RHOFADE® (oxymetazoline hydrochloride) cream, 1% is indicated for the topical treatment of persistent facial erythema associated with rosacea in adults.

{ "type": "p", "children": [], "text": "RHOFADE® (oxymetazoline hydrochloride) cream, 1% is indicated for the topical treatment of persistent facial erythema associated with rosacea in adults." }

For topical use only. RHOFADE cream is not for oral, ophthalmic, or intravaginal use.

{ "type": "p", "children": [], "text": "For topical use only. RHOFADE cream is not for oral, ophthalmic, or intravaginal use." }

Apply a pea-sized amount of RHOFADE cream, once daily in a thin layer to cover the entire face (forehead, nose, each cheek, and chin) avoiding the eyes and lips. Wash hands immediately after applying RHOFADE cream.

{ "type": "p", "children": [], "text": "Apply a pea-sized amount of RHOFADE cream, once daily in a thin layer to cover the entire face (forehead, nose, each cheek, and chin) avoiding the eyes and lips. Wash hands immediately after applying RHOFADE cream." }

RHOFADE® (oxymetazoline hydrochloride) cream, 1% is a white to off-white cream. Each gram of cream contains 10 mg (1%) oxymetazoline hydrochloride, equivalent to 8.8 mg (0.88%) of oxymetazoline free base.

{ "type": "p", "children": [], "text": "RHOFADE® (oxymetazoline hydrochloride) cream, 1% is a white to off-white cream. Each gram of cream contains 10 mg (1%) oxymetazoline hydrochloride, equivalent to 8.8 mg (0.88%) of oxymetazoline free base." }

None.

{ "type": "p", "children": [], "text": "None." }

Alpha-adrenergic agonists may impact blood pressure. RHOFADE cream should be used with caution in patients with severe or unstable or uncontrolled cardiovascular disease, orthostatic hypotension, and uncontrolled hypertension or hypotension. Advise patients with cardiovascular disease, orthostatic hypotension, and/or uncontrolled hypertension/hypotension to seek immediate medical care if their condition worsens.

RHOFADE cream should be used with caution in patients with cerebral or coronary insufficiency, Raynaud's phenomenon, thromboangitis obliterans, scleroderma, or Sjögren's syndrome. Advise patients to seek immediate medical care if signs and symptoms of potentiation of vascular insufficiency develop.

RHOFADE cream may increase the risk of angle closure glaucoma in patients with narrow-angle glaucoma. Advise patients to seek immediate medical care if signs and symptoms of acute angle closure glaucoma develop.

Because clinical trials are conducted under 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 practice.

A total of 489 subjects with persistent facial erythema associated with rosacea were treated with RHOFADE cream once daily for 4 weeks in 3 controlled clinical trials. An additional 440 subjects with persistent facial erythema associated with rosacea were also treated with RHOFADE cream once daily for up to one year in a long-term (open- label) clinical trial. Adverse reactions that occurred in at least 1% of subjects treated with RHOFADE cream through 4 weeks of treatment are presented in Table 1 below.

<div class="scrollingtable"><table width="90%"> <caption> <span>Table 1: Adverse Reactions Reported by ≥ 1% of Subjects through 4 Weeks of Treatment in Controlled Clinical Trials</span> </caption> <col align="left" valign="middle" width="34%"/> <col align="center" valign="middle" width="33%"/> <col align="center" valign="middle" width="33%"/> <thead> <tr class="Botrule First"> <th align="center" class="Lrule Rrule" rowspan="2">Adverse Reaction</th><th align="center" class="Rrule" colspan="2">Pooled Controlled Clinical Trials</th> </tr> <tr class="Last"> <th align="center" class="Rrule">RHOFADE Cream<br/> (N = 489)</th><th align="center" class="Rrule">Vehicle Cream<br/> (N = 483)</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Application site dermatitis</td><td align="center" class="Rrule">9 (2%)</td><td align="center" class="Rrule">0</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Worsening inflammatory lesions of rosacea</td><td align="center" class="Rrule">7 (1%)</td><td align="center" class="Rrule">1 (&lt;1%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Application site pruritus</td><td align="center" class="Rrule">5 (1%)</td><td align="center" class="Rrule">4 (1%)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Application site erythema</td><td align="center" class="Rrule">5 (1%)</td><td align="center" class="Rrule">2 (&lt;1%)</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Application site pain</td><td align="center" class="Rrule">4 (1%)</td><td align="center" class="Rrule">1 (&lt;1%)</td> </tr> </tbody> </table></div>

In the long-term (open-label) clinical trial, the rates of adverse reactions over a one-year treatment period were as follows: worsening inflammatory lesions of rosacea (3%), application site dermatitis (3%), application site pruritis (2%), application site pain (2%), and application site erythema (2%). Subjects with persistent erythema along with inflammatory lesions were allowed to use additional therapy for the inflammatory lesions of rosacea.

Alpha-adrenergic agonists, as a class, may impact blood pressure. Caution in using drugs such as beta-blockers, anti-hypertensives and/or cardiac glycosides is advised.

Caution should also be exercised in patients receiving alpha1 adrenergic receptor antagonists such as in the treatment of cardiovascular disease, benign prostatic hypertrophy, or Raynaud's disease.

Caution is advised in patients taking MAO inhibitors which can affect the metabolism and uptake of circulating amines.

Risk Summary

There are no available data on RHOFADE cream use in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. A literature article describing intranasal decongestant use in pregnant women identified a potential association between second-trimester exposure to oxymetazoline (with no decongestant exposure in the first trimester) and renal collecting system anomalies [see Data]. In animal reproduction studies, there were no adverse developmental effects observed after oral administration of oxymetazoline hydrochloride in pregnant rats and rabbits at systemic exposures up to 3 times and 73 times, respectively, the exposure associated with the maximum recommended human dose (MRHD) [see Data]. The estimated background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Following repeated use of oxymetazoline hydrochloride solution nasal spray for the treatment of nasal congestion at a dose 5 times higher than recommended, one case of fetal distress was reported in a 41-week pregnant patient. The fetal distress resolved hours later, prior to the delivery of the healthy infant. The anticipated exposures for the case are 8- to 18-fold higher than plasma exposures after topical administration of RHOFADE cream.

Data

Human Data

No adequate and well-controlled trials of RHOFADE cream have been conducted in pregnant women. Across all clinical trials of RHOFADE cream, two pregnancies were reported. One pregnancy resulted in the delivery of a healthy child. One pregnancy resulted in a spontaneous abortion, which was considered to be unrelated to the trial medication. A literature article summarizing the results of exploratory analyses of intranasal decongestant use during pregnancy identified a potential association between second-trimester exposure to oxymetazoline hydrochloride solution (with no decongestant exposure in the first trimester) and renal collecting system anomalies.

Animal Data

Effects on embryo-fetal development were evaluated in rats and rabbits following oral administration of oxymetazoline hydrochloride during the period of organogenesis. Oxymetazoline hydrochloride did not cause adverse effects to the fetus at oral doses up to 0.2 mg/kg/day in pregnant rats during the period of organogenesis (3 times the MRHD on an AUC comparison basis). Oxymetazoline hydrochloride did not cause adverse effects to the fetus at oral doses up to 1 mg/kg/day in pregnant rabbits during the period of organogenesis (73 times the MRHD on an AUC comparison basis). Maternal toxicity, such as decreased maternal body weight, was produced at the high dose of 1 mg/kg/day in pregnant rabbits and was associated with findings of delayed skeletal ossification.

In a rat perinatal and postnatal development study, oxymetazoline hydrochloride was orally administered to pregnant rats once daily from gestation day 6 through lactation day 20. Maternal toxicity was produced at the high dose of 0.2 mg/kg/day (3 times the MRHD on an AUC comparison basis) in pregnant rats and was associated with an increase in pup mortality and reduced pup body weights. Delayed sexual maturation was noted at 0.1 and 0.2 mg/kg/day (2 times the MRHD and 3 times the MRHD on an AUC comparison basis, respectively). Oxymetazoline hydrochloride did not have any adverse effects on fetal development at a dose of 0.05 mg/kg/day (one-half of the MRHD on an AUC comparison basis).

No clinical data are available to assess the effects of oxymetazoline on the quantity or rate of breastmilk production, or to establish the level of oxymetazoline present in human breastmilk post-dose. Oxymetazoline was detected in the milk of lactating rats. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for RHOFADE cream and any potential adverse effects on the breastfed child from RHOFADE cream or from the underlying maternal condition.

Safety and effectiveness of RHOFADE cream have not been established in pediatric patients below the age of 18 years.

One hundred and ninety-three subjects aged 65 years and older received treatment with RHOFADE cream (n = 135) or vehicle (n = 58) in clinical trials. No overall differences in safety or effectiveness were observed between subjects ≥ 65 years of age and younger subjects, based on available data. Clinical studies of RHOFADE cream did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

RHOFADE cream is not for oral use. If oral ingestion occurs, seek medical advice. Monitor patient closely and administer appropriate supportive measures as necessary. Accidental ingestion of topical solutions (nasal sprays) containing imidazoline derivatives (e.g., oxymetazoline) in children has resulted in serious adverse events requiring hospitalization, including nausea, vomiting, lethargy, tachycardia, decreased respiration, bradycardia, hypotension, hypertension, sedation, somnolence, mydriasis, stupor, hypothermia, drooling, and coma. Keep RHOFADE cream out of reach of children.

