BYNFEZIA PEN is indicated to reduce blood levels of growth hormone (GH) and insulin gro wth factor-1 (I GF-1; somatomedin C) in acromegaly patients who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses.

BYNFEZIA PEN is indicated for treat ment of severe diarrhea and flushing episodes associated with metastatic carcinoid tumors.

BYNFEZIA PEN is indicated for the treat ment of the profuse watery diarrhea associated with vasoactive intestinal peptide tumors (VIPomas)-secreting tu mors.

Improvement in clinical signs and symptoms, or reduction in tumor size or rate of growth, were not shown in clinical trials performed with octreotide injection; these trials were not optimally designed to detect such effects.

The recommended initial dosage of BYNFEZIA PEN is 50 mcg three times daily to be administered subcutaneously. Increase BYNFEZIA dose based upon GH or IGF-1 levels. The goal is to achieve GH levels less than 5 ng/mL or IGF-I levels within normal range. Monitor GH or IGF-1 every two weeks after initiating BYNFEZIA PEN therapy or with dosage change, and to guide titration.

The most common dosage is 100 mcg three times daily, but some patients require up to 500 mcg three times daily for maximum effectiveness. Doses greater than 300 mcg/day seldom result in additional biochemical benefit, and if an increase in dose fails to provide additional benefit, the dose should be reduced.

BYNFEZIA PEN should be withdrawn yearly for approximately 4 weeks from patients who have received irradiation to assess disease activity. If GH or IGF-I levels increase and signs and symptoms recur, BYNFEZIA PEN therapy may be resumed.

The recommended daily dosage of BYNFEZIA PEN during the first 2 weeks of therapy ranges from 100 to 600 mcg/day in two to four divided doses given subcutaneously (mean daily dosage is 300 mcg). In the clinical studies, the median daily maintenance dosage was approximately 450 mcg, but clinical and biochemical benefits were obtained in some patients with as little as 50 mcg, while others required doses up to 1,500 mcg/day. However, experience with doses above 750 mcg/day is limited. Measurement of urinary 5-hydroxyindole acetic acid, plasma serotonin, plasma Substance P may be useful in monitoring the progress of therapy.

Daily dosage of 200 mcg to 300 mcg in two to four divided doses given subcutaneously are recommended during the initial 2 weeks of therapy (range, 150 mcg to 750 mcg) to control symptoms of the disease. On an individual basis, dosage may be adjusted to achieve a therapeutic response; but usually doses above 450 mcg/day are not required. Measurement of Plas ma vasoactive intestinal peptide (VIP) may be useful in monitoring the progress of therapy.

BYNFEZIA PEN is available as:

{ "type": "p", "children": [], "text": "BYNFEZIA PEN is available as: " }

{ "type": "ul", "children": [ "Injection: 7,000 mcg/2.8 mL (2,500 mcg/mL) octreotide (as acetate) as a clear, colorless solution in a single-patient-use prefilled pen." ], "text": "" }

Sensitivity to this drug or any of its co mponents.

{ "type": "p", "children": [], "text": "Sensitivity to this drug or any of its co mponents." }

Cardiac conduction abnormalities have occurred during treatment with octreotide. In acromegalic patients, bradycardia (< 50 bpm) developed in 25%; conduction abnormalities occurred in 10% and arrhythmias occurred in 9% of patients during octreotide therapy [see Adverse Reactions (6)]. Other electrocardiogram (ECG) changes observed included QT prolongation, axis shifts, early repolarization, low voltage, R/S transition, and early R-wave progression. These ECG changes are not uncommon in acromegalic patients. Dose adjustments in drugs such as beta-blockers that have bradycardia effects may be necessary. In one acromegalic patient with severe congestive heart failure (CHF), initiation of octreotide therapy resulted in worsening of CHF with improvement when drug was discontinued. Confirmation of a drug effect was obtained with a positive rechallenge.

BYNFEZIA PEN may inhibit gallbladder contractility and decrease bile secretion, which may lead to gallbladder abnormalities or sludge. Acute cholecystitis, ascending cholangitis, biliary obstruction, cholestatic hepatitis, or pancreatitis have been reported with octreotide therapy. In clinical trials (primarily patients with acromegaly or psoriasis), the incidence of biliary tract abnormalities was 63% (27% gallstones, 24% sludge without stones, 12% biliary duct dilatation). The incidence of stones or sludge in patients who received octreotide for 12 months or longer was 52%. Less than 2% of patients treated with octreotide for 1 month or less developed gallstones. One patient developed ascending cholangitis during octreotide therapy and died. If complications of cholelithiasis are suspected, discontinue BYNFEZIA PEN and treat appropriately.

BYNFEZIA PEN alters the balance between the counter-regulatory hormones, insulin, glucagon and GH, which may result in hypoglycemia or hyperglycemia. The hypoglycemia or hyperglycemia which occurs during octreotide therapy is usually mild but may result in overt diabetes mellitus or necessitate dose changes in insulin or other anti-diabetic agents. Hypoglycemia and hyperglycemia occurred on octreotide in 3% and 16% of acromegalic patients, respectively [see Adverse Reactions (6)]. Severe hyperglycemia, subsequent pneumonia, and death following initiation of octreotide therapy was reported in one patient with no history of hyperglycemia.

Monitor glucose levels during BYNFEZIA PEN therapy. Adjust dosing of insulin or other anti-diabetic therapy accordingly.

Octreotide suppresses secretion of thyroid stimulating hormone (TSH), which may result in hypothyroidism. Baseline and periodic assessment of thyroid function (TSH, total, and/or free T4) is recommended during chronic therapy [see Adverse Reactions (6)].

New onset steatorrhea, stool discoloration and loose stools have been reported in patients receiving somatostatin analogs, including octreotide. Somatostatin analogs reversibly inhibit secretion of pancreatic enzymes and bile acids, which may result in malabsorption of dietary fats and subsequent symptoms of steatorrhea, loose stools, abdominal bloating, and weight loss. If new occurrence or worsening of these symptoms are reported in patients receiving octreotide, evaluate patients for potential pancreatic exocrine insufficiency and manage accordingly.

Depressed vitamin B12 levels and abnormal Schilling’s tests have been observed in some patients receiving octreotide therapy and monitoring of vitamin B12 levels is recommended during BYNFEZIA PEN therapy.

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.

The safety of BYNFEZIA PEN has been established based on clinical studies of octreotide acetate injection. Below is a description of the adverse reactions from the clinical studies.

Gallbladder Abnormalities Gallbladder abnormalities, especially stones and/or biliary sludge, frequently develop in patients on chronic octreotide therapy [see Warnings and Precautions (5.1)]. In clinical trials (primarily patients with acromegaly or psoriasis) (BYNFEZIA PEN is not indicated for the treatment of psoriasis)], the incidence of biliary tract abnormalities was 63% (27% gallstones, 24% sludge without stones, 12% biliary duct dilatation). The incidence of stones or sludge in patients who received octreotide for 12 months or longer was 52%. Less than 2% of patients treated with octreotide for 1 month or less developed gallstones.  Cardiac In acromegalics, sinus bradycardia (<50 bpm) developed in 25%; conduction abnormalities occurred in 10% and arrhythmias developed in 9% of patients during octreotide therapy [see Warnings and Precautions (5.1)].

Gastrointestinal Diarrhea, loose stools, nausea, and abdominal discomfort were each seen in 34% to 61% of acromegalic patients in U.S. studies. 2.6% of the patients discontinued therapy due to these symptoms. These symptoms were seen in 5% to 10% of patients with carcinoid tumors and VIPomas.

The frequency of these symptoms was not dose related, but diarrhea and abdominal discomfort generally resolved more quickly in patients treated with 300 mcg/day than in those treated with 750 mcg/day. Vomiting, flatulence, abnormal stools, abdominal distention, and constipation were each seen in less than 10% of patients.

In rare instances, gastrointestinal side effects may resemble acute intestinal obstruction, with progressive abdominal distension, severe epigastric pain, abdominal tenderness, and guarding.

Hypo/Hyperglycemia Hypoglycemia and hyperglycemia occurred in 3% and 16% of acromegalic patients, respectively, but only in about 1.5% of other patients. Symptoms of hypoglycemia were noted in approximately 2% of patients.

Hypothyroidism In acromegalics, biochemical hypothyroidism alone occurred in 12% while goiter occurred in 8% and 4% required initiation of thyroid replacement therapy during octreotide therapy [see Warnings and Precautions (5.4)]. In patients without acromegaly, hypothyroidism has only been reported in several isolated patients and goiter has not been reported.

Other Adverse Events Pain on injection was reported in 7.7%, headache in 6%, and dizziness in 5%. Pancreatitis was also observed [see Warnings and Precautions (5.2)].

Other Adverse Events 1% to 4% Other events, each observed in 1% to 4% of patients, included fatigue, weakness, pruritus, joint pain, backache, urinary tract infection, cold symptoms, flu symptoms, injection site hematoma, bruise, edema, flushing, blurred vision, pollakiuria, fat malabsorption, hair loss, visual disturbance, and depression.

Anaphylactoid reactions, including anaphylactic shock, have been reported in several patients receiving octreotide.

The following adverse reactions have been identified during postapproval use of octreotide acetate injection. 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.

Hepatobiliary: cholelithiasis, cholecystitis, cholangitis and pancreatitis, which have sometimes required cholecystectomy Gastrointestinal: intestinal obstruction, pancreatic exocrine insufficiency Hematologic: thrombocytopenia

Octreotide has been associated with alterations in nutrient absorption, so it may have an effect on absorption of orally administered drugs. Concomitant administration of BYNFEZIA PEN with cyclosporine may decrease blood levels of cyclosporine and result in transplant rejection.

Octreotide inhibits the secretion of insulin and glucagon. Therefore, blood glucose levels should be monitored when BYNFEZIA PEN treatment is initiated or when the dose is altered and anti-diabetic treatment should be adjusted accordingly.

Concomitant administration of octreotide and bromocriptine increases the availability of bromocriptine.

Concomitant administration of bradycardia-inducing drugs (e.g., beta-blockers) may have an additive effect on the reduction of heart rate associated with octreotide. Dose adjustments of concomitant medication may be necessary.

Octreotide has been associated with alterations in nutrient absorption, so it may have an effect on absorption of orally administered drugs.

Li mited published data indicate that so matostatin analogs might decrease the metabolic clearance of co mpounds known to be metabolized by cytochro me P450 enzy mes, which may be due to the suppression of GH. Since it cannot be excluded that octreotide may have this effect, other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (e.g., quinidine, terfenadine) should therefore be used with caution.

Octreotide competitively binds to somatostatin receptors and may interfere with the efficacy of lutetium Lu 177 dotatate. Discontinue BYNFEZIA PEN at least 24 hours prior to each lutetium Lu 177 dotatate dose.

Risk Summary The limited data with octreotide acetate in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage.   In animal reproduction studies, no adverse developmental-effects were observed with IV administration of octreotide to pregnant rats and rabbits during organogenesis at doses 7 and 13 times, respectively the maximum recommended human dose (MRHD) of 1.5 mg/day based on body surface area (BSA). Transient growth retardation, with no impact on postnatal development, was observed in rat offspring from a pre- and post-natal study of octreotide at IV doses below the MRHD based on BSA (see Data).

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

Data

Human Data In postmarketing data, a limited number of exposed pregnancies have been reported in patients with acromegaly. Most women were exposed to octreotide during the first trimester of pregnancy at doses ranging from 100 to 300 mcg/day of octreotide or 20 mg to 30 mg once a month of octreotide acetate for injectable suspension, however some women elected to continue octreotide therapy throughout pregnancy. In cases with a known outcome, no congenital malformations were reported.

Animal Data In embryo-fetal development studies in rats and rabbits, pregnant animals received IV doses of octreotide up to 1 mg/kg/day during the period of organogenesis. A slight reduction in body weight gain was noted in pregnant rats at 0.1 and 1 mg/kg/day. There were no maternal effects in rabbits or embryo-fetal effects in either species up to the maximum dose tested. At 1 mg/kg/day in rats and rabbits, the dose multiple was approximately 7 and 13 times, respectively, at the highest recommended human dose of 1.5 mg/day based on BSA.

In a pre- and post-natal development rat study at IV doses of 0.02–1 mg/kg/day, a transient growth retardation of the offspring was observed at all doses which was possibly a consequence of GH inhibition by octreotide. The doses attributed to the delayed growth are below the human dose of 1.5 mg/day, based on BSA.

Risk Summary There is no information available on the presence of octreotide in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Studies show that octreotide administered subcutaneously passes into the milk of lactating rats; however, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk (see Data).  The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BYNFEZIA PEN, and any potential adverse effects on the breastfed child from BYNFEZIA PEN or from the underlying maternal condition.

Data Following a subcutaneous dose (1 mg/kg) of octreotide to lactating rats, transfer of octreotide into milk was observed at a low concentration compared to plasma (milk/plasma ratio of 0.009).

Discuss the potential for unintended pregnancy with premenopausal women as the therapeutic benefits of a reduction in GH levels and normalization of insulin-like growth factor 1 (IGF-1) concentration in acromegalic females treated with octreotide may lead to improved fertility.

Safety and efficacy of octreotide injection in the pediatric population have not been demonstrated.

No formal controlled clinical trials have been performed to evaluate the safety and effectiveness of octreotide injection in pediatric patients under age 6 years. In post-marketing reports, serious adverse events, including hypoxia, necrotizing enterocolitis, and death, have been reported with octreotide injection use in children, most notably in children under 2 years of age. The relationship of these events to octreotide has not been established as the majority of these pediatric patients had serious underlying co-morbid conditions.

The efficacy and safety of octreotide injection using the octreotide acetate for injectable suspension formulation was examined in a single randomized, double-blind, placebo-controlled, 6 month pharmacokinetics study in 60 pediatric patients age 6 to 17 years with hypothalamic obesity resulting from cranial insult. The mean octreotide concentration after 6 doses of 40 mg octreotide acetate for injectable suspension administered by intramuscular (IM) injection every 4 weeks was approximately 3 ng/mL. Steady-state concentrations was achieved after 3 injections of a 40 mg dose. Mean body mass index (BMI) increased 0.1 kg/m2 in octreotide acetate for injectable suspension-treated subjects compared to 0.0 kg/m2 in saline control-treated subjects. Efficacy was not demonstrated. Diarrhea occurred in 11 of 30 (37%) patients treated with octreotide acetate for injectable suspension. No unexpected adverse events were observed. However, with octreotide acetate for injectable suspension at 40 mg once a month, the incidence of new cholelithiasis in this pediatric population (33%) was higher than that seen in other adult indications such as acromegaly (22%) or malignant carcinoid syndrome (24%), where octreotide acetate for injectable suspension was 10 mg to 30 mg once a month.

Clinical studies of octreotide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

In patients with severe renal failure requiring dialysis, the half-life of octreotide may be increased, necessitating adjustment of the maintenance dosage [see Clinical Pharmacology (12.3)].

In patients with liver cirrhosis, the half-life of the drug may be increased, necessitating adjustment of the maintenance dosage [see Clinical Pharmacology (12.3)].

A limited number of accidental overdoses of octreotide in adults have been reported. In adults, the doses ranged from 2,400 to 6,000 mcg/day administered by continuous infusion (100 to 250 mcg/hour) or subcutaneously (1,500 mcg 3 times a day). Adverse events in some patients included arrhythmia, hypotension, cardiac arrest, brain hypoxia, pancreatitis, hepatitis steatosis, hepatomegaly, lactic acidosis, flushing, diarrhea, lethargy, weakness, and weight loss.

{ "type": "p", "children": [], "text": "A limited number of accidental overdoses of octreotide in adults have been reported. In adults, the doses ranged from 2,400 to 6,000 mcg/day administered by continuous infusion (100 to 250 mcg/hour) or subcutaneously (1,500 mcg 3 times a day). Adverse events in some patients included arrhythmia, hypotension, cardiac arrest, brain hypoxia, pancreatitis, hepatitis steatosis, hepatomegaly, lactic acidosis, flushing, diarrhea, lethargy, weakness, and weight loss." }

If overdose occurs, symptomatic management is indicated. Up-to-date information about the treatment of overdose can often be obtained from the National Poison Control Center at 1-800-222-1222.

{ "type": "p", "children": [], "text": "If overdose occurs, symptomatic management is indicated. Up-to-date information about the treatment of overdose can often be obtained from the National Poison Control Center at 1-800-222-1222." }

BYNFEZIA PEN (octreotide acetate) injection contains octreotide as its acetate salt.  Octreotide is a somatostatin analogue. Octreotide acetate known chemically as L-Cysteinamide, D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-N-[2-hydroxy-1-(hydroxymethyl)propyl]-, cyclic (2→7)-disulfide; [R-(R*, R*)] acetate salt.

{ "type": "p", "children": [], "text": "\nBYNFEZIA PEN (octreotide acetate) injection contains octreotide as its acetate salt.  Octreotide is a somatostatin analogue. Octreotide acetate known chemically as L-Cysteinamide, D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-N-[2-hydroxy-1-(hydroxymethyl)propyl]-, cyclic (2→7)-disulfide; [R-(R*, R*)] acetate salt." }

The molecular formula of octreotide free base is C49H66N10O10S2 and its molecular weight is 1019.3 and its structural formula as acetate salt is:  

{ "type": "p", "children": [], "text": "The molecular formula of octreotide free base is C49H66N10O10S2 and its molecular weight is 1019.3 and its structural formula as acetate salt is:\n  " }

BYNFEZIA PEN (octreotide acetate) injection is available as a disposable single-patient-use prefilled pen containing 7,000 mcg of octreotide (as acetate)/2.8 mL. Each milliliter of octreotide acetate injection contains 2,500 mcg octreotide (present as octreotide acetate, USP), 3.4 mg lactic acid, 22.5 mg mannitol, 5 mg phenol, and Water for Injection (q.s.). The pH of the solution is adjusted to 4.2 ± 0.3 by the addition of aqueous sodium bicarbonate solution.

{ "type": "p", "children": [], "text": "\nBYNFEZIA PEN (octreotide acetate) injection is available as a disposable single-patient-use prefilled pen containing 7,000 mcg of octreotide (as acetate)/2.8 mL. Each milliliter of octreotide acetate injection contains 2,500 mcg octreotide (present as octreotide acetate, USP), 3.4 mg lactic acid, 22.5 mg mannitol, 5 mg phenol, and Water for Injection (q.s.). The pH of the solution is adjusted to 4.2 ± 0.3 by the addition of aqueous sodium bicarbonate solution." }

BYNFEZIA PEN (octreotide acetate) exerts pharmacologic actions similar to the natural hormone, somatostatin. It is an even more potent inhibitor of GH, glucagon, and insulin than somatostatin. Like somatostatin, it also suppresses luteinizing hormone (LH) response to gonadotropin releasing hormone (GnRH), decreases splanchnic blood flow, and inhibits release of serotonin, gastrin, VIP, secretin, motilin, and pancreatic polypeptide.

By virtue of these pharmacological actions, octreotide has been used to treat the symptoms associated with metastatic carcinoid tumors (flushing and diarrhea), and VIP secreting adenomas (watery diarrhea).

Octreotide substantially reduces GH and/or IGF-I (somatomedin C) levels in patients with acromegaly.

Single doses of octreotide have been shown to inhibit gallbladder contractility and to decrease bile secretion in normal volunteers. In controlled clinical trials, the incidence of gallstone or biliary sludge formation was markedly increased [see Warnings and Precautions (5.2)].

Octreotide suppresses secretion of TSH.

Absorption

After subcutaneous injection, octreotide is absorbed rapidly and co mpletely from the injection site. Peak concentrations of 5.2 ng/ mL (100 mcg dose) were reached 0.4 hours after dosing. Peak concentrations and area under the curve (AUC) values were dose proportional after subcutaneous single doses up to 500 mcg and after subcutaneous multiple doses up to 500 mcg 3 times a day (1,500 mcg/day). In patients with acromegaly, a mean peak concentration of 2.8 ng/mL (100 mcg dose) was reached in 0.7 hours after subcutaneous dosing.

Distribution

In healthy volunteers, the distribution of octreotide from plas ma was rapid (tα1/2 = 0.2 h), the volu me of distribution (Vdss) was esti mated to be 13.6 L, and the total body clearance ranged from 7 L/hr to 10 L/hr. In blood, the distribution into the erythrocytes was found to be negligible and about 65% was bound in the plas ma in a concentration-independent manner. Binding was mainly to lipoprotein and, to a lesser extent, to albu min. In patients with acromegaly, the volume of distribution (Vdss) was estimated to be 21.6 ± 8.5 L, and the total body clearance was increased to 18 L/h. The mean percent of the drug bound was 41.2%.

Elimination

The eli mination of octreotide from plas ma had an apparent half-life of 1.7 to 1.9 hours co m pared with 1 to 3 minutes with the natural hor mone. The duration of action of octreotide injection is variable but extends up to 12 hours depending upon the type of tu mor. About 32% of the dose is excreted unchanged into the urine. In an elderly population, dose adjustments may be necessary due to a significant increase in the half-life (46%) and a significant decrease in the clearance (26%) of the drug.

In patients with acromegaly, the disposition and elimination half-lives were similar to normal subjects.

