannot be removed, talk with your healthcare provider about the benefits and risks of continuing the pregnancy and possible effects of the hormone on your unborn baby. </p> <p>If you continue your pregnancy, see your healthcare provider regularly. Call your healthcare provider right away if you get flu-like symptoms, fever, chills, cramping, pain, bleeding, vaginal discharge, or fluid leaking from your vagina. These may be signs of infection.</p> <p> <span class="Bold">How will Skyla change my periods? </span> </p> <p>For the first 3 to 6 months, your period may become irregular and the number of bleeding days may increase. You may also have frequent spotting or light bleeding. Some women have heavy bleeding during this time. You may also have cramping during the first few weeks. After you have used Skyla for a while, the number of bleeding and spotting days is likely to lessen. For some women, periods will stop altogether. When Skyla is removed, your menstrual periods should return.</p> <p> <span class="Bold">Is it safe to breastfeed while using Skyla?</span> </p> <p>You may use Skyla when you are breastfeeding. Skyla is not likely to affect the quality or amount of your breast milk or the health of your nursing baby. However, isolated cases of decreased milk production have been reported. The risk of Skyla going into the wall of the uterus (becoming embedded) or going through the wall of the uterus is increased if Skyla is inserted while you are breastfeeding. </p> <p> <span class="Bold">Will Skyla interfere with sexual intercourse?</span> </p> <p>You and your partner should not feel Skyla during intercourse. Skyla is placed in the uterus, not in the vagina. Sometimes your partner may feel the threads. If this occurs, or if you or your partner experience pain during sex, talk with your healthcare provider.</p> <p> <span class="Bold">Can I have an MRI with Skyla in place?</span> </p> <p>Skyla can be safely scanned with MRI only under specific conditions. Before you have an MRI, tell your healthcare provider that you have Skyla, an intrauterine device (IUD), in place.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">What are the possible side effects of Skyla?</span> </p> <p> <span class="Bold">Skyla can cause serious side effects, including:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Ectopic pregnancy and intrauterine pregnancy risks.</span> There are risks if you become pregnant while using Skyla (see “What if I become pregnant while using Skyla?”). </dd> <dt>•</dt> <dd> <span class="Bold">Life-threatening infection.</span> Life-threatening infection can occur within the first few days after Skyla is placed. Call your healthcare provider immediately if you develop severe pain or fever shortly after Skyla is placed.</dd> <dt>•</dt> <dd> <span class="Bold">Pelvic inflammatory disease (PID).</span> Some IUD users get a serious pelvic infection called pelvic inflammatory disease. PID is usually sexually transmitted. You have a higher chance of getting PID if you or your partner has sex with other partners. PID can cause serious problems such as infertility, ectopic pregnancy or pelvic pain that does not go away. PID is usually treated with antibiotics. More serious cases of PID may require surgery including removal of the uterus (hysterectomy). In rare cases, infections that start as PID can even cause death.</dd> <dt> </dt> <dd>Tell your healthcare provider right away if you have any of these signs of PID: long-lasting or heavy bleeding, unusual vaginal discharge, low abdominal (stomach area) pain, painful sex, chills, fever, genital lesions or sores.</dd> <dt>•</dt> <dd> <span class="Bold">Perforation.</span> Skyla may go into the wall of the uterus (become embedded) or go through the wall of the uterus. This is called perforation. If this occurs, Skyla may no longer prevent pregnancy. If perforation occurs, Skyla may move outside the uterus and can cause internal scarring, infection, or damage to other organs, and you may need surgery to have Skyla removed. Excessive pain or vaginal bleeding during placement of Skyla, pain or bleeding that gets worse after placement, or not being able to feel the threads may happen with perforation. The risk of perforation is increased if Skyla is inserted while you are breastfeeding, or if you have recently given birth.</dd> <dt>•</dt> <dd> <span class="Bold">Expulsion.</span> Skyla may come out by itself. This is called expulsion. Expulsion occurs in about 3 out of 100 women. Excessive pain or vaginal bleeding during placement of Skyla, pain or bleeding that gets worse after placement, or not being able to feel the threads may happen with expulsion. You may become pregnant if Skyla comes out. If you think that Skyla has come out, avoid intercourse or use a non-hormonal backup birth control (such as condoms or spermicide) and call your healthcare provider. The risk of expulsion is increased with insertion right after delivery or second-trimester abortion. </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Common side effects of Skyla include: </span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Pain, bleeding or dizziness during and after placement.</span> If these symptoms do not stop 30 minutes after placement, Skyla may not have been placed correctly. Your healthcare provider will examine you to see if Skyla needs to be removed or replaced.</dd> <dt>•</dt> <dd> <span class="Bold">Changes in bleeding.</span> You may have bleeding and spotting between menstrual periods, especially during the first 3–6 months. Sometimes the bleeding is heavier than usual at first. However, the bleeding usually becomes lighter than usual and may be irregular. Call your healthcare provider if the bleeding remains heavier than usual or increases after it has been light for a while.</dd> <dt>•</dt> <dd> <span class="Bold">Missed menstrual periods.</span> About 1 out of 16 women stop having periods after 1 year of Skyla use. If you have any concerns that you may be pregnant while using Skyla, do a urine pregnancy test and call your healthcare provider. If you do not have a period for 6 weeks during Skyla use, call your healthcare provider. When Skyla is removed, your menstrual periods should return.</dd> <dt>•</dt> <dd> <span class="Bold">Cysts on the ovary.</span> About 14 out of 100 women using Skyla develop a cyst on the ovary. These cysts usually disappear on their own in two to three months. However, cysts can cause pain and sometimes cysts will need surgery.</dd> </dl> <p>Other common side effects include:</p> <dl> <dt>•</dt> <dd>abdominal or pelvic pain</dd> <dt>•</dt> <dd>acne or greasy skin</dd> <dt>•</dt> <dd>headache or migraine</dd> <dt>•</dt> <dd>inflammation or infection of the outer part of your vagina (vulvovaginitis)</dd> <dt>•</dt> <dd>painful periods</dd> </dl> <p>These are not all of the possible side effects with Skyla. For more information, ask your healthcare provider.</p> <p> <span class="Bold">Call your doctor for medical advice about side effects.</span> You may report side effects to FDA at 1-800-FDA-1088. </p> <p>You may also report side effects to Bayer Healthcare Pharmaceuticals at 1-888-842-2937.</p> <p> <span class="Bold">After Skyla has been placed, when should I call my healthcare provider?</span> </p> <p>If Skyla is accidentally removed and you had vaginal intercourse within the preceding week, you may be at risk of pregnancy, and you should talk to a healthcare provider.</p> <p>Call your healthcare provider if you have any concerns about Skyla. Be sure to call if you:</p> <dl> <dt>•</dt> <dd>think you are pregnant</dd> <dt>•</dt> <dd>have pelvic pain, abdominal pain, or pain during sex</dd> <dt>•</dt> <dd>have unusual vaginal discharge or genital sores</dd> <dt>•</dt> <dd>have unexplained fever, flu-like symptoms or chills</dd> <dt>•</dt> <dd>might be exposed to sexually transmitted infections (STIs)</dd> <dt>•</dt> <dd>are concerned that Skyla may have been expelled (came out)</dd> <dt>•</dt> <dd>cannot feel Skyla's threads</dd> <dt>•</dt> <dd>develop very severe or migraine headaches</dd> <dt>•</dt> <dd>have yellowing of the skin or whites of the eyes. These may be signs of liver problems.</dd> <dt>•</dt> <dd>have had a stroke or heart attack</dd> <dt>•</dt> <dd>become HIV positive or your partner becomes HIV positive</dd> <dt>•</dt> <dd>have severe vaginal bleeding or bleeding that lasts a long time or concerns you</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">General advice about the safe and effective use of Skyla</span> </p> <p>Medicines are sometimes prescribed for conditions other than those listed in patient information leaflets. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider for information about Skyla that is written for healthcare professionals.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">What are the ingredients in Skyla?</span> </p> <p>Active ingredient: levonorgestrel</p> <p>Inactive ingredients: silicone, polyethylene, silver, silica, barium sulfate, iron oxide</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First">Manufactured for: Bayer HealthCare Pharmaceuticals Inc.</p> <p>Whippany, NJ 07981</p> <p>© 2013, Bayer HealthCare Pharmaceuticals Inc.</p> <p>All rights reserved.</p> <p>For more information, go to www.skyla-us.com or call 1-888-842-2937.</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"51%\"/>\n<col width=\"49%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Patient Information</span>\n</p>\n<p>\n<span class=\"Bold\">Skyla (sky-lah)</span>\n</p>\n<p>(levonorgestrel-releasing intrauterine system)</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">Read this Patient Information carefully before you decide if Skyla is right for you. This information does not take the place of talking with your gynecologist or other healthcare provider who specializes in women’s health. If you have any questions about Skyla, ask your healthcare provider. You should also learn about other birth control methods to choose the one that is best for you.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Skyla does not protect against HIV infection (AIDS) and other sexually transmitted infections (STIs).</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is Skyla?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Skyla is a hormone-releasing system placed in your uterus by your healthcare provider to prevent pregnancy for up to 3 years.</dd>\n<dt>•</dt>\n<dd>Skyla can be removed by your healthcare provider at any time.</dd>\n<dt>•</dt>\n<dd>Skyla can be used whether or not you have given birth to a child.</dd>\n</dl>\n<p>Skyla is a small, flexible plastic T-shaped system that slowly releases a progestin hormone called levonorgestrel (LNG) that is often used in birth control pills. Because Skyla releases LNG into your uterus, only small amounts of the hormone enter your blood. Skyla does not contain estrogen.</p>\n<p>Two thin threads are attached to the stem (lower end) of Skyla. The threads are the only part of Skyla you can feel when Skyla is in your uterus; however, unlike a tampon string, the threads do not extend outside your body.</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule\" valign=\"top\"><a name=\"id-1428654908\"></a><img alt=\"Skyla is small\" src=\"/dailymed/image.cfm?name=image-03.jpg&amp;setid=9f44ff35-e052-49cd-a1c2-0bfd87d49309\"/><p class=\"First\">Skyla is small</p>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"><a name=\"id1852380331\"></a><img alt=\"Skyla is Flexible\" src=\"/dailymed/image.cfm?name=image-04.jpg&amp;setid=9f44ff35-e052-49cd-a1c2-0bfd87d49309\"/><p class=\"First\">and flexible</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What if I need birth control for more than 3 years?</span>\n</p>\n<p>Skyla must be removed after 3 years. Your healthcare provider can place a new Skyla during the same office visit if you choose to continue using Skyla.</p>\n<p>\n<span class=\"Bold\">What if I want to stop using Skyla?</span>\n</p>\n<p>Skyla is intended for use up to 3 years but you can stop using Skyla at any time by asking your healthcare provider to remove it. You could become pregnant as soon as Skyla is removed, so you should use another method of birth control if you do not want to become pregnant. Talk to your healthcare provider about the best birth control methods for you, because your new method may need to be started 7 days before Skyla is removed to prevent pregnancy.</p>\n<p>\n<span class=\"Bold\">What if I change my mind about birth control and want to become pregnant in less than 3 years?</span>\n</p>\n<p>Your healthcare provider can remove Skyla at any time. You may become pregnant as soon as Skyla is removed. About 3 out of 4 women who want to become pregnant will become pregnant sometime in the first year after Skyla is removed.</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How does Skyla work?</span>\n</p>\n<p>Skyla may work in several ways including thickening cervical mucus, inhibiting sperm movement, reducing sperm survival, and thinning the lining of your uterus. It is not known exactly how these actions work together to prevent pregnancy.</p>\n<a name=\"id-1360653765\"></a><img alt=\"Uterus\" src=\"/dailymed/image.cfm?name=image-05.jpg&amp;setid=9f44ff35-e052-49cd-a1c2-0bfd87d49309\"/></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How well does Skyla work for contraception?</span>\n</p>\n<p>The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant.</p>\n<p>Skyla, an intrauterine device (IUD) also known as an intrauterine system (IUS),, is in the box at the top of the chart.</p>\n<a name=\"id-1627768992\"></a><img alt=\"Pregnancy Chart\" src=\"/dailymed/image.cfm?name=image-06.jpg&amp;setid=9f44ff35-e052-49cd-a1c2-0bfd87d49309\"/><p>\n<span class=\"Bold\">Who might use Skyla? </span>\n</p>\n<p>You might choose Skyla if you:</p>\n<dl>\n<dt>•</dt>\n<dd>want long-term birth control that provides a low chance of getting pregnant (less than 1 in 100)</dd>\n<dt>•</dt>\n<dd>want birth control that works continuously for up to 3 years </dd>\n<dt>•</dt>\n<dd>want birth control that is reversible</dd>\n<dt>•</dt>\n<dd>want a birth control method that you do not need to take daily</dd>\n<dt>•</dt>\n<dd>are willing to use a birth control method that is placed in the uterus </dd>\n<dt>•</dt>\n<dd>want birth control that does not contain estrogen</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Do not use Skyla if you:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>are or might be pregnant; Skyla cannot be used as an emergency contraceptive </dd>\n<dt>•</dt>\n<dd>have a serious pelvic infection called pelvic inflammatory disease (PID) or have had PID in the past unless you have had a normal pregnancy after the infection went away</dd>\n<dt>•</dt>\n<dd>have an untreated genital infection now</dd>\n<dt>•</dt>\n<dd>have had a serious pelvic infection in the past 3 months after a pregnancy</dd>\n<dt>•</dt>\n<dd>can get infections easily. For example, if you:</dd>\n<dt>•</dt>\n<dd>have multiple sexual partners or your partner has multiple sexual partners</dd>\n<dt>•</dt>\n<dd>have problems with your immune system</dd>\n<dt>•</dt>\n<dd>use or abuse intravenous drugs</dd>\n<dt>•</dt>\n<dd>have or suspect you might have cancer of the uterus or cervix</dd>\n<dt>•</dt>\n<dd>have bleeding from the vagina that has not been explained</dd>\n<dt>•</dt>\n<dd>have liver disease or a liver tumor</dd>\n<dt>•</dt>\n<dd>have breast cancer or any other cancer that is sensitive to progestin (a female hormone), now or in the past</dd>\n<dt>•</dt>\n<dd>have an intrauterine device in your uterus already</dd>\n<dt>•</dt>\n<dd>have a condition of the uterus that changes the shape of the uterine cavity, such as large fibroid tumors</dd>\n<dt>•</dt>\n<dd>are allergic to levonorgestrel, silicone, polyethylene, silver, silica, barium sulfate or iron oxide</dd>\n</dl>\n<p>\n<span class=\"Bold\">Before having Skyla placed, tell your healthcare provider about all of your medical conditions including if you:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>have any of the conditions listed above</dd>\n<dt>•</dt>\n<dd>have had a heart attack</dd>\n<dt>•</dt>\n<dd>have had a stroke</dd>\n<dt>•</dt>\n<dd>were born with heart disease or have problems with your heart valves</dd>\n<dt>•</dt>\n<dd>have problems with blood clotting or take medicine to reduce clotting</dd>\n<dt>•</dt>\n<dd>have high blood pressure</dd>\n<dt>•</dt>\n<dd>recently had a baby or are breastfeeding</dd>\n<dt>•</dt>\n<dd>have severe headaches or migraine headaches</dd>\n<dt>•</dt>\n<dd>have AIDS, HIV, or any other sexually transmitted infection</dd>\n</dl>\n<p>Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How is Skyla placed?</span>\n</p>\n<p>Skyla is placed by your healthcare provider during an in-office visit or immediately after giving birth.</p>\n<p>First, your healthcare provider will examine your pelvis to find the exact position of your uterus. Your healthcare provider will then clean your vagina and cervix with an antiseptic solution and slide a slim plastic tube containing Skyla through the cervix into your uterus. Your healthcare provider will then remove the plastic tube, and leave Skyla in your uterus. Your healthcare provider will cut the threads to the right length.</p>\n<p>You may experience pain, bleeding or dizziness during and after placement. If your symptoms do not pass within 30 minutes after placement, Skyla may not have been placed correctly. Your healthcare provider will examine you to see if Skyla needs to be removed or replaced.</p>\n<p>\n<span class=\"Bold\">Should I check that Skyla is in place?</span>\n</p>\n<p>Yes, you should check that Skyla is in proper position by feeling the removal threads. It is a good habit to do this 1 time a month. Your healthcare provider should teach you how to check that Skyla is in place. First, wash your hands with soap and water. You can check by reaching up to the top of your vagina with clean fingers to feel the removal threads. Do not pull on the threads. If you feel more than just the threads or if you cannot feel the threads, Skyla may not be in the right position and may not prevent pregnancy. Avoid intercourse or use non-hormonal back-up birth control (such as condoms or spermicide) and ask your healthcare provider to check that Skyla is still in the right place.</p>\n<p>\n<span class=\"Bold\">How soon after placement of Skyla should I return to my healthcare provider?</span>\n</p>\n<p>Call your healthcare provider if you have any questions or concerns (see “When should I call my healthcare provider?”). Otherwise, you should return to your healthcare provider for a follow-up visit 4 to 6 weeks after Skyla is placed to make sure that Skyla is in the right position.</p>\n<p>\n<span class=\"Bold\">Can I use tampons or menstrual cups with Skyla?</span>\n</p>\n<p>Yes, tampons or menstrual cups may be used with Skyla. Change tampons or menstrual cups with care to avoid pulling the threads of Skyla. If you think you may have pulled Skyla out of place, avoid intercourse or use a non-hormonal back-up birth control (such as condoms or spermicide), and contact your healthcare provider.</p>\n<p>\n<span class=\"Bold\">What if I become pregnant while using Skyla?</span>\n</p>\n<p>Call your healthcare provider right away if you think you may be pregnant. If possible, also do a urine pregnancy test. If you get pregnant while using Skyla, you may have an ectopic pregnancy. This means that the pregnancy is not in the uterus. Unusual vaginal bleeding or abdominal pain may be a sign of ectopic pregnancy.</p>\n<p>Ectopic pregnancy is a medical emergency that often requires surgery. Ectopic pregnancy can cause internal bleeding, infertility, and even death.</p>\n<p>There are also risks if you get pregnant while using Skyla and the pregnancy is in the uterus. Severe infection, miscarriage, premature delivery, and even death can occur with pregnancies that continue with an intrauterine device (IUD). Because of this, your healthcare provider may try to remove Skyla, even though removing it may cause a miscarriage. If Skyla cannot be removed, talk with your healthcare provider about the benefits and risks of continuing the pregnancy and possible effects of the hormone on your unborn baby. </p>\n<p>If you continue your pregnancy, see your healthcare provider regularly. Call your healthcare provider right away if you get flu-like symptoms, fever, chills, cramping, pain, bleeding, vaginal discharge, or fluid leaking from your vagina. These may be signs of infection.</p>\n<p>\n<span class=\"Bold\">How will Skyla change my periods? </span>\n</p>\n<p>For the first 3 to 6 months, your period may become irregular and the number of bleeding days may increase. You may also have frequent spotting or light bleeding. Some women have heavy bleeding during this time. You may also have cramping during the first few weeks. After you have used Skyla for a while, the number of bleeding and spotting days is likely to lessen. For some women, periods will stop altogether. When Skyla is removed, your menstrual periods should return.</p>\n<p>\n<span class=\"Bold\">Is it safe to breastfeed while using Skyla?</span>\n</p>\n<p>You may use Skyla when you are breastfeeding. Skyla is not likely to affect the quality or amount of your breast milk or the health of your nursing baby. However, isolated cases of decreased milk production have been reported. The risk of Skyla going into the wall of the uterus (becoming embedded) or going through the wall of the uterus is increased if Skyla is inserted while you are breastfeeding. </p>\n<p>\n<span class=\"Bold\">Will Skyla interfere with sexual intercourse?</span>\n</p>\n<p>You and your partner should not feel Skyla during intercourse. Skyla is placed in the uterus, not in the vagina. Sometimes your partner may feel the threads. If this occurs, or if you or your partner experience pain during sex, talk with your healthcare provider.</p>\n<p>\n<span class=\"Bold\">Can I have an MRI with Skyla in place?</span>\n</p>\n<p>Skyla can be safely scanned with MRI only under specific conditions. Before you have an MRI, tell your healthcare provider that you have Skyla, an intrauterine device (IUD), in place.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of Skyla?</span>\n</p>\n<p>\n<span class=\"Bold\">Skyla can cause serious side effects, including:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Ectopic pregnancy and intrauterine pregnancy risks.</span> There are risks if you become pregnant while using Skyla (see “What if I become pregnant while using Skyla?”). </dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Life-threatening infection.</span> Life-threatening infection can occur within the first few days after Skyla is placed. Call your healthcare provider immediately if you develop severe pain or fever shortly after Skyla is placed.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Pelvic inflammatory disease (PID).</span> Some IUD users get a serious pelvic infection called pelvic inflammatory disease. PID is usually sexually transmitted. You have a higher chance of getting PID if you or your partner has sex with other partners. PID can cause serious problems such as infertility, ectopic pregnancy or pelvic pain that does not go away. PID is usually treated with antibiotics. More serious cases of PID may require surgery including removal of the uterus (hysterectomy). In rare cases, infections that start as PID can even cause death.</dd>\n<dt> </dt>\n<dd>Tell your healthcare provider right away if you have any of these signs of PID: long-lasting or heavy bleeding, unusual vaginal discharge, low abdominal (stomach area) pain, painful sex, chills, fever, genital lesions or sores.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Perforation.</span> Skyla may go into the wall of the uterus (become embedded) or go through the wall of the uterus. This is called perforation. If this occurs, Skyla may no longer prevent pregnancy. If perforation occurs, Skyla may move outside the uterus and can cause internal scarring, infection, or damage to other organs, and you may need surgery to have Skyla removed. Excessive pain or vaginal bleeding during placement of Skyla, pain or bleeding that gets worse after placement, or not being able to feel the threads may happen with perforation. The risk of perforation is increased if Skyla is inserted while you are breastfeeding, or if you have recently given birth.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Expulsion.</span> Skyla may come out by itself. This is called expulsion. Expulsion occurs in about 3 out of 100 women. Excessive pain or vaginal bleeding during placement of Skyla, pain or bleeding that gets worse after placement, or not being able to feel the threads may happen with expulsion. You may become pregnant if Skyla comes out. If you think that Skyla has come out, avoid intercourse or use a non-hormonal backup birth control (such as condoms or spermicide) and call your healthcare provider. The risk of expulsion is increased with insertion right after delivery or second-trimester abortion. </dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Common side effects of Skyla include: </span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Pain, bleeding or dizziness during and after placement.</span> If these symptoms do not stop 30 minutes after placement, Skyla may not have been placed correctly. Your healthcare provider will examine you to see if Skyla needs to be removed or replaced.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Changes in bleeding.</span> You may have bleeding and spotting between menstrual periods, especially during the first 3–6 months. Sometimes the bleeding is heavier than usual at first. However, the bleeding usually becomes lighter than usual and may be irregular. Call your healthcare provider if the bleeding remains heavier than usual or increases after it has been light for a while.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Missed menstrual periods.</span> About 1 out of 16 women stop having periods after 1 year of Skyla use. If you have any concerns that you may be pregnant while using Skyla, do a urine pregnancy test and call your healthcare provider. If you do not have a period for 6 weeks during Skyla use, call your healthcare provider. When Skyla is removed, your menstrual periods should return.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Cysts on the ovary.</span> About 14 out of 100 women using Skyla develop a cyst on the ovary. These cysts usually disappear on their own in two to three months. However, cysts can cause pain and sometimes cysts will need surgery.</dd>\n</dl>\n<p>Other common side effects include:</p>\n<dl>\n<dt>•</dt>\n<dd>abdominal or pelvic pain</dd>\n<dt>•</dt>\n<dd>acne or greasy skin</dd>\n<dt>•</dt>\n<dd>headache or migraine</dd>\n<dt>•</dt>\n<dd>inflammation or infection of the outer part of your vagina (vulvovaginitis)</dd>\n<dt>•</dt>\n<dd>painful periods</dd>\n</dl>\n<p>These are not all of the possible side effects with Skyla. For more information, ask your healthcare provider.</p>\n<p>\n<span class=\"Bold\">Call your doctor for medical advice about side effects.</span> You may report side effects to FDA at 1-800-FDA-1088. </p>\n<p>You may also report side effects to Bayer Healthcare Pharmaceuticals at 1-888-842-2937.</p>\n<p>\n<span class=\"Bold\">After Skyla has been placed, when should I call my healthcare provider?</span>\n</p>\n<p>If Skyla is accidentally removed and you had vaginal intercourse within the preceding week, you may be at risk of pregnancy, and you should talk to a healthcare provider.</p>\n<p>Call your healthcare provider if you have any concerns about Skyla. Be sure to call if you:</p>\n<dl>\n<dt>•</dt>\n<dd>think you are pregnant</dd>\n<dt>•</dt>\n<dd>have pelvic pain, abdominal pain, or pain during sex</dd>\n<dt>•</dt>\n<dd>have unusual vaginal discharge or genital sores</dd>\n<dt>•</dt>\n<dd>have unexplained fever, flu-like symptoms or chills</dd>\n<dt>•</dt>\n<dd>might be exposed to sexually transmitted infections (STIs)</dd>\n<dt>•</dt>\n<dd>are concerned that Skyla may have been expelled (came out)</dd>\n<dt>•</dt>\n<dd>cannot feel Skyla's threads</dd>\n<dt>•</dt>\n<dd>develop very severe or migraine headaches</dd>\n<dt>•</dt>\n<dd>have yellowing of the skin or whites of the eyes. These may be signs of liver problems.</dd>\n<dt>•</dt>\n<dd>have had a stroke or heart attack</dd>\n<dt>•</dt>\n<dd>become HIV positive or your partner becomes HIV positive</dd>\n<dt>•</dt>\n<dd>have severe vaginal bleeding or bleeding that lasts a long time or concerns you</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">General advice about the safe and effective use of Skyla</span>\n</p>\n<p>Medicines are sometimes prescribed for conditions other than those listed in patient information leaflets. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider for information about Skyla that is written for healthcare professionals.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in Skyla?</span>\n</p>\n<p>Active ingredient: levonorgestrel</p>\n<p>Inactive ingredients: silicone, polyethylene, silver, silica, barium sulfate, iron oxide</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\">\n<p class=\"First\">Manufactured for: Bayer HealthCare Pharmaceuticals Inc.</p>\n<p>Whippany, NJ 07981</p>\n<p>© 2013, Bayer HealthCare Pharmaceuticals Inc.</p>\n<p>All rights reserved.</p>\n<p>For more information, go to www.skyla-us.com or call 1-888-842-2937.</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