{ "type": "p", "children": [], "text": "RHOFADE cream is not for oral use. If oral ingestion occurs, seek medical advice. Monitor patient closely and administer appropriate supportive measures as necessary. Accidental ingestion of topical solutions (nasal sprays) containing imidazoline derivatives (e.g., oxymetazoline) in children has resulted in serious adverse events requiring hospitalization, including nausea, vomiting, lethargy, tachycardia, decreased respiration, bradycardia, hypotension, hypertension, sedation, somnolence, mydriasis, stupor, hypothermia, drooling, and coma. Keep RHOFADE cream out of reach of children." }

RHOFADE® (oxymetazoline hydrochloride) cream, 1% contains oxymetazoline hydrochloride, an alpha1A adrenoceptor agonist. RHOFADE is a white to off-white cream. It has a chemical name of 3-[(4,5-Dihydro1H-imidazol-2-yl)methyl]-6-(1,1-dimethylethyl)- 2,4-dimethyl-phenol hydrochloride and a molecular weight of 296.8. It is freely soluble in water and ethanol and has a partition coefficient of 0.1 in 1-octanol/water. The molecular formula of oxymetazoline HCl is C16H25ClN2O and its structural formula is:

{ "type": "p", "children": [], "text": "RHOFADE® (oxymetazoline hydrochloride) cream, 1% contains oxymetazoline hydrochloride, an alpha1A adrenoceptor agonist. RHOFADE is a white to off-white cream. It has a chemical name of 3-[(4,5-Dihydro1H-imidazol-2-yl)methyl]-6-(1,1-dimethylethyl)- 2,4-dimethyl-phenol hydrochloride and a molecular weight of 296.8. It is freely soluble in water and ethanol and has a partition coefficient of 0.1 in 1-octanol/water. The molecular formula of oxymetazoline HCl is C16H25ClN2O and its structural formula is:" }

Each gram of RHOFADE® (oxymetazoline hydrochloride) cream contains 10 mg (1%) oxymetazoline hydrochloride, equivalent to 8.8 mg (0.88%) of oxymetazoline free base. The cream contains the following inactive ingredients: sodium citrate dihydrate, citric acid anhydrous, disodium edetate dihydrate, butylated hydroxytoluene, anhydrous lanolin, medium chain triglycerides, diisopropyl adipate, oleyl alcohol, polyethylene glycol 300, PEG-6 stearate, glycol stearate, PEG-32 stearate, cetostearyl alcohol, ceteareth-6, stearyl alcohol, ceteareth-25, methylparaben, propylparaben, phenoxyethanol, and purified water.

{ "type": "p", "children": [], "text": "Each gram of RHOFADE® (oxymetazoline hydrochloride) cream contains 10 mg (1%) oxymetazoline hydrochloride, equivalent to 8.8 mg (0.88%) of oxymetazoline free base. The cream contains the following inactive ingredients: sodium citrate dihydrate, citric acid anhydrous, disodium edetate dihydrate, butylated hydroxytoluene, anhydrous lanolin, medium chain triglycerides, diisopropyl adipate, oleyl alcohol, polyethylene glycol 300, PEG-6 stearate, glycol stearate, PEG-32 stearate, cetostearyl alcohol, ceteareth-6, stearyl alcohol, ceteareth-25, methylparaben, propylparaben, phenoxyethanol, and purified water." }

Oxymetazoline is an alpha1A adrenoceptor agonist. Oxymetazoline acts as a vasoconstrictor.

The pharmacodynamics of RHOFADE cream has not been studied.

Absorption

The pharmacokinetics of oxymetazoline was evaluated following topical administration of RHOFADE cream in a thin layer to cover the entire face in adult subjects with erythema associated with rosacea. The median weight of cream for each dose administration was 0.3 g. Plasma oxymetazoline concentrations were measurable in most of the subjects. Following the first dose application, the mean ± standard deviation (SD) peak concentrations (Cmax) and area under the concentration-time curves from time 0 to 24 hours (AUC0-24hr) were 60.5 ± 53.9 pg/mL and 895 ±798 pg*hr/mL, respectively. Following once daily applications for 28 days, the mean ± SD Cmax and AUC0-24hr were 66.4 ± 67.1 pg/mL and 1050 ± 992 pg*hr/mL, respectively. Following twice daily applications (twice the recommended frequency of application) for 28 days, the mean ± SD Cmax and AUC0-24hr were 68.8 ± 61.1 pg/mL and 1530 ± 922 pg*hr/mL, respectively.

Distribution

An in vitro study demonstrated that oxymetazoline is 56.7% to 57.5% bound to human plasma proteins.

Metabolism

In vitro studies using human liver microsomes showed that oxymetazoline was minimally metabolized, generating mono-oxygenated and dehydrogenated products of oxymetazoline. The percentage of parent drug oxymetazoline remaining was 95.9% after a 120-minute incubation with human liver microsomes.

Excretion

The excretion of oxymetazoline following administration of RHOFADE cream has not been characterized in humans.

Drug Interaction

In vitro studies using human liver microsomes demonstrated that oxymetazoline up to the tested concentration of 100 nM had no inhibition on the activities of the cytochrome P450 (CYP) isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4/5. Treatment of cultured human hepatocytes with up to 100 nM oxymetazoline did not induce CYP1A2, CYP2B6, or CYP3A4.

Oxymetazoline hydrochloride was not associated with an increased incidence of neoplastic or proliferative changes in transgenic mice given oral doses of 0.5, 1.0, or 2.5 mg/kg/day oxymetazoline hydrochloride for 6 months.

Oxymetazoline hydrochloride revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames assay and human lymphocyte chromosomal aberration assay) and one in vivo genotoxicity test (mouse micronucleus assay).

Effects on fertility and early embryonic development were evaluated in rats following oral administration of 0.05, 0.1, or 0.2 mg/kg/day oxymetazoline hydrochloride prior to and during mating and through early pregnancy. Decreased number of corpora lutea and increased post-implantation losses were noted at 0.2 mg/kg/day oxymetazoline hydrochloride (3 times the MRHD on an AUC comparison basis). However, no treatment related effects on fertility or mating parameters were noted at 0.2 mg/kg/day oxymetazoline hydrochloride (3 times the MRHD on an AUC comparison basis).

RHOFADE cream was evaluated for the treatment of persistent erythema associated with rosacea in two identical, randomized, double-blind, vehicle-controlled, parallel-group clinical trials. The trials enrolled 885 subjects aged 18 years and older. Overall, 90% of subjects were Caucasian and 79% were female. Subjects applied either RHOFADE cream or vehicle once daily for 29 days.

{ "type": "p", "children": [], "text": "RHOFADE cream was evaluated for the treatment of persistent erythema associated with rosacea in two identical, randomized, double-blind, vehicle-controlled, parallel-group clinical trials. The trials enrolled 885 subjects aged 18 years and older. Overall, 90% of subjects were Caucasian and 79% were female. Subjects applied either RHOFADE cream or vehicle once daily for 29 days." }

Disease severity was graded by the clinician using a 5-point clinician erythema assessment (CEA) scale and by the subject on a similar 5-point subject self-assessment (SSA) scale, on which subjects scored either "moderate" or "severe" on both scales.

{ "type": "p", "children": [], "text": "Disease severity was graded by the clinician using a 5-point clinician erythema assessment (CEA) scale and by the subject on a similar 5-point subject self-assessment (SSA) scale, on which subjects scored either \"moderate\" or \"severe\" on both scales." }

CEA and SSA were measured over a 12-hour period at equally-spaced timepoints (hours 3, 6, 9, and 12) post dose on Days 1, 15, and 29. The primary efficacy endpoint was defined as the proportion of subjects with at least a 2-grade reduction in erythema (improvement) from baseline (pre-dose on Day 1) on both the CEA and SSA measured at hours 3, 6, 9, and 12 on Day 29. The results from both trials on the composite endpoint for Day 29 are presented in Table 2.

{ "type": "p", "children": [], "text": "CEA and SSA were measured over a 12-hour period at equally-spaced timepoints (hours 3, 6, 9, and 12) post dose on Days 1, 15, and 29. The primary efficacy endpoint was defined as the proportion of subjects with at least a 2-grade reduction in erythema (improvement) from baseline (pre-dose on Day 1) on both the CEA and SSA measured at hours 3, 6, 9, and 12 on Day 29. The results from both trials on the composite endpoint for Day 29 are presented in Table 2." }