Specific Populations

Renal Impairment

In patients with mild renal i mpair ment (C LCR 40 to 60 m L/ min), octreotide t1/2 was 2.4 hours and total body clearance was 8.8 L/hr, in moderate i mpair ment (CLCR 10 to 39 m L/ min) t1/2 was 3.0 hours and total body clearance 7.3 L/hr. In patients with severe renal i mpairment not requiring dialysis (CLCR <10 m L/ min), octreotide t1/2 was 3.1 hours and total body clearance was 7.6 L/hr. In patients with severe renal failure requiring dialysis, total body clearance was reduced to about half that found in healthy subjects (from approximately 10 L/hr to 4.5 L/hr).

Hepatic Impairment

Patients with liver cirrhosis showed prolonged elimination of drug, with octreotide t1/2 increasing to 3.7 hr and total body clearance decreasing to 5.9 L/hr, whereas patients with fatty liver disease showed t1/2 increased to 3.4 hr and total body clearance of 8.2 L/hr.

Evaluation of 20 patients treated for at least 6 months has failed to demonstrate titers of antibodies exceeding background levels. However, antibody titers to octreotide injection were subsequently reported in 3 patients and resulted in prolonged duration of drug action in 2 patients.

Studies in laboratory animals have demonstrated no mutagenic potential of octreotide injection.

No carcinogenic potential was demonstrated in mice treated subcutaneously for 85 to 99 weeks at doses up to 2,000 mcg/kg/day (8 x the human exposure based on BSA). In a 116-week subcutaneous study in rats, a 27% and 12% incidence of injection-site sarcomas or squamous cell carcinomas was observed in males and females, respectively, at the highest dose level of 1,250 mcg/kg/day (10 x the human exposure based on BSA) compared to an incidence of 8% to 10% in the vehicle-control groups. The increased incidence of injection site tumors was most probably caused by irritation and the high sensitivity of the rat to repeated subcutaneous injections at the same site. Rotating injection sites would prevent chronic irritation in humans. There have been no reports of injection-site tumors in patients treated with octreotide for up to 5 years. There was also a 15% incidence of uterine adenocarcinomas in the 1,250 mcg/kg/day females compared to 7% in the saline-control females and 0% in the vehicle-control females. The presence of endometritis coupled with the absence of corpora lutea, the reduction in mammary fibroadenomas, and the presence of uterine dilatation suggest that the uterine tumors were associated with estrogen dominance in the aged female rats which does not occur in humans.

Octreotide did not impair fertility in rats at doses up to 1,000 mcg/kg/day, which represents 7 times the human exposure based on BSA.

How Supplied

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

BYNFEZIA PEN ( octreotide acetate) injection, 7,000 mcg/2.8 mL (2,500 mcg /mL) octreotide is a clear colorless solution and it is available as:

{ "type": "p", "children": [], "text": "BYNFEZIA PEN ( octreotide acetate) injection, 7,000 mcg/2.8 mL (2,500 mcg /mL) octreotide is a clear colorless solution and it is available as:" }

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <tbody class="Headless"> <tr class="Botrule First"> <td class="Lrule Rrule" valign="middle"> <br/> <span class="Bold"> Dosage Unit</span></td><td class="Rrule" valign="middle"> <br/> <span class="Bold"> Package Size</span> </td><td class="Rrule" valign="middle"><span class="Bold"> NDC #</span> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"> 2.8 mL single -patient-use prefilled pen</td><td class="Rrule" valign="middle">  Carton of 1</td><td class="Rrule" valign="middle"> NDC 62756-452-36</td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="middle"> 2.8 mL single -patient-use prefilled pen</td><td class="Rrule" valign="middle">  Carton of 2</td><td class="Rrule" valign="middle"> NDC 62756-452-37</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td class=\"Lrule Rrule\" valign=\"middle\">\n<br/> <span class=\"Bold\"> Dosage Unit</span></td><td class=\"Rrule\" valign=\"middle\">\n<br/>\n<span class=\"Bold\"> Package Size</span> </td><td class=\"Rrule\" valign=\"middle\"><span class=\"Bold\"> NDC #</span> </td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"middle\"> 2.8 mL single -patient-use prefilled pen</td><td class=\"Rrule\" valign=\"middle\">  Carton of 1</td><td class=\"Rrule\" valign=\"middle\"> NDC 62756-452-36</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Rrule\" valign=\"middle\"> 2.8 mL single -patient-use prefilled pen</td><td class=\"Rrule\" valign=\"middle\">  Carton of 2</td><td class=\"Rrule\" valign=\"middle\"> NDC 62756-452-37</td>\n</tr>\n</tbody>\n</table></div>" }

Dispense in the original sealed carton with the enclosed Instructions for Use.

{ "type": "p", "children": [], "text": "\n Dispense in the original sealed carton with the enclosed Instructions for Use.\n" }

Storage and Handling

{ "type": "p", "children": [], "text": "\n\n Storage and Handling\n" }

Before first use, store BYNFEZIA PEN in the refrigerator between 2°C to 8°C (36°F to 46°F) and store in outer carton in order to protect from light. After first use, store pens at controlled room temperature between 20°C to 25°C (68°F to 77°F). Excursions between 15°C (59°F) and 30°C (86°F) are allowed for up to 28 days. Discard the pen 28 days after first use. Do not freeze.

{ "type": "p", "children": [], "text": "Before first use, store BYNFEZIA PEN in the refrigerator between 2°C to 8°C (36°F to 46°F) and store in outer carton in order to protect from light. After first use, store pens at controlled room temperature between 20°C to 25°C (68°F to 77°F). Excursions between 15°C (59°F) and 30°C (86°F) are allowed for up to 28 days. Discard the pen 28 days after first use. Do not freeze." }

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

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

Sterile Subcutaneous Injection Technique

{ "type": "p", "children": [], "text": "\nSterile Subcutaneous Injection Technique\n" }

Careful instruction in sterile subcutaneous injection technique should be given to the patients and to other persons who may administer BYNFEZIA PEN.

{ "type": "p", "children": [], "text": "Careful instruction in sterile subcutaneous injection technique should be given to the patients and to other persons who may administer BYNFEZIA PEN." }

Cholelithiasis and Complications of Cholelithiasis

{ "type": "p", "children": [], "text": "\nCholelithiasis and Complications of Cholelithiasis\n" }

Advise patients to contact their healthcare provider if they experience signs or symptoms of gallstones (cholelithiasis) or complications of cholelithiasis (e.g., cholecystitis, cholangitis, and pancreatitis) [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Advise patients to contact their healthcare provider if they experience signs or symptoms of gallstones (cholelithiasis) or complications of cholelithiasis (e.g., cholecystitis, cholangitis, and pancreatitis) [see Warnings and Precautions (5.2)].\n" }

Steatorrhea and Malabsorption of Dietary Fats

{ "type": "p", "children": [], "text": "\nSteatorrhea and Malabsorption of Dietary Fats\n" }

Advise patients to contact their healthcare provider if they experience new or worsening of steatorrhea, stool

{ "type": "p", "children": [], "text": "Advise patients to contact their healthcare provider if they experience new or worsening of steatorrhea, stool " }

discoloration, loose stools, abdominal bloating, and weight loss [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "discoloration, loose stools, abdominal bloating, and weight loss [see Warnings and Precautions (5.5)].\n" }

Pregnancy  

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

Inform female patients that treatment with BYNFEZIA PEN may result in unintended pregnancy [see Use in Specific Populations (8.3)].

{ "type": "p", "children": [], "text": "Inform female patients that treatment with BYNFEZIA PEN may result in unintended pregnancy [see Use in Specific Populations (8.3)].\n" }

All trademarks are the property of their respective owners.

{ "type": "p", "children": [], "text": "All trademarks are the property of their respective owners." }

Distributed by:

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

Sun Pharmaceutical Industries, Inc.

{ "type": "p", "children": [], "text": "\nSun Pharmaceutical Industries, Inc.\n" }

Cranbury, NJ 08512

{ "type": "p", "children": [], "text": "Cranbury, NJ 08512" }

Manufactured by: Sun Pharmaceutical Industries Ltd., India At M/s. OneSource Specialty Pharma Limited Plot No. 2-D1, Obadenahalli, Doddaballapura, 3rd Phase, Industrial Area, Doddaballapura Taluk, Bengaluru Rural, 561203, Karnataka INDIA

{ "type": "p", "children": [], "text": "Manufactured by:\nSun Pharmaceutical Industries Ltd., India\n At M/s. OneSource Specialty Pharma Limited Plot No. 2-D1, Obadenahalli, Doddaballapura, 3rd Phase, Industrial Area, Doddaballapura Taluk, Bengaluru Rural, 561203, Karnataka INDIA" }

BYNFEZIA PEN® (ben-FEZ-ee-uh PEN)

{ "type": "p", "children": [], "text": "\nBYNFEZIA PEN® (ben-FEZ-ee-uh PEN)\n" }

(octreotide acetate) Prefilled Pen

{ "type": "p", "children": [], "text": "\n(octreotide acetate) Prefilled Pen\n" }

Read these instructions before you start using the BYNFEZIA PEN. It is important that you understand and follow these instructions to use the pen correctly. BYNFEZIA PEN is a prefilled pen that you or your caregiver can use to give more than 1 dose of medicine. Ask your healthcare provider about your dose of BYNFEZIA PEN and how to inject BYNFEZIA PEN the right way before you inject it for the first time. If your healthcare provider decides that you or your caregiver can give your BYNFEZIA PEN at home, you or your caregiver should receive training on how to use the pen. Contact your healthcare provider if you or your caregiver have any questions.

{ "type": "p", "children": [], "text": "Read these instructions before you start using the BYNFEZIA PEN. It is important that you understand and follow these instructions to use the pen correctly. BYNFEZIA PEN is a prefilled pen that you or your caregiver can use to give more than 1 dose of medicine.\n Ask your healthcare provider about your dose of BYNFEZIA PEN and how to inject BYNFEZIA PEN the right way before you inject it for the first time. If your healthcare provider decides that you or your caregiver can give your BYNFEZIA PEN at home, you or your caregiver should receive training on how to use the pen.\n Contact your healthcare provider if you or your caregiver have any questions." }