This Patient Information has been approved by the U.S. Food and Drug Administration. 7/2021

{ "type": "p", "children": [], "text": "This Patient Information has been approved by the U.S. Food and Drug Administration.\t7/2021" }

Skyla (levonorgestrel-releasing intrauterine system) Carton

{ "type": "p", "children": [], "text": "Skyla (levonorgestrel-releasing intrauterine system) Carton " }

NDC 50419-422-01

{ "type": "p", "children": [], "text": "NDC 50419-422-01 " }

1 Sterile Unit

{ "type": "p", "children": [], "text": "1 Sterile Unit " }

IMPORTANT: To be inserted in the uterus by or under the supervision of a licensed clinician. See physician insert for detailed instructions for use.

{ "type": "p", "children": [], "text": "\nIMPORTANT: To be inserted in the uterus by or under the supervision of a licensed clinician. See physician insert for detailed instructions for use. \n" }

Skyla

{ "type": "p", "children": [], "text": "\nSkyla \n" }

(levonorgestrel-releasing intrauterine system)

{ "type": "p", "children": [], "text": "\n(levonorgestrel-releasing intrauterine system) \n" }

Rx only

{ "type": "p", "children": [], "text": "\nRx only \n" }

— 13.5 mg levonorgestrel

{ "type": "p", "children": [], "text": "— 13.5 mg levonorgestrel" }

— 1 sterile unit

{ "type": "p", "children": [], "text": "— 1 sterile unit" }

— intrauterine use

{ "type": "p", "children": [], "text": "— intrauterine use" }

TWIRLA is indicated as a method of contraception for use in women of reproductive potential with a BMI < 30 kg/m2 for whom a combined hormonal contraceptive is appropriate.

{ "type": "p", "children": [], "text": "TWIRLA is indicated as a method of contraception for use in women of reproductive potential with a BMI < 30 kg/m2 for whom a combined hormonal contraceptive is appropriate." }

Limitation of Use Consider TWIRLA’s reduced effectiveness in women with a BMI ≥ 25 to < 30 kg/m2 before prescribing TWIRLA [see Use in Specific Populations (8.9) and Clinical Studies (14)]. TWIRLA is contraindicated in women with a BMI ≥ 30 kg/m2 [see Contraindications (4)].

{ "type": "p", "children": [], "text": "\nLimitation of Use\nConsider TWIRLA’s reduced effectiveness in women with a BMI ≥ 25 to < 30 kg/m2 before prescribing TWIRLA [see Use in Specific Populations (8.9) and Clinical Studies (14)]. TWIRLA is contraindicated in women with a BMI ≥ 30 kg/m2 [see Contraindications (4)]." }

See the FDA-approved patient labeling (Instructions for Use).

The TWIRLA transdermal system (TDS) is used in a 28-day (four-week) cycle. A new TDS is applied and worn for seven days for three consecutive weeks (Weeks 1, 2, and 3). No TDS is worn during Week 4 (the TDS-Free Week), when withdrawal bleeding is expected.

On the day after Week 4 ends, a new 28-day cycle is started by applying a new TDS. Under no circumstances should there be more than a 7-day TDS-free interval between dosing cycles.

Breakthrough (Unscheduled) Bleeding or Spotting Occurrence If unscheduled (breakthrough) spotting or bleeding occurs, instruct the woman to continue the same regimen. If the bleeding is persistent or prolonged consider causes other than TWIRLA. If the bleeding is persistent or prolonged, instruct the woman to consult with her healthcare provider.

In Case of Skin Irritation If TDS use results in uncomfortable irritation, the TDS may be removed, and a new TDS may be applied to a different location until the next “Patch Change Day”. Only one TDS should be worn at a time.

Every new TDS should be applied on the same day of the week. This day is known as the “Patch Change Day.” For example, if the first TDS is applied on a Sunday, all subsequent TDS should be applied on a Sunday.

There are multiple options for starting the TDS, and the woman should choose the option that is most appropriate (see Table 1):

<div class="scrollingtable"><table border="1" cellpadding="5" cellspacing="0"> <caption> <span>Table 1: Instructions for Administration</span> </caption> <colgroup> <col class="Lrule Rrule"/> <col class="Lrule Rrule"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First First Toprule"> <td class="Lrule Lrule Rrule Rrule" valign="top"> <p class="BodyTextRA First First"> <span class="Bold">Starting TWIRLA in women with no current use of hormonal contraception</span> </p> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <p class="BodyTextRA First First"> <span class="Underline">Day 1 Start</span> </p> <ul> <li>The woman should apply the first TDS during the first 24 hours of menstruation. The woman should apply a new TDS each week for three weeks (21 total days). No TDS is worn during Week Four (the “Patch-Free Week”).</li> <li>If a TDS is applied after the first 24 hours of menstruation, non-hormonal back-up contraception (such as condoms and spermicide, or diaphragm and spermicide) is needed for the first 7 days of the first cycle only.</li> </ul> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule" valign="top"> <p class="BodyTextRA First First"> <span class="Bold">Switching from another contraceptive method </span> </p> <ul> <li> <span class="Bold">Oral combination hormonal contraception (oral CHC)</span> </li> </ul> <p class="BodyTextRA"></p> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <p class="BodyTextRA First First">Start TWIRLA:</p> <p class="BodyTextRA"></p> <ul> <li>The woman should complete the current pill cycle and apply the first TWIRLA TDS on the day the next pill cycle would normally start.</li> <li>If menses does not occur within a week after taking the last active pill, instruct the woman to consult with a healthcare professional to be sure that pregnancy has not occurred. If no pregnancy has occurred, TWIRLA may be started for contraception.</li> <li>If TWIRLA is applied more than a week after taking the last active pill, non-hormonal back-up contraception (such as condoms and spermicide, or diaphragm and spermicide) should be used concurrently for the first 7 days of TDS use.</li> </ul> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li> <span class="Bold"> Transdermal system</span> </li> </ul> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li>The woman should complete the current TDS cycle and apply the first TWIRLA TDS on the day the next TDS cycle would normally start.</li> <li>If menses does not occur within a week after removing the last TDS, instruct the woman to consult with a healthcare professional to be sure that pregnancy has not occurred. If no pregnancy has occurred, TWIRLA may be started for contraception.</li> <li>If TWIRLA is applied more than a week after removal of the last TDS, non-hormonal back-up contraception (such as condoms and spermicide, or diaphragm and spermicide) should be used concurrently for the first 7 days of TDS use.</li> </ul> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li> <span class="Bold"> Vaginal ring</span> </li> </ul> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li>The woman should complete the current vaginal ring cycle and apply the first TWIRLA TDS on the day the next vaginal ring would normally be inserted.</li> <li>If menses does not occur within a week after removing the last vaginal ring, instruct the woman to consult with a healthcare professional to be sure that pregnancy has not occurred. If no pregnancy has occurred, TWIRLA may be started for contraception.</li> <li>If TWIRLA is applied more than a week after removal of the last vaginal ring, non-hormonal back-up contraception (such as condoms and spermicide, or diaphragm and spermicide) should be used concurrently for the first 7 days of TDS use.</li> </ul> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li> <span class="Bold">Injection</span> </li> </ul> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li>The woman should apply the first TDS on the day the next injection would normally occur.</li> </ul> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li> <span class="Bold">Intrauterine system (IUS)</span> </li> </ul> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li>The woman should apply the first TDS on the day of IUS removal.</li> </ul> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li> <span class="Bold">Implant</span> </li> </ul> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li>The woman should apply the first TDS on the day of implant removal.</li> </ul> </td> </tr> <tr class="Botrule Last Last Toprule"> <td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li> <span class="Bold"> Progestin-only pill</span> </li> </ul> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li>The woman should apply the first TDS on the day the next progestin-only pill cycle would normally start.</li> </ul> </td> </tr> </tbody> </table></div>

Use after an abortion or miscarriage: TWIRLA may be started immediately for contraception within the first 5 days following a complete first trimester abortion or miscarriage without additional back-up contraception. If more than 5 days have elapsed from the first trimester abortion or miscarriage, then the woman should be advised to use non-hormonal contraception (such as condoms and spermicide, or diaphragm and spermicide) and follow instructions for starting TWIRLA for the first time. Ovulation may occur within 10 days of an abortion or miscarriage.

TWIRLA should not be started earlier than 4 weeks after a second trimester abortion or miscarriage due to the increased risk of thromboembolism [see Warnings and Precautions (5.1)].

Use of TWIRLA after childbirth: For women who elect not to breastfeed, do not start TWIRLA sooner than 4 weeks after childbirth given the increased risk for thromboembolism [see Use in Specific Populations (8.2)].

If a woman begins using TWIRLA postpartum and has not yet had a period, consider the possibility of ovulation and pregnancy. If the woman is not pregnant, instruct her to use non-hormonal back-up contraception (such as condoms and spermicide, or diaphragm and spermicide) for the first 7 days of TDS use [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].

MANAGING PARTIAL OR COMPLETE TDS DETACHMENTS (see Table 2) The TWIRLA TDS must adhere securely to the skin to work properly. Prolonged water exposure may compromise the TDS’s adherence. As a result, the woman should be instructed to check the TDS for partial or complete TDS detachment not only daily but also after prolonged water exposure.

If the TDS becomes partially or completely detached and remains detached, insufficient drug delivery may occur. Partial TDS detachment should be resolved since it can lead to the TDS getting caught on clothing and detaching. The woman should not try to reapply a TDS if it is no longer sticky, if it has become stuck to itself or another surface, and/or if it has other material stuck to it.

If a TDS edge lifts up:

If the TDS has been off or partially off:

Instruct women about the handling of missed doses (e.g., missed or delayed TDS application) and to follow the dosing instructions provided in the FDA-approved patient labeling.

FORGETTING TO CHANGE THE TDS:

<div class="scrollingtable"><table cellpadding="5" width="100%"> <caption> <span>Table 2: Managing Partial or Complete TDS Detachments and Late/Missed TDS Applications</span> </caption> <col align="left" valign="bottom" width="55%"/> <col align="left" valign="bottom" width="15%"/> <col align="left" valign="bottom" width="15%"/> <col align="left" valign="bottom" width="15%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Botrule Lrule Rrule Toprule"> Scenario</td><td align="center" class="Botrule Lrule Rrule Toprule">Results in<br/>New TDS-<br/>Change Day</td><td align="center" class="Botrule Lrule Rrule Toprule">Back-up Contraception Required<br/>(7 Days)</td><td align="center" class="Botrule Lrule Rrule Toprule">Starts<br/>New Cycle</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"> Did not apply TDS on scheduled Day 1/Week 1 of new cycle (late TDS-on day)</td><td align="center" class="Botrule Lrule Rrule Toprule">Yes</td><td align="center" class="Botrule Lrule Rrule Toprule">Yes</td><td align="center" class="Botrule Lrule Rrule Toprule">Yes</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"> TDS detached for &lt; 24 hours</td><td align="center" class="Botrule Lrule Rrule Toprule">No</td><td align="center" class="Botrule Lrule Rrule Toprule">No</td><td align="center" class="Botrule Lrule Rrule Toprule">No</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"> TDS detached for ≥ 24 hours, or unsure duration</td><td align="center" class="Botrule Lrule Rrule Toprule">Yes</td><td align="center" class="Botrule Lrule Rrule Toprule">Yes</td><td align="center" class="Botrule Lrule Rrule Toprule">Yes</td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"> &lt; 48 hours late for Patch Change Day (Day 8 or 15)</td><td align="center" class="Botrule Lrule Rrule Toprule">No</td><td align="center" class="Botrule Lrule Rrule Toprule">No</td><td align="center" class="Botrule Lrule Rrule Toprule">No </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule"> ≥ 48 hours late for Patch Change Day (Day 8 or 15)</td><td align="center" class="Botrule Lrule Rrule Toprule">Yes</td><td align="center" class="Botrule Lrule Rrule Toprule">Yes</td><td align="center" class="Botrule Lrule Rrule Toprule">Yes</td> </tr> <tr class="Last"> <td align="left" class="Botrule Lrule Rrule Toprule"> Forgets to remove last TDS on Day 22</td><td align="center" class="Botrule Lrule Rrule Toprule">No</td><td align="center" class="Botrule Lrule Rrule Toprule">No</td><td align="center" class="Botrule Lrule Rrule Toprule">No</td> </tr> </tbody> </table></div>

Under no circumstances should there be more than a seven-day TDS-free interval between cycles. If there are more than 7 TDS-free days, THE WOMAN MAY NOT BE PROTECTED FROM PREGNANCY and non-hormonal back-up contraception (such as a condoms and spermicide, or diaphragm and spermicide) must be used for 7 days. As with CHCs, the risk of ovulation increases with each day beyond the recommended drug-free period. If the woman has intercourse during such an extended TDS-free interval, consider the possibility of pregnancy.

TWIRLA (120 mcg/day levonorgestrel and 30 mcg/day ethinyl estradiol) transdermal system is a circular beige colored product with the name and strength etched on the backing membrane.

{ "type": "p", "children": [], "text": "TWIRLA (120 mcg/day levonorgestrel and 30 mcg/day ethinyl estradiol) transdermal system is a circular beige colored product with the name and strength etched on the backing membrane." }

Twirla is contraindicated in females who are known to have or develop the following conditions:

{ "type": "p", "children": [], "text": "Twirla is contraindicated in females who are known to have or develop the following conditions:" }

{ "type": "ul", "children": [ "At high risk of arterial or venous thrombotic diseases. Examples include women who\n\nSmoke, if over age 35 [see Boxed Warning and Warnings and Precautions (5.1)]\n\nHave current or history of deep vein thrombosis or pulmonary embolism [see Warnings and Precautions (5.1)]\n\nHave cerebrovascular disease [see Warnings and Precautions (5.1)]\n\nHave coronary artery disease [see Warnings and Precautions (5.1)]\n\nHave thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings and Precautions (5.1)]\n\nHave inherited or acquired hypercoagulopathies [see Warnings and Precautions (5.1)]\n\nHave uncontrolled hypertension or hypertension with vascular disease [see Warnings and Precautions (5.4)]\n\nHave diabetes mellitus and are over age 35, diabetes mellitus with hypertension or vascular disease or other end-organ damage, or diabetes mellitus of > 20 years duration [see Warnings and Precautions (5.7)]\n\n\n", "Have headaches with focal neurological symptoms, migraine headaches with aura", "Women over age 35 with any migraine headaches [see Warnings and Precautions (5.8)]\n", "BMI ≥ 30 kg/m2. Compared to women with a lower BMI, women with a BMI ≥ 30 kg/m2 had reduced effectiveness and may have a higher risk for VTEs [see Warnings and Precautions (5.1), Use in Specific Populations (8.9) and Clinical Studies (14)].\n", "Liver tumors (benign or malignant), acute viral hepatitis, or severe (decompensated) cirrhosis, or liver disease [see Warnings and Precautions (5.2)]\n", "Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.9)]\n", "Pregnancy, because there is no reason to use CHCs during pregnancy [see Use in Specific Populations (8.1)]\n", "Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions (5.11)]\n", "Hypersensitivity to any components of TWIRLA. Observed reactions include itching and irritation at the TDS application site [see Adverse Reactions (6.1)]\n", "Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for alanine aminotransferase (ALT) elevations [see Warnings and Precautions (5.3)]\n" ], "text": "" }

Women are at increased risk for a venous thromboembolic event (VTE) when using CHCs, including TWIRLA. The risk of VTE may be greater in women with a BMI ≥ 30 kg/m2 compared to women with a lower BMI, and TWIRLA is contraindicated in obese patients [see Contraindications (4)]. In the Phase 3 clinical trial, four TWIRLA-treated women experienced a VTE. All of these women had a BMI > 30 kg/m2 [see Adverse Reactions (6.1)]. 

Arterial Events CHCs increase the risk of cardiovascular events and cerebrovascular events, such as myocardial infarction and stroke. The risk is greater among older women (> 35 years of age), smokers, and women with hypertension, dyslipidemia, diabetes, or obesity.

TWIRLA is contraindicated in women over 35 years of age who smoke [see Contraindications (4)]. Cigarette smoking increases the risk of serious cardiovascular events from CHC use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked.

Venous Events The use of CHCs increases the risk of VTEs, such as deep vein thrombosis and pulmonary embolism. Risk factors for VTEs include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of CHCs. While the increased risk of VTE associated with the use of CHCs is well-established, the rates of VTE are even greater during pregnancy, especially during the postpartum period (see Figure 1). The rate of VTE in women using CHCs has been estimated to be 3 to 12 cases per 10,000 woman-years for non-oral CHCs.

The risk of VTE is highest during the first year of use of a combined oral contraceptive (COC) and when restarting hormonal contraception after a break of four weeks or longer. This initial higher risk declines during the first year, but users of CHCs remain at an increased risk of VTE compared to non-users of CHCs. Based on results from a few studies, there is some evidence that this is true for non-oral products as well. The risk of thromboembolic disease due to CHCs gradually disappears after CHC use is discontinued.

Figure 1 shows the risk of developing a VTE for women who are not pregnant and do not use hormonal contraceptives, for women who use hormonal contraceptives with a range of doses and routes of administration, for pregnant women, and for women in the postpartum period. To put the risk of developing a VTE into perspective: If 10,000 women who are not pregnant and do not use hormonal contraceptives are followed for one year, between 1 and 5 of these women will develop a VTE.

Figure 1. Likelihood of Developing a VTE Within One Year Among Pregnant and Non-Pregnant Women

*CHC = combination hormonal contraception** Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy duration is 9 months, the rate is 7 to 27 per 10,000 WY.

Elevated Liver Enzymes TWIRLA is contraindicated in women with acute viral hepatitis or severe (decompensated) cirrhosis of the liver [see Contraindications (4)]. Discontinue TWIRLA if jaundice develops. Acute liver test abnormalities may necessitate the discontinuation of CHC use until the liver tests return to normal and CHC causation has been excluded.

Liver Tumors TWIRLA is contraindicated in women with benign or malignant liver tumors [see Contraindications (4)]. CHCs increase the risk of hepatic adenomas. An estimate of the attributable risk is 3.3 cases/100,000 CHC users. Rupture of hepatic adenomas may cause death from abdominal hemorrhage.

Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (> 8 years) CHC users. The attributable risk of liver cancers in CHC users is less than one case per million users.

During clinical trials with the Hepatitis C combination drug regimen that contains ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN), including some cases greater than 20 times the ULN, were significantly more frequent in women using ethinyl estradiol-containing medications, such as CHCs. CHCs, such as TWIRLA, are contraindicated for use with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see Contraindications (4)]. Discontinue TWIRLA prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. TWIRLA can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.

TWIRLA is contraindicated in women with uncontrolled hypertension or hypertension with vascular disease [see Contraindications (4)]. For all women, including those with well-controlled hypertension, monitor blood pressure at routine visits and stop TWIRLA if blood pressure rises significantly.

An increase in blood pressure has been reported in women using CHCs, and this increase is more likely in older women with extended duration of use. The effect of CHCs on blood pressure may vary according to the progestin in the CHC.

The risk for cardiovascular disease and prevalence of risk factors for cardiovascular disease increase with age. Certain conditions, such as smoking and migraine headache without aura, that do not contraindicate CHC use in younger women, are contraindications to use in women over 35 years of age [see Contraindications (4) and Warnings and Precautions (5.1)]. Consider the presence of underlying risk factors that may increase the risk of cardiovascular disease or VTE, particularly before initiating a CHC for women over 35 years, such as:

Studies suggest an increased risk of developing gallbladder disease among CHC users. Use of CHCs may also worsen existing gallbladder disease.

A past history of CHC-related cholestasis predicts an increased risk with subsequent CHC use. Women with a history of pregnancy-related cholestasis may be at an increased risk for CHC-related cholestasis.