<div class="scrollingtable"><table width="85%"> <caption> <span>Table 2: Proportion of Subjects Achieving Composite Success<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> on Day 29</span> </caption> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <thead> <tr class="Botrule First"> <th align="center" class="Lrule Rrule" rowspan="2">Time-point<br/> (Hour)</th><th align="center" class="Rrule" colspan="2">Trial 1</th><th align="center" class="Rrule" colspan="2">Trial 2</th> </tr> <tr class="Last"> <th align="center" class="Rrule">RHOFADE Cream<br/> (N-222)</th><th align="center" class="Rrule">Vehicle Cream<br/> (N-218)</th><th align="center" class="Rrule">RHOFADE Cream<br/> (N-224)</th><th align="center" class="Rrule">Vehicle Cream<br/> (N-221)</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Composite success is defined as the proportion of subjects achieving at least a 2-grade improvement on both CEA and SSA.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td align="center" class="Lrule Rrule">3</td><td align="center" class="Rrule">12%</td><td align="center" class="Rrule">6%</td><td align="center" class="Rrule">14%</td><td align="center" class="Rrule">7%</td> </tr> <tr> <td align="center" class="Lrule Rrule">6</td><td align="center" class="Rrule">16%</td><td align="center" class="Rrule">8%</td><td align="center" class="Rrule">13%</td><td align="center" class="Rrule">5%</td> </tr> <tr> <td align="center" class="Lrule Rrule">9</td><td align="center" class="Rrule">18%</td><td align="center" class="Rrule">6%</td><td align="center" class="Rrule">16%</td><td align="center" class="Rrule">9%</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">12</td><td align="center" class="Rrule">15%</td><td align="center" class="Rrule">6%</td><td align="center" class="Rrule">12%</td><td align="center" class="Rrule">6%</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"85%\">\n<caption>\n<span>Table 2: Proportion of Subjects Achieving Composite Success<a class=\"Sup\" href=\"#footnote-1\" name=\"footnote-reference-1\">*</a> on Day 29</span>\n</caption>\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<thead>\n<tr class=\"Botrule First\">\n<th align=\"center\" class=\"Lrule Rrule\" rowspan=\"2\">Time-point<br/> (Hour)</th><th align=\"center\" class=\"Rrule\" colspan=\"2\">Trial 1</th><th align=\"center\" class=\"Rrule\" colspan=\"2\">Trial 2</th>\n</tr>\n<tr class=\"Last\">\n<th align=\"center\" class=\"Rrule\">RHOFADE Cream<br/> (N-222)</th><th align=\"center\" class=\"Rrule\">Vehicle Cream<br/> (N-218)</th><th align=\"center\" class=\"Rrule\">RHOFADE Cream<br/> (N-224)</th><th align=\"center\" class=\"Rrule\">Vehicle Cream<br/> (N-221)</th>\n</tr>\n</thead>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"5\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-1\" name=\"footnote-1\">*</a>\n</dt>\n<dd>Composite success is defined as the proportion of subjects achieving at least a 2-grade improvement on both CEA and SSA.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"First\">\n<td align=\"center\" class=\"Lrule Rrule\">3</td><td align=\"center\" class=\"Rrule\">12%</td><td align=\"center\" class=\"Rrule\">6%</td><td align=\"center\" class=\"Rrule\">14%</td><td align=\"center\" class=\"Rrule\">7%</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule\">6</td><td align=\"center\" class=\"Rrule\">16%</td><td align=\"center\" class=\"Rrule\">8%</td><td align=\"center\" class=\"Rrule\">13%</td><td align=\"center\" class=\"Rrule\">5%</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule\">9</td><td align=\"center\" class=\"Rrule\">18%</td><td align=\"center\" class=\"Rrule\">6%</td><td align=\"center\" class=\"Rrule\">16%</td><td align=\"center\" class=\"Rrule\">9%</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" class=\"Lrule Rrule\">12</td><td align=\"center\" class=\"Rrule\">15%</td><td align=\"center\" class=\"Rrule\">6%</td><td align=\"center\" class=\"Rrule\">12%</td><td align=\"center\" class=\"Rrule\">6%</td>\n</tr>\n</tbody>\n</table></div>" }

Storage: Store at 20°C-25°C (68°F-77°F); excursions permitted to 15°C-30ºC (59°F- 86ºF) [see USP Controlled Room Temperature].

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

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

Important Administration Instructions

{ "type": "p", "children": [], "text": "Important Administration Instructions" }

Advise patients of the following:

{ "type": "p", "children": [], "text": "Advise patients of the following:" }

{ "type": "ul", "children": [ "RHOFADE cream is for topical use only.", "Do not apply RHOFADE cream to irritated skin or open wounds.\\", "Avoid contact with the eyes and lips.", "Wash hands immediately after application.", "Keep RHOFADE cream out of reach of children." ], "text": "" }

Distributed by: Mayne Pharma Raleigh, NC 27609

{ "type": "p", "children": [], "text": "Distributed by:\nMayne Pharma\n Raleigh, NC 27609" }

RHOFADE and its design are registered trademarks of Mayne Pharma, LLC

{ "type": "p", "children": [], "text": "RHOFADE and its design are registered trademarks of Mayne Pharma, LLC" }

Patented. U.S. Patent Numbers: U.S. 7,812,049; U.S. 8,420,688; U.S. 8,815,929; U.S. 8,883,838; U.S. 9,974,773 and U.S. 10335391. Product of Germany.

{ "type": "p", "children": [], "text": "Patented. U.S. Patent Numbers: U.S. 7,812,049; U.S. 8,420,688; U.S. 8,815,929; U.S. 8,883,838; U.S. 9,974,773 and U.S. 10335391. Product of Germany." }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="100%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule">PATIENT INFORMATION<br/> RHOFADE<span class="Sup">®</span> (roe' fayd) <br/>(oxymetazoline hydrochloride) cream</th> </tr> </thead> <tbody> <tr class="First"> <td align="left" class="Lrule Rrule"><span class="Bold">Important:</span> RHOFADE cream is for skin (topical) use on the face only. Do not use RHOFADE cream in your eyes, mouth, or vagina.</td> </tr> <tr> <td align="left" class="Lrule Rrule"><span class="Bold">Keep RHOFADE cream out of the reach of children.</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Bold">Get medical help right away if you, a child, or anyone else swallows RHOFADE cream.</span></td> </tr> <tr> <td align="left" class="Lrule Rrule"><span class="Bold">What is RHOFADE cream?</span></td> </tr> <tr> <td align="left" class="Lrule Rrule">RHOFADE cream is a prescription medicine used on the skin (topical) to treat facial redness due to rosacea that does not go away (persistent) in adults.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">It is not known if RHOFADE cream is safe and effective in children under 18 years of age.</td> </tr> <tr> <td align="left" class="Lrule Rrule"><span class="Bold">Before you use RHOFADE cream, tell your healthcare provider about all of your medical conditions, including if you:</span> <ul class="Disc"> <li>have heart, blood vessel, or blood pressure problems. Call your healthcare provider or get medical help if these conditions worsen.</li> <li>have problems with blood circulation or have had a stroke</li> <li>have Sjögren's Syndrome</li> <li>have scleroderma</li> <li>have Raynaud's phenomenon</li> <li>have thromboangitis obliterans</li> <li>have narrow-angle glaucoma. Call your healthcare provider or get medical help if your glaucoma worsens.</li> <li>have irritated skin or open sores on the face</li> <li>are pregnant or plan to become pregnant. It is not known if RHOFADE cream will harm your unborn baby.</li> <li>are breastfeeding. It is not known if RHOFADE cream passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you use RHOFADE cream.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Bold">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, skin products, vitamins, and herbal supplements. Using RHOFADE cream with certain other medicines may affect each other and can cause serious side effects.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Bold">How should I use RHOFADE cream?</span> <ul class="Disc"> <li>See the detailed <a href="#IFU">Instructions for Use</a> that comes with your RHOFADE cream tube or pump for information about how to apply RHOFADE cream correctly.</li> <li>Use RHOFADE cream exactly as your healthcare provider tells you. Do not use more RHOFADE cream than prescribed.</li> <li>RHOFADE cream is for use on your skin only. <span class="Bold">Do not</span> use RHOFADE cream in your eyes, mouth, or vagina. Avoid contact with your lips and eyes.</li> <li> <span class="Bold">Do not</span> apply RHOFADE cream to irritated skin or open wounds.</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule"><span class="Bold">What are the possible side effects of RHOFADE cream?</span></td> </tr> <tr> <td align="left" class="Lrule Rrule">The most common side effects of RHOFADE cream include application site reactions of:<ul class="Disc"> <li>skin reactions (dermatitis)</li> <li>worsening of rosacea pimples</li> <li>itching</li> <li>redness</li> <li>pain</li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule">These are not all the possible side effects of RHOFADE cream.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td> </tr> <tr> <td align="left" class="Lrule Rrule"><span class="Bold">How should I store RHOFADE cream?</span> <ul class="Disc"> <li>Store RHOFADE cream at room temperature between 68°F to 77°F (20°C to 25°C).</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"><span class="Bold">Keep RHOFADE cream and all medicines out of the reach of children.</span></td> </tr> <tr> <td align="left" class="Lrule Rrule"><span class="Bold">General information about the safe and effective use of RHOFADE cream</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use RHOFADE cream for a condition for which it was not prescribed. Do not give RHOFADE cream to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about RHOFADE cream that is written for health professionals.</td> </tr> <tr> <td align="left" class="Lrule Rrule"><span class="Bold">What are the ingredients in RHOFADE cream? </span></td> </tr> <tr> <td align="left" class="Lrule Rrule"><span class="Bold">Active ingredient:</span> oxymetazoline hydrochloride</td> </tr> <tr> <td align="left" class="Lrule Rrule"><span class="Bold">Inactive ingredients:</span> sodium citrate dihydrate, citric acid anhydrous, disodium edetate dihydrate, butylated hydroxytoluene, anhydrous lanolin, medium chain triglycerides, diisopropyl adipate, oleyl alcohol, polyethylene glycol 300, PEG-6 stearate, glycol stearate, PEG-32 stearate, cetostearyl alcohol, ceteareth-6, stearyl alcohol, ceteareth-25, methylparaben, propylparaben, phenoxyethanol, and purified water</td> </tr> <tr> <td align="left" class="Lrule Rrule">Distributed by:<br/> <span class="Bold">Mayne Pharma</span> <br/> Raleigh, NC 27609</td> </tr> <tr> <td align="left" class="Lrule Rrule">RHOFADE and its design are registered trademarks of Mayne Pharma, LLC.</td> </tr> <tr> <td align="left" class="Lrule Rrule">Patented. U.S. Patent Numbers: U.S. 7,812,049; U.S. 8,420,688; U.S. 8,815,929; U.S. 8,883,838; U.S. 9,974,773 and U.S. 10335391. Product of Germany.</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule"></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"100%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"center\" class=\"Lrule Rrule\">PATIENT INFORMATION<br/> RHOFADE<span class=\"Sup\">®</span> (roe' fayd) <br/>(oxymetazoline hydrochloride) cream</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">Important:</span> RHOFADE cream is for skin (topical) use on the face only. Do not use RHOFADE cream in your eyes, mouth, or vagina.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">Keep RHOFADE cream out of the reach of children.</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">Get medical help right away if you, a child, or anyone else swallows RHOFADE cream.</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">What is RHOFADE cream?</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">RHOFADE cream is a prescription medicine used on the skin (topical) to treat facial redness due to rosacea that does not go away (persistent) in adults.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">It is not known if RHOFADE cream is safe and effective in children under 18 years of age.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">Before you use RHOFADE cream, tell your healthcare provider about all of your medical conditions, including if you:</span>\n<ul class=\"Disc\">\n<li>have heart, blood vessel, or blood pressure problems. Call your healthcare provider or get medical help if these conditions worsen.</li>\n<li>have problems with blood circulation or have had a stroke</li>\n<li>have Sjögren's Syndrome</li>\n<li>have scleroderma</li>\n<li>have Raynaud's phenomenon</li>\n<li>have thromboangitis obliterans</li>\n<li>have narrow-angle glaucoma. Call your healthcare provider or get medical help if your glaucoma worsens.</li>\n<li>have irritated skin or open sores on the face</li>\n<li>are pregnant or plan to become pregnant. It is not known if RHOFADE cream will harm your unborn baby.</li>\n<li>are breastfeeding. It is not known if RHOFADE cream passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you use RHOFADE cream.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, skin products, vitamins, and herbal supplements. Using RHOFADE cream with certain other medicines may affect each other and can cause serious side effects.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">How should I use RHOFADE cream?</span>\n<ul class=\"Disc\">\n<li>See the detailed <a href=\"#IFU\">Instructions for Use</a> that comes with your RHOFADE cream tube or pump for information about how to apply RHOFADE cream correctly.</li>\n<li>Use RHOFADE cream exactly as your healthcare provider tells you. Do not use more RHOFADE cream than prescribed.</li>\n<li>RHOFADE cream is for use on your skin only. <span class=\"Bold\">Do not</span> use RHOFADE cream in your eyes, mouth, or vagina. Avoid contact with your lips and eyes.</li>\n<li>\n<span class=\"Bold\">Do not</span> apply RHOFADE cream to irritated skin or open wounds.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">What are the possible side effects of RHOFADE cream?</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">The most common side effects of RHOFADE cream include application site reactions of:<ul class=\"Disc\">\n<li>skin reactions (dermatitis)</li>\n<li>worsening of rosacea pimples</li>\n<li>itching</li>\n<li>redness</li>\n<li>pain</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">These are not all the possible side effects of RHOFADE cream.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">How should I store RHOFADE cream?</span>\n<ul class=\"Disc\">\n<li>Store RHOFADE cream at room temperature between 68°F to 77°F (20°C to 25°C).</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">Keep RHOFADE cream and all medicines out of the reach of children.</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">General information about the safe and effective use of RHOFADE cream</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use RHOFADE cream for a condition for which it was not prescribed. Do not give RHOFADE cream to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about RHOFADE cream that is written for health professionals.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">What are the ingredients in RHOFADE cream? </span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">Active ingredient:</span> oxymetazoline hydrochloride</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">Inactive ingredients:</span> sodium citrate dihydrate, citric acid anhydrous, disodium edetate dihydrate, butylated hydroxytoluene, anhydrous lanolin, medium chain triglycerides, diisopropyl adipate, oleyl alcohol, polyethylene glycol 300, PEG-6 stearate, glycol stearate, PEG-32 stearate, cetostearyl alcohol, ceteareth-6, stearyl alcohol, ceteareth-25, methylparaben, propylparaben, phenoxyethanol, and purified water</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">Distributed by:<br/>\n<span class=\"Bold\">Mayne Pharma</span>\n<br/> Raleigh, NC 27609</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">RHOFADE and its design are registered trademarks of Mayne Pharma, LLC.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\">Patented. U.S. Patent Numbers: U.S. 7,812,049; U.S. 8,420,688; U.S. 8,815,929; U.S. 8,883,838; U.S. 9,974,773 and U.S. 10335391. Product of Germany.</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\"></td>\n</tr>\n</tbody>\n</table></div>" }