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <tbody class="Headless"> <tr class="Botrule First"> <td class="Lrule Rrule" colspan="3" valign="middle"><span class="Bold">Important</span></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="3" valign="middle"> <br/>• <span class="Bold">Do not</span> use a pen for more than 28 days after first use. After 28 days throw away (dispose of) the pen, even if the pen still has medicine in it.<br/> • <span class="Bold">Do not</span> place the pen in water or any other liquid.<br/> • <span class="Bold">Keep</span> your pen and needles out of the reach of children.<br/> • <span class="Bold">Do not</span> use if any part of your pen appears broken or damaged.<br/> • If you drop your pen, prime it before you use it again to make sure the pen still works correctly (see step <span class="Bold">3. Prime Your Pen</span>).<br/> • <span class="Bold">Do not </span>take BYNFEZIA PEN solution out of the pen and put it into a syringe.<br/> • <span class="Bold">Do not</span> share your pen or needles with another person. You may give an infection to them or get an infection from them.<br/> • <span class="Bold">Do not</span> remove the outer needle cover or inner needle cover until you are ready to inject.<br/> • <span class="Bold">Do not</span> press the injection button unless a needle is attached to the pen.</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="3" valign="middle"><span class="Bold">How should I store my </span><span class="Bold">BYNFEZIA PEN</span><span class="Bold">?</span></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="3" valign="middle"> <br/> <span class="Bold">Before First Use:</span> <br/> • Store new unused pens in the refrigerator between 36°F to 46°F (2°C to 8°C) and store in the outer carton in order to protect from light.<br/> • <span class="Bold">Do not</span> freeze. Throw away (dispose of) the pen if it has been frozen.<br/> • <span class="Bold">Do not</span> store the pen in direct sunlight.<br/> <br/> <span class="Bold">After First Use or During Use:</span> <br/> • Store the pen at room temperature between 68°F to 77°F (20°C to 25°C) for up to 28 days.<br/> • Store the pen with the pen cap on.<br/> • Throw away (dispose of) the pen 28 days after first use in a sharps container, even if the pen still has medicine in it (see step <span class="Bold">6. Additional Disposal Information</span>).<br/> • <span class="Bold">Do not </span>store a pen with a needle attached.</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="3" valign="middle"><span class="Bold">How do I give a dose larger than 200 mcg (more than 1 injection)?</span></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="3" valign="middle"> <br/>1. Turn the dose set knob to 200 mcg (highest dose setting) and give the first injection. <span class="Bold">Choose a different injection site for each injection</span> at least 2 inches from the area you used for your last injection.<br/> 2. Calculate the remaining dose by subtracting 200 mcg from the prescribed dose. <br/> 3. Turn the dose set knob to the line for your remaining dose up to the highest dose setting of 200 mcg. Give the second injection <span class="Bold">at least 2 inches away</span> from the first injection.<br/> 4. You may need more injections to give your total prescribed dose (see examples below).   <br/> <span class="Bold">See the following examples to give a total dose larger than 200 mcg:</span> <br/> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle"><span class="Bold">Example Dose</span></td><td class="Rrule" valign="middle"><span class="Bold">Steps to give a total dose larger than 200 mcg</span></td><td class="Rrule" valign="middle"><span class="Bold">Number of injections needed to give the total dose</span></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">For example, if your total dose is 300 mcg</td><td class="Rrule" valign="middle"> <br/> <ol class="Arabic"> <li>Turn the dose set knob to 200 mcg for your first injection.</li> <li>Your remaining dose is 100 mcg.</li> <li>For the second injection, turn your dose set knob to 100 mcg to give the remaining dose. </li> </ol> </td><td align="center" class="Rrule" valign="middle"> <br/>2</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">For example, if your total dose is 450 mcg</td><td class="Rrule" valign="middle"> <br/> <ol class="Arabic"> <li>Turn the dose set knob to 200 mcg for your first injection.</li> <li>Your remaining dose is 250 mcg.</li> <li>Turn the dose set knob to 200 mcg for your second injection.</li> <li>Your remaining dose is 50 mcg.</li> <li>For the third injection, turn your dose set knob to 50 mcg to give the remaining dose.</li> </ol> </td><td align="center" class="Rrule" valign="middle"> <br/>3</td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="3" valign="middle"><span class="Bold">1. Check the Pen</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">A. Wash your hands with soap and water (Figure A).<br/> </td><td class="Rrule" valign="middle"><img alt="spl-octreotide-figure2" src="/dailymed/image.cfm?name=spl-octreotide-figure2.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/><br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"> <br/>B. Check the expiration (EXP) date (Figure B).<br/> <ul class="Disc"> <li>Check the pen label to make sure the expiration date has not passed.</li> </ul> <br/> <span class="Bold">Do not</span> use if the expiration date has passed.</td><td class="Rrule" valign="middle"><img alt="spl-octreotide-figure3" src="/dailymed/image.cfm?name=spl-octreotide-figure3.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/><br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">C. Pull the pen cap straight o­ff the pen (Figure C).<br/> </td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure4" src="/dailymed/image.cfm?name=spl-octreotide-figure4.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"> <br/>D. Check the medicine (Figure D).<br/> <ul class="Disc"> <li>The medicine should be clear and colorless. You may see small air bubbles in the pen, which is normal and will not affect the dose.</li> </ul> <br/> <span class="Bold">Do not </span>use if the medicine looks cloudy, colored, or has lumps or particles in it. The pen cartridge may look empty because the medicine is clear and colorless.<br/> <ul class="Disc"> <li>Make sure you have enough medicine left in the pen to inject the full dose. When the plunger moves pass the thick line, your pen is almost empty (Figure E). If the dose set knob does not let you dial your prescribed dose, this means there is not enough medicine left in your pen. Throw away (dispose of) the pen and use a new pen for the injection.</li> </ul> </td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure5" src="/dailymed/image.cfm?name=spl-octreotide-figure5.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/><br/> <img alt="spl-octreotide-figure6" src="/dailymed/image.cfm?name=spl-octreotide-figure6.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/><br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">E. Allow the pen to reach room temperature.<br/> <ul class="Disc"> <li>If the pen was not stored at room temperature between 68°F to 77°F (20°C to 25°C), allow it to reach room temperature for 20 to 30 minutes before injecting. This will reduce the chance of getting a reaction at the injection site.</li> </ul> <span class="Bold">Do not</span> try to warm the pen by using a heat source such as hot water or microwave.<br/> <ul class="Disc"> <li>See the section<span class="Bold"> "How should I store my BYNFEZIA PEN ?"</span> for more information.</li> </ul> </td><td class="Rrule" valign="middle"> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="3" valign="middle"><span class="Bold">2. Attach a Needle</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">A. Gather the following additional supplies (Figure F):<br/> <ul class="Disc"> <li> <span class="Bold">2 alcohol swabs</span> </li> <li> <span class="Bold">new pen needle</span> </li> <li> <span class="Bold">sharps container</span> </li> <li> <span class="Bold">cotton ball</span> </li> </ul> <span class="Bold">Note: </span>These supplies are <span class="Bold">not included</span> with the pen.</td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure7" src="/dailymed/image.cfm?name=spl-octreotide-figure7.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">B. Wipe the rubber seal on the pen with an alcohol swab (Figure G).<br/> </td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure8" src="/dailymed/image.cfm?name=spl-octreotide-figure8.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">C. Attach a new needle.<br/> <ul class="Disc"> <li>Use only 31 gauge, 5 mm length disposable pen needles. If you have questions about which needle to use, ask your healthcare provider.</li> <li>Peel off­ the paper tab from the needle (Figure H).</li> <li>Push the needle with cap straight down onto the pen and screw it on to the pen by turning to the right (clockwise) until the needle feels secure (Figure I).</li> </ul> <span class="Bold">Do not</span> overtighten the needle. This will make it hard to remove after the injection.</td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure9" src="/dailymed/image.cfm?name=spl-octreotide-figure9.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/><br/> <img alt="spl-octreotide-figure10" src="/dailymed/image.cfm?name=spl-octreotide-figure10.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/><br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">D. Remove the outer needle cover and set it aside (Figure J).<br/> <ul class="Disc"> <li> <span class="Bold">Save</span> <span class="Bold">the outer needle cover</span> for use when you remove the needle in step 6.</li> </ul> </td><td class="Rrule" valign="middle"><img alt="spl-octreotide-figure11" src="/dailymed/image.cfm?name=spl-octreotide-figure11.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/><br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">E. Remove the inner needle cover and throw it away (Figure K).<br/> </td><td class="Rrule" valign="middle"><img alt="spl-octreotide-figure12" src="/dailymed/image.cfm?name=spl-octreotide-figure12.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/><br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="3" valign="middle"> <br/> <span class="Bold">Are you using a new pen?</span> <br/> <ul class="Disc"> <li> <span class="Bold">If Yes, complete step 3.</span> </li> <li> <span class="Bold">If No, skip step 3 and go to step 4.</span> </li> </ul> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="3" valign="middle"><span class="Bold">3. Prime Your Pen</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"><span class="Bold">Note: </span>The following steps are only needed if you are using a new pen for the first time <span class="Bold">or</span> if you drop the pen.<br/> <span class="Bold">To prime the pen, follow the steps below to dial the pen to 100 mcg and press the injection button until a stream of medicine comes from the needle tip.</span> <br/> <ul class="Disc"> <li>If you have already primed the pen, go to step 4 to prepare and give the injection.</li> <li> <span class="Bold">Do not</span> prime the pen before each dose. This will waste medicine.</li> </ul> </td><td class="Rrule" valign="middle"> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"><span class="Bold">A. Turn the dose set knob to dial the pen to 100 mcg (Figure L).</span> <br/> </td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure13" src="/dailymed/image.cfm?name=spl-octreotide-figure13.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"><span class="Bold">B. Hold the pen with the needle pointing up.</span> <br/> </td><td class="Rrule" valign="middle"> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"><span class="Bold">C. Press the injection button all the way in until it stops and the dose display window returns to “0” (Figure M).</span> <br/> </td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure14" src="/dailymed/image.cfm?name=spl-octreotide-figure14.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"><span class="Bold">D. A stream of medicine should be seen coming from the needle tip (Figure N).<br/> </span><span class="Bold"> <br/> If you do not see a stream of medicine coming from the needle tip</span>, repeat the priming steps.<br/> <br/> <span class="Bold">If you still do not see a stream of medicine coming from the needle tip after you repeat the priming steps 3 times, </span>the pen may be damaged. Throw away (dispose of) the pen and use a new pen. Call Sun Pharmaceutical Industries, Inc. at 1-800-818-4555<span class="Bold"></span>or your healthcare provider for help or to get a new pen.</td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure15" src="/dailymed/image.cfm?name=spl-octreotide-figure15.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="3" valign="middle"><span class="Bold"> 4. Prepare the Injection</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">A. Choose an injection site (see Figure O) for injection under the skin (subcutaneous).<br/> <ul class="Disc"> <li> <span class="Bold">When giving yourself the injection: </span>Inject into the stomach at least 2 inches away from the belly button (navel) or inject into the front of the middle thighs (Figure O).</li> <li> <span class="Bold">When giving someone else the injection: </span>you may also inject into the back outer area of the upper arms (Figure O).</li> <li> <span class="Bold">Always change (rotate) the injection site with each injection. Your injection site should be at least 2 inches away from your last injection site.</span> </li> </ul> <span class="Bold">Do not</span> inject into moles, scars, birthmarks, or areas where the skin is tender, bruised, red, or hard.</td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure16" src="/dailymed/image.cfm?name=spl-octreotide-figure16.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"> <br/>B. Clean your injection site with an alcohol swab (Figure P).<br/> <ul class="Disc"> <li>Wipe the skin with an alcohol swab. Let the injection site dry before you inject your dose.</li> </ul> </td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure17" src="/dailymed/image.cfm?name=spl-octreotide-figure17.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"> <br/> <br/>C. Dial your dose (Figure Q).<br/> <ul class="Disc"> <li>Turn the dose set knob until you see the prescribed dose in the dose display window. The dose number and black line should line up with the pointer. The pen can be used to deliver 50 mcg, 100 mcg, 150 mcg and 200 mcg doses. </li> </ul> <br/> <br/>If your prescribed dose is more than 200 mcg, see the section <span class="Bold">“How should I give a dose larger than 200 mcg (more than 1 injection)?” </span>in these instructions.<br/> <br/> <ul class="Disc"> <li>It is normal to hear a “clicking” sound as you turn the dose set knob.</li> <li>If you accidentally dial past the prescribed dose, turn the dose set knob back down to the correct dose.</li> </ul> </td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure18" src="/dailymed/image.cfm?name=spl-octreotide-figure18.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"><span class="Bold">Note:</span> The pen cannot be dialed past the number of micrograms (mcgs) of medicine left in the pen. If the pen does not have enough medicine to give the full dose, throw away (dispose of) the pen and use a new one.<br/> </td><td class="Rrule" valign="middle"> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="3" valign="middle"><span class="Bold">5. Give the Injection</span></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">A. Insert the needle straight into the injection site (Figure R).<br/> </td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure19" src="/dailymed/image.cfm?name=spl-octreotide-figure19.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">B. Deliver your dose.<br/> <ul class="Disc"> <li>Deliver your dose by slowly pressing the injection button all the way down until it stops. The number in the dose display window will go back to “0” when the injection is complete (Figure S).</li> </ul> </td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure20" src="/dailymed/image.cfm?name=spl-octreotide-figure20.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">C. <span class="Bold">Continue to hold the injection button down and slowly count to 10</span> to make sure the full dose of medicine is given (Figure T).<br/> </td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure21" src="/dailymed/image.cfm?name=spl-octreotide-figure21.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">D. Remove the pen from the injection site.<br/> <ul class="Disc"> <li>Lift the pen straight up from the injection site (Figure U).</li> <li>If you see 1 or 2 drops of medicine on the needle tip, this is normal and  will not a­ffect your dose.</li> <li> <span class="Bold">If you see more than 2 drops of medicine</span> on the needle tip, or you see liquid around the injection site after your injection, you may not have received your full dose.</li> </ul> <span class="Bold">If this happens: Do not</span> inject another dose. Contact your healthcare provider for help. Next time you inject, make sure to keep the pen needle in your skin and continue to hold the injection button down while slowly counting to 10 (see Figure T).<span class="Bold"> <br/> Note:</span> As the pen is used, a plunger will appear in the cartridge and move towards the thick line.</td><td class="Rrule" valign="middle"><img alt="spl-octreotide-figure22" src="/dailymed/image.cfm?name=spl-octreotide-figure22.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/><br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="3" valign="middle"><span class="Bold">6. After the Injection</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">A. <span class="Bold">Carefully place the outer needle cover back onto the needle.</span> <br/> <ul class="Disc"> <li>Place the outer needle cover on a flat surface. Hold the syringe with the needle attached in 1 hand and carefully slip the needle into the outer needle cover <span class="Bold">without </span>using the other hand. Push the outer needle cover completely on (Figure V).</li> </ul> <span class="Bold">Do not </span>recap with the inner needle cover.</td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure23" src="/dailymed/image.cfm?name=spl-octreotide-figure23.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">B. Unscrew and remove the covered needle (Figure W).<br/> <ul class="Disc"> <li>Squeeze the lower part of the covered needle while turning it to the left (counter clockwise).</li> <li>Keep turning until the covered needle lifts away from the pen. It may take several turns for the covered needle to lift away from the pen.</li> </ul> </td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure24" src="/dailymed/image.cfm?name=spl-octreotide-figure24.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">C. Throw away (dispose of) the covered needle in a FDA-cleared sharps container (Figure X).<br/> </td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure25" src="/dailymed/image.cfm?name=spl-octreotide-figure25.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"> <br/> <br/> <br/> <br/> <br/>D. Put the pen cap back on the pen (Figure Y) and store the pen.<br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <ul class="Disc"> <li>After use, store pens with the cap on at room temperature between 68°F to 77°F (20°C to 25°C) or in the refrigerator between 36°F to 46°F (2°C to 8°C) for up to 28 days.</li> <li>See the section<span class="Bold"> "How should I store my BYNFEZIA PEN</span>?" for more information on storing your pen.</li> </ul> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> </td><td class="Rrule" valign="middle"> <img alt="spl-octreotide-figure26" src="/dailymed/image.cfm?name=spl-octreotide-figure26.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b"/></td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle">E. Treat the injection site.<br/> <ul class="Disc"> <li>If needed, press the injection site lightly with a cotton ball or an alcohol swab. <span class="Bold">Do not</span> rub the area.</li> </ul> </td><td class="Rrule" valign="middle"> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="3" valign="middle"><span class="Bold">Cleaning the Pen</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="2" valign="middle"> <ul class="Disc"> <li>Wipe the outside of the pen with a clean, damp cloth.</li> <li>White particles may appear on the outside tip of the cartridge during normal use. You may remove them with an alcohol swab.</li> <li> <span class="Bold">Do not</span> put the pen in water or any other liquid.</li> </ul> </td><td class="Rrule" valign="middle"> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" colspan="3" valign="middle"><span class="Bold">Additional Disposal Information</span> <br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" colspan="2" valign="middle"> <br/>Put used pens and needles in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) pens and needles in the household trash.<br/> <br/> If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:<br/> <ul class="Disc"> <li>made of a heavy-duty plastic,</li> <li>can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,</li> <li>upright and stable during use,</li> <li>leak-resistant, and</li> <li>properly labeled to warn of hazardous waste inside the container.</li> </ul> <br/>When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal<br/> <ul class="Disc"> <li> <span class="Bold">Do not</span> dispose of your used sharps disposal container in your household trash unless your community guidelines permit this.</li> <li> <span class="Bold">Do not</span> recycle your used sharps disposal container.</li> <li> <span class="Bold">Always </span>keep the sharps disposal container out of the reach of children and pets.</li> </ul> </td><td class="Rrule" valign="middle"> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"middle\"><span class=\"Bold\">Important</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"middle\">\n<br/>• <span class=\"Bold\">Do not</span> use a pen for more than 28 days after first use. After 28 days throw away (dispose of) the pen, even if the pen still has medicine in it.<br/> • <span class=\"Bold\">Do not</span> place the pen in water or any other liquid.<br/> • <span class=\"Bold\">Keep</span> your pen and needles out of the reach of children.<br/> • <span class=\"Bold\">Do not</span> use if any part of your pen appears broken or damaged.<br/> • If you drop your pen, prime it before you use it again to make sure the pen still works correctly (see step <span class=\"Bold\">3. Prime Your Pen</span>).<br/> • <span class=\"Bold\">Do not </span>take BYNFEZIA PEN solution out of the pen and put it into a syringe.<br/> • <span class=\"Bold\">Do not</span> share your pen or needles with another person. You may give an infection to them or get an infection from them.<br/> • <span class=\"Bold\">Do not</span> remove the outer needle cover or inner needle cover until you are ready to inject.<br/> • <span class=\"Bold\">Do not</span> press the injection button unless a needle is attached to the pen.</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"middle\"><span class=\"Bold\">How should I store my </span><span class=\"Bold\">BYNFEZIA PEN</span><span class=\"Bold\">?</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"middle\">\n<br/>\n<span class=\"Bold\">Before First Use:</span>\n<br/> • Store new unused pens in the refrigerator between 36°F to 46°F (2°C to 8°C) and store in the outer carton in order to protect from light.<br/> • <span class=\"Bold\">Do not</span> freeze. Throw away (dispose of) the pen if it has been frozen.<br/> • <span class=\"Bold\">Do not</span> store the pen in direct sunlight.<br/>\n<br/>\n<span class=\"Bold\">After First Use or During Use:</span>\n<br/> • Store the pen at room temperature between 68°F to 77°F (20°C to 25°C) for up to 28 days.<br/> • Store the pen with the pen cap on.<br/> • Throw away (dispose of) the pen 28 days after first use in a sharps container, even if the pen still has medicine in it (see step <span class=\"Bold\">6. Additional Disposal Information</span>).<br/> • <span class=\"Bold\">Do not </span>store a pen with a needle attached.</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"middle\"><span class=\"Bold\">How do I give a dose larger than 200 mcg (more than 1 injection)?</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"middle\">\n<br/>1. Turn the dose set knob to 200 mcg (highest dose setting) and give the first injection. <span class=\"Bold\">Choose a different injection site for each injection</span> at least 2 inches from the area you used for your last injection.<br/> 2. Calculate the remaining dose by subtracting 200 mcg from the prescribed dose. <br/> 3. Turn the dose set knob to the line for your remaining dose up to the highest dose setting of 200 mcg. Give the second injection <span class=\"Bold\">at least 2 inches away</span> from the first injection.<br/> 4. You may need more injections to give your total prescribed dose (see examples below).   <br/>\n<span class=\"Bold\">See the following examples to give a total dose larger than 200 mcg:</span>\n<br/> <br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"middle\"><span class=\"Bold\">Example Dose</span></td><td class=\"Rrule\" valign=\"middle\"><span class=\"Bold\">Steps to give a total dose larger than 200 mcg</span></td><td class=\"Rrule\" valign=\"middle\"><span class=\"Bold\">Number of injections needed to give the total dose</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"middle\">For example, if your total dose is 300 mcg</td><td class=\"Rrule\" valign=\"middle\">\n<br/>\n<ol class=\"Arabic\">\n<li>Turn the dose set knob to 200 mcg for your first injection.</li>\n<li>Your remaining dose is 100 mcg.</li>\n<li>For the second injection, turn your dose set knob to 100 mcg to give the remaining dose. </li>\n</ol>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">\n<br/>2</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" valign=\"middle\">For example, if your total dose is 450 mcg</td><td class=\"Rrule\" valign=\"middle\">\n<br/>\n<ol class=\"Arabic\">\n<li>Turn the dose set knob to 200 mcg for your first injection.</li>\n<li>Your remaining dose is 250 mcg.</li>\n<li>Turn the dose set knob to 200 mcg for your second injection.</li>\n<li>Your remaining dose is 50 mcg.</li>\n<li>For the third injection, turn your dose set knob to 50 mcg to give the remaining dose.</li>\n</ol>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">\n<br/>3</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"middle\"><span class=\"Bold\">1. Check the Pen</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">A. Wash your hands with soap and water (Figure A).<br/>\n</td><td class=\"Rrule\" valign=\"middle\"><img alt=\"spl-octreotide-figure2\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure2.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/><br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<br/>B. Check the expiration (EXP) date (Figure B).<br/>\n<ul class=\"Disc\">\n<li>Check the pen label to make sure the expiration date has not passed.</li>\n</ul>\n<br/>\n<span class=\"Bold\">Do not</span> use if the expiration date has passed.</td><td class=\"Rrule\" valign=\"middle\"><img alt=\"spl-octreotide-figure3\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure3.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/><br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">C. Pull the pen cap straight o­ff the pen (Figure C).<br/>\n</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure4\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure4.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<br/>D. Check the medicine (Figure D).<br/>\n<ul class=\"Disc\">\n<li>The medicine should be clear and colorless. You may see small air bubbles in the pen, which is normal and will not affect the dose.</li>\n</ul>\n<br/>\n<span class=\"Bold\">Do not </span>use if the medicine looks cloudy, colored, or has lumps or particles in it. The pen cartridge may look empty because the medicine is clear and colorless.<br/>\n<ul class=\"Disc\">\n<li>Make sure you have enough medicine left in the pen to inject the full dose. When the plunger moves pass the thick line, your pen is almost empty (Figure E). If the dose set knob does not let you dial your prescribed dose, this means there is not enough medicine left in your pen. Throw away (dispose of) the pen and use a new pen for the injection.</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure5\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure5.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/><br/>\n<img alt=\"spl-octreotide-figure6\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure6.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/><br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">E. Allow the pen to reach room temperature.<br/>\n<ul class=\"Disc\">\n<li>If the pen was not stored at room temperature between 68°F to 77°F (20°C to 25°C), allow it to reach room temperature for 20 to 30 minutes before injecting. This will reduce the chance of getting a reaction at the injection site.</li>\n</ul>\n<span class=\"Bold\">Do not</span> try to warm the pen by using a heat source such as hot water or microwave.<br/>\n<ul class=\"Disc\">\n<li>See the section<span class=\"Bold\"> \"How should I store my BYNFEZIA PEN ?\"</span> for more information.</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"middle\"> </td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"middle\"><span class=\"Bold\">2. Attach a Needle</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">A. Gather the following additional supplies (Figure F):<br/>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">2 alcohol swabs</span>\n</li>\n<li>\n<span class=\"Bold\">new pen needle</span>\n</li>\n<li>\n<span class=\"Bold\">sharps container</span>\n</li>\n<li>\n<span class=\"Bold\">cotton ball</span>\n</li>\n</ul>\n<span class=\"Bold\">Note: </span>These supplies are <span class=\"Bold\">not included</span> with the pen.</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure7\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure7.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">B. Wipe the rubber seal on the pen with an alcohol swab (Figure G).<br/>\n</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure8\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure8.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">C. Attach a new needle.<br/>\n<ul class=\"Disc\">\n<li>Use only 31 gauge, 5 mm length disposable pen needles. If you have questions about which needle to use, ask your healthcare provider.</li>\n<li>Peel off­ the paper tab from the needle (Figure H).</li>\n<li>Push the needle with cap straight down onto the pen and screw it on to the pen by turning to the right (clockwise) until the needle feels secure (Figure I).</li>\n</ul>\n<span class=\"Bold\">Do not</span> overtighten the needle. This will make it hard to remove after the injection.</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure9\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure9.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/><br/>\n<img alt=\"spl-octreotide-figure10\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure10.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/><br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">D. Remove the outer needle cover and set it aside (Figure J).<br/>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Save</span> <span class=\"Bold\">the outer needle cover</span> for use when you remove the needle in step 6.</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"middle\"><img alt=\"spl-octreotide-figure11\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure11.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/><br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">E. Remove the inner needle cover and throw it away (Figure K).<br/>\n</td><td class=\"Rrule\" valign=\"middle\"><img alt=\"spl-octreotide-figure12\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure12.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/><br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"middle\">\n<br/>\n<span class=\"Bold\">Are you using a new pen?</span>\n<br/>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">If Yes, complete step 3.</span>\n</li>\n<li>\n<span class=\"Bold\">If No, skip step 3 and go to step 4.</span>\n</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"middle\"><span class=\"Bold\">3. Prime Your Pen</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\"><span class=\"Bold\">Note: </span>The following steps are only needed if you are using a new pen for the first time <span class=\"Bold\">or</span> if you drop the pen.<br/>\n<span class=\"Bold\">To prime the pen, follow the steps below to dial the pen to 100 mcg and press the injection button until a stream of medicine comes from the needle tip.</span>\n<br/>\n<ul class=\"Disc\">\n<li>If you have already primed the pen, go to step 4 to prepare and give the injection.</li>\n<li>\n<span class=\"Bold\">Do not</span> prime the pen before each dose. This will waste medicine.</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"middle\"> </td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\"><span class=\"Bold\">A. Turn the dose set knob to dial the pen to 100 mcg (Figure L).</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure13\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure13.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\"><span class=\"Bold\">B. Hold the pen with the needle pointing up.</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\"> </td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\"><span class=\"Bold\">C. Press the injection button all the way in until it stops and the dose display window returns to “0” (Figure M).</span>\n<br/>\n</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure14\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure14.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\"><span class=\"Bold\">D. A stream of medicine should be seen coming from the needle tip (Figure N).<br/>\n</span><span class=\"Bold\">\n<br/> If you do not see a stream of medicine coming from the needle tip</span>, repeat the priming steps.<br/>\n<br/>\n<span class=\"Bold\">If you still do not see a stream of medicine coming from the needle tip after you repeat the priming steps 3 times, </span>the pen may be damaged. Throw away (dispose of) the pen and use a new pen. Call Sun Pharmaceutical Industries, Inc. at 1-800-818-4555<span class=\"Bold\"></span>or your healthcare provider for help or to get a new pen.</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure15\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure15.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"middle\"><span class=\"Bold\"> 4. Prepare the Injection</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">A. Choose an injection site (see Figure O) for injection under the skin (subcutaneous).<br/>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">When giving yourself the injection: </span>Inject into the stomach at least 2 inches away from the belly button (navel) or inject into the front of the middle thighs (Figure O).</li>\n<li>\n<span class=\"Bold\">When giving someone else the injection: </span>you may also inject into the back outer area of the upper arms (Figure O).</li>\n<li>\n<span class=\"Bold\">Always change (rotate) the injection site with each injection. Your injection site should be at least 2 inches away from your last injection site.</span>\n</li>\n</ul>\n<span class=\"Bold\">Do not</span> inject into moles, scars, birthmarks, or areas where the skin is tender, bruised, red, or hard.</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure16\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure16.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<br/>B. Clean your injection site with an alcohol swab (Figure P).<br/>\n<ul class=\"Disc\">\n<li>Wipe the skin with an alcohol swab. Let the injection site dry before you inject your dose.</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure17\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure17.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<br/>\n<br/>C. Dial your dose (Figure Q).<br/>\n<ul class=\"Disc\">\n<li>Turn the dose set knob until you see the prescribed dose in the dose display window. The dose number and black line should line up with the pointer. The pen can be used to deliver 50 mcg, 100 mcg, 150 mcg and 200 mcg doses. </li>\n</ul>\n<br/>\n<br/>If your prescribed dose is more than 200 mcg, see the section <span class=\"Bold\">“How should I give a dose larger than 200 mcg (more than 1 injection)?” </span>in these instructions.<br/>\n<br/>\n<ul class=\"Disc\">\n<li>It is normal to hear a “clicking” sound as you turn the dose set knob.</li>\n<li>If you accidentally dial past the prescribed dose, turn the dose set knob back down to the correct dose.</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure18\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure18.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\"><span class=\"Bold\">Note:</span> The pen cannot be dialed past the number of micrograms (mcgs) of medicine left in the pen. If the pen does not have enough medicine to give the full dose, throw away (dispose of) the pen and use a new one.<br/>\n</td><td class=\"Rrule\" valign=\"middle\"> </td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"middle\"><span class=\"Bold\">5. Give the Injection</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">A. Insert the needle straight into the injection site (Figure R).<br/>\n</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure19\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure19.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">B. Deliver your dose.<br/>\n<ul class=\"Disc\">\n<li>Deliver your dose by slowly pressing the injection button all the way down until it stops. The number in the dose display window will go back to “0” when the injection is complete (Figure S).</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure20\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure20.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">C. <span class=\"Bold\">Continue to hold the injection button down and slowly count to 10</span> to make sure the full dose of medicine is given (Figure T).<br/>\n</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure21\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure21.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">D. Remove the pen from the injection site.<br/>\n<ul class=\"Disc\">\n<li>Lift the pen straight up from the injection site (Figure U).</li>\n<li>If you see 1 or 2 drops of medicine on the needle tip, this is normal and  will not a­ffect your dose.</li>\n<li>\n<span class=\"Bold\">If you see more than 2 drops of medicine</span> on the needle tip, or you see liquid around the injection site after your injection, you may not have received your full dose.</li>\n</ul>\n<span class=\"Bold\">If this happens: Do not</span> inject another dose. Contact your healthcare provider for help. Next time you inject, make sure to keep the pen needle in your skin and continue to hold the injection button down while slowly counting to 10 (see Figure T).<span class=\"Bold\">\n<br/> Note:</span> As the pen is used, a plunger will appear in the cartridge and move towards the thick line.</td><td class=\"Rrule\" valign=\"middle\"><img alt=\"spl-octreotide-figure22\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure22.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/><br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"middle\"><span class=\"Bold\">6. After the Injection</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">A. <span class=\"Bold\">Carefully place the outer needle cover back onto the needle.</span>\n<br/>\n<ul class=\"Disc\">\n<li>Place the outer needle cover on a flat surface. Hold the syringe with the needle attached in 1 hand and carefully slip the needle into the outer needle cover <span class=\"Bold\">without </span>using the other hand. Push the outer needle cover completely on (Figure V).</li>\n</ul>\n<span class=\"Bold\">Do not </span>recap with the inner needle cover.</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure23\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure23.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">B. Unscrew and remove the covered needle (Figure W).<br/>\n<ul class=\"Disc\">\n<li>Squeeze the lower part of the covered needle while turning it to the left (counter clockwise).</li>\n<li>Keep turning until the covered needle lifts away from the pen. It may take several turns for the covered needle to lift away from the pen.</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure24\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure24.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">C. Throw away (dispose of) the covered needle in a FDA-cleared sharps container (Figure X).<br/>\n</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure25\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure25.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<br/>\n<br/>\n<br/>\n<br/>\n<br/>D. Put the pen cap back on the pen (Figure Y) and store the pen.<br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/>\n<ul class=\"Disc\">\n<li>After use, store pens with the cap on at room temperature between 68°F to 77°F (20°C to 25°C) or in the refrigerator between 36°F to 46°F (2°C to 8°C) for up to 28 days.</li>\n<li>See the section<span class=\"Bold\"> \"How should I store my BYNFEZIA PEN</span>?\" for more information on storing your pen.</li>\n</ul> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/> <br/>\n</td><td class=\"Rrule\" valign=\"middle\"> <img alt=\"spl-octreotide-figure26\" src=\"/dailymed/image.cfm?name=spl-octreotide-figure26.jpg&amp;setid=20ed4e79-ad4c-426f-859d-83790c00439b\"/></td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">E. Treat the injection site.<br/>\n<ul class=\"Disc\">\n<li>If needed, press the injection site lightly with a cotton ball or an alcohol swab. <span class=\"Bold\">Do not</span> rub the area.</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"middle\"> </td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"middle\"><span class=\"Bold\">Cleaning the Pen</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<ul class=\"Disc\">\n<li>Wipe the outside of the pen with a clean, damp cloth.</li>\n<li>White particles may appear on the outside tip of the cartridge during normal use. You may remove them with an alcohol swab.</li>\n<li>\n<span class=\"Bold\">Do not</span> put the pen in water or any other liquid.</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"middle\"> </td>\n</tr>\n<tr class=\"Botrule\">\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"middle\"><span class=\"Bold\">Additional Disposal Information</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Rrule\" colspan=\"2\" valign=\"middle\">\n<br/>Put used pens and needles in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) pens and needles in the household trash.<br/>\n<br/> If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:<br/>\n<ul class=\"Disc\">\n<li>made of a heavy-duty plastic,</li>\n<li>can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,</li>\n<li>upright and stable during use,</li>\n<li>leak-resistant, and</li>\n<li>properly labeled to warn of hazardous waste inside the container.</li>\n</ul>\n<br/>When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal<br/>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Do not</span> dispose of your used sharps disposal container in your household trash unless your community guidelines permit this.</li>\n<li>\n<span class=\"Bold\">Do not</span> recycle your used sharps disposal container.</li>\n<li>\n<span class=\"Bold\">Always </span>keep the sharps disposal container out of the reach of children and pets.</li>\n</ul>\n</td><td class=\"Rrule\" valign=\"middle\"> </td>\n</tr>\n</tbody>\n</table></div>" }

This Instructions for Use has been approved by the U.S. Food and Drug Administration. All trademarks are the property of their respective owners.