Hyperglycemia TWIRLA is contraindicated in diabetic women over age 35, or women who have diabetes with hypertension, nephropathy, retinopathy, neuropathy, other vascular disease, or women with diabetes of > 20 years duration [see Contraindications (4)]. TWIRLA may decrease glucose tolerance. Carefully monitor prediabetic and diabetic women who are using TWIRLA.

Dyslipidemia Consider alternative contraception for women with uncontrolled dyslipidemia. TWIRLA may cause adverse lipid changes.

Women with hypertriglyceridemia, or a family history thereof, may have an increase in serum triglyceride concentrations when using TWIRLA, which may increase the risk of pancreatitis.

TWIRLA is contraindicated in women who have headaches with focal neurological symptoms or have migraine headaches with aura, and in women over age 35 years who have migraine headaches with or without aura [see Contraindications (4)].

If a woman using TWIRLA develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue TWIRLA if indicated. Consider discontinuation of TWIRLA if there is any increased frequency or severity of migraines during CHC use (which may be prodromal of a cerebrovascular event).

Unscheduled and Scheduled Bleeding and Spotting Women using TWIRLA may experience unscheduled (breakthrough or intracyclic) bleeding and spotting, especially during the first three months of use. Bleeding irregularities may resolve over time or by changing to a different contraceptive product. If bleeding persists or occurs after previously regular cycles on TWIRLA, evaluate for causes such as pregnancy or malignancy.

Based on women’s electronic diaries from a clinical trial evaluating the safety and efficacy of TWIRLA, the proportion of subjects reporting unscheduled bleeding per 28-day cycle decreased over time. At cycle 1 and 2, 60.4% and 52.6%, respectively reported unscheduled bleeding and/or spotting. At cycle 13, 42.3% of women reported unscheduled bleeding and/or spotting. Women reported a mean number of unscheduled bleeding/spotting days per month that generally decreased over the 13 cycles and was a mean of 1.6 days in Cycle 13. A total of 45 women (2.2%) discontinued the study prematurely due to menstrual disorders including metrorrhagia, vaginal hemorrhage, menorrhagia, dysmenorrhea, irregular menstruation, dysfunctional uterine bleeding, and menstrual disorder [see Clinical Trial Experience (6.1) and Clinical Studies (14)].

Amenorrhea and Oligomenorrhea Women who use TWIRLA may experience absence of scheduled (withdrawal) bleeding, even if they are not pregnant. Based on electronic patient diaries from the clinical trial, the percentages of women with no bleeding and/or spotting days (amenorrhea) in a cycle ranged from 6.3% to 11.9% over 13 cycles [see Clinical Trial Experience (6.1) and Clinical Studies (14)].

If scheduled bleeding does not occur, consider the possibility of pregnancy. If the woman has not adhered to the prescribed dosing schedule (missed days of active therapy or started her TDS on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and perform appropriate diagnostic measures. If the woman has adhered to the prescribed dosing schedule and misses two consecutive periods, rule out pregnancy.

After discontinuation of TWIRLA, amenorrhea or oligomenorrhea may occur, especially if these conditions were pre-existent.

Carefully observe women with a history of depression and discontinue TWIRLA if depression recurs to a serious degree. Data on the association of CHCs with onset of depression or exacerbation of existing depression are limited.

Breast Cancer Twirla is contraindicated in females who currently have or have had breast cancer because breast cancer may be hormonally sensitive [see Contraindications (4)].

Epidemiology studies have not found a consistent association between use of COCs and breast cancer risk. Studies do not show an association between ever (current or past) use of COCs and risk of breast cancer. However, some studies report a small increase in the risk of breast cancer among current or recent users (<6 months since last use) and current users with longer duration of COC use [see Postmarketing Experience (6.2)].

Cervical Cancer Some studies suggest that CHCs are associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. There is controversy about the extent to which these findings are due to differences in sexual behavior and other factors.

The estrogen component of TWIRLA may raise the serum concentrations of thyroxine-binding globulin, sex hormone-binding globulin, and cortisol-binding globulin. The dose of replacement thyroid hormone or cortisol therapy may need to be increased.

In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.

Chloasma may occur with TWIRLA use, especially in women with a history of chloasma gravidarum. Advise women with a history of chloasma to avoid exposure to the sun or ultraviolet radiation while using TWIRLA.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of one product cannot be directly compared to rates in the clinical trials of another product and may not reflect the rates observed in practice.

The safety of TWIRLA was evaluated in a 12-month, multicenter, open-label, single-arm clinical trial (NCT02158572) conducted in the United States [see Clinical Studies (14)]. Women applied TWIRLA (120 mcg LNG/30 mcg EE) for 13 28-day treatment cycles. One treatment cycle is defined as three consecutive weeks that one TWIRLA TDS is applied for seven-day wear followed by one week that TWIRLA is not applied.

The safety population for this clinical trial was composed of 2,031 women that contributed 18,841 treatment cycles of exposure. Of these 2,031 women, 989 women completed 13 treatment cycles. The mean age was 27.5 years. The mean BMI for the safety population was 28.3 kg/m2. The BMI of the safety population was widely distributed: 39.4% had a BMI < 25 kg/m2, 25.3% had a BMI ≥ 25 kg/m2 and < 30 kg/m2, and 35.3% had a BMI ≥ 30 kg/m2.

For women who received TWIRLA, the most common reasons for discontinuation from the study were a womans decision (15.3%) and lost to follow-up (11.3%).

Discontinuation due to an adverse reaction occurred in 10.9% of women. The most common (≥ 2%) adverse reactions leading to discontinuation were application site disorder (3.1%) and any bleeding irregularities (2.2%).

The most common adverse reactions that occurred in ≥ 2% of the 2,031 women that used TWIRLA are shown in Table 3.

<div class="scrollingtable"><table cellpadding="5" width="80%"> <caption> <span>Table 3: Adverse Drug Reactions Reported by 2% of TWIRLA-Treated Women in One Phase 3 Clinical Trial</span> </caption> <colgroup> <col class="Lrule Rrule"/> <col align="center" class="Lrule Rrule" valign="bottom"/> </colgroup> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Represents a bundle of similar terms that include the following adverse reactions: application site acne, hemorrhage, pustules, dermatitis, hypersensitivity, rash, discoloration, induration, reaction, dryness, irritation, ulcer, erosion, pain, urticaria, erythema, papules, vesicles, exfoliation, pruritis.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="Bold Botrule First First Toprule"> <td class="Lrule Lrule Rrule Rrule">Adverse reaction</td><td align="center" class="Lrule Lrule Rrule Rrule">TWIRLA (n=2,031)</td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule"><span class="Bold">General disorders and administration site conditions</span> <br/>Application site disorder<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></td><td align="center" class="Lrule Lrule Rrule Rrule">6.2%</td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule"><span class="Bold">Gastrointestinal disorders</span> <br/>Nausea</td><td align="center" class="Lrule Lrule Rrule Rrule">4.1%</td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule"><span class="Bold">Nervous system disorders</span> <br/>Headache</td><td align="center" class="Lrule Lrule Rrule Rrule">3.6%</td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule"><span class="Bold">Reproductive system and breast disorder</span> <br/>Dysmenorrhoea</td><td align="center" class="Lrule Lrule Rrule Rrule">2.3%</td> </tr> <tr class="Botrule Last Last Toprule"> <td class="Lrule Lrule Rrule Rrule"><span class="Bold">Investigations</span> <br/>Weight increased</td><td align="center" class="Lrule Lrule Rrule Rrule">2.0%</td> </tr> </tbody> </table></div>

Venous Thromboembolic Events (VTEs)

A total of four VTEs (including pulmonary embolism and deep vein thrombosis) in TWIRLA-treated patients were identified in the clinical trial. Of these, all were in women with a BMI > 30 kg/m2 [see Contraindications (4)].

Other Serious Adverse Reactions The following serious adverse reactions occurred in < 1% of women who received TWIRLA: cholelithiasis, cholecystitis, major depression, suicidal ideation, appendicitis, ectopic pregnancy, pneumonia, and gastroenteritis.

Five studies that compared breast cancer risk between ever-users (current or past use) of combined oral contraceptives (COCs) and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 - 1.12 (Figure 2).

Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 2). One of these studies reported no association between breast cancer risk and COC use. The other two studies found an increased relative risk of 1.19 - 1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8-10 years of COC use.

Figure 2. Relevant Studies of Risk of Breast Cancer with Combined Oral Contraceptives

RR = relative risk; OR = odds ratio; HR = hazard ratio. “ever COC” are females with current or past COC use; “never COC use” are females that never used COCs.

Substances Decreasing Plasma Concentration of CHCs and Potentially Diminishing the Efficacy of CHCs:

Table 4 includes substances that demonstrated an important drug interaction with TWIRLA.

<div class="scrollingtable"><table border="1" cellpadding="5" cellspacing="0" width="100%"> <caption> <span>Table 4: Significant Drug Interactions Involving Substances That Affect CHCs</span> </caption> <colgroup> <col class="Lrule Rrule" width="30%"/> <col class="Lrule Rrule" valign="bottom" width="70%"/> </colgroup> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>Induction potency of St. John’s wort may vary widely based on preparation.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First First Toprule"> <td class="Lrule Lrule Rrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Metabolic Enzyme Inducers</span> </p> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule" valign="top"> <p class="Default First First">Clinical effect</p> <p></p> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li>Concomitant use of CHCs with metabolic enzyme inducers may decrease the plasma concentrations of the estrogen and/or progestin component of CHCs <span class="Italics">[see Clinical Pharmacology (<a href="#L0b970c57-fdd2-4cb4-bf35-cab67d347cb1">12.3</a>)].</span> </li> <li>Decreased exposure of the estrogen and/or progestin component of CHCs may potentially diminish the effectiveness of CHCs and may lead to contraceptive failure or an increase in breakthrough bleeding.</li> </ul> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule" valign="top"> <p class="Default First First">Prevention or management</p> <p></p> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li>Counsel women to use an alternative method of contraception or a backup method when enzyme inducers are used with CHCs.</li> <li>Continue backup contraception for 28 days after discontinuing the enzyme inducer to maintain contraceptive reliability.</li> </ul> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule" valign="top"> <p class="Default First First">Examples</p> <p></p> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li>Aprepitant, barbiturates, bosentan, carbamazepine, efavirenz, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, rifabutin, rufinamide, topiramate, products containing St. John’s wort,<a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a> and certain protease inhibitors (see separate section on protease inhibitors below).</li> </ul> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule" colspan="2" valign="top"> <p class="Default First First"> <span class="Bold">Colesevelam</span> </p> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule" valign="top"> <p class="Default First First">Clinical effect</p> <p></p> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li>Concomitant use of CHCs with Colesevelam significantly decreases systemic exposure of ethinyl estradiol <span class="Italics">[see Clinical Pharmacology (<a href="#L0b970c57-fdd2-4cb4-bf35-cab67d347cb1">12.3</a>)]</span>.</li> <li>Decreased exposure of the estrogen component of CHCs may potentially reduce contraceptive efficacy or result in an increase in breakthrough bleeding, depending on the strength of ethinyl estradiol in the CHC.</li> </ul> </td> </tr> <tr class="Botrule Last Last Toprule"> <td class="Lrule Lrule Rrule Rrule" valign="top"> <p class="Default First First">Prevention or management</p> <p class="Default"></p> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <p class="Default First First">Administer 4 or more hours apart to attenuate this drug interaction.</p> </td> </tr> </tbody> </table></div>

Substances increasing the systemic exposure of CHCs:Co-administration of atorvastatin or rosuvastatin and CHCs containing ethinyl estradiol increase systemic exposure of ethinyl estradiol by approximately 20 to 25 percent. Ascorbic acid and acetaminophen may increase systemic exposure of ethinyl estradiol, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs.

Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant decreases in systemic exposure of the estrogen and/or progestin have been noted when CHCs are co-administered with some HIV protease inhibitors (e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir), some HCV protease inhibitors (e.g., boceprevir and telaprevir), and some non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine).

In contrast, significant increases in systemic exposure of the estrogen and/or progestin have been noted when CHCs are co-administered with certain other HIV protease inhibitors (e.g., indinavir and atazanavir/ritonavir) and with other non-nucleoside reverse transcriptase inhibitors (e.g., etravirine).

Table 5 provides significant drug interaction information for drugs co-administered with TWIRLA.

<div class="scrollingtable"><table border="1" cellpadding="5" cellspacing="0" width="100%"> <caption> <span>Table 5: Significant Drug Interaction Information for Drugs Co-Administered with CHCs</span> </caption> <colgroup> <col class="Lrule Rrule" width="30%"/> <col class="Lrule Rrule" valign="bottom" width="70%"/> </colgroup> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Lrule Rrule Rrule Toprule" colspan="2"> <p class="Default First First"> <span class="Bold">Lamotrigine</span> </p> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule"> <p class="Default First First">Clinical effect</p> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <ul> <li>Concomitant use of CHCs with lamotrigine may significantly decrease systemic exposure of lamotrigine due to induction of lamotrigine glucuronidation <span class="Italics">[see Clinical Pharmacology (<a href="#L0b970c57-fdd2-4cb4-bf35-cab67d347cb1">12.3</a>)]</span>.</li> <li>Decreased systemic exposure of lamotrigine may reduce seizure control.</li> </ul> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule"> <p class="Default First First">Prevention or management</p> </td><td class="Lrule Lrule Rrule Rrule"> <p class="Default First First">Dose adjustment may be necessary. Consult the approved product labeling for lamotrigine.</p> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule" colspan="2"> <p class="Default First First"> <span class="Bold">Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy </span> </p> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule"> <p class="Default First First">Clinical effect</p> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <p class="Default First First">Concomitant use of CHCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin <span class="Italics">[see Warnings and Precautions (<a href="#L4a5554a1-6d33-44f1-b1ee-17cd409d28e2">5.12</a>)]</span>.</p> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule"> <p class="Default First First">Prevention or management</p> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <p class="Default First First">The dose of replacement thyroid hormone or cortisol therapy may need to be increased. Consult the approved product labeling for the therapy in use. <span class="Italics">[see Warnings and Precautions (<a href="#L4a5554a1-6d33-44f1-b1ee-17cd409d28e2">5.12</a>)]</span>.</p> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule" colspan="2"> <p class="Default First First"> <span class="Bold">Other Drugs </span> </p> </td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule"> <p class="Default First First">Clinical effect</p> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <p class="Default First First">Concomitant use of CHCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. Concomitant use with ethinyl estradiol-containing CHCs may increase systemic exposure of other drugs (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole).</p> </td> </tr> <tr class="Botrule Last Last Toprule"> <td class="Lrule Lrule Rrule Rrule"> <p class="Default First First">Prevention or management</p> </td><td class="Lrule Lrule Rrule Rrule" valign="top"> <p class="Default First First">The dosage of drugs that can be affected by this interaction may need to be increased. Consult the approved product labeling for the concomitantly used drug.</p> </td> </tr> </tbody> </table></div>

The use of CHCs may influence the results of some laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.

CHCs are contraindicated for use with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see Warnings and Precautions (5.4) and Contraindications (4)]. Discontinue TWIRLA prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. TWIRLA can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.

Risk Summary TWIRLA is contraindicated in pregnancy because there is no reason to use CHCs in pregnancy. Discontinue TWIRLA if pregnancy occurs. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to CHCs before conception or during early pregnancy.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.

Risk Summary Contraceptive hormones and/or metabolites are present in human milk. CHCs can reduce milk production in breastfeeding women. This reduction can occur at any time but is less likely to occur once breastfeeding is well established. Advise the nursing woman to use another method of contraception until she discontinues breastfeeding [see Dosage and Administration (2.1)].

Human Data No studies have been conducted on the use of TWIRLA in breastfeeding women.

The safety and effectiveness of TWIRLA as a method of contraception have been established in females of reproductive potential with a BMI < 30 kg/m2. Efficacy is expected to be the same in postmenarcheal females regardless of age. TWIRLA is not indicated in females before menarche.

TWIRLA has not been studied in postmenopausal women and is not indicated in this population.

No studies have been conducted to evaluate the effect of hepatic impairment on the disposition of TWIRLA. However, steroid hormones may be poorly metabolized in patients with impaired liver function. Acute or chronic disturbances of liver function may necessitate the discontinuation of CHC use until markers of liver function return to normal and CHC causation has been excluded [see Contraindications (4) and Warnings and Precautions (5.2)].

Compared to women with a lower BMI, women with a BMI ≥ 30 kg/m2 had reduced effectiveness and may have a higher risk for VTEs. Therefore, TWIRLA is contraindicated in women with a BMI ≥ 30 kg/m2 [see Contraindications (4) and Clinical Studies (14)].

TWIRLA has demonstrated reduced efficacy in women with a BMI ≥ 25 and < 30 kg/m2 [see Clinical Studies (14)]. Consider this before prescribing TWIRLA to women with a BMI ≥ 25 to < 30 kg/m2.

There have been no reports of serious adverse outcomes from overdose of CHCs, including ingestion by children. Overdose may cause uterine bleeding in women and nausea. In case of suspected overdose, the TWIRLA TDS should be removed and symptomatic treatment given.

{ "type": "p", "children": [], "text": "There have been no reports of serious adverse outcomes from overdose of CHCs, including ingestion by children. Overdose may cause uterine bleeding in women and nausea. In case of suspected overdose, the TWIRLA TDS should be removed and symptomatic treatment given." }

TWIRLA (levonorgestrel and ethinyl estradiol) transdermal system (TDS) contains 2.60 mg levonorgestrel (LNG) (17α)-(–) [13-ethyl-17¬hydroxy-18, 19-dinorpregn-4-en-20-yn-3-one], a progestin, and 2.30 mg ethinyl estradiol (EE), [(17α)-19-norpregna-1, 3, 5(10)-trien-20-yne-3, 17-diol] an estrogen (Figure 3).

{ "type": "p", "children": [], "text": "TWIRLA (levonorgestrel and ethinyl estradiol) transdermal system (TDS) contains 2.60 mg levonorgestrel (LNG) (17α)-(–) [13-ethyl-17¬hydroxy-18, 19-dinorpregn-4-en-20-yn-3-one], a progestin, and 2.30 mg ethinyl estradiol (EE), [(17α)-19-norpregna-1, 3, 5(10)-trien-20-yne-3, 17-diol] an estrogen (Figure 3)." }

Figure 3. Structural Formulas

{ "type": "p", "children": [], "text": "\nFigure 3. Structural Formulas\n" }

TWIRLA is designed to provide daily exposure of 120 mcg LNG and 30 mcg EE. TWIRLA is a matrix type TDS consisting of a 15 cm2 active adhesive laminate center, surrounded by a peripheral inactive adhesive laminate. The entire area of TWIRLA is 28 cm2.

{ "type": "p", "children": [], "text": "TWIRLA is designed to provide daily exposure of 120 mcg LNG and 30 mcg EE. TWIRLA is a matrix type TDS consisting of a 15 cm2 active adhesive laminate center, surrounded by a peripheral inactive adhesive laminate. The entire area of TWIRLA is 28 cm2." }

TWIRLA consists of 5 layers and a release liner which is removed and discarded prior to application. The two innermost layers contain the active ingredients (LNG and EE), as well as inactive components. Proceeding from the outer surface toward the surface adhering to the skin, the layers are (1) a woven peripheral backing layer, which is etched with “TWIRLA Levonorgestrel 120 mcg/day Ethinyl Estradiol 30 mcg/day”; (2) an inactive peripheral acrylic adhesive layer; (3) an inactive peripheral polyisobutylene adhesive layer; (4) an internal membrane to separate the active adhesive matrix from the inactive adhesive laminate; (5) the active adhesive matrix (Figure 4).

{ "type": "p", "children": [], "text": "TWIRLA consists of 5 layers and a release liner which is removed and discarded prior to application. The two innermost layers contain the active ingredients (LNG and EE), as well as inactive components. Proceeding from the outer surface toward the surface adhering to the skin, the layers are (1) a woven peripheral backing layer, which is etched with “TWIRLA Levonorgestrel 120 mcg/day Ethinyl Estradiol 30 mcg/day”; (2) an inactive peripheral acrylic adhesive layer; (3) an inactive peripheral polyisobutylene adhesive layer; (4) an internal membrane to separate the active adhesive matrix from the inactive adhesive laminate; (5) the active adhesive matrix (Figure 4)." }

Figure 4. Schematic Depiction of the TWIRLA TDS

{ "type": "p", "children": [], "text": "\nFigure 4. Schematic Depiction of the TWIRLA TDS\n" }

The inactive components are acrylic adhesives, capric acid, copovidone, crospovidone, dimethyl sulfoxide, ethyl lactate, lauryl lactate, polybutene, polyester internal membrane, polyester release liner, polyisobutylene adhesives, and woven polyester backing membrane. TWIRLA is not made with latex.

{ "type": "p", "children": [], "text": "The inactive components are acrylic adhesives, capric acid, copovidone, crospovidone, dimethyl sulfoxide, ethyl lactate, lauryl lactate, polybutene, polyester internal membrane, polyester release liner, polyisobutylene adhesives, and woven polyester backing membrane. TWIRLA is not made with latex." }

Combination hormonal contraceptives lower the risk of becoming pregnant primarily by suppressing ovulation.

TWIRLA exhibited ovulation inhibition as defined by serum progesterone concentrations. In one study subjects were treated with TWIRLA for three cycles. In this study, approximately 80% of these subjects had serum progesterone concentrations < 4.7 ng/mL.

TWIRLA is a TDS designed with an active matrix core containing LNG and EE. TWIRLA delivers medication to the systemic circulation by absorption of LNG and EE through the skin.

Absorption Following application of TWIRLA, both LNG and EE reach a plateau by 24 to 48 hours (Figures 5 and 6). Delivery of hormones is continuous over the 7 days of TWIRLA wear. The mean pharmacokinetic parameters (Css and AUC0‑168) for LNG and EE following two consecutive cycles of TWIRLA are summarized in Table 6.