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

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

Revised 10/2023

{ "type": "p", "children": [], "text": "Revised 10/2023" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="100%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule">INSTRUCTIONS FOR USE<br/> RHOFADE<span class="Sup">®</span> (roe' fayd) <br/> (oxymetazoline hydrochloride) cream <br/> Tube</th> </tr> </thead> <tbody> <tr class="First Last"> <td align="left" class="Lrule Rrule"><span class="Bold">Important:</span> <ul class="Disc"> <li>RHOFADE cream is for skin (topical) use on the face only. Do not use RHOFADE cream in your eyes, mouth, or vagina.</li> <li> <span class="Bold">Keep RHOFADE cream out of the reach of children.</span> </li> <li> <span class="Bold">Get medical help right away if you, a child, or anyone else swallows RHOFADE cream.</span> </li> </ul> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"100%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"center\" class=\"Lrule Rrule\">INSTRUCTIONS FOR USE<br/> RHOFADE<span class=\"Sup\">®</span> (roe' fayd) <br/> (oxymetazoline hydrochloride) cream <br/> Tube</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First Last\">\n<td align=\"left\" class=\"Lrule Rrule\"><span class=\"Bold\">Important:</span>\n<ul class=\"Disc\">\n<li>RHOFADE cream is for skin (topical) use on the face only. Do not use RHOFADE cream in your eyes, mouth, or vagina.</li>\n<li>\n<span class=\"Bold\">Keep RHOFADE cream out of the reach of children.</span>\n</li>\n<li>\n<span class=\"Bold\">Get medical help right away if you, a child, or anyone else swallows RHOFADE cream.</span>\n</li>\n</ul>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Read and follow the steps below so that you use your tube of RHOFADE cream correctly:

{ "type": "p", "children": [], "text": "Read and follow the steps below so that you use your tube of RHOFADE cream correctly:" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="70%"/> <col align="center" valign="top" width="30%"/> <tbody class="Headless"> <tr class="First"> <td align="left" class="Lrule Rrule" valign="bottom"><span class="Bold">Step 1:</span> Open the tube of RHOFADE cream by gently pressing down on the child-resistant cap and twisting it counterclockwise until the cap is removed. Do not squeeze the tube while opening or closing.<br/> <span class="Bold"> Note:</span> When the cap is removed, the tube is not child-resistant.</td><td align="center" class="Rrule"><img alt="Image" src="/dailymed/image.cfm?name=rhofade-02.jpg&amp;setid=f7dbf12e-a802-4261-bae2-c20977698933"/></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule"></td><td align="center" class="Rrule"><img alt="Image" src="/dailymed/image.cfm?name=rhofade-03.jpg&amp;setid=f7dbf12e-a802-4261-bae2-c20977698933"/></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="middle"><span class="Bold">Step 2:</span> To apply RHOFADE cream to your face, squeeze a pea- sized amount of RHOFADE cream from the tube onto your fingertip.</td><td align="center" class="Rrule"><img alt="Image" src="/dailymed/image.cfm?name=rhofade-04.jpg&amp;setid=f7dbf12e-a802-4261-bae2-c20977698933"/></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Step 3:</span> Apply the pea-sized amount of RHOFADE cream to cover your entire face (forehead, nose, each cheek, and chin) 1 time each day. Spread the cream smoothly and evenly in a thin layer over your face.<ul class="Disc"> <li>Avoid contact with your eyes and lips.</li> <li> <span class="Bold">Do not</span> apply cream to irritated skin or open wounds.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" valign="middle"><span class="Bold">Step 4:</span> To close your RHOFADE cream tube, place the cap back on the tube. Press down on the child-resistant cap and twist clockwise until it stops. The tube is child-resistant again.</td><td align="center" class="Rrule"><img alt="Image" src="/dailymed/image.cfm?name=rhofade-05.jpg&amp;setid=f7dbf12e-a802-4261-bae2-c20977698933"/></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Step 5:</span> Wash your hands right away after applying RHOFADE cream.</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">How do I store RHOFADE cream?</span> <ul class="Disc"> <li>Store RHOFADE cream at room temperature between 68°F to 77°F (20°C to 25°C).</li> <li> <span class="Bold">Keep RHOFADE cream and al medicines out of the reach of children.</span> </li> </ul> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"70%\"/>\n<col align=\"center\" valign=\"top\" width=\"30%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"left\" class=\"Lrule Rrule\" valign=\"bottom\"><span class=\"Bold\">Step 1:</span> Open the tube of RHOFADE cream by gently pressing down on the child-resistant cap and twisting it counterclockwise until the cap is removed. Do not squeeze the tube while opening or closing.<br/>\n<span class=\"Bold\"> Note:</span> When the cap is removed, the tube is not child-resistant.</td><td align=\"center\" class=\"Rrule\"><img alt=\"Image\" src=\"/dailymed/image.cfm?name=rhofade-02.jpg&amp;setid=f7dbf12e-a802-4261-bae2-c20977698933\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\"></td><td align=\"center\" class=\"Rrule\"><img alt=\"Image\" src=\"/dailymed/image.cfm?name=rhofade-03.jpg&amp;setid=f7dbf12e-a802-4261-bae2-c20977698933\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" valign=\"middle\"><span class=\"Bold\">Step 2:</span> To apply RHOFADE cream to your face, squeeze a pea- sized amount of RHOFADE cream from the tube onto your fingertip.</td><td align=\"center\" class=\"Rrule\"><img alt=\"Image\" src=\"/dailymed/image.cfm?name=rhofade-04.jpg&amp;setid=f7dbf12e-a802-4261-bae2-c20977698933\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">Step 3:</span> Apply the pea-sized amount of RHOFADE cream to cover your entire face (forehead, nose, each cheek, and chin) 1 time each day. Spread the cream smoothly and evenly in a thin layer over your face.<ul class=\"Disc\">\n<li>Avoid contact with your eyes and lips.</li>\n<li>\n<span class=\"Bold\">Do not</span> apply cream to irritated skin or open wounds.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" valign=\"middle\"><span class=\"Bold\">Step 4:</span> To close your RHOFADE cream tube, place the cap back on the tube. Press down on the child-resistant cap and twist clockwise until it stops. The tube is child-resistant again.</td><td align=\"center\" class=\"Rrule\"><img alt=\"Image\" src=\"/dailymed/image.cfm?name=rhofade-05.jpg&amp;setid=f7dbf12e-a802-4261-bae2-c20977698933\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">Step 5:</span> Wash your hands right away after applying RHOFADE cream.</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">How do I store RHOFADE cream?</span>\n<ul class=\"Disc\">\n<li>Store RHOFADE cream at room temperature between 68°F to 77°F (20°C to 25°C).</li>\n<li>\n<span class=\"Bold\">Keep RHOFADE cream and al medicines out of the reach of children.</span>\n</li>\n</ul>\n</td>\n</tr>\n</tbody>\n</table></div>" }