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration. All trademarks are the property of their respective owners." }

Distributed by:

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

Sun Pharmaceutical Industries, Inc.

{ "type": "p", "children": [], "text": "\nSun Pharmaceutical Industries, Inc.\n" }

Cranbury, NJ 08512

{ "type": "p", "children": [], "text": "Cranbury, NJ 08512" }

Manufactured by: Sun Pharmaceutical Industries Ltd., India At M/s. OneSource Specialty Pharma Limited Plot No. 2-D1, Obadenahalli, Doddaballapura, 3rd Phase, Industrial Area, Doddaballapura Taluk, Bengaluru Rural, 561203, Karnataka INDIA

{ "type": "p", "children": [], "text": "Manufactured by:\nSun Pharmaceutical Industries Ltd., India\n At M/s. OneSource Specialty Pharma Limited Plot No. 2-D1, Obadenahalli, Doddaballapura, 3rd Phase, Industrial Area, Doddaballapura Taluk, Bengaluru Rural, 561203, Karnataka INDIA" }

For more information, call 1-800-818-4555.

{ "type": "p", "children": [], "text": "\nFor more information, call 1-800-818-4555.\n" }

Issued: 10/2024

{ "type": "p", "children": [], "text": "Issued: 10/2024" }

Rx only NDC 62756-452-37 Bynfezia Pen®  (octreotide acetate Injection) 7,000 mcg/2.8mL (2,500 mcg/mL) Two 2.8 mL disposable single-patient-use prefilled pens Subcutaneous use only For doses of 50 mcg, 100 mcg, 150 mcg, and 200 mcg of octreotide per injection. For Single Patient Use Only Dispense in this sealed carton SUN PHARMA

{ "type": "p", "children": [], "text": "\nRx only\n\nNDC 62756-452-37\n\nBynfezia Pen®  (octreotide acetate Injection)\n\n7,000 mcg/2.8mL (2,500 mcg/mL)\n\nTwo 2.8 mL disposable single-patient-use prefilled pens Subcutaneous use only\n For doses of 50 mcg, 100 mcg, 150 mcg, and 200 mcg of octreotide per injection.\nFor Single Patient Use Only Dispense in this sealed carton\n\nSUN PHARMA\n" }

Long-term maintenance therapy in acromegalic patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy, is not an option. The goal of treatment in acromegaly is to reduce GH and IGF-1 levels to normal [see Clinical Studies (14), Dosage and Administration (2)].

Long-term treatment of the severe diarrhea and flushing episodes associated with metastatic carcinoid tumors.

Long-term treatment of the profuse watery diarrhea associated with VIP-secreting tumors.

In patients with carcinoid syndrome and VIPomas, the effect of Sandostatin Injection and SANDOSTATIN LAR DEPOT on tumor size, rate of growth and development of metastases, has not been determined.

Patients Not Currently Receiving Octreotide Acetate

Patients not currently receiving octreotide acetate should begin therapy with Sandostatin Injection given subcutaneously in an initial dose of 50 mcg three times daily which may be titrated. Most patients require doses of 100 mcg to 200 mcg three times daily for maximum effect but some patients require up to 500 mcg three times daily.

Patients should be maintained on Sandostatin Injection subcutaneous for at least 2 weeks to determine tolerance to octreotide acetate. Patients who are considered to be “responders” to the drug, based on GH and IGF-1 levels and who tolerate the drug, can then be switched to SANDOSTATIN LAR DEPOT in the dosage scheme described below (Patients Currently Receiving Sandostatin Injection).

Patients Currently Receiving Sandostatin Injection

Patients currently receiving Sandostatin Injection can be switched directly to SANDOSTATIN LAR DEPOT in a dose of 20 mg given IM intragluteally at 4-week intervals for 3 months. After 3 months, dosage may be adjusted as follows:

In patients who have received pituitary irradiation, SANDOSTATIN LAR DEPOT should be withdrawn yearly for approximately 8 weeks to assess disease activity. If GH or IGF-1 levels increase and signs and symptoms recur, SANDOSTATIN LAR DEPOT therapy may be resumed.

Patients Not Currently Receiving Octreotide Acetate

Patients not currently receiving octreotide acetate should begin therapy with Sandostatin Injection given subcutaneously. The suggested daily dosage for carcinoid tumors during the first 2 weeks of therapy ranges from 100 to 600 mcg/day in 2 to 4 divided doses (mean daily dosage is 300 mcg). Some patients may require doses up to 1,500 mcg/day. The suggested daily dosage for VIPomas is 200 to 300 mcg in 2 to 4 divided doses (range, 150 to 750 mcg); dosage may be adjusted on an individual basis to control symptoms but usually doses above 450 mcg/day are not required.

Sandostatin Injection should be continued for at least 2 weeks. Thereafter, patients who are considered “responders” to octreotide acetate, and who tolerate the drug, may be switched to SANDOSTATIN LAR DEPOT in the dosage regimen as described below (Patients Currently Receiving Sandostatin Injection).

Patients Currently Receiving Sandostatin Injection

Patients currently receiving Sandostatin Injection can be switched to SANDOSTATIN LAR DEPOT in a dosage of 20 mg given IM intragluteally at 4-week intervals for 2 months. Because of the need for serum octreotide to reach therapeutically effective levels following initial injection of SANDOSTATIN LAR DEPOT, carcinoid tumor and VIPoma patients should continue to receive Sandostatin Injection subcutaneously for at least 2 weeks in the same dosage they were taking before the switch. Failure to continue subcutaneous injections for this period may result in exacerbation of symptoms (some patients may require 3 or 4 weeks of such therapy).

After 2 months, dosage may be adjusted as follows:

Despite good overall control of symptoms, patients with carcinoid tumors and VIPomas often experience periodic exacerbation of symptoms (regardless of whether they are being maintained on Sandostatin Injection or SANDOSTATIN LAR DEPOT). During these periods, they may be given Sandostatin Injection subcutaneously for a few days at the dosage they were receiving prior to switching to SANDOSTATIN LAR DEPOT. When symptoms are again controlled, the Sandostatin Injection subcutaneous can be discontinued.

In patients with renal failure requiring dialysis, the starting dose should be 10 mg every 4 weeks. In other patients with renal impairment, the starting dose should be similar to a nonrenal patient (i.e., 20 mg every 4 weeks) [see Clinical Pharmacology (12)].

In patients with established cirrhosis of the liver, the starting dose should be 10 mg every 4 weeks [see Clinical Pharmacology (12.3)].

SANDOSTATIN LAR DEPOT is available in single-dose kits for injectable suspension containing a 6-mL single-dose vial of 10 mg, 20 mg, or 30 mg strength, a prefilled syringe containing 2 mL of diluent, one vial adapter, and one sterile 1½” 19 gauge safety injection needle. An instruction booklet for the preparation of drug suspension for injection is also included with each kit.

{ "type": "p", "children": [], "text": "SANDOSTATIN LAR DEPOT is available in single-dose kits for injectable suspension containing a 6-mL single-dose vial of 10 mg, 20 mg, or 30 mg strength, a prefilled syringe containing 2 mL of diluent, one vial adapter, and one sterile 1½” 19 gauge safety injection needle. An instruction booklet for the preparation of drug suspension for injection is also included with each kit." }

None.

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

SANDOSTATIN LAR DEPOT may inhibit gallbladder contractility and decrease bile secretion, which may lead to gallbladder abnormalities or sludge. There have been postmarketing reports of cholelithiasis (gallstones) resulting in complications, including cholecystitis, cholangitis, pancreatitis and requiring cholecystectomy in patients taking SANDOSTATIN LAR DEPOT [see Adverse Reactions (6)]. Patients should be monitored periodically. If complications of cholelithiasis are suspected, discontinue SANDOSTATIN LAR DEPOT and treat appropriately.

Octreotide alters the balance between the counter-regulatory hormones, insulin, glucagon, and growth hormone (GH), which may result in hypoglycemia or hyperglycemia. Blood glucose levels should be monitored when SANDOSTATIN LAR DEPOT treatment is initiated, or when the dose is altered. Anti-diabetic treatment should be adjusted accordingly [see Adverse Reactions (6)].

Octreotide suppresses the secretion of thyroid-stimulating hormone (TSH), which may result in hypothyroidism. Baseline and periodic assessment of thyroid function (TSH, total and/or free T4) is recommended during chronic octreotide therapy [see Adverse Reactions (6)].

In both acromegalic and carcinoid syndrome patients, bradycardia, arrhythmias and conduction abnormalities have been reported during octreotide therapy. Other electrocardiogram (ECG) changes were observed, such as QT prolongation, axis shifts, early repolarization, low voltage, R/S transition, early R wave progression, and nonspecific ST-T wave changes. The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac disease. Dose adjustments in drugs, such as beta-blockers that have bradycardic effects may be necessary. In one acromegalic patient with severe congestive heart failure (CHF), initiation of Sandostatin Injection-therapy resulted in worsening of CHF with improvement when drug was discontinued. Confirmation of a drug effect was obtained with a positive rechallenge [see Adverse Reactions (6)].

New onset steatorrhea, stool discoloration and loose stool have been reported in patients receiving somatostatin analogs, including SANDOSTATIN LAR DEPOT. Somatostatin analogs reversibly inhibit secretion of pancreatic enzymes and bile acids, which may result in malabsorption of dietary fats and subsequent symptoms of steatorrhea, loose stools, abdominal bloating, and weight loss. If new occurrence or worsening of these symptoms are reported in patients receiving SANDOSTATIN LAR DEPOT, evaluate patients for potential pancreatic exocrine insufficiency and manage accordingly.

Depressed vitamin B12 levels and abnormal Schilling tests have been observed in some patients receiving octreotide therapy, and monitoring of vitamin B12 levels is recommended during therapy with SANDOSTATIN LAR DEPOT.

Octreotide has been investigated for the reduction of excessive fluid loss from the GI tract in patients with conditions producing such a loss. If such patients are receiving total parenteral nutrition (TPN), serum zinc may rise excessively when the fluid loss is reversed. Patients on TPN and octreotide should have periodic monitoring of zinc levels.

Laboratory tests that may be helpful as biochemical markers in determining and following patient response depend on the specific tumor. Based on diagnosis, measurement of the following substances may be useful in monitoring the progress of therapy [see Dosage and Administration (2.1, 2.2)].

Acromegaly: Growth Hormone, IGF-1 (somatomedin C)

Carcinoid: 5-HIAA (urinary 5-hydroxyindole acetic acid), plasma serotonin, plasma Substance P

VIPoma: VIP (plasma vasoactive intestinal peptide) baseline and periodic total and/or free T4 measurements should be performed during chronic therapy

Octreotide has been associated with alterations in nutrient absorption, so it may have an effect on absorption of orally administered drugs. Concomitant administration of octreotide injection with cyclosporine may decrease blood levels of cyclosporine [see Drug Interactions (7.1)].

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 trial of another drug and may not reflect the rates observed in practice.

Acromegaly

The safety of SANDOSTATIN LAR DEPOT in the treatment of acromegaly has been evaluated in three Phase 3 studies in 261 patients, including 209 exposed for 48 weeks and 96 exposed for greater than 108 weeks. SANDOSTATIN LAR DEPOT was studied primarily in a double-blind, cross-over manner. Patients on subcutaneous Sandostatin Injection were switched to the LAR formulation followed by an open-label extension. The population age range was 14 to 81 years old and 53% were female. Approximately 35% of these acromegaly patients had not been treated with surgery and/or radiation. Most patients received a starting dose of 20 mg every 4 weeks intramuscularly. Dose was up or down titrated based on efficacy and tolerability to a final dose between 10 mg to 60 mg every 4 weeks. Table 1 below reflects adverse events from these studies regardless of presumed causality to study drug.

<div class="scrollingtable"><table> <caption> <span>Table 1. Adverse Events Occurring in ≥ 10% of Acromegalic Patients in the Phase 3 Studies</span> </caption> <col width="390"/> <col width="345"/> <tfoot> <tr class="First Last"> <td colspan="2">Abbreviation: AEs, adverse events.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td valign="top"><span class="Bold">WHO Preferred Term</span></td><td align="center"><span class="Bold">Phase 3 Studies (Pooled)</span> <br/> <span class="Bold">Number (%) of Subjects with AEs</span> <br/> <span class="Bold">10 mg/20 mg/30 mg</span> <br/> <span class="Bold">(n = 261)</span> <br/> <span class="Bold">n (%)</span></td> </tr> <tr> <td class="Toprule">Diarrhea</td><td align="center" class="Toprule">93 (35.6)</td> </tr> <tr> <td>Abdominal Pain</td><td align="center">75 (28.7)</td> </tr> <tr> <td>Flatulence</td><td align="center">66 (25.3)</td> </tr> <tr> <td>Influenza-Like Symptoms</td><td align="center">52 (19.9)</td> </tr> <tr> <td>Constipation</td><td align="center">46 (17.6)</td> </tr> <tr> <td>Headache</td><td align="center">40 (15.3)</td> </tr> <tr> <td>Anemia</td><td align="center">40 (15.3)</td> </tr> <tr> <td>Injection-Site Pain</td><td align="center">36 (13.8)</td> </tr> <tr> <td>Cholelithiasis</td><td align="center">35 (13.4)</td> </tr> <tr> <td>Hypertension</td><td align="center">33 (12.6)</td> </tr> <tr> <td>Dizziness</td><td align="center">30 (11.5)</td> </tr> <tr class="Last"> <td>Fatigue</td><td align="center">29 (11.1)</td> </tr> </tbody> </table></div>

The safety of SANDOSTATIN LAR DEPOT in the treatment of acromegaly was also evaluated in a postmarketing randomized Phase 4 study. One-hundred four (104) patients were randomized to either pituitary surgery or 20 mg of SANDOSTATIN LAR DEPOT. All the patients were treatment naïve (‘de novo’). Crossover was allowed according to treatment response and a total of 76 patients were exposed to Sandostatin LAR. Approximately half of the patients initially randomized to SANDOSTATIN LAR DEPOT were exposed to SANDOSTATIN LAR DEPOT up to 1 year. The population age range was between 20 to 76 years old, 45% were female, 93% were Caucasian, and 1% Black. The majority of these patients were exposed to 30 mg every 4 weeks. Table 2 below reflects the adverse events occurring in this study regardless of presumed causality to study drug.

<div class="scrollingtable"><table> <caption> <span>Table 2. Adverse Events Occurring in ≥ 10% of Acromegalic Patients in Phase 4 Study</span> </caption> <col width="299"/> <col width="209"/> <col width="227"/> <tbody class="Headless"> <tr class="First"> <td class="Toprule" valign="top"><span class="Bold">WHO Preferred Term</span></td><td align="center" class="Toprule"><span class="Bold">Phase 4 Study</span> <br/> <span class="Bold">SANDOSTATIN LAR DEPOT</span> <br/> <span class="Bold">N = 76</span> <br/> <span class="Bold">n (%)</span></td><td align="center" class="Toprule"><span class="Bold">Phase 4 Study</span> <br/> <span class="Bold">Surgery</span> <br/> <span class="Bold">N = 64</span> <br/> <span class="Bold">n (%)</span></td> </tr> <tr> <td class="Toprule">Diarrhea</td><td align="center" class="Toprule">36 (47.4)</td><td align="center" class="Toprule">2 (3.1)</td> </tr> <tr> <td>Cholelithiasis</td><td align="center">29 (38.2)</td><td align="center">3 (4.7)</td> </tr> <tr> <td>Abdominal Pain</td><td align="center">19 (25.0)</td><td align="center">2 (3.1)</td> </tr> <tr> <td>Nausea</td><td align="center">12 (15.8)</td><td align="center">5 (7.8)</td> </tr> <tr> <td>Alopecia</td><td align="center">10 (13.2)</td><td align="center">5 (7.8)</td> </tr> <tr> <td>Injection-Site Pain</td><td align="center">9 (11.8)</td><td align="center">0</td> </tr> <tr> <td>Abdominal Pain Upper</td><td align="center">8 (10.5)</td><td align="center">0</td> </tr> <tr> <td>Headache</td><td align="center">8 (10.5)</td><td align="center">6 (9.4)</td> </tr> <tr class="Last"> <td>Epistaxis</td><td align="center">0</td><td align="center">7 (10.9)</td> </tr> </tbody> </table></div>

Gallbladder Abnormalities

Single doses of Sandostatin Injection have been shown to inhibit gallbladder contractility and decrease bile secretion in normal volunteers. In clinical trials with Sandostatin Injection (primarily patients with acromegaly or psoriasis) in patients who had not previously received octreotide acetate, the incidence of biliary tract abnormalities was 63% (27% gallstones, 24% sludge without stones, 12% biliary duct dilatation). The incidence of stones or sludge in patients who received Sandostatin Injection for 12 months or longer was 52%. The incidence of gallbladder abnormalities did not appear to be related to age, sex, or dose but was related to duration of exposure.

In clinical trials, 52% of acromegalic patients, most of whom received SANDOSTATIN LAR DEPOT for 12 months or longer, developed new biliary abnormalities including gallstones, microlithiasis, sediment, sludge, and dilatation. The incidence of new cholelithiasis was 22%, of which 7% were microstones.

Across all trials, a few patients developed acute cholecystitis, ascending cholangitis, biliary obstruction, cholestatic hepatitis, or pancreatitis during octreotide therapy or following its withdrawal. One patient developed ascending cholangitis during Sandostatin Injection therapy and died. Despite the high incidence of new gallstones in patients receiving octreotide acetate, 1% of patients developed acute symptoms requiring cholecystectomy.

Glucose Metabolism - Hypoglycemia/Hyperglycemia

In acromegaly patients treated with either Sandostatin Injection or SANDOSTATIN LAR DEPOT, hypoglycemia occurred in approximately 2% and hyperglycemia in approximately 15% of patients [see Warnings and Precautions (5.2)].