<div class="scrollingtable"><table cellpadding="5" width="100%"> <caption> <span>Table 6: Mean (%CV<a class="Sup" href="#footnote-3" name="footnote-reference-3">*</a>) Pharmacokinetic Parameters of Levonorgestrel and Ethinyl Estradiol Following Two Consecutive Cycles of TWIRLA Wear on the Buttock</span> </caption> <colgroup> <col class="Lrule Rrule" width="15%"/> <col align="center" class="Lrule Rrule" width="17%"/> <col align="center" class="Lrule Rrule" width="17%"/> <col align="center" class="Lrule Rrule" width="17%"/> <col align="center" class="Lrule Rrule" width="17%"/> <col align="center" class="Lrule Rrule" width="17%"/> </colgroup> <tfoot> <tr> <td align="left" colspan="6"> <dl class="Footnote"> <dt> <a href="#footnote-reference-3" name="footnote-3">*</a> </dt> <dd>Coefficient of Variation</dd> <dt> <a href="#footnote-reference-4" name="footnote-4">†</a> </dt> <dd>Average concentration within the 48-168 h time interval</dd> <dt> <a href="#footnote-reference-5" name="footnote-5">‡</a> </dt> <dd>AUC0-168: area under the plasma drug concentration-time curve calculated between 0 and 168 h</dd> <dt> <a href="#footnote-reference-6" name="footnote-6">§</a> </dt> <dd>t<span class="Sub">1/2</span>: elimination half-life</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First First Last"> <td align="left" class="Lrule Rrule" colspan="6" valign="bottom"> <p class="First First Footnote Last">NC: not calculable</p> </td> </tr> <tr align="center" class="Botrule First Toprule" valign="bottom"> <td align="left" class="Lrule Lrule Rrule Rrule"><span class="Bold"> Analyte</span></td><td align="left" class="Lrule Lrule Rrule Rrule"><span class="Bold"> Parameter</span></td><td align="left" class="Lrule Lrule Rrule Rrule"><span class="Bold"> Cycle 1</span> <br/> <span class="Bold"> Week 1</span> <br/> <span class="Bold"> (N=18)</span></td><td align="left" class="Lrule Lrule Rrule Rrule"><span class="Bold"> Cycle 1</span> <br/> <span class="Bold"> Week 3</span> <br/> <span class="Bold"> (N=18)</span></td><td align="left" class="Lrule Lrule Rrule Rrule"><span class="Bold"> Cycle 2</span> <br/> <span class="Bold"> Week 1</span> <br/> <span class="Bold"> (N=18)</span></td><td align="left" class="Lrule Lrule Rrule Rrule"><span class="Bold"> Cycle 2</span> <br/> <span class="Bold"> Week 3</span> <br/> <span class="Bold"> (N=18)</span></td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule" rowspan="3"> LNG</td><td align="left" class="Lrule Lrule Rrule Rrule"> C<span class="Sub">ss</span> (pg/mL)<a class="Sup" href="#footnote-4" name="footnote-reference-4">†</a></td><td align="left" class="Lrule Lrule Rrule Rrule"> 842 (41.2)</td><td align="left" class="Lrule Lrule Rrule Rrule"> 2009 (47.2)</td><td align="left" class="Lrule Lrule Rrule Rrule"> 1389 (46.5)</td><td align="left" class="Lrule Lrule Rrule Rrule"> 2209 (44.5)</td> </tr> <tr class="Botrule Toprule"> <td align="left" class="Lrule Lrule Rrule Rrule"> AUC<span class="Sub">0-168</span> <br/> (ng∙h/mL)<a class="Sup" href="#footnote-5" name="footnote-reference-5">‡</a></td><td align="left" class="Lrule Lrule Rrule Rrule"> 120.0 (39.1)</td><td align="left" class="Lrule Lrule Rrule Rrule"> 339.0 (41.1)</td><td align="left" class="Lrule Lrule Rrule Rrule"> 207.0 (44.1)</td><td align="left" class="Lrule Lrule Rrule Rrule"> 378.0 (43.8)</td> </tr> <tr class="Botrule Toprule"> <td align="left" class="Lrule Lrule Rrule Rrule"> t<span class="Sub">1/2</span> (h)<a class="Sup" href="#footnote-6" name="footnote-reference-6">§</a></td><td align="left" class="Lrule Lrule Rrule Rrule"> NC</td><td align="left" class="Lrule Lrule Rrule Rrule"> 38.2 (22.7)</td><td align="left" class="Lrule Lrule Rrule Rrule"> NC</td><td align="left" class="Lrule Lrule Rrule Rrule"> 40.5 (15.4)</td> </tr> <tr class="Botrule Toprule"> <td class="Lrule Lrule Rrule Rrule" rowspan="3"> EE</td><td align="left" class="Lrule Lrule Rrule Rrule"> C<span class="Sub">ss</span> (pg/mL)<a class="Sup" href="#footnote-4">†</a></td><td align="left" class="Lrule Lrule Rrule Rrule"> 31.9 (37.4)</td><td align="left" class="Lrule Lrule Rrule Rrule"> 34.8 (37.4)</td><td align="left" class="Lrule Lrule Rrule Rrule"> 38.6 (41.7)</td><td align="left" class="Lrule Lrule Rrule Rrule"> 40.3 (38.9)</td> </tr> <tr class="Botrule Toprule"> <td align="left" class="Lrule Lrule Rrule Rrule"> AUC<span class="Sub">0-168</span> <br/> (pg∙h/mL)<a class="Sup" href="#footnote-5">‡</a></td><td align="left" class="Lrule Lrule Rrule Rrule"> 5040 (35.4)</td><td align="left" class="Lrule Lrule Rrule Rrule"> 6210 (34.2)</td><td align="left" class="Lrule Lrule Rrule Rrule"> 6060 (35.9)</td><td align="left" class="Lrule Lrule Rrule Rrule"> 7120 (36.6)</td> </tr> <tr class="Botrule Last Last Toprule"> <td align="left" class="Lrule Lrule Rrule Rrule"> t<span class="Sub">1/2</span> (h)<a class="Sup" href="#footnote-6">§</a></td><td align="left" class="Lrule Lrule Rrule Rrule"> NC</td><td align="left" class="Lrule Lrule Rrule Rrule"> 19.7 (18.8)</td><td align="left" class="Lrule Lrule Rrule Rrule"> NC</td><td align="left" class="Lrule Lrule Rrule Rrule"> 20.5 (18.2)</td> </tr> </tbody> </table></div>

In multiple dose studies, AUC0-168 for LNG and EE showed within-cycle and between cycle increases and the mean serum concentrations of EE and LNG were highest during the third Week of Cycle 2 after two consecutive cycles of wear (Figures 5 and 6). In a three-cycle study, the steady-state pharmacokinetics of EE and LNG was reached during Cycle 2. Upon removal of TWIRLA, serum levels of EE and LNG reach non‑measurable levels and low levels within 3 days, respectively.

Figure 5. Mean Serum Ethinyl Estradiol Concentrations in Healthy Female Volunteers Following Two Consecutive Cycles of TWIRLA Wear on the Buttock (Vertical arrow indicates time of TWIRLA removal)

Figure 6. Mean Serum Levonorgestrel Concentrations in Healthy Female Volunteers Following Two Consecutive Cycles of TWIRLA Wear on the Buttock (Vertical arrow indicates time of TWIRLA removal)

The absorption of LNG and EE following application of TWIRLA to the buttock, abdomen, and upper torso (excluding the breasts) was examined. While absorption from the abdomen was slightly lower than from other sites, absorption from all three anatomic sites was considered to be therapeutically equivalent.

The absorption of LNG and EE following application of TWIRLA was studied under various external conditions including sauna, whirlpool, treadmill, and in a cold-water bath. Somewhat lower drug concentration levels were reported for whirlpool and treadmill with geometric ratios within the 78-90% range for both LNG and EE and dry sauna (LNG only).

Distribution LNG in serum is primarily bound to sex hormone-binding globulin (SHBG). EE is about 97% bound to plasma albumin. EE does not bind to SHBG but induces SHBG synthesis.

Elimination Metabolism Since TWIRLA is applied transdermally, first-pass metabolism (via the gastrointestinal tract and/or liver) of LNG and EE that would be expected with oral administration does not occur. Hepatic metabolism of LNG and EE occurs as described below.

Levonorgestrel: The most important metabolic pathways are reduction of the Δ4-3-oxo group and hydroxylation at positions 2α, 1β, and 16β, followed by conjugation. Most of the circulating metabolites are sulfates of 3α, 5β-tetrahydro-levonorgestrel, while excretion occurs predominantly in the form of glucuronides. Some of the parent LNG also circulates as 17β-sulfate. Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for the wide variation observed in LNG concentrations among users.

Ethinyl estradiol: Cytochrome P450 enzymes (CYP3A4) in the liver are responsible for the 2-hydroxylation that is the major oxidative reaction. The 2-hydroxy metabolite is further transformed by methylation and glucuronidation prior to urinary and fecal excretion. Levels of CYP3A4 vary widely among individuals and can explain the variation in rates of EE 2-hydroxylation.

Excretion LNG and its metabolites are excreted in the urine (40% to 68%) and in feces (16% to 48%). The mean terminal elimination half-life for LNG in TWIRLA is approximately 41 ± 6.2 hours at steady state.

EE is excreted in the urine and feces as glucuronide and sulfate conjugates and undergoes enterohepatic recirculation. The terminal elimination half-life of EE in TWIRLA is approximately 21 ± 3.7 hours at steady state.

[see Warnings and Precautions (5.11) and Use in Specific Populations (8.1)]

The efficacy of TWIRLA was evaluated in one open label, single arm, multicenter trial in the United States (Study 1) (NCT02158572) of one-year duration that enrolled 2,031 women, ranging in age between 18 and 60 years, who were healthy and sexually active with regular menstrual cycles. For the primary efficacy analysis, 1,736 women between the ages 18 and 35 years completed 15,165 evaluable 28-day cycles with TWIRLA, where no back-up contraception was used, and sexual intercourse occurred.

{ "type": "p", "children": [], "text": "The efficacy of TWIRLA was evaluated in one open label, single arm, multicenter trial in the United States (Study 1) (NCT02158572) of one-year duration that enrolled 2,031 women, ranging in age between 18 and 60 years, who were healthy and sexually active with regular menstrual cycles. For the primary efficacy analysis, 1,736 women between the ages 18 and 35 years completed 15,165 evaluable 28-day cycles with TWIRLA, where no back-up contraception was used, and sexual intercourse occurred." }

The racial/ethnic distribution for the primary analysis was White (67%), Black/African American (24%), Asian (4%), American Indian/Alaskan Native (0.5%), Native Hawaiian/Pacific Islander (0.5%), Other/Multiple races (5%); 19% of the study population were Hispanic. The mean age was 26 years.

{ "type": "p", "children": [], "text": "The racial/ethnic distribution for the primary analysis was White (67%), Black/African American (24%), Asian (4%), American Indian/Alaskan Native (0.5%), Native Hawaiian/Pacific Islander (0.5%), Other/Multiple races (5%); 19% of the study population were Hispanic. The mean age was 26 years." }

The mean BMI in the primary efficacy analysis group was 28.3 kg/m2, and 35.3% of subjects had a BMI 30 kg/m2. The primary efficacy endpoint was the Pearl Index (PI) defined as the pregnancy rate per 100 woman-years of use. The overall PI for the primary analysis population (TWIRLA-treated patients) was 5.8 (95% CI 4.5, 7.2). There were clear differences in efficacy by BMI category as shown in Table 7 below.

{ "type": "p", "children": [], "text": "The mean BMI in the primary efficacy analysis group was 28.3 kg/m2, and 35.3% of subjects had a BMI 30 kg/m2. The primary efficacy endpoint was the Pearl Index (PI) defined as the pregnancy rate per 100 woman-years of use. The overall PI for the primary analysis population (TWIRLA-treated patients) was 5.8 (95% CI 4.5, 7.2). There were clear differences in efficacy by BMI category as shown in Table 7 below." }

<div class="scrollingtable"><table cellpadding="5" width="100%"> <caption> <span>Table 7: Pearl Index Efficacy Analysis in TWIRLA-Treated Patients by BMI Subgroup in Study 1<a class="Sup" href="#footnote-7" name="footnote-reference-7">*</a></span> </caption> <tfoot> <tr> <td align="left" colspan="0"> <dl class="Footnote"> <dt> <a href="#footnote-reference-7" name="footnote-7">*</a> </dt> <dd>TWIRLA is contraindicated in women with a BMI ≥ 30 kg/m<span class="Sup">2</span> </dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold"> BMI</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold"> Number of evaluable cycles</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold"> Pearl Index (95% CI)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> &lt; 25 kg/m<span class="Sup">2</span></td><td align="center" class="Botrule Lrule Rrule Toprule">6007</td><td align="center" class="Botrule Lrule Rrule Toprule"> 3.5 (1.8 - 5.2)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> ≥ 25 and &lt; 30 kg/m<span class="Sup">2</span></td><td align="center" class="Botrule Lrule Rrule Toprule">3881 </td><td align="center" class="Botrule Lrule Rrule Toprule"> 5.7 (3.0 - 8.4)</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> ≥ 30 kg/m<span class="Sup">2</span></td><td align="center" class="Botrule Lrule Rrule Toprule">5264 </td><td align="center" class="Botrule Lrule Rrule Toprule"> 8.6 (5.8 - 11.5)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"5\" width=\"100%\">\n<caption>\n<span>Table 7: Pearl Index Efficacy Analysis in TWIRLA-Treated Patients by BMI Subgroup in Study 1<a class=\"Sup\" href=\"#footnote-7\" name=\"footnote-reference-7\">*</a></span>\n</caption>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"0\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-7\" name=\"footnote-7\">*</a>\n</dt>\n<dd>TWIRLA is contraindicated in women with a BMI ≥ 30 kg/m<span class=\"Sup\">2</span>\n</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\"> BMI</span></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\"> Number of evaluable cycles</span></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\"> Pearl Index (95% CI)</span></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> &lt; 25 kg/m<span class=\"Sup\">2</span></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">6007</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"> 3.5 (1.8 - 5.2)</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"> ≥ 25 and &lt; 30 kg/m<span class=\"Sup\">2</span></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">3881 </td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"> 5.7 (3.0 - 8.4)</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\"> ≥ 30 kg/m<span class=\"Sup\">2</span></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">5264 </td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"> 8.6 (5.8 - 11.5)</td>\n</tr>\n</tbody>\n</table></div>" }

Figure 7 shows a model of the rate of pregnancy as BMI increases based on data from Study 1. There is an increase in pregnancy rate (i.e., the number of pregnancies per 100 woman-years), as BMI increased based on the primary analysis population (N = 1,735). TWIRLA is contraindicated in women with a BMI ≥ 30 kg/m2 [see Indications and Usage (1) and Contraindications (4)].

{ "type": "p", "children": [], "text": "Figure 7 shows a model of the rate of pregnancy as BMI increases based on data from Study 1. There is an increase in pregnancy rate (i.e., the number of pregnancies per 100 woman-years), as BMI increased based on the primary analysis population (N = 1,735). TWIRLA is contraindicated in women with a BMI ≥ 30 kg/m2 [see Indications and Usage (1) and Contraindications (4)]." }

Figure 7. Pregnancy Rates (Estimated*) in TWIRLA-Treated Patients as BMI Increases for Women ≤ 35 Years of Age in Study 1

{ "type": "p", "children": [], "text": "\nFigure 7. Pregnancy Rates (Estimated*) in TWIRLA-Treated Patients as BMI Increases for Women ≤ 35 Years of Age in Study 1\n" }

*Plot is based on Poisson Model with continuous BMI as the predictor (N=1,735); one woman in the primary analysis population had no BMI information. The solid line displays the estimated pregnancy rate, and the shaded area displays the 95% confidence interval for the estimated pregnancy rate.

{ "type": "p", "children": [], "text": "*Plot is based on Poisson Model with continuous BMI as the predictor (N=1,735); one woman in the primary analysis population had no BMI information. The solid line displays the estimated pregnancy rate, and the shaded area displays the 95% confidence interval for the estimated pregnancy rate." }

Adhesion Based on a Phase 1 study in 78 subjects wearing one TWIRLA on the lower abdomen for 7 days, 77 systems applied (98.7%) exhibited 75% or greater surface area adhesion at all timepoints evaluated (every 24 hours) throughout the wear period. In the Phase 3 trial, 5.0% of all transdermal systems worn during the year-long trial (55,900 transdermal systems) fully detached. Subject-reported adhesion was generally better for the abdomen as compared to the upper torso and buttock. Full detachment rates were higher for transdermal systems exposed to water as compared to transdermal systems with no water exposure.

{ "type": "p", "children": [], "text": "\nAdhesion\nBased on a Phase 1 study in 78 subjects wearing one TWIRLA on the lower abdomen for 7 days, 77 systems applied (98.7%) exhibited 75% or greater surface area adhesion at all timepoints evaluated (every 24 hours) throughout the wear period. In the Phase 3 trial, 5.0% of all transdermal systems worn during the year-long trial (55,900 transdermal systems) fully detached. Subject-reported adhesion was generally better for the abdomen as compared to the upper torso and buttock. Full detachment rates were higher for transdermal systems exposed to water as compared to transdermal systems with no water exposure." }

TWIRLA (levonorgestrel and ethinyl estradiol) transdermal system is a beige 28 cm2 round product etched with “TWIRLA Levonorgestrel 120 mcg/day Ethinyl Estradiol 30 mcg/day” and supplied as:

Store at room temperature 20°C to 25°C (68°F to 77°F) with excursions permitted 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Store in original unopened pouch.

Used TDS still contain some active hormones. To discard, fold the sticky sides of the TDS together, place in a sturdy container, preferably with a child-resistant cap, and place this container in the trash. Used TDS should not be flushed down the toilet. See www.fda.gov/drugdisposal for more information about disposal of medicines.

Advise the woman to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

{ "type": "p", "children": [], "text": "Advise the woman to read the FDA-approved patient labeling (Patient Information and Instructions for Use)." }

Cigarette Smoking Advise the woman that cigarette smoking increases the risk of serious cardiovascular events from CHC use. Women who are over 35 years old and smoke should not use TWIRLA [see Boxed Warning and Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "\nCigarette Smoking\nAdvise the woman that cigarette smoking increases the risk of serious cardiovascular events from CHC use. Women who are over 35 years old and smoke should not use TWIRLA [see Boxed Warning and Warnings and Precautions (5.1)]." }

Venous Thromboembolism Advise the woman that there is an increased risk of VTE compared to non-users of CHCs is greatest after initially starting a CHC or restarting (following a 4-week or greater interruption in intake) the same or a different CHC.

{ "type": "p", "children": [], "text": "\nVenous Thromboembolism\nAdvise the woman that there is an increased risk of VTE compared to non-users of CHCs is greatest after initially starting a CHC or restarting (following a 4-week or greater interruption in intake) the same or a different CHC." }

Use during Pregnancy TWIRLA is not to be used during pregnancy. Instruct the woman to stop TWIRLA if pregnancy is confirmed during treatment [see Contraindications (4)].

{ "type": "p", "children": [], "text": "\nUse during Pregnancy\nTWIRLA is not to be used during pregnancy. Instruct the woman to stop TWIRLA if pregnancy is confirmed during treatment [see Contraindications (4)].\n" }

Sexually Transmitted Infections Advise the woman that TWIRLA does not protect against HIV infection and other sexually transmitted infections.

{ "type": "p", "children": [], "text": "\nSexually Transmitted Infections\nAdvise the woman that TWIRLA does not protect against HIV infection and other sexually transmitted infections." }

Missed Dosing Instructions Apply one TDS weekly for 3 weeks followed by one TDS free week. Instruct women what to do in the event TDS change is missed. See “What if you forget to change your patch (left your patch on more than 7 days)?” and “What if you forget to remove your patch for the patch free week?” in the FDA-approved patient labeling (Instructions for Use) [see Dosage and Administration (2.3)].

{ "type": "p", "children": [], "text": "\nMissed Dosing Instructions\nApply one TDS weekly for 3 weeks followed by one TDS free week. Instruct women what to do in the event TDS change is missed. See “What if you forget to change your patch (left your patch on more than 7 days)?” and “What if you forget to remove your patch for the patch free week?” in the FDA-approved patient labeling (Instructions for Use) [see Dosage and Administration (2.3)]." }

Need for Additional Contraception Postpartum women who have not yet had a period when they start TWIRLA need to use an additional method of contraception until they have used the TDS for one week [see Dosage and Administration (2.1)].

{ "type": "p", "children": [], "text": "\nNeed for Additional Contraception\nPostpartum women who have not yet had a period when they start TWIRLA need to use an additional method of contraception until they have used the TDS for one week [see Dosage and Administration (2.1)]." }

A back-up or alternative method of contraception is needed when enzyme inducers are used with TWIRLA [see Drug Interactions (7.1)].

{ "type": "p", "children": [], "text": "A back-up or alternative method of contraception is needed when enzyme inducers are used with TWIRLA [see Drug Interactions (7.1)].\n" }

Lactation TWIRLA may reduce breast milk production. This is less likely to occur if breast-feeding is well established. When possible, nursing women should use other methods of contraception until they have discontinued breast-feeding [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "\nLactation\nTWIRLA may reduce breast milk production. This is less likely to occur if breast-feeding is well established. When possible, nursing women should use other methods of contraception until they have discontinued breast-feeding [see Use in Specific Populations (8.2)]." }

Amenorrhea and Possible Symptoms of Pregnancy Amenorrhea may occur. Advise the woman to contact a health care provider in the event of amenorrhea in two or more consecutive cycles or in case of symptoms of pregnancy such as morning sickness or unusual breast tenderness [see Warnings and Precautions (5.9)].

{ "type": "p", "children": [], "text": "\nAmenorrhea and Possible Symptoms of Pregnancy\nAmenorrhea may occur. Advise the woman to contact a health care provider in the event of amenorrhea in two or more consecutive cycles or in case of symptoms of pregnancy such as morning sickness or unusual breast tenderness [see Warnings and Precautions (5.9)].\n" }

Fertility following Discontinuation of TWIRLA Resumption of fertility after discontinuing TWIRLA is expected.

{ "type": "p", "children": [], "text": "\nFertility following Discontinuation of TWIRLA\nResumption of fertility after discontinuing TWIRLA is expected." }

Avoidance of TDS Detachment Advise women to avoid frequent or prolonged water exposure (e.g., swimming) and also to avoid use of large amounts of body lotions or oils. Advise women to check the TDS for partial or complete TDS detachment not only daily but also after frequent or prolonged water exposure.