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration." }

Distributed by: Mayne Pharma Raleigh, NC 27609

{ "type": "p", "children": [], "text": "Distributed by:\nMayne Pharma\n Raleigh, NC 27609" }

RHOFADE and its design are registered trademarks of Mayne Pharma, LLC

{ "type": "p", "children": [], "text": "RHOFADE and its design are registered trademarks of Mayne Pharma, LLC" }

Patented. U.S. Patent Numbers: U.S. 7,812,049; U.S. 8,420,688; U.S. 8,815,929; U.S. 8,883,838; U.S. 9,974,773 and U.S. 10335391. Product of Germany.

{ "type": "p", "children": [], "text": "Patented. U.S. Patent Numbers: U.S. 7,812,049; U.S. 8,420,688; U.S. 8,815,929; U.S. 8,883,838; U.S. 9,974,773 and U.S. 10335391. Product of Germany." }

Revised: 10/2023

{ "type": "p", "children": [], "text": "Revised: 10/2023" }

NDC 51862-765-30

{ "type": "p", "children": [], "text": "NDC 51862-765-30" }

Rhofade® (oxymetazoline hydrochloride) cream, 1%*

{ "type": "p", "children": [], "text": "Rhofade®\n (oxymetazoline hydrochloride) cream, 1%*" }

*Each gram of RHOFADE® cream contains 10 mg of oxymetazoline hydrochloride, equivalent to 8.8 mg of oxymetazoline free base

{ "type": "p", "children": [], "text": "*Each gram of RHOFADE® cream contains 10 mg of oxymetazoline hydrochloride, equivalent to 8.8 mg of oxymetazoline free base" }

For Topical Use Only Keep Out of Reach of Children

{ "type": "p", "children": [], "text": "For Topical Use Only Keep Out of Reach of Children" }

Rx Only 30 g

{ "type": "p", "children": [], "text": "Rx Only 30 g" }

mayne pharma

{ "type": "p", "children": [], "text": "mayne pharma" }

UPNEEQ is indicated for the treatment of acquired blepharoptosis in adults.

{ "type": "p", "children": [], "text": "UPNEEQ is indicated for the treatment of acquired blepharoptosis in adults." }

Instill one drop of UPNEEQ into one or both ptotic eye(s) once daily. Discard the single patient-use container immediately after dosing.

{ "type": "p", "children": [], "text": "Instill one drop of UPNEEQ into one or both ptotic eye(s) once daily. Discard the single patient-use container immediately after dosing." }

Contact lenses should be removed prior to instillation of UPNEEQ and may be reinserted 15 minutes following its administration.

{ "type": "p", "children": [], "text": "Contact lenses should be removed prior to instillation of UPNEEQ and may be reinserted 15 minutes following its administration." }

If more than one topical ophthalmic drug is being used, the drugs should be administered at least 15 minutes between applications.

{ "type": "p", "children": [], "text": "If more than one topical ophthalmic drug is being used, the drugs should be administered at least 15 minutes between applications." }

UPNEEQ (oxymetazoline hydrochloride ophthalmic solution), 0.1%, equivalent to 0.09% as oxymetazoline base, is formulated for topical ocular delivery as a sterile, non-preserved, clear, colorless to slightly yellow ophthalmic solution.

{ "type": "p", "children": [], "text": "UPNEEQ (oxymetazoline hydrochloride ophthalmic solution), 0.1%, equivalent to 0.09% as oxymetazoline base, is formulated for topical ocular delivery as a sterile, non-preserved, clear, colorless to slightly yellow ophthalmic solution." }

None. 

{ "type": "p", "children": [], "text": "None. " }

Ptosis may be associated with neurologic or orbital diseases such as stroke and/or cerebral aneurysm, Horner syndrome, myasthenia gravis, external ophthalmoplegia, orbital infection and orbital masses. Consideration should be given to these conditions in the presence of ptosis with decreased levator muscle function and/or other neurologic signs.

Alpha-adrenergic agonists may impact blood pressure. UPNEEQ should be used with caution in patients with severe or unstable cardiovascular disease, orthostatic hypotension, and uncontrolled hypertension or hypotension. Advise patients with cardiovascular disease, orthostatic hypotension, and/or uncontrolled hypertension/hypotension to seek immediate medical care if their condition worsens.

UPNEEQ should be used with caution in patients with cerebral or coronary insufficiency, or Sjögren’s syndrome. Advise patients to seek immediate medical care if signs and symptoms of potentiation of vascular insufficiency develop.

UPNEEQ may increase the risk of angle closure glaucoma in patients with untreated narrow-angle glaucoma. Advise patients to seek immediate medical care if signs and symptoms of acute angle closure glaucoma develop.

Patients should not touch the tip of the single patient-use container to their eye or to any surface, in order to avoid eye injury or contamination of the solution.

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 practice.

A total of 360 subjects with acquired blepharoptosis were treated with UPNEEQ once daily in each eye for at least 6 weeks in three controlled Phase 3 clinical trials, including 203 subjects treated with UPNEEQ for 6 weeks and 157 subjects treated with UPNEEQ for 12 weeks. Adverse reactions that occurred in 1-5% of subjects treated with UPNEEQ were punctate keratitis, conjunctival hyperemia, dry eye, blurred vision, instillation site pain, eye irritation and headache.

Alpha-adrenergic agonists, as a class, may impact blood pressure. Caution in using drugs such as beta-blockers, anti-hypertensives, and/or cardiac glycosides is advised.

Caution should also be exercised in patients receiving alpha adrenergic receptor antagonists such as in the treatment of cardiovascular disease, or benign prostatic hypertrophy.

Caution is advised in patients taking MAO inhibitors which can affect the metabolism and uptake of circulating amines.

Risk Summary There are no available data on UPNEEQ use in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, there were no adverse developmental effects observed after oral administration of oxymetazoline hydrochloride in pregnant rats and rabbits at systemic exposures up to 7 and 278 times the maximum recommended human ophthalmic dose (MRHOD), respectively, based on dose comparison. [see Data]. The estimated background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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.

Animal Data Effects on embryo-fetal development were evaluated in rats and rabbits following oral administration of oxymetazoline hydrochloride during the period of organogenesis. Oxymetazoline hydrochloride did not cause adverse effects to the fetus at oral doses up to 0.2 mg/kg/day in pregnant rats during the period of organogenesis (28 times the MRHOD, on a dose comparison basis). Oxymetazoline hydrochloride did not cause adverse effects to the fetus at oral doses up to 1 mg/kg/day in pregnant rabbits during the period of organogenesis (278 times the MRHOD, on a dose comparison basis). Maternal toxicity, including decreased maternal body weight, was produced at the high dose of 1 mg/kg/day in pregnant rabbits and was associated with findings of delayed skeletal ossification.

In a rat prenatal and postnatal development study, oxymetazoline hydrochloride was orally administered to pregnant rats once daily from gestation day 6 through lactation day 20. Maternal toxicity was produced at the high dose of 0.2 mg/kg/day (28 times the MRHOD, on a dose comparison basis) in pregnant rats and was associated with an increase in pup mortality and reduced pup body weights. Delayed sexual maturation was noted at 0.1 mg/kg/day (14 times the MRHOD, on a dose comparison basis). Oxymetazoline hydrochloride did not have any adverse effects on fetal development at a dose of 0.05 mg/kg/day (7 times the MRHOD, on a dose comparison basis).

Risk Summary No clinical data are available to assess the effects of oxymetazoline on the quantity or rate of breastmilk production, or to establish the level of oxymetazoline present in human breastmilk post-dose. Oxymetazoline was detected in the milk of lactating rats. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for UPNEEQ and any potential adverse effects on the breastfed child from UPNEEQ.

Safety and effectiveness of UPNEEQ have not been established in pediatric patients under 13 years of age.

Three hundred and fifteen subjects aged 65 years and older received treatment with UPNEEQ (n = 216) or vehicle (n = 99) in clinical trials. No overall differences in safety or effectiveness were observed between subjects 65 years of age and older and younger subjects.

Accidental oral ingestion of topical intended solutions (including ophthalmic solutions and nasal sprays) containing imidazoline derivatives (e.g., oxymetazoline) in children has resulted in serious adverse events requiring hospitalization, including nausea, vomiting, lethargy, tachycardia, decreased respiration, bradycardia, hypotension, hypertension, sedation, somnolence, mydriasis, stupor, hypothermia, drooling, and coma. Keep UPNEEQ out of reach of children.