Hypothyroidism

In acromegaly patients receiving Sandostatin Injection, 12% developed biochemical hypothyroidism, 8% developed goiter, and 4% required initiation of thyroid replacement therapy while receiving Sandostatin Injection. In acromegalic patients treated with SANDOSTATIN LAR DEPOT, hypothyroidism was reported as an adverse event in 2% and goiter in 2%. Two patients receiving SANDOSTATIN LAR DEPOT required initiation of thyroid hormone replacement therapy [see Warnings and Precautions (5.3)].

Cardiac

In acromegalic patients, sinus bradycardia (< 50 bpm) developed in 25%; conduction abnormalities occurred in 10% and arrhythmias developed in 9% of patients during Sandostatin Injection-therapy. The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac disease [see Warnings and Precautions (5.4)].

Gastrointestinal

The most common symptoms are gastrointestinal. The overall incidence of the most frequent of these symptoms in clinical trials of acromegalic patients treated for approximately 1 to 4 years is shown in Table 3.

<div class="scrollingtable"><table> <caption> <span>Table 3. Number (%) of Acromegalic Patients With Common GI Adverse Events</span> </caption> <col width="263"/> <col width="92"/> <col width="155"/> <col width="84"/> <col width="141"/> <tbody class="Headless"> <tr class="First"> <td valign="top"><span class="Bold">Adverse Event</span></td><td align="center" colspan="2"><span class="Bold">Sandostatin Injection S.C.</span> <br/> <span class="Bold">Three Times Daily</span> <br/> <span class="Bold">n = 114</span></td><td align="center" colspan="2"><span class="Bold">SANDOSTATIN LAR DEPOT</span> <br/> <span class="Bold">Every 28 Days</span> <br/> <span class="Bold">n = 261</span></td> </tr> <tr> <td class="Toprule"></td><td align="center" class="Toprule">n</td><td align="center" class="Toprule">%</td><td align="center" class="Toprule">n</td><td align="center" class="Toprule">%</td> </tr> <tr> <td>Diarrhea</td><td align="center">66</td><td align="center">(57.9)</td><td align="center">95</td><td align="center">(36.4)</td> </tr> <tr> <td>Abdominal Pain or Discomfort</td><td align="center">50</td><td align="center">(43.9)</td><td align="center">76</td><td align="center">(29.1)</td> </tr> <tr> <td>Nausea</td><td align="center">34</td><td align="center">(29.8)</td><td align="center">27</td><td align="center">(10.3)</td> </tr> <tr> <td>Flatulence</td><td align="center">15</td><td align="center">(13.2)</td><td align="center">67</td><td align="center">(25.7)</td> </tr> <tr> <td>Constipation</td><td align="center">10</td><td align="center">(8.8)</td><td align="center">49</td><td align="center">(18.8)</td> </tr> <tr class="Last"> <td>Vomiting</td><td align="center">5</td><td align="center">(4.4)</td><td align="center">17</td><td align="center">(6.5)</td> </tr> </tbody> </table></div>

Only 2.6% of the patients on Sandostatin Injection in US clinical trials discontinued therapy due to these symptoms. No acromegalic patient receiving SANDOSTATIN LAR DEPOT discontinued therapy for a GI event.

In patients receiving SANDOSTATIN LAR DEPOT, the incidence of diarrhea was dose related. Diarrhea, abdominal pain, and nausea developed primarily during the first month of treatment with SANDOSTATIN LAR DEPOT. Thereafter, new cases of these events were uncommon. The vast majority of these events were mild-to-moderate in severity.

In rare instances, gastrointestinal adverse effects may resemble acute intestinal obstruction, with progressive abdominal distention, severe epigastric pain, abdominal tenderness, and guarding.

Dyspepsia, steatorrhea, discoloration of feces, and tenesmus were reported in 4% to 6% of patients.

In a clinical trial of carcinoid syndrome, nausea, abdominal pain, and flatulence were reported in 27% to 38% and constipation or vomiting in 15% to 21% of patients treated with SANDOSTATIN LAR DEPOT. Diarrhea was reported as an adverse event in 14% of patients, but since most of the patients had diarrhea as a symptom of carcinoid syndrome, it is difficult to assess the actual incidence of drug-related diarrhea.

Pain at the Injection Site

Pain on injection, which is generally mild-to-moderate, and short-lived (usually about 1 hour) is dose related, being reported by 2%, 9%, and 11% of acromegalic patients receiving doses of 10 mg, 20 mg, and 30 mg, respectively, of SANDOSTATIN LAR DEPOT. In carcinoid patients, where a diary was kept, pain at the injection site was reported by about 20%-25% at a 10-mg dose and about 30%-50% at the 20-mg and 30-mg dose.

Antibodies to Octreotide

Studies to date have shown that antibodies to octreotide develop in up to 25% of patients treated with octreotide acetate. These antibodies do not influence the degree of efficacy response to octreotide; however, in two acromegalic patients who received Sandostatin Injection, the duration of GH suppression following each injection was about twice as long as in patients without antibodies. It has not been determined whether octreotide antibodies will also prolong the duration of GH suppression in patients being treated with SANDOSTATIN LAR DEPOT.

Carcinoid and VIPomas

The safety of SANDOSTATIN LAR DEPOT in the treatment of carcinoid tumors and VIPomas has been evaluated in one Phase 3 study. Study 1 randomized 93 patients with carcinoid syndrome to SANDOSTATIN LAR DEPOT 10 mg, 20 mg, or 30 mg in a blind fashion or to open-label Sandostatin Injection subcutaneously. The population age range was between 25 to 78 years old and 44% were female, 95% were Caucasian and 3% Black. All the patients had symptom control on their previous Sandostatin subcutaneous treatment. Eighty (80) patients finished the initial 24 weeks of Sandostatin exposure in Study 1. In Study 1, comparable numbers of patients were randomized to each dose. Table 4 below reflects the adverse events occurring in ≥ 15% of patients regardless of presumed causality to study drug.

<div class="scrollingtable"><table> <caption> <span>Table 4. Adverse Events Occurring in ≥ 15% of Carcinoid Tumor and VIPoma Patients in Study 1</span> </caption> <col width="277"/> <col width="114"/> <col width="114"/> <col width="114"/> <col width="115"/> <tbody class="Headless"> <tr class="First"> <td valign="bottom"></td><td align="center" colspan="4"><span class="Bold">Number (%) of Subjects With AEs</span> <br/> <span class="Bold">(n = 93)</span></td> </tr> <tr> <td class="Toprule"><span class="Bold">WHO Preferred Term</span></td><td align="center" class="Toprule"><span class="Bold">S.C.</span> <br/> <span class="Bold">N = 26</span></td><td align="center" class="Toprule"><span class="Bold">10 mg</span> <br/> <span class="Bold">N = 22</span></td><td align="center" class="Toprule"><span class="Bold">20 mg</span> <br/> <span class="Bold">N = 20</span></td><td align="center" class="Toprule"><span class="Bold">30 mg</span> <br/> <span class="Bold">N = 25</span></td> </tr> <tr> <td class="Toprule">Abdominal Pain</td><td align="center" class="Toprule">8 (30.8)</td><td align="center" class="Toprule">8 (35.4)</td><td align="center" class="Toprule">2 (10.0)</td><td align="center" class="Toprule">5 (20.0)</td> </tr> <tr> <td>Arthropathy</td><td align="center">5 (19.2)</td><td align="center">2 (9.1)</td><td align="center">3 (15.0)</td><td align="center">2 (8.0)</td> </tr> <tr> <td>Back Pain</td><td align="center">7 (26.9)</td><td align="center">6 (27.3)</td><td align="center">2 (10.0)</td><td align="center">2 (8.0)</td> </tr> <tr> <td>Dizziness</td><td align="center">4 (15.4)</td><td align="center">4 (18.2)</td><td align="center">4 (20.0)</td><td align="center">5 (20.0)</td> </tr> <tr> <td>Fatigue</td><td align="center">3 (11.5)</td><td align="center">7 (31.8)</td><td align="center">2 (10.0)</td><td align="center">2 (8.0)</td> </tr> <tr> <td>Flatulence</td><td align="center">3 (11.5)</td><td align="center">2 (9.1)</td><td align="center">2 (10.0)</td><td align="center">4 (16.0)</td> </tr> <tr> <td>Generalized Pain</td><td align="center">4 (15.4)</td><td align="center">2 (9.1)</td><td align="center">3 (15.0)</td><td align="center">1 (4.0)</td> </tr> <tr> <td>Headache</td><td align="center">5 (19.2)</td><td align="center">4 (18.2)</td><td align="center">6 (30.0)</td><td align="center">4 (16.0)</td> </tr> <tr> <td>Musculoskeletal Pain</td><td align="center">4 (15.4)</td><td align="center">0</td><td align="center">1 (5.0)</td><td align="center">0</td> </tr> <tr> <td>Myalgia</td><td align="center">0</td><td align="center">4 (18.2)</td><td align="center">1 (5.0)</td><td align="center">1 (4.0)</td> </tr> <tr> <td>Nausea</td><td align="center">8 (30.8)</td><td align="center">9 (40.9)</td><td align="center">6 (30.0)</td><td align="center">6 (24.0)</td> </tr> <tr> <td>Pruritus</td><td align="center">0</td><td align="center">4 (18.2)</td><td align="center">0</td><td align="center">0</td> </tr> <tr> <td>Rash</td><td align="center">1 (3.8)</td><td align="center">0</td><td align="center">3 (15.0)</td><td align="center">0</td> </tr> <tr> <td>Sinusitis</td><td align="center">4 (15.4)</td><td align="center">0</td><td align="center">1 (5.0)</td><td align="center">3 (12.0)</td> </tr> <tr> <td>URTI</td><td align="center">6 (23.1)</td><td align="center">4 (18.2)</td><td align="center">2 (10.0)</td><td align="center">3 (12.0)</td> </tr> <tr class="Last"> <td>Vomiting</td><td align="center">3 (11.5)</td><td align="center">0</td><td align="center">0</td><td align="center">4 (16.0)</td> </tr> </tbody> </table></div>

Gallbladder Abnormalities

In clinical trials, 62% of malignant carcinoid patients, who received SANDOSTATIN LAR DEPOT for up to 18 months, developed new biliary abnormalities including jaundice, gallstones, sludge, and dilatation. New gallstones occurred in a total of 24% of patients.

Glucose Metabolism - Hypoglycemia/Hyperglycemia

In carcinoid patients, hypoglycemia occurred in 4% and hyperglycemia in 27% of patients treated with SANDOSTATIN LAR DEPOT [see Warnings and Precautions (5.2)].

Hypothyroidism

In carcinoid patients, hypothyroidism has only been reported in isolated patients and goiter has not been reported [see Warnings and Precautions (5.3)].

Cardiac

Electrocardiograms were performed only in carcinoid patients receiving SANDOSTATIN LAR DEPOT. In carcinoid syndrome patients, sinus bradycardia developed in 19%, conduction abnormalities occurred in 9%, and arrhythmias developed in 3%. The relationship of these events to octreotide acetate is not established because many of these patients have underlying cardiac disease [see Warnings and Precautions (5.4)].

Other Clinical Studies Adverse Events

Other clinically significant adverse events (relationship to drug not established) in acromegalic and/or carcinoid syndrome patients receiving SANDOSTATIN LAR DEPOT were malignant hyperpyrexia, cerebral vascular disorder, rectal bleeding, ascites, pulmonary embolism, pneumonia, and pleural effusion.

The following adverse reactions have been identified during the postapproval use of SANDOSTATIN LAR DEPOT. 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.

Blood and lymphatic: pancytopenia, thrombocytopenia

Cardiac: myocardial infarction, cardiac arrest, atrial fibrillation

Ear and labyrinth: deafness

Endocrine: diabetes insipidus, adrenal insufficiency in patients 18 months of age and under, pituitary apoplexy

Eye: glaucoma, visual field defect, scotoma, retinal vein thrombosis

Gastrointestinal: intestinal obstruction, peptic/gastric ulcer, abdomen enlarged, pancreatic exocrine insufficiency

General and administration site: generalized edema, facial edema

Hepatobiliary: gallbladder polyp, fatty liver, hepatitis

Immune: anaphylactoid reactions including anaphylactic shock

Infections and infestations: appendicitis

Laboratory abnormalities: increased liver enzymes, CK increased, creatinine increased

Metabolism and nutrition: diabetes mellitus

Musculoskeletal: arthritis, joint effusion, Raynaud’s syndrome

Nervous system: convulsions, aneurysm, intracranial hemorrhage, hemiparesis, paresis, suicide attempt, paranoia, migraines, Bell’s palsy, aphasia

Renal and urinary: renal failure, renal insufficiency

Reproductive and breast: gynecomastia, galactorrhea, libido decrease, breast carcinoma

Respiratory: status asthmaticus, pulmonary hypertension, pulmonary nodule, pneumothorax aggravated

Skin and subcutaneous tissue: urticaria, cellulitis, petechiae

Vascular: orthostatic hypotension, hematuria, gastrointestinal hemorrhage, arterial thrombosis of the arm

Concomitant administration of octreotide injection with cyclosporine may decrease blood levels of cyclosporine and result in transplant rejection.

Octreotide inhibits the secretion of insulin and glucagon. Therefore, blood glucose levels should be monitored when SANDOSTATIN LAR DEPOT treatment is initiated and when the dose is altered and anti-diabetic treatment should be adjusted accordingly.

Concomitant administration of octreotide and bromocriptine increases the availability of bromocriptine.

Concomitant administration of bradycardia-inducing drugs (e.g., beta-blockers) may have an additive effect on the reduction of heart rate associated with octreotide. Dose adjustments of concomitant medication may be necessary.

Octreotide has been associated with alterations in nutrient absorption, so it may have an effect on absorption of orally administered drugs.

Limited published data indicate that somatostatin analogs may decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes, which may be due to the suppression of growth hormone. Since it cannot be excluded that octreotide may have this effect, other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (e.g., quinidine, terfenadine) should therefore be used with caution.

Octreotide competitively binds to somatostatin receptors and may interfere with the efficacy of lutetium Lu 177 dotatate. Discontinue SANDOSTATIN LAR DEPOT at least 4 weeks prior to each lutetium Lu 177 dotatate dose.

Risk Summary

The limited data with SANDOSTATIN LAR DEPOT in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, no adverse developmental effects were observed with intravenous administration of octreotide to pregnant rats and rabbits during organogenesis at doses 7- and 13-times, respectively the maximum recommended human dose (MRHD) of 1.5 mg/day based on body surface area (BSA). Transient growth retardation, with no impact on postnatal development, was observed in rat offspring from a pre- and post-natal study of octreotide at intravenous doses below the MRHD based on BSA (see Data).

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

Data

Animal Data

In embryo-fetal development studies in rats and rabbits, pregnant animals received intravenous doses of octreotide up to 1 mg/kg/day during the period of organogenesis. A slight reduction in body weight gain was noted in pregnant rats at 0.1 and 1 mg/kg/day. There were no maternal effects in rabbits or embryo-fetal effects in either species up to the maximum dose tested. At 1 mg/kg/day in rats and rabbits, the dose multiple was approximately 7- and 13-times, respectively, at the highest recommended human dose of 1.5 mg/day based on BSA.

In a pre- and post-natal development rat study at intravenous doses of 0.02-1 mg/kg/day, a transient growth retardation of the offspring was observed at all doses which was possibly a consequence of growth hormone inhibition by octreotide. The doses attributed to the delayed growth are below the human dose of 1.5 mg/day, based on BSA.

Risk Summary

There is no information available on the presence of SANDOSTATIN LAR DEPOT in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Studies show that octreotide administered subcutaneously passes into the milk of lactating rats; however, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk (see Data). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SANDOSTATIN LAR DEPOT, and any potential adverse effects on the breastfed child from SANDOSTATIN LAR DEPOT or from the underlying maternal condition.

Data

Following a subcutaneous dose (1 mg/kg) of octreotide to lactating rats, transfer of octreotide into milk was observed at a low concentration compared to plasma (milk/plasma ratio of 0.009).

Discuss the potential for unintended pregnancy with premenopausal women as the therapeutic benefits of a reduction in GH levels and normalization of insulin-like growth factor 1 (IGF-1) concentration in acromegalic females treated with octreotide may lead to improved fertility.

Safety and efficacy of SANDOSTATIN LAR DEPOT in the pediatric population have not been demonstrated.

No formal controlled clinical trials have been performed to evaluate the safety and effectiveness of SANDOSTATIN LAR DEPOT in pediatric patients under 6 years of age. In postmarketing reports, serious adverse events, including hypoxia, necrotizing enterocolitis, and death, have been reported with Sandostatin use in children, most notably in children under 2 years of age. The relationship of these events to octreotide acetate has not been established as the majority of these pediatric patients had serious underlying comorbid conditions.

The efficacy and safety of SANDOSTATIN LAR DEPOT was examined in a single randomized, double-blind, placebo-controlled, 6-month pharmacokinetics study in 60 pediatric patients age 6 to 17 years with hypothalamic obesity resulting from cranial insult. The mean octreotide concentration after 6 doses of 40 mg SANDOSTATIN LAR DEPOT administered by IM injection every four weeks was approximately 3 ng/mL. Steady-state concentrations were achieved after 3 injections of a 40-mg dose. Mean BMI increased 0.1 kg/m2 in SANDOSTATIN LAR DEPOT-treated subjects compared to 0.0 kg/m2 in saline control-treated subjects. Efficacy was not demonstrated. Diarrhea occurred in 11 of 30 (37%) patients treated with SANDOSTATIN LAR DEPOT. No unexpected adverse events were observed. However, with SANDOSTATIN LAR DEPOT 40 mg once a month, the incidence of new cholelithiasis in this pediatric population (33%) was higher than that seen in other adult indications, such as acromegaly (22%) or malignant carcinoid syndrome (24%), where SANDOSTATIN LAR DEPOT was dosed at 10 mg to 30 mg once a month.

Clinical studies of Sandostatin did not include sufficient numbers of subjects age 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

In patients with renal failure requiring dialysis, the starting dose should be 10 mg. This dose should be up titrated based on clinical response and speed of response as deemed necessary by the physician. In patients with mild, moderate, or severe renal impairment there is no need to adjust the starting dose of Sandostatin. The maintenance dose should be adjusted thereafter based on clinical response and tolerability as in nonrenal patients [see Clinical Pharmacology (12)].

In patients with established liver cirrhosis, the starting dose should be 10 mg. This dose should be up titrated based on clinical response and speed of response as deemed necessary by the physician. Once at a higher dose, patient should be maintained or dose adjusted based on response and tolerability as in any noncirrhotic patients [see Clinical Pharmacology (12)].

Doses of 2.5 mg (2500 mcg) of Sandostatin Injection subcutaneously have caused hypoglycemia, flushing, dizziness, and nausea.

{ "type": "p", "children": [], "text": "Doses of 2.5 mg (2500 mcg) of Sandostatin Injection subcutaneously have caused hypoglycemia, flushing, dizziness, and nausea." }

Contact Poison Control (1-800-222-1222) for latest recommendations.

{ "type": "p", "children": [], "text": "Contact Poison Control (1-800-222-1222) for latest recommendations." }

Octreotide is the acetate salt of a cyclic octapeptide. It is a long-acting octapeptide with pharmacologic properties mimicking those of the natural hormone somatostatin. Octreotide is known chemically as L-Cysteinamide, D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-N-[2-hydroxy-1-(hydroxy-methyl) propyl]-, cyclic (2→7)-disulfide; [R-(R*,R*)].

{ "type": "p", "children": [], "text": "Octreotide is the acetate salt of a cyclic octapeptide. It is a long-acting octapeptide with pharmacologic properties mimicking those of the natural hormone somatostatin. Octreotide is known chemically as L-Cysteinamide, D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-N-[2-hydroxy-1-(hydroxy-methyl) propyl]-, cyclic (2→7)-disulfide; [R-(R*,R*)]." }

The molecular weight of octreotide is 1019.3 g/mol (free peptide, C49H66N10O10S2) and its amino acid sequence is:

{ "type": "p", "children": [], "text": "The molecular weight of octreotide is 1019.3 g/mol (free peptide, C49H66N10O10S2) and its amino acid sequence is:" }

SANDOSTATIN LAR DEPOT is available in a single-dose vial containing the sterile drug product, which when mixed with diluent, becomes a suspension that is given as a monthly intragluteal injection. The octreotide is uniformly distributed within the microspheres which are made of a biodegradable glucose star polymer, D,L-lactic and glycolic acids copolymer. Sterile mannitol is added to the microspheres to improve suspendability.