{ "type": "p", "children": [], "text": "\nAvoidance of TDS Detachment\nAdvise women to avoid frequent or prolonged water exposure (e.g., swimming) and also to avoid use of large amounts of body lotions or oils. Advise women to check the TDS for partial or complete TDS detachment not only daily but also after frequent or prolonged water exposure." }

Manufactured by:Corium International, Inc.4558 50th Street, SEGrand Rapids, MI 49512

{ "type": "p", "children": [], "text": "Manufactured by:Corium International, Inc.4558 50th Street, SEGrand Rapids, MI 49512" }

Manufactured for:Agile Therapeutics, Inc.500 College Rd. E, Suite 310Princeton, NJ 08540

{ "type": "p", "children": [], "text": "Manufactured for:Agile Therapeutics, Inc.500 College Rd. E, Suite 310Princeton, NJ 08540" }

<div class="scrollingtable"><table cellpadding="5"> <colgroup> <col valign="top" width="20%"/> <col valign="top" width="20%"/> <col valign="top" width="20%"/> <col valign="top" width="20%"/> <col valign="top" width="20%"/> </colgroup> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">PATIENT INFORMATION<br/>TWIRLA<span class="Sup">®</span> (TWER-la)<br/>(levonorgestrel and ethinyl estradiol) transdermal system</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">What is the most important information I should know about TWIRLA? </span> </p> <ul> <li> <span class="Bold">Do not use TWIRLA if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects from combination hormonal contraceptives (CHCs), including death from heart attack, blood clots or stroke.  This risk increases with age and the number of cigarettes you smoke.</span> </li> <li> <span class="Bold">Do not use TWIRLA if your Body Mass Index (BMI) is 30 kg/m<span class="Sup">2 </span>or more. If you do not know what your BMI is, please talk to your health care provider. Women with a BMI of 30 kg/m<span class="Sup">2 </span>or more who use CHCs may have a higher risk for developing side effects like blood clots compared to women with a BMI lower than 30 kg/m<span class="Sup">2</span>. </span> </li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First">Hormonal birth control methods help to lower the chances of becoming pregnant when taken as directed. TWIRLA does not protect against HIV infection (AIDS) and other sexually transmitted infections (STIs).</p> <p></p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">What is TWIRLA? </span> </p> <p>TWIRLA is:</p> <ul> <li>a birth control patch for women with a BMI less than 30 kg/m<span class="Sup">2</span> who can become pregnant. It contains two female hormones, a progestin called levonorgestrel, and an estrogen called ethinyl estradiol. Birth control methods that have both an estrogen and a progestin are called combination hormonal contraceptives (CHCs).</li> </ul> <p></p> <p>TWIRLA is less effective in women with a BMI of 25 kg/m<span class="Sup">2 </span>or more.</p> <p></p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">How well does TWIRLA work?</span> </p> <p>Your chance of getting pregnant depends on how well you follow the directions for using TWIRLA. The better you follow the directions, the less chance you have of getting pregnant.</p> <p></p> <p> <br/>For TWIRLA to be most effective, you must use TWIRLA exactly as your healthcare provider tells you to. Each patch must be fully attached to the skin during the 7 days in order for it to work the best.</p> <p></p> <p> <br/>TWIRLA is less effective in women who have a BMI of 25 kg/m2 or more. If you have a BMI of 30 kg/m2 or more, talk to your healthcare provider about other methods of birth control which may be right for you.</p> <p></p> <p></p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"></p> <p> <span class="Bold">Do not use TWIRLA if you:</span> </p> <ul> <li>smoke and are over 35 years old.</li> <li>have or have had blood clots in your arms, legs, eyes or lungs.</li> <li>have had a stroke. </li> <li>have had a heart attack. </li> <li>have certain heart valve problems or heart rhythm problems that can cause blood clots to form in the heart.</li> <li>have a problem that makes your blood clot more than normal that you were born with (inherited) or that has happened for other reasons such as medicines, surgery or injuries (acquired).</li> <li>have high blood pressure that is not controlled. </li> <li>have diabetes and you are over the age of 35, have high blood pressure or have kidney, eye, nerve, or blood vessel damage, or have had diabetes for more than 20 years. </li> <li>have had certain kinds of severe migraine headaches with aura, numbness, weakness or changes in vision, or have any migraine headaches if you are over age 35.</li> <li>have a BMI of 30 kg/m<span class="Sup">2 </span>or more.</li> <li>have liver problems including liver tumors, hepatitis, cirrhosis, or liver disease.</li> <li>have unexplained vaginal bleeding. </li> <li>are pregnant or think you may be pregnant. However, TWIRLA is not known to cause birth defects when used by accident during pregnancy.</li> <li>have had breast cancer or any cancer that is sensitive to female hormones.</li> <li>are allergic to any of the ingredients in TWIRLA. See a complete list of ingredients at the end of this Patient Information leaflet. Symptoms of an allergic reaction you may include itching and irritation at the patch site.</li> <li>take any Hepatitis C drug combination containing ombitasvir, paritaprevir, ritonavir, with or without dasabuvir. This may increase levels of a liver enzyme called alanine aminotransferase (ALT) in the blood. </li> </ul> <p></p> <p>TWIRLA may not be a good choice for you if you have ever had jaundice (yellowing of the skin or eyes) caused by pregnancy (also called cholestasis of pregnancy) or related to previous use of hormonal birth control.</p> <p></p> <p> <br/>Tell your healthcare provider if you have ever had any of the above conditions. Your healthcare provider may recommend another method of birth control.</p> <p></p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"></p> <p> <span class="Bold">Before using TWIRLA, tell your healthcare provider about all of your medical conditions, including if you:</span> </p> <ul> <li>are pregnant or think you are pregnant. TWIRLA is not for pregnant women. If you think you are pregnant, you should have a pregnancy test and know the results. Do not use TWIRLA if the test is positive and talk to your healthcare provider.</li> <li>are scheduled for surgery. TWIRLA may increase your risk of blood clots after surgery. You should stop using your TWIRLA patch at least 4 weeks before you have surgery and not restart it until at least 2 weeks after your surgery.</li> <li>have or have had gallbladder problems including yellowing of the skin or eyes during pregnancy. </li> <li>have high cholesterol that is not controlled.</li> <li>have or have had depression.</li> <li>have a history of hereditary angioedema.</li> <li>have had dark patches of skin on your forehead, cheeks, upper lip, and chin (chloasma).</li> <li>are breastfeeding or plan to breastfeed. CHC medicines that contain estrogen, like TWIRLA, may decrease the amount of milk you make. A small amount of hormones from the TWIRLA patch may pass into your breast milk. You may want to use another method of birth control until you are ready to stop breastfeeding.</li> </ul> <p></p> <p> <span class="Bold">Tell your healthcare provider about all the medicines you take, including</span> prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines and herbal products may make TWIRLA less effective or cause breakthrough bleeding, including, but not limited to:  </p> <ul> <li>certain anti-seizure medicines (such as barbiturates, carbamazepine, felbamate, oxcarbazepine, phenytoin, rufinamide, or topiramate).</li> <li>medicine to treat chemotherapy-induced nausea and vomiting (aprepitant).</li> <li>medicine to treat high blood pressure in the vessels of the lung (bosentan).  </li> <li>a certain medicine used to treat fungal infections (griseofulvin).</li> <li>certain combinations of HIV medicines (nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/rotinavir, and tipranavir/ritonavir).</li> <li>certain non-nucleoside reverse transcriptase inhibitors (such as nevirapine and efavirenz).</li> <li>rifampin and rifabutin.</li> <li>certain hepatitis C (HCV) medicines (such as boceprevir, telaprevir).</li> <li>St. John’s wort.</li> <li>Use another birth control method (such as condoms and spermicide, or diaphragm and spermicide) when you take medicines that may make TWIRLA less effective and for 28 days after stopping the medicine.</li> <li>Some medicines and grapefruit juice may increase your level of the hormone ethinyl estradiol if used together, including:<ul> <li>the pain reliever acetaminophen.</li> <li>ascorbic acid (vitamin C).</li> <li>certain medicines used to treat fungal infections (itraconazole, ketoconazole, voriconazole, and fluconazole).</li> <li>certain HIV medicines (atazanavir/ritonavir, indinavir).</li> <li>non-nucleoside reverse transcriptase inhibitors (such as etravirine).</li> <li>medicines to lower cholesterol (such as atorvastatin and rosuvastatin).</li> </ul> </li> <li>TWIRLA may affect the way that lamotrigine, a medicine used to treat seizures, works and may increase the risk of seizures. Your healthcare provider may need to adjust the dose of lamotrigine while you are on TWIRLA.</li> <li>If you are scheduled for any laboratory tests, tell your healthcare provider that you are using TWIRLA. Certain blood tests may be affected by CHC methods.</li> <li>Women on thyroid replacement therapy may need increased doses of thyroid replacement medicine or corticosteroid replacement medicine may need increased doses of their thyroid hormone or cortisol medicines.</li> </ul> <p></p> <p>Ask your healthcare provider if you are not sure if you take any of the medicines listed above.</p> <p></p> <p> <br/>Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. Talk to your healthcare provider before you start taking a new medicine.</p> <p></p> <p></p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">How should I use TWIRLA?</span> </p> <ul> <li> <span class="Bold">For detailed instructions, see the step-by-step instructions for using TWIRLA at the end of this Patient Information leaflet. </span> </li> <li>Use TWIRLA exactly as your healthcare provider tells you to use it.</li> <li>Wear 1 TWIRLA patch at a time.</li> <li> <span class="Bold">Do not</span> skip using any TWIRLA patches, even if you do not have sex often.</li> <li>TWIRLA is applied in a 4 week patch cycle. Each patch cycle includes 4 weeks (28 days). You will put on 1 patch every week for 3 weeks. You will not wear a patch during week 4. Each patch is worn for 7 days (1 week).</li> <li>Apply a new TWIRLA patch on the same day each week (this is called your <span class="Bold">Patch Change Day</span>). For example, if you apply your first patch on a Monday, all of your TWIRLA patches should be applied on Monday.</li> <li>You<span class="Bold"> will not</span> wear a TWIRLA patch during week 4 (this is called your <span class="Bold">Patch Free Week</span>). Make sure you remove the old patch from your body. Your period should begin during your <span class="Bold">Patch Free Week.</span> After you have finished week 4, apply a new TWIRLA patch on the day after Week 4 ends. Repeat the patch cycle of 1 patch a week for 3 weeks followed by your <span class="Bold">Patch Free Week</span>.</li> <li>Do not cut, damage or change the TWIRLA patch in any way. If the patch is cut, damaged or changed in any way, it may be less effective.</li> <li> <span class="Bold">Your TWIRLA patch should never be off more than 7 days in a row. </span>If you ever go more than 7 days without a patch, you should use another non-hormonal back up birth control method.</li> <li>If you miss your <span class="Bold">Patch Change Day</span>, put the patch on late or if it comes off of your skin before your <span class="Bold">Patch Change Day,</span> you may or may not need to use another non-hormonal back up birth control method. See the detailed table in the Instructions for Use for more information.</li> <li>If you miss a period you might be pregnant. Some women miss their periods or have light periods on hormonal birth control methods even when they are not pregnant. Call your healthcare provider if you miss 1 period and have not used your TWIRLA patch every day or you miss 2 periods in row.</li> </ul> <p></p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">What should I avoid while using TWIRLA?</span> </p> <ul> <li>Smoking</li> <li>The following can cause the patch to not stick the right way making TWIRLA less effective:</li> <li>Avoid using makeup, creams, lotions, oils, powders or any other products on the skin area where you put or plan to put the patch.</li> <li>Swimming or contact with water often or for long periods of time (30 minutes or more). Talk with your healthcare provider about the best method of birth control if you are a swimmer or you often come in contact with water for 30 minutes or more.</li> <li>Women who tend to get chloasma should avoid spending a long time in sunlight, tanning booths, and under sun lamps while using TWIRLA. Use sunscreen if you have to be in the sunlight.</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">What are the possible side effects of TWIRLA?</span> </p> <p></p> <p> <span class="Bold">TWIRLA may cause serious side effects, including: </span> </p> <ul> <li> <span class="Bold">See “What is the most important information I should know about TWIRLA?”</span> </li> <li> <span class="Bold">blood clots. </span>Like pregnancy, hormonal birth control may increase the risk of serious blood clots (see following graph), especially in women who have other risk factors, such as smoking, high blood pressure, high levels of fat in the blood, diabetes, obesity, a family history of blood clots or are older than 35 years old. This increased risk is highest when you first start using hormonal birth control and when you restart the same or different hormonal birth control after not using it for a month or more. Some studies have reported that women who use levonorgestrel and ethinyl estradiol transdermal system have a higher risk of getting a blood clot. Talk to your healthcare provider about your risk of getting a blood clot before using TWIRLA or deciding which type of birth control is right for you.</li> </ul> <p> <span class="Bold">It is possible to die or be permanently disabled from a problem caused by a blood clot, such as a heart attack or a stroke. </span>Some examples of serious blood clots are blood clots in the:</p> <p></p> </td> </tr> <tr> <td class="Lrule" colspan="1"> <ul> <li>legs (deep vein thrombosis)</li> </ul> </td><td colspan="1"> <ul> <li>lungs (pulmonary embolus)</li> </ul> </td><td colspan="1"> <ul> <li>eyes (loss of eyesight)</li> </ul> </td><td colspan="1"> <ul> <li>heart (heart attack)</li> </ul> </td><td class="Rrule" colspan="1"> <ul> <li>brain (stroke)</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="5"> <ul> <li>To put the risk of developing a blood clot into perspective: If 10,000 women who are not pregnant and do not use hormonal birth control are followed for one year, between 1 and 5 of these women will develop a blood clot. The figure below shows the likelihood of developing a serious blood clot for women who are not pregnant and do not use hormonal birth control, for women who use hormonal birth control, for pregnant women, and for women in the first 12 weeks after delivering a baby.</li> </ul> <p class="First"> <span class="Bold">Likelihood of Developing a Serious Blood Clot (Venous Thromboembolism [VTE])</span> </p> <p></p> <img alt="figure-1" src="/dailymed/image.cfm?name=figure-1.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6"/><p></p> <p>*CHC = combination hormonal contraception</p> <p>**Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy duration is nine months, the rate is 7 to 27 per 10,000 Woman Years (WY).</p> <p></p> <p></p> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">C</span><span class="Bold">all your healthcare provider right away if you have: </span> </p> <p>       ο   leg pain that does not go away</p> <p>       ο   sudden shortness of breath<br/>       ο   sudden changes to your vision or blindness<br/>       ο   severe pain or pressure in your chest<br/>       ο   sudden, severe headache unlike your usual headaches<br/>       ο   weakness or numbness in an arm or leg<br/>       ο   trouble speaking</p> <ul> <li> <span class="Bold">liver problems, including liver tumors. </span>Stop using TWIRLA and tell your healthcare provider right away if you have yellowing of your skin or eyes (jaundice).</li> <li> <span class="Bold">high blood pressure. </span>Your healthcare provider will check your blood pressure and may stop you from using TWIRLA if your blood pressure rises.</li> <li> <span class="Bold">gallbladder problems or worsening of a gallbladder problem you already have</span>. You may have an increased risk of gallbladder problems with the use of TWIRLA especially if you have had gallbladder problems before or gallbladder problems when you were pregnant.</li> <li> <span class="Bold">headaches. </span>Headaches can be a common but serious side effect. Tell your healthcare provider if you have new headaches that keep coming back, that do not go away, or are severe. Also tell your healthcare provider if your migraine headaches happen more often or are more severe than normal. Your healthcare provider may stop you from using TWIRLA.</li> <li> <span class="Bold">irregular or unusual vaginal bleeding and spotting between your menstrual periods or absence of menstrual periods (amenorrhea). </span>This can happen especially during the first 3 months of using TWIRLA. You also may have no bleeding at all. Tell your healthcare provider if you miss 2 or more menstrual cycles. After you stop using TWIRLA, your periods may not happen as often or you may have no bleeding at all, especially if you had these types of menstrual cycles before taking TWIRLA.</li> <li> <span class="Bold">depression.</span> </li> <li> <span class="Bold">swelling of your skin especially around your mouth, eyes, and in your throat (angioedema).</span> Call your healthcare provider or get emergency medical care right away if you have a swollen face, lips, mouth, tongue or throat as this may lead to difficulty swallowing or breathing. Your risk of having angioedema is higher if you have a history of angioedema.</li> <li> <span class="Bold">dark patches of skin on your forehead, cheeks, upper lip, and chin (chloasma).</span> Your risk of getting chloasma with the use of TWIRLA is higher if you had chloasma during pregnancy.</li> </ul> <p></p> <p> <span class="Bold">The most common side effects of TWIRLA include:</span> </p> </td> </tr> <tr> <td class="Lrule" colspan="1"> <ul> <li>skin reactions at the patch site such as bumps, redness or changes in color of your skin, bleeding itching, rash, dryness, pain and swelling.</li> </ul> </td><td colspan="1"> <ul> <li>headache</li> </ul> </td><td colspan="1"> <ul> <li>weight gain</li> </ul> </td><td colspan="1"></td><td class="Rrule" colspan="1"></td> </tr> <tr> <td class="Lrule" colspan="1"> <ul> <li>nausea</li> </ul> </td><td colspan="1"> <ul> <li>menstrual cramps</li> </ul> </td><td colspan="1"></td><td colspan="1"></td><td class="Rrule" colspan="1"></td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="5"> <p class="First">These are not all the possible side effects of TWIRLA.</p> <p></p> <p> <br/> <span class="Bold">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</span> </p> <p></p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">How should I store TWIRLA?</span> </p> <ul> <li>Store at room temperature between 68°F to 77°F (20°C to 25°C).</li> <li>Store TWIRLA in the original unopened pouch it comes in.  Apply TWIRLA immediately after taking it out from the pouch.</li> <li>Do not store TWIRLA in the refrigerator or freezer.</li> <li>Used TWIRLA patches may still have some active hormones. To throw away the TWIRLA patch, fold the sticky side of the patch together, and place this container in the trash.  Do not flush used TWIRLA patches down the toilet.</li> </ul> <p></p> <p> <span class="Bold">Keep TWIRLA and all medicines out of the reach of children.</span> </p> <p></p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">General information about the safe and effective use of TWIRLA.</span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use TWIRLA for a condition for which it was not prescribed. Do not give TWIRLA to other people. It may harm them. You can ask your pharmacist or healthcare provider for information about TWIRLA that is written for health professionals.</p> <p></p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">Does hormonal birth control cause cancer? </span> </p> <p>It is not known if hormonal birth control causes breast cancer. Some studies, but not all, suggest that there could be a slight increase in the risk of breast cancer among current users with longer duration of use.</p> <p> <br/>If you have breast cancer now, or have had it in the past, do not use hormonal birth control because some breast cancers are sensitive to hormones.</p> <p></p> <p> <br/>Women who use hormonal birth control may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as an increased number of sexual partners.</p> <p></p> <p> <br/> <span class="Bold">What should I know about my period when using TWIRLA? </span> </p> <p>When you use TWIRLA you may have bleeding and spotting between periods, called unplanned bleeding. Unplanned bleeding may vary from light slight staining between menstrual periods to breakthrough bleeding which is a flow much like a regular period. Unplanned bleeding occurs most often during the first few months of hormonal contraceptive use but may also occur after you have been using the patch for some time. Such bleeding may be temporary and usually does not indicate any serious problems. It is important to continue using the patch on schedule. If the unplanned bleeding or spotting occurs in more cycles, is unusually heavy, or lasts for more than a few days, talk to your healthcare provider. </p> <p></p> <p> <br/> <span class="Bold">What if I miss my scheduled period when using TWIRLA? </span> </p> <p>You should consider the possibility that you are pregnant if you miss your scheduled period. Because scheduled periods may not happen as often when you are using TWIRLA, tell your healthcare provider that you have missed your period and that you are using TWIRLA. Also, notify your healthcare provider if you have symptoms of pregnancy such as morning sickness or unusual breast tenderness. It is important that your healthcare provider checks to see if you are pregnant. Stop using TWIRLA if you are pregnant.</p> <p></p> <p> <br/> <span class="Bold">What if I want to become pregnant? </span> </p> <p>You may stop using TWIRLA whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy check-up before you stop using TWIRLA.</p> <p></p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" colspan="5"> <p class="First"> <span class="Bold">What are the ingredients in TWIRLA?</span> </p> <p> <span class="Bold">Active ingredients:</span> levonorgestrel (a progestin) and ethinyl estradiol (an estrogen)</p> <p> <span class="Bold">Inactive ingredients:</span> polyester release liner, woven polyester backing membrane, acrylic adhesives, polyester internal membrane, polyisobutylene adhesives, copovidone, polybutene, crospovidone, lauryl lactate, dimethyl sulfoxide, capric acid, and ethyl lactate.</p> <p></p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"5\">\n<colgroup>\n<col valign=\"top\" width=\"20%\"/>\n<col valign=\"top\" width=\"20%\"/>\n<col valign=\"top\" width=\"20%\"/>\n<col valign=\"top\" width=\"20%\"/>\n<col valign=\"top\" width=\"20%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">PATIENT INFORMATION<br/>TWIRLA<span class=\"Sup\">®</span> (TWER-la)<br/>(levonorgestrel and ethinyl estradiol) transdermal system</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">What is the most important information I should know about TWIRLA? </span>\n</p>\n<ul>\n<li>\n<span class=\"Bold\">Do not use TWIRLA if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects from combination hormonal contraceptives (CHCs), including death from heart attack, blood clots or stroke.  This risk increases with age and the number of cigarettes you smoke.</span>\n</li>\n<li>\n<span class=\"Bold\">Do not use TWIRLA if your Body Mass Index (BMI) is 30 kg/m<span class=\"Sup\">2 </span>or more. If you do not know what your BMI is, please talk to your health care provider. Women with a BMI of 30 kg/m<span class=\"Sup\">2 </span>or more who use CHCs may have a higher risk for developing side effects like blood clots compared to women with a BMI lower than 30 kg/m<span class=\"Sup\">2</span>. </span>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"5\">\n<p class=\"First\">Hormonal birth control methods help to lower the chances of becoming pregnant when taken as directed. TWIRLA does not protect against HIV infection (AIDS) and other sexually transmitted infections (STIs).</p>\n<p></p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">What is TWIRLA? </span>\n</p>\n<p>TWIRLA is:</p>\n<ul>\n<li>a birth control patch for women with a BMI less than 30 kg/m<span class=\"Sup\">2</span> who can become pregnant. It contains two female hormones, a progestin called levonorgestrel, and an estrogen called ethinyl estradiol. Birth control methods that have both an estrogen and a progestin are called combination hormonal contraceptives (CHCs).</li>\n</ul>\n<p></p>\n<p>TWIRLA is less effective in women with a BMI of 25 kg/m<span class=\"Sup\">2 </span>or more.</p>\n<p></p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">How well does TWIRLA work?</span>\n</p>\n<p>Your chance of getting pregnant depends on how well you follow the directions for using TWIRLA. The better you follow the directions, the less chance you have of getting pregnant.</p>\n<p></p>\n<p>\n<br/>For TWIRLA to be most effective, you must use TWIRLA exactly as your healthcare provider tells you to. Each patch must be fully attached to the skin during the 7 days in order for it to work the best.</p>\n<p></p>\n<p>\n<br/>TWIRLA is less effective in women who have a BMI of 25 kg/m2 or more. If you have a BMI of 30 kg/m2 or more, talk to your healthcare provider about other methods of birth control which may be right for you.</p>\n<p></p>\n<p></p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"5\">\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\">Do not use TWIRLA if you:</span>\n</p>\n<ul>\n<li>smoke and are over 35 years old.</li>\n<li>have or have had blood clots in your arms, legs, eyes or lungs.</li>\n<li>have had a stroke. </li>\n<li>have had a heart attack. </li>\n<li>have certain heart valve problems or heart rhythm problems that can cause blood clots to form in the heart.</li>\n<li>have a problem that makes your blood clot more than normal that you were born with (inherited) or that has happened for other reasons such as medicines, surgery or injuries (acquired).</li>\n<li>have high blood pressure that is not controlled. </li>\n<li>have diabetes and you are over the age of 35, have high blood pressure or have kidney, eye, nerve, or blood vessel damage, or have had diabetes for more than 20 years. </li>\n<li>have had certain kinds of severe migraine headaches with aura, numbness, weakness or changes in vision, or have any migraine headaches if you are over age 35.</li>\n<li>have a BMI of 30 kg/m<span class=\"Sup\">2 </span>or more.</li>\n<li>have liver problems including liver tumors, hepatitis, cirrhosis, or liver disease.</li>\n<li>have unexplained vaginal bleeding. </li>\n<li>are pregnant or think you may be pregnant. However, TWIRLA is not known to cause birth defects when used by accident during pregnancy.</li>\n<li>have had breast cancer or any cancer that is sensitive to female hormones.</li>\n<li>are allergic to any of the ingredients in TWIRLA. See a complete list of ingredients at the end of this Patient Information leaflet. Symptoms of an allergic reaction you may include itching and irritation at the patch site.</li>\n<li>take any Hepatitis C drug combination containing ombitasvir, paritaprevir, ritonavir, with or without dasabuvir. This may increase levels of a liver enzyme called alanine aminotransferase (ALT) in the blood. </li>\n</ul>\n<p></p>\n<p>TWIRLA may not be a good choice for you if you have ever had jaundice (yellowing of the skin or eyes) caused by pregnancy (also called cholestasis of pregnancy) or related to previous use of hormonal birth control.</p>\n<p></p>\n<p>\n<br/>Tell your healthcare provider if you have ever had any of the above conditions. Your healthcare provider may recommend another method of birth control.</p>\n<p></p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"5\">\n<p class=\"First\"></p>\n<p>\n<span class=\"Bold\">Before using TWIRLA, tell your healthcare provider about all of your medical conditions, including if you:</span>\n</p>\n<ul>\n<li>are pregnant or think you are pregnant. TWIRLA is not for pregnant women. If you think you are pregnant, you should have a pregnancy test and know the results. Do not use TWIRLA if the test is positive and talk to your healthcare provider.</li>\n<li>are scheduled for surgery. TWIRLA may increase your risk of blood clots after surgery. You should stop using your TWIRLA patch at least 4 weeks before you have surgery and not restart it until at least 2 weeks after your surgery.</li>\n<li>have or have had gallbladder problems including yellowing of the skin or eyes during pregnancy. </li>\n<li>have high cholesterol that is not controlled.</li>\n<li>have or have had depression.</li>\n<li>have a history of hereditary angioedema.</li>\n<li>have had dark patches of skin on your forehead, cheeks, upper lip, and chin (chloasma).</li>\n<li>are breastfeeding or plan to breastfeed. CHC medicines that contain estrogen, like TWIRLA, may decrease the amount of milk you make. A small amount of hormones from the TWIRLA patch may pass into your breast milk. You may want to use another method of birth control until you are ready to stop breastfeeding.</li>\n</ul>\n<p></p>\n<p>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take, including</span> prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines and herbal products may make TWIRLA less effective or cause breakthrough bleeding, including, but not limited to:  </p>\n<ul>\n<li>certain anti-seizure medicines (such as barbiturates, carbamazepine, felbamate, oxcarbazepine, phenytoin, rufinamide, or topiramate).</li>\n<li>medicine to treat chemotherapy-induced nausea and vomiting (aprepitant).</li>\n<li>medicine to treat high blood pressure in the vessels of the lung (bosentan).  </li>\n<li>a certain medicine used to treat fungal infections (griseofulvin).</li>\n<li>certain combinations of HIV medicines (nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/rotinavir, and tipranavir/ritonavir).</li>\n<li>certain non-nucleoside reverse transcriptase inhibitors (such as nevirapine and efavirenz).</li>\n<li>rifampin and rifabutin.</li>\n<li>certain hepatitis C (HCV) medicines (such as boceprevir, telaprevir).</li>\n<li>St. John’s wort.</li>\n<li>Use another birth control method (such as condoms and spermicide, or diaphragm and spermicide) when you take medicines that may make TWIRLA less effective and for 28 days after stopping the medicine.</li>\n<li>Some medicines and grapefruit juice may increase your level of the hormone ethinyl estradiol if used together, including:<ul>\n<li>the pain reliever acetaminophen.</li>\n<li>ascorbic acid (vitamin C).</li>\n<li>certain medicines used to treat fungal infections (itraconazole, ketoconazole, voriconazole, and fluconazole).</li>\n<li>certain HIV medicines (atazanavir/ritonavir, indinavir).</li>\n<li>non-nucleoside reverse transcriptase inhibitors (such as etravirine).</li>\n<li>medicines to lower cholesterol (such as atorvastatin and rosuvastatin).</li>\n</ul>\n</li>\n<li>TWIRLA may affect the way that lamotrigine, a medicine used to treat seizures, works and may increase the risk of seizures. Your healthcare provider may need to adjust the dose of lamotrigine while you are on TWIRLA.</li>\n<li>If you are scheduled for any laboratory tests, tell your healthcare provider that you are using TWIRLA. Certain blood tests may be affected by CHC methods.</li>\n<li>Women on thyroid replacement therapy may need increased doses of thyroid replacement medicine or corticosteroid replacement medicine may need increased doses of their thyroid hormone or cortisol medicines.</li>\n</ul>\n<p></p>\n<p>Ask your healthcare provider if you are not sure if you take any of the medicines listed above.</p>\n<p></p>\n<p>\n<br/>Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. Talk to your healthcare provider before you start taking a new medicine.</p>\n<p></p>\n<p></p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">How should I use TWIRLA?</span>\n</p>\n<ul>\n<li>\n<span class=\"Bold\">For detailed instructions, see the step-by-step instructions for using TWIRLA at the end of this Patient Information leaflet. </span>\n</li>\n<li>Use TWIRLA exactly as your healthcare provider tells you to use it.</li>\n<li>Wear 1 TWIRLA patch at a time.</li>\n<li>\n<span class=\"Bold\">Do not</span> skip using any TWIRLA patches, even if you do not have sex often.</li>\n<li>TWIRLA is applied in a 4 week patch cycle. Each patch cycle includes 4 weeks (28 days). You will put on 1 patch every week for 3 weeks. You will not wear a patch during week 4. Each patch is worn for 7 days (1 week).</li>\n<li>Apply a new TWIRLA patch on the same day each week (this is called your <span class=\"Bold\">Patch Change Day</span>). For example, if you apply your first patch on a Monday, all of your TWIRLA patches should be applied on Monday.</li>\n<li>You<span class=\"Bold\"> will not</span> wear a TWIRLA patch during week 4 (this is called your <span class=\"Bold\">Patch Free Week</span>). Make sure you remove the old patch from your body. Your period should begin during your <span class=\"Bold\">Patch Free Week.</span> After you have finished week 4, apply a new TWIRLA patch on the day after Week 4 ends. Repeat the patch cycle of 1 patch a week for 3 weeks followed by your <span class=\"Bold\">Patch Free Week</span>.</li>\n<li>Do not cut, damage or change the TWIRLA patch in any way. If the patch is cut, damaged or changed in any way, it may be less effective.</li>\n<li>\n<span class=\"Bold\">Your TWIRLA patch should never be off more than 7 days in a row. </span>If you ever go more than 7 days without a patch, you should use another non-hormonal back up birth control method.</li>\n<li>If you miss your <span class=\"Bold\">Patch Change Day</span>, put the patch on late or if it comes off of your skin before your <span class=\"Bold\">Patch Change Day,</span> you may or may not need to use another non-hormonal back up birth control method. See the detailed table in the Instructions for Use for more information.</li>\n<li>If you miss a period you might be pregnant. Some women miss their periods or have light periods on hormonal birth control methods even when they are not pregnant. Call your healthcare provider if you miss 1 period and have not used your TWIRLA patch every day or you miss 2 periods in row.</li>\n</ul>\n<p></p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">What should I avoid while using TWIRLA?</span>\n</p>\n<ul>\n<li>Smoking</li>\n<li>The following can cause the patch to not stick the right way making TWIRLA less effective:</li>\n<li>Avoid using makeup, creams, lotions, oils, powders or any other products on the skin area where you put or plan to put the patch.</li>\n<li>Swimming or contact with water often or for long periods of time (30 minutes or more). Talk with your healthcare provider about the best method of birth control if you are a swimmer or you often come in contact with water for 30 minutes or more.</li>\n<li>Women who tend to get chloasma should avoid spending a long time in sunlight, tanning booths, and under sun lamps while using TWIRLA. Use sunscreen if you have to be in the sunlight.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of TWIRLA?</span>\n</p>\n<p></p>\n<p>\n<span class=\"Bold\">TWIRLA may cause serious side effects, including: </span>\n</p>\n<ul>\n<li>\n<span class=\"Bold\">See “What is the most important information I should know about TWIRLA?”</span>\n</li>\n<li>\n<span class=\"Bold\">blood clots. </span>Like pregnancy, hormonal birth control may increase the risk of serious blood clots (see following graph), especially in women who have other risk factors, such as smoking, high blood pressure, high levels of fat in the blood, diabetes, obesity, a family history of blood clots or are older than 35 years old. This increased risk is highest when you first start using hormonal birth control and when you restart the same or different hormonal birth control after not using it for a month or more. Some studies have reported that women who use levonorgestrel and ethinyl estradiol transdermal system have a higher risk of getting a blood clot. Talk to your healthcare provider about your risk of getting a blood clot before using TWIRLA or deciding which type of birth control is right for you.</li>\n</ul>\n<p>\n<span class=\"Bold\">It is possible to die or be permanently disabled from a problem caused by a blood clot, such as a heart attack or a stroke. </span>Some examples of serious blood clots are blood clots in the:</p>\n<p></p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"1\">\n<ul>\n<li>legs (deep vein thrombosis)</li>\n</ul>\n</td><td colspan=\"1\">\n<ul>\n<li>lungs (pulmonary embolus)</li>\n</ul>\n</td><td colspan=\"1\">\n<ul>\n<li>eyes (loss of eyesight)</li>\n</ul>\n</td><td colspan=\"1\">\n<ul>\n<li>heart (heart attack)</li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"1\">\n<ul>\n<li>brain (stroke)</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"5\">\n<ul>\n<li>To put the risk of developing a blood clot into perspective: If 10,000 women who are not pregnant and do not use hormonal birth control are followed for one year, between 1 and 5 of these women will develop a blood clot. The figure below shows the likelihood of developing a serious blood clot for women who are not pregnant and do not use hormonal birth control, for women who use hormonal birth control, for pregnant women, and for women in the first 12 weeks after delivering a baby.</li>\n</ul>\n<p class=\"First\">\n<span class=\"Bold\">Likelihood of Developing a Serious Blood Clot (Venous Thromboembolism [VTE])</span>\n</p>\n<p></p>\n<img alt=\"figure-1\" src=\"/dailymed/image.cfm?name=figure-1.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6\"/><p></p>\n<p>*CHC = combination hormonal contraception</p>\n<p>**Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy duration is nine months, the rate is 7 to 27 per 10,000 Woman Years (WY).</p>\n<p></p>\n<p></p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">C</span><span class=\"Bold\">all your healthcare provider right away if you have: </span>\n</p>\n<p>       ο   leg pain that does not go away</p>\n<p>       ο   sudden shortness of breath<br/>       ο   sudden changes to your vision or blindness<br/>       ο   severe pain or pressure in your chest<br/>       ο   sudden, severe headache unlike your usual headaches<br/>       ο   weakness or numbness in an arm or leg<br/>       ο   trouble speaking</p>\n<ul>\n<li>\n<span class=\"Bold\">liver problems, including liver tumors. </span>Stop using TWIRLA and tell your healthcare provider right away if you have yellowing of your skin or eyes (jaundice).</li>\n<li>\n<span class=\"Bold\">high blood pressure. </span>Your healthcare provider will check your blood pressure and may stop you from using TWIRLA if your blood pressure rises.</li>\n<li>\n<span class=\"Bold\">gallbladder problems or worsening of a gallbladder problem you already have</span>. You may have an increased risk of gallbladder problems with the use of TWIRLA especially if you have had gallbladder problems before or gallbladder problems when you were pregnant.</li>\n<li>\n<span class=\"Bold\">headaches. </span>Headaches can be a common but serious side effect. Tell your healthcare provider if you have new headaches that keep coming back, that do not go away, or are severe. Also tell your healthcare provider if your migraine headaches happen more often or are more severe than normal. Your healthcare provider may stop you from using TWIRLA.</li>\n<li>\n<span class=\"Bold\">irregular or unusual vaginal bleeding and spotting between your menstrual periods or absence of menstrual periods (amenorrhea). </span>This can happen especially during the first 3 months of using TWIRLA. You also may have no bleeding at all. Tell your healthcare provider if you miss 2 or more menstrual cycles. After you stop using TWIRLA, your periods may not happen as often or you may have no bleeding at all, especially if you had these types of menstrual cycles before taking TWIRLA.</li>\n<li>\n<span class=\"Bold\">depression.</span>\n</li>\n<li>\n<span class=\"Bold\">swelling of your skin especially around your mouth, eyes, and in your throat (angioedema).</span> Call your healthcare provider or get emergency medical care right away if you have a swollen face, lips, mouth, tongue or throat as this may lead to difficulty swallowing or breathing. Your risk of having angioedema is higher if you have a history of angioedema.</li>\n<li>\n<span class=\"Bold\">dark patches of skin on your forehead, cheeks, upper lip, and chin (chloasma).</span> Your risk of getting chloasma with the use of TWIRLA is higher if you had chloasma during pregnancy.</li>\n</ul>\n<p></p>\n<p>\n<span class=\"Bold\">The most common side effects of TWIRLA include:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"1\">\n<ul>\n<li>skin reactions at the patch site such as bumps, redness or changes in color of your skin, bleeding itching, rash, dryness, pain and swelling.</li>\n</ul>\n</td><td colspan=\"1\">\n<ul>\n<li>headache</li>\n</ul>\n</td><td colspan=\"1\">\n<ul>\n<li>weight gain</li>\n</ul>\n</td><td colspan=\"1\"></td><td class=\"Rrule\" colspan=\"1\"></td>\n</tr>\n<tr>\n<td class=\"Lrule\" colspan=\"1\">\n<ul>\n<li>nausea</li>\n</ul>\n</td><td colspan=\"1\">\n<ul>\n<li>menstrual cramps</li>\n</ul>\n</td><td colspan=\"1\"></td><td colspan=\"1\"></td><td class=\"Rrule\" colspan=\"1\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"5\">\n<p class=\"First\">These are not all the possible side effects of TWIRLA.</p>\n<p></p>\n<p>\n<br/>\n<span class=\"Bold\">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</span>\n</p>\n<p></p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">How should I store TWIRLA?</span>\n</p>\n<ul>\n<li>Store at room temperature between 68°F to 77°F (20°C to 25°C).</li>\n<li>Store TWIRLA in the original unopened pouch it comes in.  Apply TWIRLA immediately after taking it out from the pouch.</li>\n<li>Do not store TWIRLA in the refrigerator or freezer.</li>\n<li>Used TWIRLA patches may still have some active hormones. To throw away the TWIRLA patch, fold the sticky side of the patch together, and place this container in the trash.  Do not flush used TWIRLA patches down the toilet.</li>\n</ul>\n<p></p>\n<p>\n<span class=\"Bold\">Keep TWIRLA and all medicines out of the reach of children.</span>\n</p>\n<p></p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of TWIRLA.</span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use TWIRLA for a condition for which it was not prescribed. Do not give TWIRLA to other people. It may harm them. You can ask your pharmacist or healthcare provider for information about TWIRLA that is written for health professionals.</p>\n<p></p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">Does hormonal birth control cause cancer? </span>\n</p>\n<p>It is not known if hormonal birth control causes breast cancer. Some studies, but not all, suggest that there could be a slight increase in the risk of breast cancer among current users with longer duration of use.</p>\n<p>\n<br/>If you have breast cancer now, or have had it in the past, do not use hormonal birth control because some breast cancers are sensitive to hormones.</p>\n<p></p>\n<p>\n<br/>Women who use hormonal birth control may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as an increased number of sexual partners.</p>\n<p></p>\n<p>\n<br/>\n<span class=\"Bold\">What should I know about my period when using TWIRLA? </span>\n</p>\n<p>When you use TWIRLA you may have bleeding and spotting between periods, called unplanned bleeding. Unplanned bleeding may vary from light slight staining between menstrual periods to breakthrough bleeding which is a flow much like a regular period. Unplanned bleeding occurs most often during the first few months of hormonal contraceptive use but may also occur after you have been using the patch for some time. Such bleeding may be temporary and usually does not indicate any serious problems. It is important to continue using the patch on schedule. If the unplanned bleeding or spotting occurs in more cycles, is unusually heavy, or lasts for more than a few days, talk to your healthcare provider. </p>\n<p></p>\n<p>\n<br/>\n<span class=\"Bold\">What if I miss my scheduled period when using TWIRLA? </span>\n</p>\n<p>You should consider the possibility that you are pregnant if you miss your scheduled period. Because scheduled periods may not happen as often when you are using TWIRLA, tell your healthcare provider that you have missed your period and that you are using TWIRLA. Also, notify your healthcare provider if you have symptoms of pregnancy such as morning sickness or unusual breast tenderness. It is important that your healthcare provider checks to see if you are pregnant. Stop using TWIRLA if you are pregnant.</p>\n<p></p>\n<p>\n<br/>\n<span class=\"Bold\">What if I want to become pregnant? </span>\n</p>\n<p>You may stop using TWIRLA whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy check-up before you stop using TWIRLA.</p>\n<p></p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"5\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in TWIRLA?</span>\n</p>\n<p>\n<span class=\"Bold\">Active ingredients:</span> levonorgestrel (a progestin) and ethinyl estradiol (an estrogen)</p>\n<p>\n<span class=\"Bold\">Inactive ingredients:</span> polyester release liner, woven polyester backing membrane, acrylic adhesives, polyester internal membrane, polyisobutylene adhesives, copovidone, polybutene, crospovidone, lauryl lactate, dimethyl sulfoxide, capric acid, and ethyl lactate.</p>\n<p></p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table cellpadding="5" cellspacing="0" width="100%"> <tbody class="Headless"> <tr class="First First Last Last"> <td align="center" valign="top"> <p class="First"> <span class="Bold">INSTRUCTIONS FOR USE</span> </p> <p> <span class="Bold">TWIRLA<span class="Sup">®</span> (TWER-la)</span> </p> <p> <span class="Bold">(levonorgestrel and ethinyl estradiol) transdermal system</span> </p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"5\" cellspacing=\"0\" width=\"100%\">\n<tbody class=\"Headless\">\n<tr class=\"First First Last Last\">\n<td align=\"center\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">INSTRUCTIONS FOR USE</span>\n</p>\n<p>\n<span class=\"Bold\">TWIRLA<span class=\"Sup\">®</span> (TWER-la)</span>\n</p>\n<p>\n<span class=\"Bold\">(levonorgestrel and ethinyl estradiol) transdermal system</span>\n</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