{ "type": "p", "children": [], "text": "Accidental oral ingestion of topical intended solutions (including ophthalmic solutions and nasal sprays) containing imidazoline derivatives (e.g., oxymetazoline) in children has resulted in serious adverse events requiring hospitalization, including nausea, vomiting, lethargy, tachycardia, decreased respiration, bradycardia, hypotension, hypertension, sedation, somnolence, mydriasis, stupor, hypothermia, drooling, and coma. Keep UPNEEQ out of reach of children." }

UPNEEQ (oxymetazoline hydrochloride ophthalmic solution), 0.1% contains oxymetazoline hydrochloride, an alpha adrenoceptor agonist. UPNEEQ is an aseptically prepared, sterile, non-preserved ophthalmic solution. The chemical name is 6-tert-Butyl-3-(2-imidazolin-2-ylmethyl)-2,4- dimethylphenol monohydrochloride, and the molecular mass is 296.84. Oxymetazoline HCl is freely soluble in water and ethanol and has a partition coefficient of 0.1 in 1-octanol/water. The molecular formula of oxymetazoline HCl is C16H24N2O∙HCl, and its structural formula is:

{ "type": "p", "children": [], "text": "UPNEEQ (oxymetazoline hydrochloride ophthalmic solution), 0.1% contains oxymetazoline hydrochloride, an alpha adrenoceptor agonist. UPNEEQ is an aseptically prepared, sterile, non-preserved ophthalmic solution. The chemical name is 6-tert-Butyl-3-(2-imidazolin-2-ylmethyl)-2,4- dimethylphenol monohydrochloride, and the molecular mass is 296.84. Oxymetazoline HCl is freely soluble in water and ethanol and has a partition coefficient of 0.1 in 1-octanol/water. The molecular formula of oxymetazoline HCl is C16H24N2O∙HCl, and its structural formula is:" }

Each mL of UPNEEQ (oxymetazoline hydrochloride ophthalmic solution) 0.1% contains 1 mg of oxymetazoline hydrochloride, equivalent to 0.9 mg (0.09%) of oxymetazoline free base. The ophthalmic solution contains the following inactive ingredients: calcium chloride, hydrochloric acid (used to adjust pH to 5.8 to 6.8), hypromellose, magnesium chloride, potassium chloride, sodium acetate, sodium chloride, sodium citrate, and water for injection.

{ "type": "p", "children": [], "text": "Each mL of UPNEEQ (oxymetazoline hydrochloride ophthalmic solution) 0.1% contains 1 mg of oxymetazoline hydrochloride, equivalent to 0.9 mg (0.09%) of oxymetazoline free base. The ophthalmic solution contains the following inactive ingredients: calcium chloride, hydrochloric acid (used to adjust pH to 5.8 to 6.8), hypromellose, magnesium chloride, potassium chloride, sodium acetate, sodium chloride, sodium citrate, and water for injection." }

Oxymetazoline is an alpha adrenoceptor agonist targeting a subset of adrenoreceptors in Mueller’s muscle of the eyelid.

In safety and efficacy studies, Study RVL-1201-201 and Study RVL-1201-202, the pharmacodynamics of UPNEEQ was assessed using an objective photographic measure, marginal reflex distance 1 (MRD1). MRD1 is the distance from the central pupillary light reflex to the central margin of the upper lid. The maximum increase in MRD1 was observed approximately 2 hours post dose in both studies. The MRD1 increase continued through 8 hours post dose.

Absorption The pharmacokinetics of oxymetazoline was evaluated in 24 healthy adult subjects following single-drop administration of UPNEEQ to each eye. The total dose of oxymetazoline HCl was 0.07 mg. Following ocular administration of UPNEEQ, the time to reach peak oxymetazoline concentration (Tmax) values ranged from 0.5 to 12 hours with a median Tmax of 2 hours. The oxymetazoline mean ± standard deviation (SD) peak concentration (Cmax) and area under the concentration-time curve (AUCinf) were 30.5 ± 12.7 pg/mL and 468 ±214 pg*hr/mL, respectively.

Distribution An in vitro study demonstrated that oxymetazoline is 56.7% to 57.5% bound to human plasma proteins.

Elimination The oxymetazoline mean terminal half-life (t½) following administration of UPNEEQ in healthy adult subjects is 8.3 hours and ranged from 5.6 to 13.9 hours.

Metabolism In vitro studies using human liver microsomes showed that oxymetazoline was minimally metabolized, generating mono-oxygenated and dehydrogenated products of oxymetazoline. The percentage of parent drug oxymetazoline remaining was 95.9% after a 120-minute incubation with human liver microsomes.

Excretion The excretion of oxymetazoline following administration of UPNEEQ has not been characterized in humans.

Carcinogenesis Oxymetazoline hydrochloride was not associated with an increased incidence of neoplastic or proliferative changes in transgenic mice given oral doses of 0.5, 1.0, or 2.5 mg/kg/day oxymetazoline hydrochloride for 6 months.

Mutagenesis Oxymetazoline hydrochloride revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames assay and human lymphocyte chromosomal aberration assay) and one in vivo gentoxicity test (mouse micronucleus assay).

Impairment of Fertility Effects on fertility and early embryonic development were evaluated in rats following oral administration of 0.05, 0.1, or 0.2 mg/kg/day oxymetazoline hydrochloride prior to and during mating and through early pregnancy. Decreased number of corpora lutea and increased post-implantation losses were noted at 0.2 mg/kg/day oxymetazoline hydrochloride (28 times the MRHOD, on a dose comparison basis). However, no treatment related effects on mating parameters were noted at 0.2 mg/kg/day oxymetazoline hydrochloride.

UPNEEQ was evaluated for the treatment of acquired blepharoptosis in two randomized, double-masked, vehicle-controlled, parallel-group clinical efficacy trials. Both studies were randomized in an approximate 2:1 ratio of active versus vehicle. Efficacy was assessed with the Leicester Peripheral Field Test (LPFT) (primary) and photographic measurement of Marginal reflex distance 1 (MRD1). The primary efficacy endpoints were ordered in a hierarchy to compare UPNEEQ to vehicle on the mean increase from baseline (Day 1 Hour 0) in number of points seen on the top 4 rows of the LPFT in the study eye at Hour 6 on Day 1 and Hour 2 on Day 14.

{ "type": "p", "children": [], "text": "UPNEEQ was evaluated for the treatment of acquired blepharoptosis in two randomized, double-masked, vehicle-controlled, parallel-group clinical efficacy trials. Both studies were randomized in an approximate 2:1 ratio of active versus vehicle. Efficacy was assessed with the Leicester Peripheral Field Test (LPFT) (primary) and photographic measurement of Marginal reflex distance 1 (MRD1). The primary efficacy endpoints were ordered in a hierarchy to compare UPNEEQ to vehicle on the mean increase from baseline (Day 1 Hour 0) in number of points seen on the top 4 rows of the LPFT in the study eye at Hour 6 on Day 1 and Hour 2 on Day 14." }

In Trial 1, a total of 140 subjects were randomized 94 patients to the UPNEEQ group and 46 patients to the vehicle group. Treatments were administered once daily to each eye for 42 days (6 weeks). The mean age of the subjects was 64 years. In Trial 2, a total of 164 subjects were randomized 109 patients to the UPNEEQ group and 55 patients to the vehicle group. Treatments were administered once daily to each eye for 42 days (6 weeks). The mean age of the subjects was 63 years.

{ "type": "p", "children": [], "text": "\nIn Trial 1, a total of 140 subjects were randomized 94 patients to the UPNEEQ group and 46 patients to the vehicle group. Treatments were administered once daily to each eye for 42 days (6 weeks). The mean age of the subjects was 64 years. In Trial 2, a total of 164 subjects were randomized 109 patients to the UPNEEQ group and 55 patients to the vehicle group. Treatments were administered once daily to each eye for 42 days (6 weeks). The mean age of the subjects was 63 years." }

In both trials, each patient had a designated study eye. The increases in the number of points seen in the superior visual field in the study eye of the UPNEEQ group compared to the vehicle group were statistically significant at both time points, showing that the improvement in superior visual field was evident at the 2-hour time point and maintained at the 6-hour time point. The results from both trials on the primary endpoint are presented below.

{ "type": "p", "children": [], "text": "\nIn both trials, each patient had a designated study eye. The increases in the number of points seen in the superior visual field in the study eye of the UPNEEQ group compared to the vehicle group were statistically significant at both time points, showing that the improvement in superior visual field was evident at the 2-hour time point and maintained at the 6-hour time point. The results from both trials on the primary endpoint are presented below." }

Observed and Change from Baseline in Mean Points Seen in Superior Visual Field on LPFT in the Study Eye at Primary Efficacy Time Points (ITT Population)

{ "type": "p", "children": [], "text": "\nObserved and Change from Baseline in Mean Points Seen in Superior Visual Field on LPFT in the Study Eye at Primary Efficacy Time Points (ITT Population)\n" }

CL = confidence limit; LPFT = Leicester Peripheral Field Test; ITT (intent-to-treat) – included all randomized subjectswho received at least one dose of study medication; SD = standard deviation a p-value and 95% CI were based on ANCOVA model adjusted for baseline LFPT points.

{ "type": "p", "children": [], "text": "CL = confidence limit; LPFT = Leicester Peripheral Field Test; ITT (intent-to-treat) – included all randomized subjectswho received at least one dose of study medication; SD = standard deviation\na p-value and 95% CI were based on ANCOVA model adjusted for baseline LFPT points." }

Marginal reflex distance 1 (MRD1), showed a positive effect with UPNEEQ treatment. Greater MRD1 increases were observed for the UPNEEQ group than the vehicle group on day 1 at 6 hours post dose and on day 14 at 2 hours post dose.

{ "type": "p", "children": [], "text": "Marginal reflex distance 1 (MRD1), showed a positive effect with UPNEEQ treatment. Greater MRD1 increases were observed for the UPNEEQ group than the vehicle group on day 1 at 6 hours post dose and on day 14 at 2 hours post dose." }

UPNEEQ (oxymetazoline hydrochloride ophthalmic solution), 0.1% is an aseptically prepared, sterile, non-preserved, clear, colorless to slightly yellow ophthalmic solution; 0.3 mL fill in a clear, low-density polyethylene, single patient-use container in a child-resistant foil pouch.