{ "type": "p", "children": [], "text": "SANDOSTATIN LAR DEPOT is available in a single-dose vial containing the sterile drug product, which when mixed with diluent, becomes a suspension that is given as a monthly intragluteal injection. The octreotide is uniformly distributed within the microspheres which are made of a biodegradable glucose star polymer, D,L-lactic and glycolic acids copolymer. Sterile mannitol is added to the microspheres to improve suspendability." }

SANDOSTATIN LAR DEPOT is available as: sterile 6-mL single-dose vials in 3 strengths delivering 10 mg, 20 mg, or 30 mg octreotide-free peptide. Each single-dose vial of SANDOSTATIN LAR DEPOT delivers:

{ "type": "p", "children": [], "text": "SANDOSTATIN LAR DEPOT is available as: sterile 6-mL single-dose vials in 3 strengths delivering 10 mg, 20 mg, or 30 mg octreotide-free peptide. Each single-dose vial of SANDOSTATIN LAR DEPOT delivers:" }

<div class="scrollingtable"><table> <col width="253"/> <col width="84"/> <col width="84"/> <col width="84"/> <tfoot> <tr class="First Last"> <td colspan="4">*Equivalent to 10 mg, 20 mg, or 30 mg octreotide, respectively.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td valign="bottom">Name of Ingredient</td><td align="center" valign="bottom">10 mg</td><td align="center" valign="bottom">20 mg</td><td align="center" valign="bottom">30 mg</td> </tr> <tr> <td class="Toprule">octreotide acetate</td><td align="center" class="Toprule">11.2 mg<span class="Sup">*</span></td><td align="center" class="Toprule">22.4 mg<span class="Sup">*</span></td><td align="center" class="Toprule">33.6 mg<span class="Sup">*</span></td> </tr> <tr> <td>D,L-lactic and glycolic acids copolymer</td><td align="center">188.8 mg</td><td align="center">377.6 mg</td><td align="center">566.4 mg</td> </tr> <tr class="Last"> <td>mannitol</td><td align="center">41.0 mg</td><td align="center">81.9 mg</td><td align="center">122.9 mg</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col width=\"253\"/>\n<col width=\"84\"/>\n<col width=\"84\"/>\n<col width=\"84\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td colspan=\"4\">*Equivalent to 10 mg, 20 mg, or 30 mg octreotide, respectively.</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td valign=\"bottom\">Name of Ingredient</td><td align=\"center\" valign=\"bottom\">10 mg</td><td align=\"center\" valign=\"bottom\">20 mg</td><td align=\"center\" valign=\"bottom\">30 mg</td>\n</tr>\n<tr>\n<td class=\"Toprule\">octreotide acetate</td><td align=\"center\" class=\"Toprule\">11.2 mg<span class=\"Sup\">*</span></td><td align=\"center\" class=\"Toprule\">22.4 mg<span class=\"Sup\">*</span></td><td align=\"center\" class=\"Toprule\">33.6 mg<span class=\"Sup\">*</span></td>\n</tr>\n<tr>\n<td>D,L-lactic and glycolic acids copolymer</td><td align=\"center\">188.8 mg</td><td align=\"center\">377.6 mg</td><td align=\"center\">566.4 mg</td>\n</tr>\n<tr class=\"Last\">\n<td>mannitol</td><td align=\"center\">41.0 mg</td><td align=\"center\">81.9 mg</td><td align=\"center\">122.9 mg</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table> <col width="253"/> <col width="84"/> <tbody class="Headless"> <tr class="First"> <td valign="bottom">Each prefilled syringe of diluent contains:</td><td valign="bottom"></td> </tr> <tr> <td class="Toprule" valign="bottom">       carboxymethylcellulose sodium</td><td align="center" class="Toprule" valign="bottom">14 mg</td> </tr> <tr> <td valign="bottom">       mannitol</td><td align="center" valign="bottom">12 mg</td> </tr> <tr> <td valign="bottom">       poloxamer 188</td><td align="center" valign="bottom">4 mg</td> </tr> <tr class="Last"> <td valign="bottom">       water for injection</td><td align="center" valign="bottom">q.s. to 2 mL</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col width=\"253\"/>\n<col width=\"84\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td valign=\"bottom\">Each prefilled syringe of diluent contains:</td><td valign=\"bottom\"></td>\n</tr>\n<tr>\n<td class=\"Toprule\" valign=\"bottom\">\n\t\t     \n\tcarboxymethylcellulose sodium</td><td align=\"center\" class=\"Toprule\" valign=\"bottom\">14 mg</td>\n</tr>\n<tr>\n<td valign=\"bottom\">\n\t\t     \n\tmannitol</td><td align=\"center\" valign=\"bottom\">12 mg</td>\n</tr>\n<tr>\n<td valign=\"bottom\">\n\t\t     \n\tpoloxamer 188</td><td align=\"center\" valign=\"bottom\">4 mg</td>\n</tr>\n<tr class=\"Last\">\n<td valign=\"bottom\">\n\t\t     \n\twater for injection</td><td align=\"center\" valign=\"bottom\">q.s. to 2 mL</td>\n</tr>\n</tbody>\n</table></div>" }

Octreotide exerts pharmacologic actions similar to the natural hormone, somatostatin. It is an even more potent inhibitor of growth hormone, glucagon, and insulin than somatostatin. Like somatostatin, it also suppresses LH response to GnRH, decreases splanchnic blood flow, and inhibits release of serotonin, gastrin, vasoactive intestinal peptide, secretin, motilin, and pancreatic polypeptide.

By virtue of these pharmacological actions, octreotide has been used to treat the symptoms associated with metastatic carcinoid tumors (flushing and diarrhea), and VIP secreting adenomas (watery diarrhea).

Octreotide substantially reduces and in many cases can normalize growth hormone and/or IGF-1 (somatomedin C) levels in patients with acromegaly.

Single doses of Sandostatin Injection given subcutaneously have been shown to inhibit gallbladder contractility and to decrease bile secretion in normal volunteers. In controlled clinical trials, the incidence of gallstone or biliary sludge formation was markedly increased [see Warnings and Precautions (5.1)].

Octreotide may cause clinically significant suppression of TSH.

Sandostatin Injection

According to data obtained with the immediate-release formulation, Sandostatin Injection solution, after subcutaneous injection, octreotide is absorbed rapidly and completely from the injection site. Peak concentrations of 5.2 ng/mL (100-mcg dose) were reached 0.4 hours after dosing. Using a specific radioimmunoassay, intravenous and subcutaneous doses were found to be bioequivalent. Peak concentrations and area under the curve (AUC) values were dose proportional both after subcutaneous or intravenous single doses up to 400 mcg and with multiple doses of 200 mcg 3 times daily (600 mcg/day). Clearance was reduced by about 66% suggesting nonlinear kinetics of the drug at daily doses of 600 mcg/day compared to 150 mcg/day. The relative decrease in clearance with doses above 600 mcg/day is not defined.

In healthy volunteers, the distribution of octreotide from plasma was rapid (tα1/2 = 0.2 h), the volume of distribution (Vdss) was estimated to be 13.6 L and the total body clearance was 10 L/h.

In blood, the distribution of octreotide into the erythrocytes was found to be negligible and about 65% was bound in the plasma in a concentration-independent manner. Binding was mainly to lipoprotein and, to a lesser extent, to albumin.

The elimination of octreotide from plasma had an apparent half-life of 1.7 hours, compared with the 1-3 minutes with the natural hormone, somatostatin. The duration of action of subcutaneously administered Sandostatin Injection solution is variable but extends up to 12 hours depending upon the type of tumor, necessitating multiple daily dosing with this immediate-release dosage form. About 32% of the dose is excreted unchanged into the urine. In an elderly population, dose adjustments may be necessary due to a significant increase in the half-life (46%) and a significant decrease in the clearance (26%) of the drug.

In patients with acromegaly, the pharmacokinetics differ somewhat from those in healthy volunteers. A mean peak concentration of 2.8 ng/mL (100-mcg dose) was reached in 0.7 hours after subcutaneous dosing. The Vdss was estimated to be 21.6 ± 8.5 L and the total body clearance was increased to 18 L/h. The mean percent of the drug bound was 41.2%. The disposition and elimination half-lives were similar to normals.

The half-life in renal-impaired patients was slightly longer than normal subjects (2.4-3.1 h versus 1.9 h). The clearance in renal-impaired patients was 7.3-8.8 L/h as compared to 8.3 L/h in healthy subjects. In patients with severe renal failure requiring dialysis, clearance was reduced to about half that found in healthy subjects (from approximately 10 L/h to 4.5 L/h).

Patients with liver cirrhosis showed prolonged elimination of drug, with octreotide half-life increasing to 3.7 h and total body clearance decreasing to 5.9 L/h, whereas patients with fatty liver disease showed half-life increasing to 3.4 h and total body clearance of 8.4 L/h. In normal subjects, octreotide half-life is 1.9 h and the clearance is 8.3 L/h which is comparable with the clearance in fatty-liver patients.

SANDOSTATIN LAR DEPOT

The magnitude and duration of octreotide serum concentrations after an intramuscular injection of the long-acting depot formulation SANDOSTATIN LAR DEPOT reflect the release of drug from the microsphere polymer matrix. Drug release is governed by the slow biodegradation of the microspheres in the muscle, but once present in the systemic circulation, octreotide distributes and is eliminated according to its known pharmacokinetic properties which are as follows.

After a single IM injection of the long-acting depot dosage form SANDOSTATIN LAR DEPOT in healthy volunteer subjects, the serum octreotide concentration reached a transient initial peak of about 0.03 ng/mL/mg within 1 hour after administration progressively declining over the following 3 to 5 days to a nadir of < 0.01 ng/mL/mg, then slowly increasing and reaching a plateau about 2 to 3 weeks postinjection. Plateau concentrations were maintained over a period of nearly 2 to 3 weeks, showing dose proportional peak concentrations of about 0.07 ng/mL/mg. After about 6 weeks postinjection, octreotide concentration slowly decreased, to < 0.01 ng/mL/mg by Weeks 12 to 13, concomitant with the terminal degradation phase of the polymer matrix of the dosage form. The relative bioavailability of the long-acting release SANDOSTATIN LAR DEPOT compared to immediate-release Sandostatin Injection solution given subcutaneously was 60% to 63%.

In patients with acromegaly, the octreotide concentrations after single doses of 10 mg, 20 mg, and 30 mg SANDOSTATIN LAR DEPOT were dose proportional. The transient Day 1 peak, amounting to 0.3 ng/mL, 0.8 ng/mL, and 1.3 ng/mL, respectively, was followed by plateau concentrations of 0.5 ng/mL, 1.3 ng/mL, and 2.0 ng/mL, respectively, achieved about 3 weeks postinjection. These plateau concentrations were maintained for nearly 2 weeks.

Following multiple doses of SANDOSTATIN LAR DEPOT given every 4 weeks, steady-state octreotide serum concentrations were achieved after the third injection. Concentrations were dose proportional and higher by a factor of approximately 1.6 to 2.0 compared to the concentrations after a single dose. The steady-state octreotide concentrations were 1.2 ng/mL and 2.1 ng/mL, respectively, at trough and 1.6 ng/mL and 2.6 ng/mL, respectively, at peak with 20 mg and 30 mg SANDOSTATIN LAR DEPOT given every 4 weeks. No accumulation of octreotide beyond that expected from the overlapping release profiles occurred over a duration of up to 28 monthly injections of SANDOSTATIN LAR DEPOT. With the long-acting depot formulation SANDOSTATIN LAR DEPOT administered IM every 4 weeks the peak-to-trough variation in octreotide concentrations ranged from 44% to 68%, compared to the 163% to 209% variation encountered with the daily subcutaneous three times daily regimen of Sandostatin Injection solution.

In patients with carcinoid tumors, the mean octreotide concentrations after 6 doses of 10 mg, 20 mg, and 30 mg SANDOSTATIN LAR DEPOT administered by IM injection every 4 weeks were 1.2 ng/mL, 2.5 ng/mL, and 4.2 ng/mL, respectively. Concentrations were dose proportional and steady-state concentrations were reached after 2 injections of 20 mg and 30 mg and after 3 injections of 10 mg.

SANDOSTATIN LAR DEPOT has not been studied in patients with renal impairment.

SANDOSTATIN LAR DEPOT has not been studied in patients with hepatic impairment.

Studies in laboratory animals have demonstrated no mutagenic potential of Sandostatin. No mutagenic potential of the polymeric carrier in SANDOSTATIN LAR DEPOT, D,L-lactic and glycolic acids copolymer, was observed in the Ames mutagenicity test.

No carcinogenic potential was demonstrated in mice treated subcutaneously with octreotide for 85-99 weeks at doses up to 2 mg/kg/day (8-times the human exposure based on BSA). In a 116-week subcutaneous study in rats administered octreotide, a 27% and 12% incidence of injection-site sarcomas or squamous cell carcinomas was observed in males and females, respectively, at the highest dose level of 1.25 mg/kg/day (10-times the human exposure based on BSA) compared to an incidence of 8% to 10% in the vehicle-control groups. The increased incidence of injection-site tumors was most probably caused by irritation and the high sensitivity of the rat to repeated subcutaneous injections at the same site. Rotating injection sites would prevent chronic irritation in humans. There have been no reports of injection-site tumors in patients treated with Sandostatin Injection for at least 5 years. There was also a 15% incidence of uterine adenocarcinomas in the 1.25 mg/kg/day females compared to 7% in the saline-control females and 0% in the vehicle-control females. The presence of endometritis coupled with the absence of corpora lutea, the reduction in mammary fibroadenomas, and the presence of uterine dilatation suggest that the uterine tumors were associated with estrogen dominance in the aged female rats which does not occur in humans.

Octreotide did not impair fertility in rats at doses up to 1 mg/kg/day, which represents 7-times the human exposure based on BSA.

The clinical trials of SANDOSTATIN LAR DEPOT were performed in patients who had been receiving Sandostatin Injection for a period of weeks to as long as 10 years. The acromegaly studies with SANDOSTATIN LAR DEPOT described below were performed in patients who achieved GH levels of < 10 ng/mL (and, in most cases < 5 ng/mL) while on subcutaneous Sandostatin Injection. However, some patients enrolled were partial responders to subcutaneous Sandostatin Injection, i.e., GH levels were reduced by > 50% on subcutaneous Sandostatin Injection compared to the untreated state, although not suppressed to < 5 ng/mL.

SANDOSTATIN LAR DEPOT was evaluated in three clinical trials in acromegalic patients.

In 2 of the clinical trials, a total of 101 patients were entered who had, in most cases, achieved a GH level < 5 ng/mL on Sandostatin Injection given in doses of 100 mcg or 200 mcg three times daily. Most patients were switched to 20 mg or 30 mg doses of SANDOSTATIN LAR DEPOT given once every 4 weeks for up to 27 to 28 injections. A few patients received doses of 10 mg and a few required doses of 40 mg. Growth hormone and IGF-1 levels were at least as well controlled with SANDOSTATIN LAR DEPOT as they had been on Sandostatin Injection and this level of control remained for the entire duration of the trials.

A third trial was a 12-month study that enrolled 151 patients who had a GH level < 10 ng/mL after treatment with Sandostatin Injection (most had levels < 5 ng/mL). The starting dose of SANDOSTATIN LAR DEPOT was 20 mg every 4 weeks for 3 doses. Thereafter, patients received 10 mg, 20 mg, or 30 mg every 4 weeks, depending upon the degree of GH suppression [see Dosage and Administration (2)]. Growth hormone and IGF-1 were at least as well controlled on SANDOSTATIN LAR DEPOT as they had been on Sandostatin Injection.

Table 5 summarizes the data on hormonal control (GH and IGF-1) for those patients in the first two clinical trials who received all 27 to 28 injections of SANDOSTATIN LAR DEPOT.

<div class="scrollingtable"><table> <caption> <span>Table 5. Hormonal Response in Acromegalic Patients Receiving 27 to 28 Injections During<span class="Sup">1</span> Treatment With SANDOSTATIN LAR DEPOT</span> </caption> <col width="279"/> <col width="148"/> <col width="90"/> <col width="135"/> <col width="83"/> <tfoot> <tr class="First Last"> <td colspan="5"><span class="Sup">1</span>Average of monthly levels of GH and IGF-1 over the course of the trials.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td><span class="Bold">Mean Hormone Level</span></td><td align="center" colspan="2"><span class="Bold">Sandostatin Injection S.C.</span></td><td align="center" colspan="2"><span class="Bold">SANDOSTATIN LAR DEPOT</span></td> </tr> <tr> <td></td><td align="center"><span class="Bold">n</span></td><td align="center"><span class="Bold">%</span></td><td align="center"><span class="Bold">n</span></td><td align="center"><span class="Bold">%</span></td> </tr> <tr> <td class="Toprule">GH &lt; 5.0 ng/mL</td><td align="center" class="Toprule">69/88</td><td align="center" class="Toprule">78</td><td align="center" class="Toprule">73/88</td><td align="center" class="Toprule">83</td> </tr> <tr> <td>&lt; 2.5 ng/mL</td><td align="center">44/88</td><td align="center">50</td><td align="center">41/88</td><td align="center">47</td> </tr> <tr> <td>&lt; 1.0 ng/mL</td><td align="center">6/88</td><td align="center">7</td><td align="center">10/88</td><td align="center">11</td> </tr> <tr> <td>IGF-1 normalized</td><td align="center">36/88</td><td align="center">41</td><td align="center">45/88</td><td align="center">51</td> </tr> <tr> <td>GH &lt; 5.0 ng/mL + IGF-1 normalized</td><td align="center">36/88</td><td align="center">41</td><td align="center">45/88</td><td align="center">51</td> </tr> <tr> <td>&lt; 2.5 ng/mL + IGF-1 normalized</td><td align="center">30/88</td><td align="center">34</td><td align="center">37/88</td><td align="center">42</td> </tr> <tr class="Last"> <td>&lt; 1.0 ng/mL + IGF-1 normalized</td><td align="center">5/88</td><td align="center">6</td><td align="center">10/88</td><td align="center">11</td> </tr> </tbody> </table></div>

For the 88 patients in Table 5, a mean GH level of < 2.5 ng/mL was observed in 47% receiving SANDOSTATIN LAR DEPOT. Over the course of the trials, 42% of patients maintained mean growth hormone levels of < 2.5 ng/mL and mean normal IGF-1 levels.

Table 6 summarizes the data on hormonal control (GH and IGF-1) for those patients in the third clinical trial who received all 12 injections of SANDOSTATIN LAR DEPOT.

<div class="scrollingtable"><table> <caption> <span>Table 6. Hormonal Response in Acromegalic Patients Receiving 12 Injections During<span class="Sup">1</span> Treatment With SANDOSTATIN LAR DEPOT</span> </caption> <col width="301"/> <col width="152"/> <col width="71"/> <col width="143"/> <col width="67"/> <tfoot> <tr class="First Last"> <td colspan="5"><span class="Sup">1</span>Average of monthly levels of GH and IGF-1 over the course of the trial.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td><span class="Bold">Mean Hormone Level</span></td><td align="center" colspan="2"><span class="Bold">Sandostatin Injection S.C.</span></td><td align="center" colspan="2"><span class="Bold">SANDOSTATIN LAR DEPOT</span></td> </tr> <tr> <td></td><td align="center"><span class="Bold">n</span></td><td align="center"><span class="Bold">%</span></td><td align="center"><span class="Bold">n</span></td><td align="center"><span class="Bold">%</span></td> </tr> <tr> <td class="Toprule">GH &lt; 5.0 ng/mL</td><td align="center" class="Toprule">116/122</td><td align="center" class="Toprule">95</td><td align="center" class="Toprule">118/122</td><td align="center" class="Toprule">97</td> </tr> <tr> <td>&lt; 2.5 ng/mL</td><td align="center">84/122</td><td align="center">69</td><td align="center">80/122</td><td align="center">66</td> </tr> <tr> <td>&lt; 1.0 ng/mL</td><td align="center">25/122</td><td align="center">21</td><td align="center">28/122</td><td align="center">23</td> </tr> <tr> <td>IGF-1 normalized</td><td align="center">82/122</td><td align="center">67</td><td align="center">82/122</td><td align="center">67</td> </tr> <tr> <td>GH &lt; 5.0 ng/mL + IGF-1 normalized</td><td align="center">80/122</td><td align="center">66</td><td align="center">82/122</td><td align="center">67</td> </tr> <tr> <td>&lt; 2.5 ng/mL + IGF-1 normalized</td><td align="center">65/122</td><td align="center">53</td><td align="center">70/122</td><td align="center">57</td> </tr> <tr class="Last"> <td>&lt; 1.0 ng/mL + IGF-1 normalized</td><td align="center">23/122</td><td align="center">19</td><td align="center">27/122</td><td align="center">22</td> </tr> </tbody> </table></div>

For the 122 patients in Table 6, who received all 12 injections in the third trial, a mean GH level of < 2.5 ng/mL was observed in 66% receiving SANDOSTATIN LAR DEPOT. Over the course of the trial, 57% of patients maintained mean growth hormone levels of < 2.5 ng/mL and mean normal IGF-1 levels. In comparing the hormonal response in these trials, note that a higher percentage of patients in the third trial suppressed their mean GH to < 5 ng/mL on subcutaneous Sandostatin Injection, 95%, compared to 78% across the 2 previous trials.

In all 3 trials, GH, IGF-1, and clinical symptoms were similarly controlled on SANDOSTATIN LAR DEPOT as they had been on Sandostatin Injection.

Of the 25 patients who completed the trials and were partial responders to Sandostatin Injection (GH > 5.0 ng/mL but reduced by > 50% relative to untreated levels), 1 patient (4%) responded to SANDOSTATIN LAR DEPOT with a reduction of GH to < 2.5 ng/mL and 8 patients (32%) responded with a reduction of GH to < 5.0 ng/mL.