TWIRLA is for skin use only.

{ "type": "p", "children": [], "text": "\nTWIRLA is for skin use only.\n" }

Read this Instructions for Use before you start using the TWIRLA transdermal system (TDS) (also called a patch) and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your contraceptive treatment.

{ "type": "p", "children": [], "text": "Read this Instructions for Use before you start using the TWIRLA transdermal system (TDS) (also called a patch) and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your contraceptive treatment." }

Do not cut, damage or change the TWIRLA patch in any way. If the patch is cut, damaged or changed in any way, it may be less effective.

{ "type": "p", "children": [], "text": "\nDo not cut, damage or change the TWIRLA patch in any way. If the patch is cut, damaged or changed in any way, it may be less effective." }

Starting TWIRLA for the first time: If you are starting TWIRLA for the first time, you should wait until you begin your menstrual period.

{ "type": "p", "children": [], "text": "\nStarting TWIRLA for the first time: If you are starting TWIRLA for the first time, you should wait until you begin your menstrual period." }

{ "type": "ul", "children": [ "\nDay 1 Start. You should apply your first patch during the first 24 hours of your menstrual period. Your Patch Change Day will be on this day every week. If you start after Day 1 of your menstrual period, non-hormonal back up birth control (such as condoms and spermicide, or diaphragm and spermicide) should be used in addition to the patch for the first 7 days of your first patch cycle." ], "text": "" }

If you are changing from the oral hormone birth control pills, vaginal contraceptive ring or another transdermal patch to TWIRLA:

{ "type": "p", "children": [], "text": "\nIf you are changing from the oral hormone birth control pills, vaginal contraceptive ring or another transdermal patch to TWIRLA:\n" }

{ "type": "ul", "children": [ "\nDay 1 Start: You should apply your first patch during the first 24 hours of your menstrual period. Your Patch Change Day will be on this day every week. If you start after Day 1 of your menstrual period, non-hormonal back up birth control (such as condoms and spermicide, or diaphragm and spermicide) should be used in addition to the patch for the first 7 days of your first patch cycle." ], "text": "" }

{ "type": "ul", "children": [ "Finish your current oral hormone birth control pill cycle, vaginal ring cycle or other transdermal patch cycle. Apply your first TWIRLA patch on the day you would normally start your next oral birth control pill, patch or insert your next vaginal ring." ], "text": "" }

{ "type": "ul", "children": [ "If you do not get your period within 1 week after taking your last active oral hormone birth control pill, removing your last vaginal ring or other transdermal patch cycle, check with your healthcare provider to make sure you are not pregnant. You may still go ahead and start TWIRLA for contraception." ], "text": "" }

{ "type": "ul", "children": [ "If you apply your TWIRLA patch more than 1 week after taking your last active oral hormone birth control pill, removing your last vaginal ring or other transdermal patch cycle use a non-hormonal contraceptive method with the TWIRLA patch for the first 7 days of using the patch." ], "text": "" }

If you are starting TWIRLA after a miscarriage or abortion:

{ "type": "p", "children": [], "text": "\nIf you are starting TWIRLA after a miscarriage or abortion:\n" }

{ "type": "ul", "children": [ "You may start TWIRLA right away after a miscarriage or abortion that occurs in the first 12 weeks (first trimester) of pregnancy. If you start TWIRLA within 5 days of your first trimester abortion or miscarriage, you do not need to use another back up contraceptive method." ], "text": "" }

{ "type": "ul", "children": [ "If you do not start TWIRLA within 5 days after a first trimester miscarriage or abortion, use a non-hormonal contraceptive method of birth control, such as a condom and spermicide or diaphragm and spermicide, while you wait for your period to start." ], "text": "" }

{ "type": "ul", "children": [ "If you are starting TWIRLA after a miscarriage or abortion that occurs after the first 12 weeks of pregnancy (second trimester), wait 4 weeks before using TWIRLA and use a non-hormonal contraceptive method of birth control, such as a condom and spermicide or diaphragm and spermicide, for the first 7 days of your first patch cycle only." ], "text": "" }

If you are starting TWIRLA after childbirth:

{ "type": "p", "children": [], "text": "\nIf you are starting TWIRLA after childbirth:\n" }

{ "type": "ul", "children": [ "If you are not breastfeeding, wait 4 weeks before using TWIRLA and use a non-hormonal contraceptive method of birth control, such as a condom and spermicide or diaphragm and spermicide, for the first 7 days of your first patch cycle only. If you start using TWIRLA after childbirth and have not had your menstrual period, tell your healthcare provider. They will need to make sure you are not ovulating or pregnant before starting TWIRLA. If your healthcare provider tells you are not pregnant, use a non-hormonal contraceptive method for the first 7 days of patch of your first patch cycle." ], "text": "" }

How to Apply TWIRLA:

{ "type": "p", "children": [], "text": "\nHow to Apply TWIRLA:\n" }

Where should the patch be applied?

{ "type": "p", "children": [], "text": "\nWhere should the patch be applied?\n" }

{ "type": "ul", "children": [ "Wear only 1 patch at a time. ", "Before applying the patch, make sure your skin is clean and dry.", "Avoid using make up, creams, lotions, oils, powders or any other products on the skin area where you put or plan to put the patch.", "Application sites to apply the patch include the lower stomach area (abdomen), buttock, or the upper torso. See diagrams above.", "When you put the patch on, it should lay flat and smooth with no wrinkles or folds.", "On Patch Change Day, remove the current patch and immediately put on a new patch. Do not apply the new patch directly over skin where the old patch site was.  You should use a new application site." ], "text": "" }

Where not to place the patch.