{ "type": "p", "children": [], "text": "UPNEEQ (oxymetazoline hydrochloride ophthalmic solution), 0.1% is an aseptically prepared, sterile, non-preserved, clear, colorless to slightly yellow ophthalmic solution; 0.3 mL fill in a clear, low-density polyethylene, single patient-use container in a child-resistant foil pouch." }

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <col width="136.25pt"/> <col width="399.25pt"/> <tbody class="Headless"> <tr class="First"> <td> <p class="First">NDC 73687-062-32</p> </td><td> <p class="First">Carton of 30 single patient-use containers in individual child-resistant foil pouches.</p> </td> </tr> <tr class="Last"> <td>NDC 73687-062-45</td><td> Carton of 45 single patient-use containers in individual child-resistant foil pouches.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n<col width=\"136.25pt\"/>\n<col width=\"399.25pt\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td>\n<p class=\"First\">NDC 73687-062-32</p>\n</td><td>\n<p class=\"First\">Carton of 30 single patient-use containers in individual child-resistant foil pouches.</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td>NDC 73687-062-45</td><td> Carton of 45 single patient-use containers in individual child-resistant foil pouches.</td>\n</tr>\n</tbody>\n</table></div>" }

Storage: Store at 20°C to 25°C (68°F to 77°F). Protect from excessive heat. Keep out of reach of children.

{ "type": "p", "children": [], "text": "\n\nStorage: Store at 20°C to 25°C (68°F to 77°F). Protect from excessive heat. Keep out of reach of children." }

Store single patient-use containers in the child-resistant foil pouches. Opened containers should be discarded immediately after use.

{ "type": "p", "children": [], "text": "\nStore single patient-use containers in the child-resistant foil pouches. Opened containers should be discarded immediately after use. " }

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Instructions for Use).

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

When to Seek Medical Care

{ "type": "p", "children": [], "text": "\nWhen to Seek Medical Care\n" }

{ "type": "ul", "children": [ "Ptosis may be associated with neurologic or orbital diseases such as stroke and/or cerebral aneurysm, Horner syndrome, myasthenia gravis, external ophthalmoplegia, orbital infection and orbital masses. Consideration should be given to these conditions in the presence of ptosis with decreased levator muscle function and/or other neurologic signs [see Warnings and Precautions (5.1)].", "Alpha-adrenergic agonists as a class may impact blood pressure. Advise patients with cardiovascular disease, orthostatic hypotension, and/or uncontrolled hypertension or hypotension to seek medical care if their condition worsens [see Warnings and Precautions (5.2)].", "Use with caution in patients with cerebral or coronary insufficiency or Sjögren’s syndrome and advise patients to seek medical care if signs and symptoms of potentiation of vascular insufficiency develop [see Warnings and Precautions (5.3)].", "Advise patients to seek immediate medical care if signs and symptoms of acute narrow-angle glaucoma develop [see Warnings and Precautions (5.4)]." ], "text": "" }

Administration Instructions Use with Contact Lenses Advise patients that contact lenses should be removed prior to administration of UPNEEQ and can be re-inserted 15 minutes following administration [see Dosage and Administration (2)].

{ "type": "p", "children": [], "text": "\nAdministration Instructions\n\nUse with Contact Lenses\n\nAdvise patients that contact lenses should be removed prior to administration of UPNEEQ and can be re-inserted 15 minutes following administration [see Dosage and Administration (2)]." }

Use with Other Ophthalmic Drugs If more than one topical ophthalmic drug is being used, the drugs should be administered at least 15 minutes between applications.

{ "type": "p", "children": [], "text": "\nUse with Other Ophthalmic Drugs\n\nIf more than one topical ophthalmic drug is being used, the drugs should be administered at least 15 minutes between applications." }

Administration Advise patients that the solution from one single patient-use container is to be used immediately after opening to dose one or both eye(s). The single patient-use container, including any remaining contents, should be discarded immediately after administration [see Dosage and Administration (2)].

{ "type": "p", "children": [], "text": "\nAdministration\n\nAdvise patients that the solution from one single patient-use container is to be used immediately after opening to dose one or both eye(s). The single patient-use container, including any remaining contents, should be discarded immediately after administration [see Dosage and Administration (2)]." }

Storage and Handling Instructions Handling the Single Patient-Use Container Advise patients not to touch the tip of the single patient-use container to their eye or to any surface, in order to avoid eye injury or contamination of the solution.

{ "type": "p", "children": [], "text": "\nStorage and Handling Instructions\n\nHandling the Single Patient-Use Container\n\nAdvise patients not to touch the tip of the single patient-use container to their eye or to any surface, in order to avoid eye injury or contamination of the solution." }

Storage Information Instruct patients to keep the single patient-use containers in the child-resistant foil pouches until ready to use. Keep out of reach of children.

{ "type": "p", "children": [], "text": "\nStorage Information\n\nInstruct patients to keep the single patient-use containers in the child-resistant foil pouches until ready to use. Keep out of reach of children." }

To report SUSPECTED ADVERSE REACTIONS, contact RVL Pharmaceuticals, Inc. at 1-877-482-3788 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

{ "type": "p", "children": [], "text": "To report SUSPECTED ADVERSE REACTIONS, contact RVL Pharmaceuticals, Inc. at 1-877-482-3788 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch." }

© 2024 RVL Pharmaceuticals, Inc. All rights reserved. Bridgewater, New Jersey 08807 Patents 8357714, 9867808, 10799481, 10814001, 10898573, 10912765, 10940138, 11103482, 11311515, 11324722, 11541036, and 11701343

{ "type": "p", "children": [], "text": "© 2024 RVL Pharmaceuticals, Inc. All rights reserved.\nBridgewater, New Jersey 08807\nPatents 8357714, 9867808, 10799481, 10814001, 10898573, 10912765, 10940138, 11103482, 11311515, 11324722, 11541036, and 11701343" }

Made in the U.S.A. Manufactured for: RVL Pharmaceuticals, Inc. PLR-UPN-00007-8                                                                                                                                                                 IC # 2284

{ "type": "p", "children": [], "text": "Made in the U.S.A.\nManufactured for: \nRVL Pharmaceuticals, Inc.\nPLR-UPN-00007-8                                                                                                                                                                 IC # 2284" }

UPNEEQ® (up-NEEK) (oxymetazoline hydrochloride ophthalmic solution), 0.1% for topical ophthalmic use

{ "type": "p", "children": [], "text": "\n\n\nUPNEEQ® (up-NEEK)\n\n(oxymetazoline hydrochloride ophthalmic solution), 0.1%\nfor topical ophthalmic use\n" }

Read this Instructions for Use before you start using UPNEEQ and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or your treatment.

{ "type": "p", "children": [], "text": "Read this Instructions for Use before you start using UPNEEQ and each time you get a refill. There\nmay be new information. This leaflet does not take the place of talking to your healthcare provider\nabout your medical condition or your treatment." }

UPNEEQ single patient-use container after removal from its individual child-resistant foil pouch 

{ "type": "p", "children": [], "text": "UPNEEQ single patient-use container after removal from its individual child-resistant foil pouch " }

Important Information You Need to Know Before Using UPNEEQ

{ "type": "p", "children": [], "text": "\nImportant Information You Need to Know Before Using UPNEEQ\n" }

{ "type": "ul", "children": [ "\nUPNEEQ is for use in the eye.\n", "UPNEEQ can be harmful if swallowed.", "UPNEEQ is supplied as single patient-use containers individually packaged in a child-resistant foil pouch. Do not remove a single patient-use container from the child-resistant foil pouch until you are ready to use UPNEEQ.", "Wash your hands before each use to make sure you do not infect your eyes while using UPNEEQ.", "If you are using UPNEEQ with other eye (ophthalmic) medicines, you should wait at least 15 minutes between using UPNEEQ and the other medicines.", "If you wear contact lenses, remove them before using UPNEEQ. You should wait at least 15\n minutes before placing them back into your eyes." ], "text": "" }

Using UPNEEQ

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

{ "type": "ul", "children": [ "Do not let the tip of the UPNEEQ single patient-use container touch your eye or any other surfaces to avoid contamination or injury to your eye.", "Use 1 drop of UPNEEQ in the affected eye 1 time each day.", "Each single patient-use container of UPNEEQ will give you enough medicine to treat both eyes 1 time each day if needed.", "There is some extra UPNEEQ in each single patient-use container in case you miss getting the drop into your eye." ], "text": "" }

Storing UPNEEQ

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

{ "type": "ul", "children": [ "Store UPNEEQ at room temperature between 68°F to 77°F (20°C to 25°C).", "Store UPNEEQ single patient-use containers in the child-resistant foil pouches they come in.", "Protect UPNEEQ from excessive heat.", "\nKeep UPNEEQ and all medicines out of the reach of children.\n" ], "text": "" }

Disposing of UPNEEQ

{ "type": "p", "children": [], "text": "\nDisposing of UPNEEQ\n" }

{ "type": "ul", "children": [ "After you have applied the daily dose of medicine, throw away (dispose of) the single patient-use container and any unused UPNEEQ.", "Do not save any unused UPNEEQ." ], "text": "" }

Follow Step 1 to Step 11 each time you use UPNEEQ:

{ "type": "p", "children": [], "text": "\nFollow Step 1 to Step 11 each time you use UPNEEQ:\n" }