Two open-label clinical studies investigated a 48-week treatment with SANDOSTATIN LAR DEPOT in 143 untreated (de novo) acromegalic patients. The median reduction in tumor volume was 20.6% in Study 1 (49 patients) at 24 weeks and 24.5% in Study 2 (94 patients) at 24 weeks and 36.2% at 48 weeks.

A 6-month clinical trial of malignant carcinoid syndrome was performed in 93 patients who had previously been shown to be responsive to Sandostatin Injection. Sixty-seven (67) patients were randomized at baseline to receive double-blind doses of 10 mg, 20 mg, or 30 mg SANDOSTATIN LAR DEPOT every 28 days and 26 patients continued, unblinded, on their previous Sandostatin Injection regimen (100 to 300 mcg three times daily).

In any given month after steady-state levels of octreotide were reached, approximately 35% to 40% of the patients who received SANDOSTATIN LAR DEPOT required supplemental subcutaneous Sandostatin Injection therapy usually for a few days, to control exacerbation of carcinoid symptoms. In any given month, the percentage of patients randomized to subcutaneous Sandostatin Injection, who required supplemental treatment with an increased dose of Sandostatin Injection, was similar to the percentage of patients randomized to SANDOSTATIN LAR DEPOT. Over the 6-month treatment period, approximately 50% to 70% of patients who completed the trial on SANDOSTATIN LAR DEPOT required subcutaneous Sandostatin Injection supplemental therapy to control exacerbation of carcinoid symptoms although steady-state serum SANDOSTATIN LAR DEPOT levels had been reached.

Table 7 presents the average number of daily stools and flushing episodes in malignant carcinoid patients.

<div class="scrollingtable"><table> <caption> <span>Table 7. Average Number of Daily Stools and Flushing Episodes in Patients With Malignant Carcinoid Syndrome</span> </caption> <col width="250"/> <col width="44"/> <col width="104"/> <col width="102"/> <col width="129"/> <col width="104"/> <tbody class="Headless"> <tr class="First"> <td><span class="Bold">Treatment</span></td><td></td><td colspan="2"><span class="Bold">Daily Stools</span> <br/> <span class="Bold">(Average Number)</span></td><td colspan="2"><span class="Bold">Daily Flushing Episodes</span> <br/> <span class="Bold">(Average Number)</span></td> </tr> <tr> <td></td><td><span class="Bold">n</span></td><td><span class="Bold">Baseline</span></td><td><span class="Bold">Last Visit</span></td><td><span class="Bold">Baseline</span></td><td><span class="Bold">Last Visit</span></td> </tr> <tr> <td class="Toprule">Sandostatin Injection S.C.</td><td class="Toprule">26</td><td class="Toprule">3.7</td><td class="Toprule">2.6</td><td class="Toprule">3.0</td><td class="Toprule">0.5</td> </tr> <tr> <td>SANDOSTATIN LAR DEPOT</td><td></td><td></td><td></td><td></td><td></td> </tr> <tr> <td>10 mg</td><td>22</td><td>4.6</td><td>2.8</td><td>3.0</td><td>0.9</td> </tr> <tr> <td>20 mg</td><td>20</td><td>4.0</td><td>2.1</td><td>5.9</td><td>0.6</td> </tr> <tr class="Last"> <td>30 mg</td><td>24</td><td>4.9</td><td>2.8</td><td>6.1</td><td>1.0</td> </tr> </tbody> </table></div>

Overall, mean daily stool frequency was as well controlled on SANDOSTATIN LAR DEPOT as on Sandostatin Injection (approximately 2 to 2.5 stools/day).

Mean daily flushing episodes were similar at all doses of SANDOSTATIN LAR DEPOT and on Sandostatin Injection (approximately 0.5 to 1 episode/day).

In a subset of patients with variable severity of disease, median 24 hour urinary 5-HIAA (5-hydroxyindole acetic acid) levels were reduced by 38% to 50% in the groups randomized to SANDOSTATIN LAR DEPOT.

The reductions are within the range reported in the published literature for patients treated with octreotide (about 10% to 50%).

Seventy-eight (78) patients with malignant carcinoid syndrome who had participated in this 6-month trial subsequently participated in a 12-month extension study in which they received 12 injections of SANDOSTATIN LAR DEPOT at 4-week intervals. For those who remained in the extension trial, diarrhea and flushing were as well controlled as during the 6-month trial. Because malignant carcinoid disease is progressive, as expected, a number of deaths (8 patients: 10%) occurred due to disease progression or complications from the underlying disease. An additional 22% of patients prematurely discontinued SANDOSTATIN LAR DEPOT due to disease progression or worsening of carcinoid symptoms.

SANDOSTATIN LAR DEPOT is available in single-dose kits containing a 6-mL single-dose vial of 10 mg, 20 mg or 30 mg strength, a prefilled syringe containing 2 mL of diluent, one vial adapter, and one sterile 1½” 19 gauge safety injection needle. An instruction booklet for the preparation of drug suspension for injection is also included with each kit.

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Drug Product Kits

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10 mg kit       NDC 0078-0811-81

{ "type": "p", "children": [], "text": "10 mg kit\n\t\t     \n\tNDC 0078-0811-81" }

20 mg kit       NDC 0078-0818-81

{ "type": "p", "children": [], "text": "20 mg kit\n\t\t     \n\tNDC 0078-0818-81" }

30 mg kit       NDC 0078-0825-81

{ "type": "p", "children": [], "text": "30 mg kit\n\t\t     \n\tNDC 0078-0825-81" }

Demonstration kit       0078-9825-81

{ "type": "p", "children": [], "text": "Demonstration kit\n\t\t     \n\t\t\t0078-9825-81" }

For prolonged storage, SANDOSTATIN LAR DEPOT should be stored at refrigerated temperatures between 2°C to 8°C (36°F to 46°F) and protected from light until the time of use. SANDOSTATIN LAR DEPOT drug product kit should remain at room temperature for 30 to 60 minutes prior to preparation of the drug suspension. However, after preparation the drug suspension must be administered immediately.

{ "type": "p", "children": [], "text": "For prolonged storage, SANDOSTATIN LAR DEPOT should be stored at refrigerated temperatures between 2°C to 8°C (36°F to 46°F) and protected from light until the time of use. SANDOSTATIN LAR DEPOT drug product kit should remain at room temperature for 30 to 60 minutes prior to preparation of the drug suspension. However, after preparation the drug suspension must be administered immediately." }

Cholelithiasis and Complications of Cholelithiasis

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Advise patients to contact their healthcare provider if they experience signs or symptoms of gallstones (cholelithiasis) or complications of cholelithiasis (e.g., cholecystitis, cholangitis and pancreatitis) [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Advise patients to contact their healthcare provider if they experience signs or symptoms of gallstones (cholelithiasis) or complications of cholelithiasis (e.g., cholecystitis, cholangitis and pancreatitis) [see Warnings and Precautions (5.1)]." }

Carcinoid Tumors and VIPomas

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Patients with carcinoid tumors and VIPomas should be advised to adhere closely to their scheduled return visits for reinjection in order to minimize exacerbation of symptoms [see Dosage and Administration (2.2)].

{ "type": "p", "children": [], "text": "Patients with carcinoid tumors and VIPomas should be advised to adhere closely to their scheduled return visits for reinjection in order to minimize exacerbation of symptoms [see Dosage and Administration (2.2)]." }

Acromegaly

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Patients with acromegaly should also be urged to adhere to their return visit schedule to help assure steady control of GH and IGF-1 levels [see Dosage and Administration (2.1)].

{ "type": "p", "children": [], "text": "Patients with acromegaly should also be urged to adhere to their return visit schedule to help assure steady control of GH and IGF-1 levels [see Dosage and Administration (2.1)]." }

Steatorrhea and Malabsorption of Dietary Fats

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Advise patients to contact their healthcare provider if they experience new or worsening symptoms of steatorrhea, stool discoloration, loose stools, abdominal bloating, and weight loss [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "Advise patients to contact their healthcare provider if they experience new or worsening symptoms of steatorrhea, stool discoloration, loose stools, abdominal bloating, and weight loss [see Warnings and Precautions (5.5)]." }

Pregnancy

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Inform female patients that treatment with SANDOSTATIN LAR DEPOT may result in unintended pregnancy [see Use in Specific Populations (8.3)].

{ "type": "p", "children": [], "text": "Inform female patients that treatment with SANDOSTATIN LAR DEPOT may result in unintended pregnancy [see Use in Specific Populations (8.3)]." }

Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936

{ "type": "p", "children": [], "text": "Distributed by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936" }

© Novartis

{ "type": "p", "children": [], "text": "© Novartis" }

T2024-51

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NDC 0078-0811-81

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Sandostatin® LAR Depot

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(octreotide acetate) for injectable suspension,for gluteal intramuscular use

{ "type": "p", "children": [], "text": "(octreotide acetate) for injectable suspension,for gluteal intramuscular use" }

10 mg

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For Intragluteal Injection

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Rx only

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NOVARTIS

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NDC 0078-0818-81

{ "type": "p", "children": [], "text": "NDC 0078-0818-81" }

Sandostatin® LAR Depot

{ "type": "p", "children": [], "text": "Sandostatin® LAR Depot" }

(octreotide acetate) for injectable suspension,for gluteal intramuscular use

{ "type": "p", "children": [], "text": "(octreotide acetate) for injectable suspension,for gluteal intramuscular use" }

20 mg

{ "type": "p", "children": [], "text": "20 mg" }

For Intragluteal Injection

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Rx only

{ "type": "p", "children": [], "text": "Rx only" }

NOVARTIS

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

NDC 0078-0825-81

{ "type": "p", "children": [], "text": "NDC 0078-0825-81" }

Sandostatin® LAR Depot

{ "type": "p", "children": [], "text": "Sandostatin® LAR Depot" }

(octreotide acetate) for injectable suspension,for gluteal intramuscular use

{ "type": "p", "children": [], "text": "(octreotide acetate) for injectable suspension,for gluteal intramuscular use" }

30 mg

{ "type": "p", "children": [], "text": "30 mg" }

For Intragluteal Injection

{ "type": "p", "children": [], "text": "For Intragluteal Injection" }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

NOVARTIS

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Octreotide acetate injection is indicated to reduce blood levels of growth hormone (GH) and insulin growth factor-1 (IGF-1; somatomedin C) in acromegaly patients who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, and bromocriptine mesylate at maximally tolerated doses.

Octreotide acetate injection is indicated for treatment of severe diarrhea and flushing episodes associated with metastatic carcinoid tumors.

Octreotide acetate injection is indicated for the treatment of the profuse watery diarrhea associated with vasoactive intestinal peptide tumors (VIPomas)-secreting tumors.

Improvement in clinical signs and symptoms, or reduction in tumor size or rate of growth, were not shown in clinical trials performed with octreotide acetate injection; these trials were not optimally designed to detect such effects.

The recommended initial dosage of octreotide acetate is 50 mcg three times daily to be administered subcutaneously. Increase octreotide acetate dose based upon GH or IGF-1 levels. The goal is to achieve GH levels less than 5 ng/mL or IGF-1 levels within normal range. Monitor GH or IGF-1 every two weeks after initiating octreotide acetate therapy or with dosage change, and to guide titration.

The most common dosage is 100 mcg three times daily, but some patients require up to 500 mcg three times daily for maximum effectiveness. Doses greater than 300 mcg/day seldom result in additional biochemical benefit, and if an increase in dose fails to provide additional benefit, the dose should be reduced.

Octreotide acetate injection should be withdrawn yearly for approximately 4 weeks from patients who have received irradiation to assess disease activity. If GH or IGF-1 levels increase and signs and symptoms recur, octreotide acetate injection therapy may be resumed.

The recommended daily dosage of octreotide acetate injection during the first 2 weeks of therapy ranges from 100 to 600 mcg/day in two to four divided doses given subcutaneously (mean daily dosage is 300 mcg). In the clinical studies, the median daily maintenance dosage was approximately 450 mcg, but clinical and biochemical benefits were obtained in some patients with as little as 50 mcg, while others required doses up to 1500 mcg/day. However, experience with doses above 750 mcg/day is limited. Measurement of urinary 5-hydroxyindole acetic acid, plasma serotonin, plasma Substance P may be useful in monitoring the progress of therapy.

Daily dosages of 200 mcg to 300 mcg in two to four divided doses given subcutaneously are recommended during the initial 2 weeks of therapy (range, 150 mcg to 750 mcg) to control symptoms of the disease. On an individual basis, dosage may be adjusted to achieve a therapeutic response, but usually doses above 450 mcg/day are not required. Measurement of Plasma vasoactive intestinal peptide (VIP) may be useful in monitoring the progress of therapy.

Injection: 50 mcg/mL, 100 mcg/mL, or 500 mcg/mL of octreotide (as acetate) in a single-dose amber vial. (3). 200 mcg/mL, or 1000 mcg/mL of octreotide (as acetate) in a multi-dose amber vials individually boxed. (3)

{ "type": "p", "children": [], "text": "Injection: 50 mcg/mL, 100 mcg/mL, or 500 mcg/mL of octreotide (as acetate) in a single-dose amber vial. (3). 200 mcg/mL, or 1000 mcg/mL of octreotide (as acetate) in a multi-dose amber vials individually boxed. (3)" }

Sensitivity to this drug or any of its components.

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Complete Atrioventricular Block

Patients who receive octreotide acetate injection intravenously may be at increased risk for higher degree atrioventricular blocks. In postmarketing reports, complete atrioventricular block was reported in patients receiving IV octreotide acetate injection during surgical procedures. In the majority of patients, octreotide acetate injection was given at higher than recommended doses and/or as a continuous IV infusion. The safety of continuous IV infusion has not been established in patients receiving octreotide acetate injection for the approved indications. Consider cardiac monitoring in patients receiving octreotide acetate injection intravenously.

Other Cardiac Conduction Abnormalities

Other cardiac conduction abnormalities have occurred during treatment with octreotide acetate injection. In acromegalic patients, bradycardia (< 50 bpm) developed in 25%; conduction abnormalities occurred in 10% and arrhythmias occurred in 9% of patients during octreotide acetate injection therapy [see Adverse Reactions (6)]. Other electrocardiogram (ECG) changes observed included QT prolongation, axis shifts, early repolarization, low voltage, R/S transition, and early R-wave progression. These ECG changes are not uncommon in acromegalic patients. Dose adjustments in drugs such as beta-blockers that have bradycardia effects may be necessary. In one acromegalic patient with severe congestive heart failure (CHF), initiation of octreotide acetate injection therapy resulted in worsening of CHF with improvement when drug was discontinued. Confirmation of a drug effect was obtained with a positive rechallenge.

Octreotide acetate injection may inhibit gallbladder contractility and decrease bile secretion, which may lead to gallbladder abnormalities or sludge. Acute cholecystitis, ascending cholangitis, biliary obstruction, cholestatic hepatitis, or pancreatitis have been reported with octreotide acetate injection therapy. In clinical trials (primarily patients with acromegaly or psoriasis), the incidence of biliary tract abnormalities was 63% (27% gallstones, 24% sludge without stones, 12% biliary duct dilatation). The incidence of stones or sludge in patients who received octreotide acetate injection for 12 months or longer was 52%. Less than 2% of patients treated with octreotide acetate injection for 1 month or less developed gallstones. One patient developed ascending cholangitis during octreotide acetate injection therapy and died. If complications of cholelithiasis are suspected, discontinue octreotide acetate injection and treat appropriately.

Octreotide acetate injection alters the balance between the counter-regulatory hormones, insulin, glucagon and GH, which may result in hypoglycemia or hyperglycemia. The hypoglycemia or hyperglycemia which occurs during octreotide acetate injection therapy is usually mild but may result in overt diabetes mellitus or necessitate dose changes in insulin or other anti-diabetic agents. Hypoglycemia and hyperglycemia occurred on octreotide acetate injection in 3% and 16% of acromegalic patients, respectively [see Adverse Reactions (6)]. Severe hyperglycemia, subsequent pneumonia, and death following initiation of octreotide acetate injection therapy was reported in one patient with no history of hyperglycemia.

Monitor glucose levels during octreotide acetate injection therapy. Adjust dosing of insulin or other anti-diabetic therapy accordingly.

Octreotide suppresses secretion of thyroid stimulating hormone (TSH), which may result in hypothyroidism. Baseline and periodic assessment of thyroid function (TSH, total, and/or free T4) is recommended during chronic therapy [see Adverse Reactions (6)].

Octreotide acetate injection may alter absorption of dietary fats.

Depressed vitamin B12 levels and abnormal Schilling’s tests have been observed in some patients receiving octreotide acetate injection therapy, and monitoring of vitamin B12 levels is recommended during octreotide acetate injection therapy.

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.

Gallbladder Abnormalities

Gallbladder abnormalities, especially stones and/or biliary sludge, frequently develop in patients on chronic octreotide acetate injection therapy [see Warnings and Precautions (5.1)]. In clinical trials (primarily patients with acromegaly or psoriasis), the incidence of biliary tract abnormalities was 63% (27% gallstones, 24% sludge without stones, 12% biliary duct dilatation). The incidence of stones or sludge in patients who received octreotide acetate injection for 12 months or longer was 52%. Less than 2% of patients treated with octreotide acetate injection for 1 month or less developed gallstones.

Cardiac

In acromegalics, sinus bradycardia (< 50 bpm) developed in 25%; conduction abnormalities occurred in 10% and arrhythmias developed in 9% of patients during octreotide acetate injection therapy [see Warnings and Precautions (5.1)].

Gastrointestinal

Diarrhea, loose stools, nausea, and abdominal discomfort were each seen in 34% to 61% of acromegalic patients in U.S. studies. 2.6% of the patients discontinued therapy due to these symptoms. These symptoms were seen in 5% to 10% of patients with carcinoid tumors and VIPomas.

The frequency of these symptoms was not dose related, but diarrhea and abdominal discomfort generally resolved more quickly in patients treated with 300 mcg/day than in those treated with 750 mcg/day. Vomiting, flatulence, abnormal stools, abdominal distention, and constipation were each seen in less than 10% of patients.

In rare instances, gastrointestinal side effects may resemble acute intestinal obstruction, with progressive abdominal distension, severe epigastric pain, abdominal tenderness, and guarding.

Hypo/Hyperglycemia

Hypoglycemia and hyperglycemia occurred in 3% and 16% of acromegalic patients, respectively, but only in about 1.5% of other patients. Symptoms of hypoglycemia were noted in approximately 2% of patients.

Hypothyroidism

In acromegalics, biochemical hypothyroidism alone occurred in 12% while goiter occurred in 8% and 4% required initiation of thyroid replacement therapy during octreotide acetate injection therapy [see Warnings and Precautions (5.4)]. In patients without acromegaly, hypothyroidism has only been reported in several isolated patients and goiter has not been reported.

Other Adverse Events

Pain on injection was reported in 7.7%, headache in 6%, and dizziness in 5%. Pancreatitis was also observed [see Warnings and Precautions (5.2)].

Other Adverse Events 1% to 4%

Other events, each observed in 1% to 4% of patients, included fatigue, weakness, pruritus, joint pain, backache, urinary tract infection, cold symptoms, flu symptoms, injection site hematoma, bruise, edema, flushing, blurred vision, pollakiuria, fat malabsorption, hair loss, visual disturbance, and depression.

Anaphylactoid reactions, including anaphylactic shock, have been reported in several patients receiving octreotide acetate injection.

The following adverse reactions have been identified during postapproval use of octreotide acetate injection. 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.

Hepatobiliary: cholelithiasis, cholecystitis, cholangitis and pancreatitis, which have sometimes required Cholecystectomy

Gastrointestinal: intestinal obstruction

Hematologic: thrombocytopenia

Octreotide has been associated with alterations in nutrient absorption, so it may have an effect on absorption of orally administered drugs. Concomitant administration of octreotide acetate injection with cyclosporine may decrease blood levels of cyclosporine and result in transplant rejection.

Octreotide inhibits the secretion of insulin and glucagon. Therefore, blood glucose levels should be monitored when octreotide acetate injection treatment is initiated or when the dose is altered and anti-diabetic treatment should be adjusted accordingly.

Concomitant administration of octreotide and bromocriptine increases the availability of bromocriptine.

Concomitant administration of bradycardia-inducing drugs (e.g., beta-blockers) may have an additive effect on the reduction of heart rate associated with octreotide. Dose adjustments of concomitant medication may be necessary.

Octreotide has been associated with alterations in nutrient absorption, so it may have an effect on absorption of orally administered drugs.

Limited published data indicate that somatostatin analogs might decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes, which may be due to the suppression of GH. Since it cannot be excluded that octreotide may have this effect, other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (e.g., quinidine, terfenadine) should therefore be used with caution.

Octreotide competitively binds to somatostatin receptors and may interfere with the efficacy of lutetium Lu 177 dotatate. Discontinue octreotide acetate injection at least 24 hours prior to each lutetium Lu 177 dotatate dose.

Risk Summary

The limited data with octreotide acetate injection in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, no adverse developmental-effects were observed with IV administration of octreotide to pregnant rats and rabbits during organogenesis at doses 7- and 13-times, respectively the maximum recommended human dose (MRHD) of 1.5 mg/day based on body surface area (BSA). Transient growth retardation, with no impact on postnatal development, was observed in rat offspring from a pre- and post-natal study of octreotide at IV doses below the MRHD based on BSA (see Data).