{ "type": "p", "children": [], "text": "\nWhere not to place the patch.\n" }

{ "type": "ul", "children": [ "\nDo not put the patch on your waistline or near clothing or undergarment seams.", "\nDo not put the patch on the breasts, on cut or irritated skin (rashes or other skin problems), or on the same location as the old patch." ], "text": "" }

<div class="scrollingtable"><table border="1" cellpadding="5" cellspacing="0"> <caption> <span>Patch Application Instructions</span> </caption> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule"><img alt="image description" src="/dailymed/image.cfm?name=twirla-application-0.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6"/></td><td class="Botrule Lrule Rrule Toprule"> <ul> <li>Before the patch is applied, make sure your skin is clean and dry. Also make sure you have not used any make up, creams, lotions, oils, powders or any other products on the skin area where you put or plan to put the patch</li> <li>Each patch is individually sealed in a pouch.</li> <li> <span class="Bold">It is important that you immediately apply the patch after being removed from the pouch.</span> </li> </ul> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><img alt="image description" src="/dailymed/image.cfm?name=twirla-application-1.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6"/></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 1.  </span>Tear the pouch open at the notch on the pouch.</p> <p></p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><img alt="image description" src="/dailymed/image.cfm?name=twirla-application-2.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6"/></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 2. </span>Open the pouch and carefully remove the patch. The patch is attached to a clear protective liner.</p> <p></p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Avoid touching the sticky side of the patch</span><img alt="image description" src="/dailymed/image.cfm?name=twirla-application-4.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6"/></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 3a.</span> Hold the patch with the clear protective liner facing you. You will see two sections: a large section and a small section.</p> <p></p> <p> <span class="Bold"> <br/>Avoid touching the sticky side of the patch with your fingers.</span> </p> <p></p> <p> <span class="Bold"> <br/>Step 3b. </span>Hold the small section of the liner.  Remove and throw away (discard) the large section of the liner while still holding the small section of the liner.</p> <p></p> </td><td class="Botrule Lrule Rrule Toprule"></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><img alt="image description" src="/dailymed/image.cfm?name=twirla-application-5.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6"/></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 4. </span>Hold the small section of the liner and apply the sticky side of the patch to the chosen patch site.</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><img alt="image description" src="/dailymed/image.cfm?name=twirla-application-6.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6"/></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 5.</span> Press the sticky side of the patch firmly onto your skin and smooth it down.</p> <p></p> </td> </tr> <tr> <td align="right" class="Lrule Rrule Toprule"><span class="Bold">Avoid wrinkles or folds     </span></td><td class="Lrule Rrule Toprule"></td><td></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule"><img alt="image description" src="/dailymed/image.cfm?name=twirla-application-6a.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6"/></td><td class="Botrule Lrule Rrule"><span class="Bold">Step 6.</span> If the patch is not flat on the skin or there are large wrinkles, gently pull the patch off the skin while holding only the remaining protective liner and then put it on again.</td><td></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><img alt="image description" src="/dailymed/image.cfm?name=twirla-application-7.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6"/></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 7. </span>After the patch is flat with no wrinkles, pull an edge of the remaining protective liner and gently pull it off.</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><img alt="image description" src="/dailymed/image.cfm?name=twirla-application-8.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6"/></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 8a. </span>After the patch is on your body, press the entire patch firmly into place with your hand for 10 seconds, making sure the edges stick well.</p> <p></p> <p> <span class="Bold"> <br/>Step 8b.</span> Make sure the patch is on your skin all the way.</p> </td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"><img alt="image description" src="/dailymed/image.cfm?name=twirla-application-9.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6"/></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 9. </span>The edges of the patch should be smoothed over with your finger and make sure there is good contact around the patch with your skin and make sure there are no wrinkles.</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule"><img alt="image description" src="/dailymed/image.cfm?name=twirla-application-10.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6"/></td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 10. </span>It is important that you check the patch every day to make sure it is in the right place. The patch should be checked after any water exposure (such as bathing, showering, or swimming) to make sure it is in the right place because water may affect how well the patch sticks to your skin<span class="Italics">.</span> </p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"5\" cellspacing=\"0\">\n<caption>\n<span>Patch Application Instructions</span>\n</caption>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><img alt=\"image description\" src=\"/dailymed/image.cfm?name=twirla-application-0.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6\"/></td><td class=\"Botrule Lrule Rrule Toprule\">\n<ul>\n<li>Before the patch is applied, make sure your skin is clean and dry. Also make sure you have not used any make up, creams, lotions, oils, powders or any other products on the skin area where you put or plan to put the patch</li>\n<li>Each patch is individually sealed in a pouch.</li>\n<li>\n<span class=\"Bold\">It is important that you immediately apply the patch after being removed from the pouch.</span>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><img alt=\"image description\" src=\"/dailymed/image.cfm?name=twirla-application-1.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6\"/></td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 1.  </span>Tear the pouch open at the notch on the pouch.</p>\n<p></p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><img alt=\"image description\" src=\"/dailymed/image.cfm?name=twirla-application-2.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6\"/></td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 2. </span>Open the pouch and carefully remove the patch. The patch is attached to a clear protective liner.</p>\n<p></p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Avoid touching the sticky side of the patch</span><img alt=\"image description\" src=\"/dailymed/image.cfm?name=twirla-application-4.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6\"/></td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 3a.</span> Hold the patch with the clear protective liner facing you. You will see two sections: a large section and a small section.</p>\n<p></p>\n<p>\n<span class=\"Bold\">\n<br/>Avoid touching the sticky side of the patch with your fingers.</span>\n</p>\n<p></p>\n<p>\n<span class=\"Bold\">\n<br/>Step 3b. </span>Hold the small section of the liner.  Remove and throw away (discard) the large section of the liner while still holding the small section of the liner.</p>\n<p></p>\n</td><td class=\"Botrule Lrule Rrule Toprule\"></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><img alt=\"image description\" src=\"/dailymed/image.cfm?name=twirla-application-5.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6\"/></td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 4. </span>Hold the small section of the liner and apply the sticky side of the patch to the chosen patch site.</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><img alt=\"image description\" src=\"/dailymed/image.cfm?name=twirla-application-6.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6\"/></td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 5.</span> Press the sticky side of the patch firmly onto your skin and smooth it down.</p>\n<p></p>\n</td>\n</tr>\n<tr>\n<td align=\"right\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Avoid wrinkles or folds     </span></td><td class=\"Lrule Rrule Toprule\"></td><td></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\"><img alt=\"image description\" src=\"/dailymed/image.cfm?name=twirla-application-6a.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6\"/></td><td class=\"Botrule Lrule Rrule\"><span class=\"Bold\">Step 6.</span> If the patch is not flat on the skin or there are large wrinkles, gently pull the patch off the skin while holding only the remaining protective liner and then put it on again.</td><td></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><img alt=\"image description\" src=\"/dailymed/image.cfm?name=twirla-application-7.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6\"/></td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 7. </span>After the patch is flat with no wrinkles, pull an edge of the remaining protective liner and gently pull it off.</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><img alt=\"image description\" src=\"/dailymed/image.cfm?name=twirla-application-8.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6\"/></td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 8a. </span>After the patch is on your body, press the entire patch firmly into place with your hand for 10 seconds, making sure the edges stick well.</p>\n<p></p>\n<p>\n<span class=\"Bold\">\n<br/>Step 8b.</span> Make sure the patch is on your skin all the way.</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><img alt=\"image description\" src=\"/dailymed/image.cfm?name=twirla-application-9.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6\"/></td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 9. </span>The edges of the patch should be smoothed over with your finger and make sure there is good contact around the patch with your skin and make sure there are no wrinkles.</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><img alt=\"image description\" src=\"/dailymed/image.cfm?name=twirla-application-10.jpg&amp;setid=bcaf8db0-1750-425d-b008-255b5e7a9cc6\"/></td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 10. </span>It is important that you check the patch every day to make sure it is in the right place. The patch should be checked after any water exposure (such as bathing, showering, or swimming) to make sure it is in the right place because water may affect how well the patch sticks to your skin<span class=\"Italics\">.</span>\n</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

How do I throw away TWIRLA patches?

{ "type": "p", "children": [], "text": "\nHow do I throw away TWIRLA patches?\n" }

{ "type": "ul", "children": [ "To throw away your TWIRLA patch, fold the sticky side of the patch together and place in the trash right away so that children and pets cannot reach it. Do not flush used TWIRLA patches down the toilet." ], "text": "" }

{ "type": "ul", "children": [ "For more information on how to safely throw away medicines, see www.fda.gov/drugdisposal." ], "text": "" }

When should I change the TWIRLA patch?

{ "type": "p", "children": [], "text": "\nWhen should I change the TWIRLA patch?\n" }

{ "type": "ul", "children": [ "TWIRLA is applied in a 4 week patch cycle. Each patch cycle includes 4 weeks (28 days). You will put on 1 patch every week for 3 weeks. You will not wear a patch during week 4. Each patch is worn for 7 days (1 week). " ], "text": "" }

{ "type": "ul", "children": [ "Apply a new TWIRLA patch on the same day each week (this is called your Patch Change Day). For example, if you apply your first patch on a Monday, all of your TWIRLA patches should be applied on Monday. " ], "text": "" }

{ "type": "ul", "children": [ "You will not wear a TWIRLA patch during week 4 (this is called your Patch Free Week). Make sure you remove the old patch from your body. Your period should begin during your Patch Free Week. " ], "text": "" }

{ "type": "ul", "children": [ "After you have finished week 4, apply a new TWIRLA patch on the day after Week 4 ends. Repeat the patch cycle of 1 patch a week for 3 weeks followed by your Patch Free Week. " ], "text": "" }

What if a patch starts to lift off your skin or completely comes off?

{ "type": "p", "children": [], "text": "\nWhat if a patch starts to lift off your skin or completely comes off?\n" }

{ "type": "ul", "children": [ "If your patch starts to lift off your skin or completely comes off and you do not replace it, you may not get enough hormones to keep you from getting pregnant." ], "text": "" }

{ "type": "ul", "children": [ "If a patch starts to lift off your skin or is completely off for less than one day (up to 24 hours), you should try and put it on again to the same place or replace it with a new patch immediately. No back up birth control is needed and your Patch Change Day will remain the same." ], "text": "" }

{ "type": "ul", "children": [ "If a patch starts to lift off your skin or is completely off for more than 1 day (24 hours or more) or if you are not sure how long the patch has been not attached to your skin, you may not be protected from pregnancy. You should stop your current patch cycle and start over on a new patch cycle right away by putting on a new patch. The day you apply your new patch is now your new Day 1 and your new Patch Change Day. Non-hormonal back up birth control, (such as condoms and spermicide, or diaphragm and spermicide) must be used for the first week of the new patch cycle." ], "text": "" }

{ "type": "ul", "children": [ "Do not put a patch on again if it is no longer sticky, if it has become stuck to itself or another surface or if it has other material stuck to it. If your patch cannot be put on again, a new patch should be put on right away. If you need help applying a patch, contact Agile Medical Information at 1-855-389-4752 or email: medicalaffairs@agiletherapeutics.com." ], "text": "" }

Can I wear the patch when I am exercising, or using a sauna, swimming pool, or whirlpool?

{ "type": "p", "children": [], "text": "\nCan I wear the patch when I am exercising, or using a sauna, swimming pool, or whirlpool?\n" }

{ "type": "ul", "children": [ "Yes, women can maintain all their normal daily activities while using the patch." ], "text": "" }

{ "type": "ul", "children": [ "It is important to check your patch after any water that touches your patch during bathing, showering, or swimming, as prolonged water exposure may affect how well the patch sticks to your skin." ], "text": "" }

{ "type": "ul", "children": [ "If the patch starts to come off or completely lifts off the skin, try to put it on again." ], "text": "" }

{ "type": "ul", "children": [ "A patch should not be put on again if it is no longer sticky, if it has become stuck to itself or another surface or if it has other material stuck to it." ], "text": "" }

{ "type": "ul", "children": [ "If your current patch cannot be put on again, a new patch should be put on right away. Before applying the patch, make sure your skin is clean and dry." ], "text": "" }

{ "type": "ul", "children": [ "Make sure you have not used any make up, creams, lotions, oils, powders or any other products on the skin area where you put or plan to put the patch. If you find yourself in need of an additional patch because you needed to replace a patch, contact Agile Medical Information at 1-855-389-4752 or email: medicalaffairs@agiletherapeutics.com." ], "text": "" }

What if you forget to change your patch (left your patch on more than 7 days)?

{ "type": "p", "children": [], "text": "\nWhat if you forget to change your patch (left your patch on more than 7 days)?\n" }

{ "type": "ul", "children": [ "\nIf you forget to change your patch at the start of any patch cycle (Day 1): You may not be protected from pregnancy. You should apply the first patch of your new patch cycle as soon as you remember. This is now your new Patch Change Day and your new Day 1. You must use non-hormonal back up birth control (such as condoms and spermicide, or diaphragm and spermicide) for the first week of your new patch cycle." ], "text": "" }

{ "type": "ul", "children": [ "\nIf you forget to change your patch in the middle of the patch cycle (Day 8 or Day 15): for 1 or 2 days (up to 48 hours): you should apply a new patch right away. The next patch should be applied on your usual Patch Change Day. No back up birth control is needed." ], "text": "" }

{ "type": "ul", "children": [ "\nIf you forget to change your patch for more than 2 days (48 hours or more): You may not be protected from pregnancy. You should stop your current patch cycle and start a new 4 week patch cycle right away by putting on a new patch. This is now your new Patch Change Day and your new Day 1. You must use non-hormonal back up birth control for the first week of your new patch cycle." ], "text": "" }

<div class="scrollingtable"><table border="1" cellpadding="5" cellspacing="0" width="100%"> <caption> <span>What to do if the patch starts to lift or the patch completely comes off from the skin and Late or Missed Patch Applications</span> </caption> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Frequent Patch Situations</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Will I have a  <br/> New Patch- <br/> Change Day</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Will I need to start a New 4 week Patch Cycle</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Will I need a backup Birth Control method  </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Did not apply patch on scheduled Day 1 of new patch cycle</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Yes</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Yes</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Yes (for 7 days)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Patch not attached for less than 24 hours</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">No</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">No</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">No</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Patch not attached for 24 hours or more, or unsure how long</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Yes</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Yes</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Yes (for 7 days)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Less than 48 hours late for <span class="Bold">Patch Change Day</span> (Day 8 or 15)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">No</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">No</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">No</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">48 hours or more late for <span class="Bold">Patch Change Day</span> (Day 8 or 15)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Yes</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Yes</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">Yes (for 7 days)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First">Forgets to remove last patch on Day 22</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">No</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">No</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">No</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"5\" cellspacing=\"0\" width=\"100%\">\n<caption>\n<span>What to do if the patch starts to lift or the patch completely comes off from the skin and Late or Missed Patch Applications</span>\n</caption>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Frequent Patch Situations</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Will I have a  <br/> New Patch- <br/> Change Day</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Will I need to start a New 4 week Patch Cycle</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Will I need a backup Birth Control method  </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Did not apply patch on scheduled Day 1 of new patch cycle</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Yes</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Yes</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Yes (for 7 days)</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Patch not attached for less than 24 hours</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">No</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">No</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">No</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Patch not attached for 24 hours or more, or unsure how long</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Yes</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Yes</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Yes (for 7 days)</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Less than 48 hours late for <span class=\"Bold\">Patch Change Day</span> (Day 8 or 15)</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">No</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">No</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">No</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">48 hours or more late for <span class=\"Bold\">Patch Change Day</span> (Day 8 or 15)</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Yes</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Yes</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Yes (for 7 days)</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">Forgets to remove last patch on Day 22</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">No</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">No</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">No</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

What if you forget to remove your patch for the patch free week?

{ "type": "p", "children": [], "text": "\nWhat if you forget to remove your patch for the patch free week?\n" }

{ "type": "ul", "children": [ "\nPast Day 22: You should take it off as soon as you remember. No other change is needed.  You should still start the next patch cycle on the usual Patch Change Day, which is the day after Day 28. No back up birth control is needed." ], "text": "" }

{ "type": "ul", "children": [ "\nYour TWIRLA patch should never be off more than 7 days in a row. If you ever go more than 7 days without a patch, you should use another birth control method. \n" ], "text": "" }

{ "type": "ul", "children": [ "As with all hormonal birth control, the risk of getting pregnant increases with each day you go past the recommended 7 day patch free period." ], "text": "" }

What if you wish to change your Patch Change Day?

{ "type": "p", "children": [], "text": "\nWhat if you wish to change your Patch Change Day?\n" }

{ "type": "ul", "children": [ "If you want to change your Patch Change Day you should complete your current patch cycle, removing the third patch on the correct day. During the Patch Free Week, you may select an earlier Patch Change Day by applying a new patch on the chosen day." ], "text": "" }

Your TWIRLA patch should never be off more than 7 days in a row.

{ "type": "p", "children": [], "text": "\nYour TWIRLA patch should never be off more than 7 days in a row.\n" }

Manufactured by:Corium International, Inc.4558 50th Street, SEGrand Rapids, MI 49512

{ "type": "p", "children": [], "text": "Manufactured by:Corium International, Inc.4558 50th Street, SEGrand Rapids, MI 49512" }

Manufactured for:Agile Therapeutics, Inc.500 College Rd. E, Suite 310Princeton, NJ 08540

{ "type": "p", "children": [], "text": "Manufactured for:Agile Therapeutics, Inc.500 College Rd. E, Suite 310Princeton, NJ 08540" }

For more information call 1-855-389-4752 or email: medicalaffairs@agiletherapeutics.com.

{ "type": "p", "children": [], "text": "For more information call 1-855-389-4752 or email: medicalaffairs@agiletherapeutics.com." }

<div class="scrollingtable"><table cellpadding="5" cellspacing="0"> <tbody class="Headless"> <tr class="First First Last Last"> <td valign="top"> <p class="First">This Instructions for Use has been approved by the U.S. Food and Drug Administration                                      </p> </td><td valign="top"> <p class="First">Approved:  04/2022</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"5\" cellspacing=\"0\">\n<tbody class=\"Headless\">\n<tr class=\"First First Last Last\">\n<td valign=\"top\">\n<p class=\"First\">This Instructions for Use has been approved by the U.S. Food and Drug Administration                                      </p>\n</td><td valign=\"top\">\n<p class=\"First\">Approved:  04/2022</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

TwirlaTM (levonorgestrel and ethinyl estradiol) transdermal system 120 mcg/day levonogestrel and 30 mcg/day ethinyl estradiol

{ "type": "p", "children": [], "text": "TwirlaTM\n(levonorgestrel and ethinyl estradiol)\n transdermal system\n 120 mcg/day levonogestrel and 30 mcg/day ethinyl estradiol" }

Contains 1 transdermal system

{ "type": "p", "children": [], "text": "Contains 1\n transdermal\n system" }

NDC 71671-100-11

{ "type": "p", "children": [], "text": "NDC 71671-100-11" }

Each 28 cm2 system contains 2.6 mg levonorgestrel (LNG) and 2.3 mg ethyinyl estradiol (EE). The inactive components are acrylic adhesives, capric acid, copovidone, crospovidone, dimethyl sulfoxide, ethyl lactate, lauryl lactate, polyester backing, polyester release liner, polyisobutylene adhesive, and woven polyester fabric.

{ "type": "p", "children": [], "text": "Each 28 cm2 system contains 2.6 mg levonorgestrel (LNG) and 2.3 mg ethyinyl estradiol\n (EE). The inactive components are acrylic adhesives, capric acid, copovidone,\n crospovidone, dimethyl sulfoxide, ethyl lactate, lauryl lactate, polyester backing,\n polyester release liner, polyisobutylene adhesive, and woven polyester fabric." }

This product is intended to prevent pregnancy. It does not protect against HIV (AIDS) and other sexually trasmitted diseases.

{ "type": "p", "children": [], "text": "\nThis product is intended to prevent pregnancy. It does not protect against HIV\n\n(AIDS) and other sexually trasmitted diseases.\n" }

Rx only. For Transdermal Use Only.

{ "type": "p", "children": [], "text": "\nRx only. For Transdermal Use Only.\n" }

Keep out of reach of children. Package not child resistant. Store at room temperature 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F).

{ "type": "p", "children": [], "text": "Keep out of reach of children. Package not child resistant.\n Store at room temperature 20°C to 25°C (68°F to 77°F) with excursions permitted\n to 15°C to 30°C (59°F to 86°F)." }

Recommended Dosage: See prescribing information. Apply immediately upon removal from pouch. Each transdermal system is intended to be worn for 7 days - Fold used system and discard prior to applying new system.

{ "type": "p", "children": [], "text": "Recommended Dosage: See prescribing information. Apply immediately upon removal\n from pouch. Each transdermal system is intended to be worn for 7 days - Fold used\n system and discard prior to applying new system." }

Mfd. For: Agile Therapeutics, Inc. Princeton, NJ 08540 Mfd. By: Corium, Inc. Grand Rapids, MI 49512

{ "type": "p", "children": [], "text": "Mfd. For: Agile Therapeutics, Inc.\n Princeton, NJ 08540\n Mfd. By: Corium, Inc.\n Grand Rapids, MI 49512" }

CAW1011

{ "type": "p", "children": [], "text": "\nCAW1011\n" }

NDC 71671-100-03

{ "type": "p", "children": [], "text": "NDC 71671-100-03" }

TwirlaTM (levonorgestrel and ethinyl estradiol) transdermal system 120 mcg/day levonogestrel and 30 mcg/day ethinyl estradiol

{ "type": "p", "children": [], "text": "TwirlaTM\n(levonorgestrel and ethinyl estradiol)\n transdermal system\n 120 mcg/day levonogestrel and 30 mcg/day ethinyl estradiol" }

Contents: 3 transdermal systems

{ "type": "p", "children": [], "text": "\nContents: 3 transdermal systems\n" }

Each 28 cm2 system contains 2.6 mg levonorgestrel (LNG) and 2.3 mg ethyinyl estradiol (EE). The inactive components are acrylic adhesives, capric acid, copovidone, crospovidone, dimethyl sulfoxide, ethyl lactate, lauryl lactate, polyester backing, polyester release liner, polyisobutylene adhesive, and woven polyester fabric.

{ "type": "p", "children": [], "text": "Each 28 cm2 system contains 2.6 mg levonorgestrel (LNG) and 2.3 mg\n ethyinyl estradiol (EE). The inactive components are acrylic adhesives, capric\n acid, copovidone, crospovidone, dimethyl sulfoxide, ethyl lactate, lauryl\n lactate, polyester backing, polyester release liner, polyisobutylene adhesive,\n and woven polyester fabric." }

This product is intended to prevent pregnancy. It does not protect against HIV (AIDS) and other sexually trasmitted diseases.

{ "type": "p", "children": [], "text": "\nThis product is intended to prevent pregnancy. It does not protect against\n HIV (AIDS) and other sexually trasmitted diseases.\n" }

Rx only. For Transdermal Use Only.