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0"> <col width="287.75pt"/> <col width="190.15pt"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 1.</span> Remove 1 UPNEEQ child-resistant foil-pouch  <span class="Bold"> </span>from the carton.</p> <p> <span class="Bold"> </span><span class="Bold">Step 2</span>. Make sure the single patient-use container within the foil is moved completely away from the dotted line (see <span class="Bold">Figure A</span>).</p> <p> <span class="Bold"><span class="Bold">Step 3. </span></span>Cut the foil along the dotted line using scissors (see <span class="Bold"><span class="Bold">Figure B</span>)</span>.</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First"> <span class="Bold">Figure A</span> </p> <p> <span class="Bold"><img alt="Figure A" src="/dailymed/image.cfm?name=upneeq-4.jpg&amp;setid=cf6c9a1f-2367-46d2-99c3-c7d67ec6f519"/></span> </p> <p> <span class="Bold">Figure B</span> </p> <p> <span class="Bold"><img alt="Figure B" src="/dailymed/image.cfm?name=upneeq-5.jpg&amp;setid=cf6c9a1f-2367-46d2-99c3-c7d67ec6f519"/></span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 4.</span> Remove the single patient-use container from the foil pouch and then hold it by the long flat end (see <span class="Bold">Figure C</span>).</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Figure C</span> </p> <p> <span class="Bold"><img alt="Figure C" src="/dailymed/image.cfm?name=upneeq-6.jpg&amp;setid=cf6c9a1f-2367-46d2-99c3-c7d67ec6f519"/></span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold"><span class="Bold">Step 5.</span> </span>Hold the single patient-use container upright and tap the top of the container gently to make sure that the medicine is in the bottom part of the container (see <span class="Bold">Figure D</span>).</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Figure D</span> </p> <img alt="Figure D" src="/dailymed/image.cfm?name=upneeq-7.jpg&amp;setid=cf6c9a1f-2367-46d2-99c3-c7d67ec6f519"/></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n<col width=\"287.75pt\"/>\n<col width=\"190.15pt\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 1.</span> Remove 1 UPNEEQ child-resistant foil-pouch  <span class=\"Bold\"> </span>from the carton.</p>\n<p>\n<span class=\"Bold\"> </span><span class=\"Bold\">Step 2</span>. Make sure the single patient-use container within the foil is moved completely away from the dotted line (see <span class=\"Bold\">Figure A</span>).</p>\n<p>\n<span class=\"Bold\"><span class=\"Bold\">Step 3. </span></span>Cut the foil along the dotted line using scissors (see <span class=\"Bold\"><span class=\"Bold\">Figure B</span>)</span>.</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" rowspan=\"2\">\n<p class=\"First\">\n<span class=\"Bold\">Figure A</span>\n</p>\n<p>\n<span class=\"Bold\"><img alt=\"Figure A\" src=\"/dailymed/image.cfm?name=upneeq-4.jpg&amp;setid=cf6c9a1f-2367-46d2-99c3-c7d67ec6f519\"/></span>\n</p>\n<p>\n<span class=\"Bold\">Figure B</span>\n</p>\n<p>\n<span class=\"Bold\"><img alt=\"Figure B\" src=\"/dailymed/image.cfm?name=upneeq-5.jpg&amp;setid=cf6c9a1f-2367-46d2-99c3-c7d67ec6f519\"/></span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 4.</span> Remove the single patient-use container from the foil pouch and then hold it by the long flat end (see <span class=\"Bold\">Figure C</span>).</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Figure C</span>\n</p>\n<p>\n<span class=\"Bold\"><img alt=\"Figure C\" src=\"/dailymed/image.cfm?name=upneeq-6.jpg&amp;setid=cf6c9a1f-2367-46d2-99c3-c7d67ec6f519\"/></span>\n</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\"><span class=\"Bold\">Step 5.</span> </span>Hold the single patient-use container upright and tap the top of the container gently to make sure that the medicine is in the bottom part of the container (see <span class=\"Bold\">Figure D</span>).</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Figure D</span>\n</p>\n<img alt=\"Figure D\" src=\"/dailymed/image.cfm?name=upneeq-7.jpg&amp;setid=cf6c9a1f-2367-46d2-99c3-c7d67ec6f519\"/></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0"> <col width="287.75pt"/> <col width="190.15pt"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 6.</span> Open the single patient-use container by twisting off the tab (see <span class="Bold">Figure E</span>).</p> <p> <span class="Bold">Do not</span> let the tip of the container touch your eye or any other surfaces.</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Figure E</span> </p> <p> <span class="Bold"><img alt="Figure E" src="/dailymed/image.cfm?name=upneeq-8.jpg&amp;setid=cf6c9a1f-2367-46d2-99c3-c7d67ec6f519"/></span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 7.</span> Tilt your head backwards. If you are not able to tilt your head, lie down.</p> <p> <span class="Bold">Step 8.</span> Gently pull your lower eyelid downwards and look up (see <span class="Bold">Figure F</span>).</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Figure F</span> </p> <img alt="Figure F" src="/dailymed/image.cfm?name=upneeq-9.jpg&amp;setid=cf6c9a1f-2367-46d2-99c3-c7d67ec6f519"/></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 9.</span> Place the tip of the single patient-use container close to your eye, but be careful not to touch your eye with it (see <span class="Bold">Figure G)</span>.</p> <p> <span class="Bold">Step 10.</span> Gently squeeze the single patient-use container and let 1 drop of UPNEEQ fall into the space between your lower eyelid and your eye (see <span class="Bold">Figure G</span>). If a drop misses your eye, try again.</p> </td><td align="center" class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Figure G</span> </p> <img alt="Figure G" src="/dailymed/image.cfm?name=upneeq-10.jpg&amp;setid=cf6c9a1f-2367-46d2-99c3-c7d67ec6f519"/></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Step 11.</span> Repeat <span class="Bold">Step 7 to Step 10</span> for your other eye if instructed to do so by your healthcare provider.</p> <p>There is enough UPNEEQ in one container for both eyes if needed.</p> <ul class="Disk"> <li>After you have applied the daily dose of UPNEEQ, throw away the opened single patient-use container with any remaining medicine.  </li> <li>Be sure to keep this medicine away from children.</li> <li>If you use contact lenses, wait at least 15 minutes before placing them back into your eyes.</li> </ul> </td><td align="center" class="Botrule Lrule Rrule Toprule"></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n<col width=\"287.75pt\"/>\n<col width=\"190.15pt\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 6.</span> Open the single patient-use container by twisting off the tab (see <span class=\"Bold\">Figure E</span>).</p>\n<p>\n<span class=\"Bold\">Do not</span> let the tip of the container touch your eye or any other surfaces.</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Figure E</span>\n</p>\n<p>\n<span class=\"Bold\"><img alt=\"Figure E\" src=\"/dailymed/image.cfm?name=upneeq-8.jpg&amp;setid=cf6c9a1f-2367-46d2-99c3-c7d67ec6f519\"/></span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 7.</span> Tilt your head backwards. If you are not able to tilt your head, lie down.</p>\n<p>\n<span class=\"Bold\">Step 8.</span> Gently pull your lower eyelid downwards and look up (see <span class=\"Bold\">Figure F</span>).</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Figure F</span>\n</p>\n<img alt=\"Figure F\" src=\"/dailymed/image.cfm?name=upneeq-9.jpg&amp;setid=cf6c9a1f-2367-46d2-99c3-c7d67ec6f519\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 9.</span> Place the tip of the single patient-use container close to your eye, but be careful not to touch your eye with it (see <span class=\"Bold\">Figure G)</span>.</p>\n<p>\n<span class=\"Bold\">Step 10.</span> Gently squeeze the single patient-use container and let 1 drop of UPNEEQ fall into the space between your lower eyelid and your eye (see <span class=\"Bold\">Figure G</span>). If a drop misses your eye, try again.</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Figure G</span>\n</p>\n<img alt=\"Figure G\" src=\"/dailymed/image.cfm?name=upneeq-10.jpg&amp;setid=cf6c9a1f-2367-46d2-99c3-c7d67ec6f519\"/></td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\">\n<p class=\"First\">\n<span class=\"Bold\">Step 11.</span> Repeat <span class=\"Bold\">Step 7 to Step 10</span> for your other eye if instructed to do so by your healthcare provider.</p>\n<p>There is enough UPNEEQ in one container for both eyes if needed.</p>\n<ul class=\"Disk\">\n<li>After you have applied the daily dose of UPNEEQ, throw away the opened single patient-use container with any remaining medicine.  </li>\n<li>Be sure to keep this medicine away from children.</li>\n<li>If you use contact lenses, wait at least 15 minutes before placing them back into your eyes.</li>\n</ul>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"></td>\n</tr>\n</tbody>\n</table></div>" }

Manufactured for: RVL Pharmaceuticals, Inc. Bridgewater, NJ 08807 1-877-482-3788 PLR-UPN-00007-8

{ "type": "p", "children": [], "text": "Manufactured for:\nRVL Pharmaceuticals, Inc.\nBridgewater, NJ 08807\n1-877-482-3788\nPLR-UPN-00007-8" }

This Instruction for Use has been approved by the U.S. Food and Drug Administration. Approved: August 2020

{ "type": "p", "children": [], "text": "This Instruction for Use has been approved by the U.S. Food and Drug Administration.\nApproved: August 2020" }

UPNEEQ 30ct Trade Carton

{ "type": "p", "children": [], "text": "UPNEEQ 30ct Trade Carton" }

NDC: 73687-062-32

{ "type": "p", "children": [], "text": "NDC: 73687-062-32" }

UPNEEQ Trade Foil Pouch

{ "type": "p", "children": [], "text": "UPNEEQ Trade Foil Pouch" }

NDC: 73687-062-70

{ "type": "p", "children": [], "text": "NDC: 73687-062-70" }

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

UPNEEQ 45ct Trade Carton

{ "type": "p", "children": [], "text": "UPNEEQ 45ct Trade Carton" }

NDC: 73687-062-45

{ "type": "p", "children": [], "text": "NDC: 73687-062-45" }