{ "type": "p", "children": [], "text": "\nRx only. For Transdermal Use Only.\n" }

Agile® THERAPEUTICS

{ "type": "p", "children": [], "text": "\nAgile® THERAPEUTICS\n" }

REPLACEMENRONLY-UP TO 1 WEEKTHERAPY

{ "type": "p", "children": [], "text": "REPLACEMENRONLY-UP TO 1 WEEKTHERAPY" }

NDC 71671-100-01

{ "type": "p", "children": [], "text": "NDC 71671-100-01" }

TwirlaTM (levonorgestrel and ethinyl estradiol) transdermal system 120 mcg/day levonogestrel and 30 mcg/day ethinyl estradiol

{ "type": "p", "children": [], "text": "TwirlaTM\n(levonorgestrel and ethinyl estradiol) transdermal system 120 mcg/day levonogestrel and 30 mcg/day ethinyl estradiol" }

Contents: 1 replacement transdermal system

{ "type": "p", "children": [], "text": "\nContents: 1 replacement transdermal system\n" }

Each 28 cm2 system contains 2.6 mg levonorgestrel (LNG) and 2.3 mg ethyinyl estradiol (EE). The inactive components are acrylic adhesives, capric acid, copovidone, crospovidone, dimethyl sulfoxide, ethyl lactate, lauryl lactate, polyester backing, polyester release liner, polyisobutylene adhesive, and woven polyester fabric.

{ "type": "p", "children": [], "text": "Each 28 cm2 system contains 2.6 mg levonorgestrel (LNG) and 2.3 mg ethyinyl estradiol (EE). The inactive components are acrylic adhesives, capric acid, copovidone, crospovidone, dimethyl sulfoxide, ethyl lactate, lauryl lactate, polyester backing, polyester release liner, polyisobutylene adhesive, and woven polyester fabric." }

This product is intended to prevent pregnancy. It does not protect against HIV (AIDS) and other sexually trasmitted diseases.

{ "type": "p", "children": [], "text": "\nThis product is intended to prevent pregnancy. It does not protect against HIV (AIDS) and other sexually trasmitted diseases.\n" }

Rx only. For Transdermal Use Only.

{ "type": "p", "children": [], "text": "\nRx only. For Transdermal Use Only.\n" }

Agile® THERAPEUTICS

{ "type": "p", "children": [], "text": "\nAgile® THERAPEUTICS\n" }

Levonorgestrel tablets, 0.75 mg are progestin-only emergency contraceptive indicated for prevention of pregnancy following unprotected intercourse or a known or suspected contraceptive failure. To obtain optimal efficacy, the first tablet should be taken as soon as possible within 72 hours of intercourse. The second tablet should be taken 12 hours later.

Levonorgestrel tablets, 0.75 mg are available only by prescription for women younger than age 17 years, and available over the counter for women 17 years and older.

Levonorgestrel tablets, 0.75 mg are not indicated for routine use as a contraceptive.

Take one tablet of levonorgestrel tablet, 0.75 mg orally as soon as possible within 72 hours after unprotected intercourse or a known or suspected contraceptive failure. Efficacy is better if the tablet is taken as soon as possible after unprotected intercourse. The second tablet should be taken 12 hours after the first dose. Levonorgestrel tablets, 0.75 mg can be used at any time during the menstrual cycle.

If vomiting occurs within two hours of taking either dose of medication, consideration should be given to repeating the dose.

Each levonorgestrel tablet, 0.75 mg is supplied as a white to off white round biconvex tablets, debossed with ‘LU’ on one side and ‘S24’ on the other side.

Levonorgestrel tablets, 0.75 mg are contraindicated for use in the case of known or suspected pregnancy.

Ectopic pregnancies account for approximately 2% of all reported pregnancies. Up to 10% of pregnancies reported in clinical studies of routine use of progestin-only contraceptives are ectopic.

A history of ectopic pregnancy is not a contraindication to use of this emergency contraceptive method. Healthcare providers, however, should consider the possibility of an ectopic pregnancy in women who become pregnant or complain of lower abdominal pain after taking levonorgestrel tablets, 0.75 mg. A follow-up physical or pelvic examination is recommended if there is any doubt concerning the general health or pregnancy status of any woman after taking levonorgestrel tablets, 0.75 mg.

Levonorgestrel tablets, 0.75 mg are not effective in terminating an existing pregnancy.

Some women may experience spotting a few days after taking levonorgestrel tablets, 0.75 mg. Menstrual bleeding patterns are often irregular among women using progestin-only oral contraceptives and women using levonorgestrel for postcoital and emergency contraception.

If there is a delay in the onset of expected menses beyond 1 week, consider the possibility of pregnancy.

Levonorgestrel tablets, 0.75 mg do not protect against HIV infection (AIDS) or other sexually transmitted infections (STIs).

A physical examination is not required prior to prescribing levonorgestrel tablets, 0.75 mg. A follow-up physical or pelvic examination is recommended if there is any doubt concerning the general health or pregnancy status of any woman after taking levonorgestrel tablets, 0.75 mg.

A rapid return of fertility is likely following treatment with levonorgestrel tablets, 0.75 mg for emergency contraception; therefore, routine contraception should be continued or initiated as soon as possible following use of levonorgestrel tablets, 0.75 mg to ensure ongoing prevention of pregnancy.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

A double-blind, controlled clinical trial in 1,955 evaluable women compared the efficacy and safety of levonorgestrel tablet, 0.75 mg (one 0.75 mg tablet of levonorgestrel taken within 72 hours of unprotected intercourse, and one tablet taken 12 hours later) to the Yuzpe regimen (two tablets each containing 0.25 mg levonorgestrel and 0.05 mg ethinyl estradiol, taken within 72 hours of intercourse, and two tablets taken 12 hours later).

The most common adverse events (>10%) in the clinical trial for women receiving levonorgestrel tablets, 0.75 mg included menstrual changes (26%), nausea (23%), abdominal pain (18%), fatigue (17%), headache (17%), dizziness (11%), and breast tenderness (11%). Table 1 lists those adverse events that were reported in ≥5% of levonorgestrel tablets, 0.75 mg users.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1. Adverse Events in ≥ 5% of Women, by % Frequency</span> </caption> <col width="55%"/> <col width="45%"/> <thead> <tr class="First Last"> <td align="justify" class="Botrule Lrule Rrule Toprule" colspan="1" valign="middle"> <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="1" valign="middle"><span class="Bold">Levonorgestrel </span><span class="Bold">Tablets</span><span class="Bold">, </span><span class="Bold">0</span><span class="Bold">.</span><span class="Bold">75 </span><span class="Bold">mg</span><span class="Bold"> <br/> </span><span class="Bold">N </span><span class="Bold">= </span><span class="Bold">977 </span><span class="Bold">(%)</span> <br/> </td> </tr> </thead> <tbody> <tr class="First"> <td align="justify" class="Botrule Lrule Rrule Toprule" valign="middle">Nausea <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">23.1<br/> </td> </tr> <tr> <td align="justify" class="Botrule Lrule Rrule Toprule" valign="middle">Abdominal Pain <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">17.6<br/> </td> </tr> <tr> <td align="justify" class="Botrule Lrule Rrule Toprule" valign="middle">Fatigue <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">16.9<br/> </td> </tr> <tr> <td align="justify" class="Botrule Lrule Rrule Toprule" valign="middle">Headache <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">16.8<br/> </td> </tr> <tr> <td align="justify" class="Botrule Lrule Rrule Toprule" valign="middle">Heavier Menstrual Bleeding <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">13.8<br/> </td> </tr> <tr> <td align="justify" class="Botrule Lrule Rrule Toprule" valign="middle">Lighter Menstrual Bleeding <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">12.5<br/> </td> </tr> <tr> <td align="justify" class="Botrule Lrule Rrule Toprule" valign="middle">Dizziness <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">11.2<br/> </td> </tr> <tr> <td align="justify" class="Botrule Lrule Rrule Toprule" valign="middle">Breast Tenderness <br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">10.7<br/> </td> </tr> <tr> <td align="justify" class="Botrule Lrule Rrule Toprule" valign="middle">Vomiting<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">5.6<br/> </td> </tr> <tr class="Last"> <td align="justify" class="Botrule Lrule Rrule Toprule" valign="middle">Diarrhea<br/> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="middle">5.0<br/> </td> </tr> </tbody> </table></div>

The following adverse reactions have been identified during post-approval use of levonorgestrel tablets, 0.75 mg. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal Disorders

Abdominal Pain, Nausea, Vomiting

General Disorders and Administration Site Conditions

Fatigue

Nervous System Disorders

Dizziness, Headache

Reproductive System and Breast Disorders

Dysmenorrhea, Irregular Menstruation, Oligomenorrhea, Pelvic Pain

Drugs or herbal products that induce enzymes, including CYP3A4, that metabolize progestins may decrease the plasma concentrations of progestins, and may decrease the effectiveness of progestin-only pills. Some drugs or herbal products that may decrease the effectiveness of progestin-only pills include:

Significant changes (increase or decrease) in the plasma levels of the progestin have been noted in some cases of co-administration with HIV protease inhibitors or with non-nucleoside reverse transcriptase inhibitors. Concomitant administration of efavirenz has been found to reduce plasma levels of levonorgestrel (AUC) by around 50%, which may reduce the effectiveness of levonorgestrel tablets, 0.75 mg.

Consult the labeling of all concurrently used drugs to obtain further information about interactions with progestin-only pills or the potential for enzyme alterations.

Many studies have found no harmful effects on fetal development associated with long-term use of contraceptive doses of oral progestins. The few studies of infant growth and development that have been conducted with progestin-only pills have not demonstrated significant adverse effects.

In general, no adverse effects of progestin-only pills have been found on breastfeeding performance or on the health, growth or development of the infant. However, isolated post-marketing cases of decreased milk production have been reported. Small amounts of progestins pass into the breast milk of nursing mothers taking progestin-only pills for long-term contraception, resulting in detectable steroid levels in infant plasma.

Safety and efficacy of progestin-only pills for long-term contraception have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of levonorgestrel tablets, 0.75 mg emergency contraception before menarche is not indicated.

This product is not intended for use in postmenopausal women.

No formal studies have evaluated the effect of race. However, clinical trials demonstrated a higher pregnancy rate in Chinese women with both levonorgestrel tablets, 0.75 mg and the Yuzpe regimen (another form of emergency contraception). The reason for this apparent increase in the pregnancy rate with emergency contraceptives in Chinese women is unknown.

No formal studies were conducted to evaluate the effect of hepatic disease on the disposition of levonorgestrel tablets, 0.75 mg.

No formal studies were conducted to evaluate the effect of renal disease on the disposition of levonorgestrel tablets, 0.75 mg.

Levonorgestrel is not a controlled substance. There is no information about dependence associated with the use of levonorgestrel tablets, 0.75 mg.

{ "type": "p", "children": [], "text": "\nLevonorgestrel is not a controlled substance. There is no information about dependence associated with the use of levonorgestrel tablets, 0.75 mg. " }

There are no data on overdosage of levonorgestrel tablets, 0.75 mg, although the common adverse event of nausea and associated vomiting may be anticipated.

{ "type": "p", "children": [], "text": "\nThere are no data on overdosage of levonorgestrel tablets, 0.75 mg, although the common adverse event of nausea and associated vomiting may be anticipated. " }

Each levonorgestrel tablets, 0.75 mg contains 0.75 mg of a single active steroid ingredient, levonorgestrel [18,19-Dinorpregn-4-en-20-yn-3-one-13-ethyl-17-hydroxy-, (17 α)-(-)-], a totally synthetic progestogen. The inactive ingredients present are colloidal silicon dioxide, corn starch, lactose monohydrate, magnesium stearate, and povidone.

{ "type": "p", "children": [], "text": "\nEach levonorgestrel tablets, 0.75 mg contains 0.75 mg of a single active steroid ingredient, levonorgestrel [18,19-Dinorpregn-4-en-20-yn-3-one-13-ethyl-17-hydroxy-, (17 α)-(-)-], a totally synthetic progestogen. The inactive ingredients present are colloidal silicon dioxide, corn starch, lactose monohydrate, magnesium stearate, and povidone." }

Levonorgestrel has a molecular weight of 312.45, and the following structural and molecular formulas:

{ "type": "p", "children": [], "text": "Levonorgestrel has a molecular weight of 312.45, and the following structural and molecular formulas:" }

Emergency contraceptive pills are not effective if a woman is already pregnant. Levonorgestrel tablets, 0.75 mg are believed to act as an emergency contraceptive principally by preventing ovulation or fertilization (by altering tubal transport of sperm and/or ova). In addition, it may inhibit implantation (by altering the endometrium). It is not effective once the process of implantation has begun.

Absorption

No specific investigation of the absolute bioavailability of levonorgestrel in humans has been conducted. However, literature indicates that levonorgestrel is rapidly and completely absorbed after oral administration (bioavailability about 100%) and is not subject to first pass metabolism.

After a single dose of levonorgestrel (0.75 mg) administered to 16 women under fasting conditions, the maximum serum concentrations of levonorgestrel were 14.1 + 7.7 ng/mL (mean + SD)  at an average of 1.6 + 0.7 hours.

<div class="scrollingtable"><table width="0"> <col width="111"/> <col width="89"/> <col width="86"/> <col width="87"/> <col width="87"/> <col width="86"/> <col width="97"/> <tfoot> <tr class="First"> <td align="left" colspan="7"> <p class="First Footnote">C<span class="Sub">max</span> = maximum concentration </p> </td> </tr> <tr> <td align="left" colspan="7"> <p class="First Footnote">T<span class="Sub">max</span> = time to maximum concentration </p> </td> </tr> <tr> <td align="left" colspan="7"> <p class="First Footnote">CL = clearance</p> </td> </tr> <tr> <td align="left" colspan="7"> <p class="First Footnote">V<span class="Sub">d</span> = volume of distribution</p> </td> </tr> <tr> <td align="left" colspan="7"> <p class="First Footnote">t<span class="Bold"><span class="Sub">½</span></span> = elimination half life</p> </td> </tr> <tr class="Last"> <td align="left" colspan="7"> <p class="First Footnote">AUC<span class="Sub">inf</span> = area under the drug concentration curve from time 0 to infinity </p> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Rrule Toprule" colspan="6" valign="top"><span class="Bold"> Mean (± SD)</span> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> C<span class="Sub">max</span> (ng/mL)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> T<span class="Sub">max</span></span> <br/> <span class="Bold"> (h)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> CL </span> <br/> <span class="Bold"> (L/h)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> V<span class="Sub">d</span></span> <br/> <span class="Bold"> (L)</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> t</span><span class="Bold"><span class="Sub">½</span></span> <br/> <span class="Bold"> (h)</span> <br/> </td><td align="left" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> AUC<span class="Sub">inf </span>(</span> ng/mL.h)  <br/> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule" valign="top"> Levonorgestrel<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 14.1 (7.7)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 1.6 (0.7)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 7.7 (2.7)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 260.0<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 24.4 (5.3)<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 123.1 (50.1)<br/> </td> </tr> </tbody> </table></div>

Effect of Food: The effect of food on the rate and the extent of levonorgestrel absorption following single oral administration of levonorgestrel tablets, 0.75 mg have not been evaluated.

Distribution

The apparent volume of distribution of levonorgestrel is reported to be approximately 1.8 L/kg. It is about 97.5 to 99% protein-bound, principally to sex hormone binding globulin (SHBG) and, to a lesser extent, serum albumin.

Metabolism

Following absorption, levonorgestrel is conjugated at the 17β-OH position to form sulfate conjugates and, to a lesser extent, glucuronide conjugates in plasma. Significant amounts of conjugated and unconjugated 3α, 5β-tetrahydrolevonorgestrel are also present in plasma, along with much smaller amounts of 3α, 5α-tetrahydrolevonorgestrel and 16βhydroxylevonorgestrel. Levonorgestrel and its phase I metabolites are excreted primarily as glucuronide conjugates. Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for the wide variation observed in levonorgestrel concentrations among users.

Excretion

About 45% of levonorgestrel and its metabolites are excreted in the urine and about 32% are excreted in feces, mostly as glucuronide conjugates.

Specific Populations

Pediatric

This product is not intended for use in the pediatric (pre-menarcheal) population, and pharmacokinetic data are not available for this population.

Geriatric

This product is not intended for use in postmenopausal women and pharmacokinetic data are not available for this population.

Race

No formal studies have evaluated the effect of race on pharmacokinetics of levonorgestrel tablets, 0.75 mg. However, clinical trials demonstrated a higher pregnancy rate in Chinese women with both levonorgestrel tablets, 0.75 mg and the Yuzpe regimen (another form of emergency contraception). The reason for this apparent increase in the pregnancy rate with emergency contraceptives in Chinese women is unknown [see USE IN SPECIFIC POPULATIONS (8.6)].

Hepatic Impairment

No formal studies were conducted to evaluate the effect of hepatic disease on the disposition of levonorgestrel tablets, 0.75 mg.

Renal Impairment

No formal studies were conducted to evaluate the effect of renal disease on the disposition of levonorgestrel tablets, 0.75 mg.

Drug-Drug Interactions

No formal drug-drug interaction studies were conducted with levonorgestrel tablets, 0.75 mg [see DRUG INTERACTIONS (7)].

Carcinogenicity: There is no evidence of increased risk of cancer with short-term use of progestins. There was no increase in tumorgenicity following administration of levonorgestrel to rats for 2 years at approximately 5 μg/day, to dogs for 7 years at up to 0.125 mg/kg/day, or to rhesus monkeys for 10 years at up to 250 μg/kg/day. In another 7 year dog study, administration of levonorgestrel at 0.5 mg/kg/day did increase the number of mammary adenomas in treated dogs compared to controls. There were no malignancies.

Genotoxicity: Levonorgestrel was not found to be mutagenic or genotoxic in the Ames Assay, in vitro mammalian culture assays utilizing mouse lymphoma cells and Chinese hamster ovary cells, and in an in vivo micronucleus assay in mice.

Fertility: There are no irreversible effects on fertility following cessation of exposures to levonorgestrel or progestins in general.

A double-blind, randomized, multinational controlled clinical trial in 1,955 evaluable women (mean age 27) compared the efficacy and safety of levonorgestrel tablets, 0.75 mg (one 0.75 mg tablet of levonorgestrel taken within 72 hours of unprotected intercourse, and one tablet taken 12 hours later) to the Yuzpe regimen (two tablets each containing 0.25 mg levonorgestrel and 0.05 mg ethinyl estradiol, taken within 72 hours of intercourse, and two additional tablets taken 12 hours later). After a single act of intercourse occurring anytime during the menstrual cycle, the expected pregnancy rate of 8% (with no contraceptive use) was reduced to approximately 1% with levonorgestrel tablets, 0.75 mg.

{ "type": "p", "children": [], "text": "\nA double-blind, randomized, multinational controlled clinical trial in 1,955 evaluable women (mean age 27) compared the efficacy and safety of levonorgestrel tablets, 0.75 mg (one 0.75 mg tablet of levonorgestrel taken within 72 hours of unprotected intercourse, and one tablet taken 12 hours later) to the Yuzpe regimen (two tablets each containing 0.25 mg levonorgestrel and 0.05 mg ethinyl estradiol, taken within 72 hours of intercourse, and two additional tablets taken 12 hours later). After a single act of intercourse occurring anytime during the menstrual cycle, the expected pregnancy rate of 8% (with no contraceptive use) was reduced to approximately 1% with levonorgestrel tablets, 0.75 mg. " }

Emergency contraceptives are not as effective as routine hormonal contraception since their failure rate, while low based on a single use, would accumulate over time with repeated use [see INDICATIONS AND USAGE (1)].

{ "type": "p", "children": [], "text": "Emergency contraceptives are not as effective as routine hormonal contraception since their failure rate, while low based on a single use, would accumulate over time with repeated use [see INDICATIONS AND USAGE (1)]. \n" }

At the time of expected menses, approximately 74% of women using levonorgestrel tablets, 0.75 mg had vaginal bleeding similar to their normal menses, 14% bled more than usual, and 12% bled less than usual. The majority of women (87%) had their next menstrual period at the expected time or within +7 days, while 13% had a delay of more than 7 days beyond the anticipated onset of menses.

{ "type": "p", "children": [], "text": "At the time of expected menses, approximately 74% of women using levonorgestrel tablets, 0.75 mg had vaginal bleeding similar to their normal menses, 14% bled more than usual, and 12% bled less than usual. The majority of women (87%) had their next menstrual period at the expected time or within +7 days, while 13% had a delay of more than 7 days beyond the anticipated onset of menses." }

Levonorgestrel Tablets, 0.75 mg are white to off white round biconvex tablets, debossed with "LU" on one side and "S24" on the other side.

{ "type": "p", "children": [], "text": "\nLevonorgestrel Tablets, 0.75 mg are white to off white round biconvex tablets, debossed with \"LU\" on one side and \"S24\" on the other side. " }

Levonorgestrel Tablets, 0.75 mg are available in a wallet containing 2 tablets (NDC 68180-851-11). Each wallet is packed in a carton (NDC 68180-851-13).

{ "type": "p", "children": [], "text": "Levonorgestrel Tablets, 0.75 mg are available in a wallet containing 2 tablets (NDC 68180-851-11). Each wallet is packed in a carton (NDC 68180-851-13)." }

Store Levonorgestrel Tablets, 0.75 mg at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). [see USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store Levonorgestrel Tablets, 0.75 mg at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). [see USP Controlled Room Temperature]." }

Distributed by:

{ "type": "p", "children": [], "text": "\nDistributed by:" }

Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "\nLupin Pharmaceuticals, Inc.\n" }

Baltimore, Maryland 21202

{ "type": "p", "children": [], "text": "Baltimore, Maryland 21202" }

United States

{ "type": "p", "children": [], "text": "United States" }

Manufactured by:

{ "type": "p", "children": [], "text": "Manufactured by:" }

Lupin Limited

{ "type": "p", "children": [], "text": "\nLupin Limited\n" }

Pithampur (M.P.) - 454 775

{ "type": "p", "children": [], "text": "Pithampur (M.P.) - 454 775" }

INDIA

{ "type": "p", "children": [], "text": "INDIA" }

January 2018                                                               ID#: 226728

{ "type": "p", "children": [], "text": "January 2018                                                               ID#: 226728" }

Levonorgestrel Tablets, 0.75 mg

{ "type": "p", "children": [], "text": "\nLevonorgestrel Tablets, 0.75 mg\n" }

Rx only for age 17 and younger

{ "type": "p", "children": [], "text": "\nRx only for age 17 and younger\n" }

NDC 68180-851-11

{ "type": "p", "children": [], "text": "NDC 68180-851-11" }

Wallet Label: 2 Tablets

{ "type": "p", "children": [], "text": "Wallet Label: 2 Tablets" }

Levonorgestrel Tablets, 0.75 mg

{ "type": "p", "children": [], "text": "\nLevonorgestrel Tablets, 0.75 mg\n" }

Rx only for age 17 and younger

{ "type": "p", "children": [], "text": "\nRx only for age 17 and younger\n" }

NDC 68180-851-13

{ "type": "p", "children": [], "text": "NDC 68180-851-13" }

Carton Label: 2 Tablets

{ "type": "p", "children": [], "text": "Carton Label: 2 Tablets " }