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

Data

Human Data

In postmarketing data, a limited number of exposed pregnancies have been reported in patients with acromegaly. Most women were exposed to octreotide during the first trimester of pregnancy at doses ranging from 100 to 300 mcg/day of octreotide acetate injection or 20 mg to 30 mg once a month of octreotide acetate for injectable suspension, however some women elected to continue octreotide therapy throughout pregnancy. In cases with a known outcome, no congenital malformations were reported.

Animal Data

In embryo-fetal development studies in rats and rabbits, pregnant animals received IV doses of octreotide up to 1 mg/kg/day during the period of organogenesis. A slight reduction in body weight gain was noted in pregnant rats at 0.1 and 1 mg/kg/day. There were no maternal effects in rabbits or embryo-fetal effects in either species up to the maximum dose tested. At 1 mg/kg/day in rats and rabbits, the dose multiple was approximately 7- and 13-times, respectively, at the highest recommended human dose of 1.5 mg/day based on BSA.

In a pre- and post-natal development rat study at IV doses of 0.02-1 mg/kg/day, a transient growth retardation of the offspring was observed at all doses which was possibly a consequence of GH inhibition by octreotide. The doses attributed to the delayed growth are below the human dose of 1.5 mg/day, based on BSA.

Risk Summary

There is no information available on the presence of octreotide acetate injection in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Studies show that octreotide administered subcutaneously passes into the milk of lactating rats; however, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk (see Data). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for octreotide acetate injection, and any potential adverse effects on the breastfed child from octreotide acetate injection or from the underlying maternal condition.

Data

Following a subcutaneous dose (1 mg/kg) of octreotide to lactating rats, transfer of octreotide into milk was observed at a low concentration compared to plasma (milk/plasma ratio of 0.009).

Discuss the potential for unintended pregnancy with premenopausal women as the therapeutic benefits of a reduction in GH levels and normalization of insulin-like growth factor 1 (IGF-1) concentration in acromegalic females treated with octreotide may lead to improved fertility.

Safety and efficacy of octreotide acetate injection in the pediatric population have not been demonstrated.

No formal controlled clinical trials have been performed to evaluate the safety and effectiveness of octreotide acetate injection in pediatric patients under age 6 years. In postmarketing reports, serious adverse events, including hypoxia, necrotizing enterocolitis, and death, have been reported with octreotide acetate injection use in children, most notably in children under 2 years of age. The relationship of these events to octreotide has not been established as the majority of these pediatric patients had serious underlying co-morbid conditions.

The efficacy and safety of octreotide acetate injection using the octreotide acetate for injectable suspension formulation was examined in a single randomized, double-blind, placebo-controlled, 6 month pharmacokinetics study in 60 pediatric patients age 6 to 17 years with hypothalamic obesity resulting from cranial insult. The mean octreotide concentration after 6 doses of 40 mg octreotide acetate for injectable suspension administered by intramuscular (IM) injection every 4 weeks was approximately 3 ng/mL. Steady-state concentrations was achieved after 3 injections of a 40-mg dose. Mean body mass index (BMI) increased 0.1 kg/m2 in octreotide acetate for injectable suspension-treated subjects compared to 0.0 kg/m2 in saline control-treated subjects.

Efficacy was not demonstrated. Diarrhea occurred in 11 of 30 (37%) patients treated with octreotide acetate for injectable suspension. No unexpected adverse events were observed. However, with octreotide acetate for injectable suspension at 40 mg once a month, the incidence of new cholelithiasis in this pediatric population (33%) was higher than that seen in other adult indications such as acromegaly (22%) or malignant carcinoid syndrome (24%), where octreotide acetate for injectable suspension was 10 mg to 30 mg once a month.

Clinical studies of octreotide acetate injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

In patients with severe renal failure requiring dialysis, the half-life of octreotide acetate may be increased, necessitating adjustment of the maintenance dosage. [See Clinical Pharmacology (12.3)]

In patients with liver cirrhosis, the half-life of the drug may be increased, necessitating adjustment of the maintenance dosage. [see Clinical Pharmacology (12.3)].

A limited number of accidental overdoses of octreotide acetate injection in adults have been reported. In adults, the doses ranged from 2,400 to 6,000 mcg/day administered by continuous infusion (100 to 250 mcg/hour) or subcutaneously (1,500 mcg 3 times a day). Adverse events in some patients included arrhythmia, complete atrioventricular block, hypotension, cardiac arrest, brain hypoxia, pancreatitis, hepatitis steatosis, hepatomegaly, lactic acidosis, flushing, diarrhea, lethargy, weakness, and weight loss.

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If overdose occurs, symptomatic management is indicated. Up-to-date information about the treatment of overdose can often be obtained from the National Poison Control Center at 1-800-222-1222.

{ "type": "p", "children": [], "text": "If overdose occurs, symptomatic management is indicated. Up-to-date information about the treatment of overdose can often be obtained from the National Poison Control Center at 1-800-222-1222." }

Octreotide acetate injection a cyclic octapeptide prepared as a clear sterile solution of octreotide, acetate salt, in a buffered lactic acid solution for administration by deep subcutaneous (intrafat) or intravenous (IV) injection. Octreotide acetate, known chemically as L- Cysteinamide, D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-N-[2-hydroxy-1-(hydroxymethyl) propyl]-,cyclic (2 → 7)-disulfide; [R-(R*, R*)] acetate salt, is a long-acting octapeptide with pharmacologic actions mimicking those of the natural hormone somatostatin.

{ "type": "p", "children": [], "text": "Octreotide acetate injection a cyclic octapeptide prepared as a clear sterile solution of octreotide, acetate salt, in a buffered lactic acid solution for administration by deep subcutaneous (intrafat) or intravenous (IV) injection. Octreotide acetate, known chemically as L- Cysteinamide, D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-N-[2-hydroxy-1-(hydroxymethyl) propyl]-,cyclic (2 → 7)-disulfide; [R-(R*, R*)] acetate salt, is a long-acting octapeptide with pharmacologic actions mimicking those of the natural hormone somatostatin." }

Octreotide acetate injection is available as sterile 1 mL vials in 3 strengths, each mL containing 50 mcg, 100 mcg, or 500 mcg of octreotide (as acetate) as the active and the following inactive ingredients: L-lactic acid 3 mg, sodium chloride 7 mg, sodium hydroxide, and water for injection, q.s.

{ "type": "p", "children": [], "text": "Octreotide acetate injection is available as sterile 1 mL vials in 3 strengths, each mL containing 50 mcg, 100 mcg, or 500 mcg of octreotide (as acetate) as the active and the following inactive ingredients: L-lactic acid 3 mg, sodium chloride 7 mg, sodium hydroxide, and water for injection, q.s." }

Octreotide acetate injection is also available as sterile 5 mL multiple dose vials in 2 strengths, each mL containing 200 mcg or 1,000 mcg of octreotide (as acetate) as the active and the following inactive ingredients: L-lactic acid 3 mg, sodium chloride 7 mg, sodium hydroxide, and water for injection, q.s. Phenol 5 mg has been added as a preservative.

{ "type": "p", "children": [], "text": "Octreotide acetate injection is also available as sterile 5 mL multiple dose vials in 2 strengths, each mL containing 200 mcg or 1,000 mcg of octreotide (as acetate) as the active and the following inactive ingredients: L-lactic acid 3 mg, sodium chloride 7 mg, sodium hydroxide, and water for injection, q.s. Phenol 5 mg has been added as a preservative." }

L-Lactic acid and sodium hydroxide are added to provide a buffered solution, pH range 3.9 to 4.5.

{ "type": "p", "children": [], "text": "L-Lactic acid and sodium hydroxide are added to provide a buffered solution, pH range 3.9 to 4.5." }

The molecular weight of octreotide acetate is 1019.3 g/mol (free peptide, C49H66N10O10S2) and its amino acid sequence is:

{ "type": "p", "children": [], "text": "The molecular weight of octreotide acetate is 1019.3 g/mol (free peptide, C49H66N10O10S2) and its amino acid sequence is:" }

Octreotide acetate injection exerts pharmacologic actions similar to the natural hormone, somatostatin. It is an even more potent inhibitor of GH, glucagon, and insulin than somatostatin. Like somatostatin, it also suppresses luteinizing hormone (LH) response to gonadotropin releasing hormone (GnRH), decreases splanchnic blood flow, and inhibits release of serotonin, gastrin, VIP, secretin, motilin, and pancreatic polypeptide.

By virtue of these pharmacological actions, octreotide has been used to treat the symptoms associated with metastatic carcinoid tumors (flushing and diarrhea), and VIP secreting adenomas (watery diarrhea).

Octreotide substantially reduces GH and/or IGF-1 (somatomedin C) levels in patients with acromegaly.

Single doses of octreotide have been shown to inhibit gallbladder contractility and to decrease bile secretion in normal volunteers. In controlled clinical trials, the incidence of gallstone or biliary sludge formation was markedly increased [see Warnings and Precautions (5.2)].

Octreotide suppresses secretion of TSH.

Absorption

After subcutaneous injection, octreotide is absorbed rapidly and completely from the injection site. Peak concentrations of 5.2 ng/mL (100-mcg dose) were reached 0.4 hours after dosing. Using a specific radioimmunoassay, IV and subcutaneous doses were found to be bioequivalent. Peak concentrations and area under the curve (AUC) values were dose proportional after IV single doses up to 200 mcg and subcutaneous single doses up to 500 mcg and after subcutaneous multiple doses up to 500 mcg 3 times a day (1,500 mcg/day). In patients with acromegaly, a mean peak concentration of 2.8 ng/mL (100-mcg dose) was reached in 0.7 hours after subcutaneous dosing.

Distribution

In healthy volunteers, the distribution of octreotide from plasma was rapid (tα1/2; = 0.2 h), the volume of distribution (Vdss) was estimated to be 13.6 L, and the total body clearance ranged from 7 L/hr to 10 L/hr. In blood, the distribution into the erythrocytes was found to be negligible and about 65% was bound in the plasma in a concentration-independent manner. Binding was mainly to lipoprotein and, to a lesser extent, to albumin. In patients with acromegaly, the volume of distribution (Vdss) was estimated to be 21.6 ± 8.5 L, and the total body clearance was increased to 18 L/h. The mean percent of the drug bound was 41.2%.

Elimination

The elimination of octreotide from plasma had an apparent half-life of 1.7 to 1.9 hours compared with 1 to 3 minutes with the natural hormone. The duration of action of octreotide acetate injection is variable but extends up to 12 hours depending upon the type of tumor. About 32% of the dose is excreted unchanged into the urine. In an elderly population, dose adjustments may be necessary due to a significant increase in the half-life (46%) and a significant decrease in the clearance (26%) of the drug.

In patients with acromegaly, the disposition and elimination half-lives were similar to normal subjects.

Specific Populations

Renal Impairment

In patients with mild renal impairment (CLCR 40 to 60 mL/min), octreotide t1/2 was 2.4 hours and total body clearance was 8.8 L/hr, in moderate impairment (CLCR 10 to 39 mL/min) t1/2 was 3.0 hours and total body clearance 7.3 L/hr. In patients with severe renal impairment not requiring dialysis (CLCR < 10 mL/min), octreotide t1/2 was 3.1 hours and total body clearance was 7.6 L/hr. In patients with severe renal failure requiring dialysis, total body clearance was reduced to about half that found in healthy subjects (from approximately 10 L/hr to 4.5 L/hr).

Hepatic Impairment

Patients with liver cirrhosis showed prolonged elimination of drug, with octreotide t1/2 increasing to 3.7 hr and total body clearance decreasing to 5.9 L/hr, whereas patients with fatty liver disease showed t1/2 increased to 3.4 hr and total body clearance of 8.2 L/hr.

Evaluation of 20 patients treated for at least 6 months has failed to demonstrate titers of antibodies exceeding background levels. However, antibody titers to octreotide acetate injection were subsequently reported in 3 patients and resulted in prolonged duration of drug action in 2 patients.

Studies in laboratory animals have demonstrated no mutagenic potential of octreotide acetate injection.

No carcinogenic potential was demonstrated in mice treated subcutaneously for 85 to 99 weeks at doses up to 2,000 mcg/kg/day (8 x the human exposure based on BSA). In a 116-week subcutaneous study in rats, a 27% and 12% incidence of injection-site sarcomas or squamous cell carcinomas was observed in males and females, respectively, at the highest dose level of 1,250 mcg/kg/day (10 x the human exposure based on BSA) compared to an incidence of 8% to 10% in the vehicle-control groups. The increased incidence of injection-site tumors was most probably caused by irritation and the high sensitivity of the rat to repeated subcutaneous injections at the same site. Rotating injection sites would prevent chronic irritation in humans. There have been no reports of injection-site tumors in patients treated with octreotide acetate for up to 5 years. There was also a 15% incidence of uterine adenocarcinomas in the 1,250 mcg/kg/day females compared to 7% in the saline-control females and 0% in the vehicle-control females. The presence of endometritis coupled with the absence of corpora lutea, the reduction in mammary fibroadenomas, and the presence of uterine dilatation suggest that the uterine tumors were associated with estrogen dominance in the aged female rats which does not occur in humans.

Octreotide did not impair fertility in rats at doses up to 1,000 mcg/kg/day, which represents 7-times the human exposure based on BSA.

How Supplied

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Octreotide acetate injection is available as follows:

{ "type": "p", "children": [], "text": "Octreotide acetate injection is available as follows:\n\n" }

NDC 0641-6174-10, 50 mcg/mL octreotide (as acetate), 1 mL Single Dose amber vial supplied in a carton of 10

{ "type": "p", "children": [], "text": "NDC 0641-6174-10, 50 mcg/mL octreotide (as acetate), 1 mL Single Dose amber vial supplied in a carton of 10\n\n" }

NDC 0641-6175-10, 100 mcg/mL octreotide (as acetate), 1 mL Single Dose amber vial supplied in a carton of 10

{ "type": "p", "children": [], "text": "NDC 0641-6175-10, 100 mcg/mL octreotide (as acetate), 1 mL Single Dose amber vial supplied in a carton of 10\n\n" }

NDC 0641-6176-10, 500 mcg/mL octreotide (as acetate), 1 mL Single Dose amber vial supplied in a carton of 10

{ "type": "p", "children": [], "text": "NDC 0641-6176-10, 500 mcg/mL octreotide (as acetate), 1 mL Single Dose amber vial supplied in a carton of 10\n\n" }

NDC 0641-6177-01, 200 mcg/mL octreotide (as acetate), 5 mL Multiple Dose amber vials individually boxed

{ "type": "p", "children": [], "text": "NDC 0641-6177-01, 200 mcg/mL octreotide (as acetate), 5 mL Multiple Dose amber vials individually boxed\n\n" }

NDC 0641-6178-01, 1,000 mcg/mL octreotide (as acetate), 5 mL Multiple Dose amber vials individually boxed

{ "type": "p", "children": [], "text": "NDC 0641-6178-01, 1,000 mcg/mL octreotide (as acetate), 5 mL Multiple Dose amber vials individually boxed" }

Storage and Handling

{ "type": "p", "children": [], "text": "\nStorage and Handling\n" }

For prolonged storage, octreotide acetate injection vials should be stored at refrigerated temperatures 2°C to 8°C (36°F to 46°F) and store in outer carton in order to protect from light. At room temperature (20°C to 30°C or 70°F to 86°F), octreotide acetate injection is stable for 14 days if protected from light. The solution can be allowed to come to room temperature prior to administration. Do not warm artificially. After initial use, the 5 mL multiple dose vials should be discarded within 14 days. Dispose unused product or waste properly. Octreotide acetate injection is stable in sterile isotonic saline solutions or sterile solutions of dextrose 5% in water for 24 hours.

{ "type": "p", "children": [], "text": "For prolonged storage, octreotide acetate injection vials should be stored at refrigerated temperatures 2°C to 8°C (36°F to 46°F) and store in outer carton in order to protect from light. At room temperature (20°C to 30°C or 70°F to 86°F), octreotide acetate injection is stable for 14 days if protected from light. The solution can be allowed to come to room temperature prior to administration. Do not warm artificially. After initial use, the 5 mL multiple dose vials should be discarded within 14 days. Dispose unused product or waste properly. Octreotide acetate injection is stable in sterile isotonic saline solutions or sterile solutions of dextrose 5% in water for 24 hours." }

Sterile Subcutaneous Injection Technique

{ "type": "p", "children": [], "text": "\nSterile Subcutaneous Injection Technique\n" }

Careful instruction in sterile subcutaneous injection technique should be given to the patients and to other persons who may administer octreotide acetate injection.

{ "type": "p", "children": [], "text": "Careful instruction in sterile subcutaneous injection technique should be given to the patients and to other persons who may administer octreotide acetate injection." }

Cholelithiasis and Complications of Cholelithiasis

{ "type": "p", "children": [], "text": "\nCholelithiasis and Complications of Cholelithiasis\n" }

Advise patients to contact their healthcare provider if they experience signs or symptoms of gallstones (cholelithiasis) or complications of cholelithiasis (e.g., cholecystitis, cholangitis, and pancreatitis) [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Advise patients to contact their healthcare provider if they experience signs or symptoms of gallstones (cholelithiasis) or complications of cholelithiasis (e.g., cholecystitis, cholangitis, and pancreatitis) [see Warnings and Precautions (5.2)].\n" }

Pregnancy

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

Inform female patients that treatment with octreotide acetate injection may result in unintended pregnancy [see Use in Specific Populations (8.3)].

{ "type": "p", "children": [], "text": "Inform female patients that treatment with octreotide acetate injection may result in unintended pregnancy [see Use in Specific Populations (8.3)].\n" }

Manufactured by:                                                 

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

Hikma Pharmaceuticals USA Inc.

{ "type": "p", "children": [], "text": "Hikma Pharmaceuticals USA Inc." }

Berkeley Heights, NJ 07922

{ "type": "p", "children": [], "text": "Berkeley Heights, NJ 07922" }

Revised: March 2024                                                                                 462-729-06

{ "type": "p", "children": [], "text": "Revised: March 2024                                                                                 462-729-06" }

NDC 0641-6174-01     Rx only Octreotide Acetate Injection 50 mcg/mL For Subcutaneous or Intravenous Use Store at 2º to 8ºC 1 mL Single Dose Vial

{ "type": "p", "children": [], "text": "NDC 0641-6174-01     Rx only\nOctreotide\nAcetate Injection\n50 mcg/mL\nFor\nSubcutaneous or\nIntravenous Use\nStore at 2º to 8ºC\n\n1 mL Single Dose Vial" }

NDC 0641-6175-01     Rx only

{ "type": "p", "children": [], "text": "NDC 0641-6175-01     Rx only" }

Octreotide

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

Acetate Injection

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

100 mcg/mL

{ "type": "p", "children": [], "text": "\n100 mcg/mL\n" }

For

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

Subcutaneous or

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

Intravenous Use

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

Store at 2º to 8ºC

{ "type": "p", "children": [], "text": "\nStore at 2º to 8ºC\n" }

1 mL Single Dose Vial

{ "type": "p", "children": [], "text": "1 mL Single Dose Vial" }

NDC 0641-6176-01     Rx only Octreotide Acetate Injection 500 mcg/mL For Subcutaneous or  Intravenous Use Store at 2º to 8ºC 1 mL Single Dose Vial

{ "type": "p", "children": [], "text": "NDC 0641-6176-01     Rx only\nOctreotide\nAcetate Injection\n500 mcg/mL\nFor\nSubcutaneous or \nIntravenous Use\nStore at 2º to 8ºC\n\n1 mL Single Dose Vial" }

NDC 0641-6177-01     Rx only Octreotide Acetate Injection 1,000 mcg per 5 mL (200 mcg/mL) For Subcutaneous or Intravenous Use 5 mL Multiple Dose Vial

{ "type": "p", "children": [], "text": "NDC 0641-6177-01     Rx only\nOctreotide\nAcetate Injection\n1,000 mcg per 5 mL\n(200 mcg/mL)\nFor Subcutaneous or Intravenous Use\n5 mL Multiple Dose Vial" }

NDC 0641-6178-01     Rx only Octreotide Acetate Injection 5,000 mcg per 5 mL (1,000 mcg/mL) For Subcutaneous or Intravenous Use 5 mL Multiple Dose Vial

{ "type": "p", "children": [], "text": "NDC 0641-6178-01     Rx only\nOctreotide\nAcetate Injection\n5,000 mcg per 5 mL\n(1,000 mcg/mL)\nFor Subcutaneous or Intravenous Use\n5 mL Multiple Dose Vial" }

MYCAPSSA is indicated for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide.

{ "type": "p", "children": [], "text": "MYCAPSSA is indicated for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide." }

For patients with end-stage renal disease, initiate MYCAPSSA at a dosage of 20 mg orally once daily. Titrate and adjust the maintenance dosage of MYCAPSSA based on IGF-1 levels, patient's signs and symptoms and tolerability [see Dosage and Administration (‎2.2, ‎2.3), Use in Specific Populations (‎8.6)].

Patients taking proton pump inhibitors, H2-receptor antagonists, or antacids concomitantly with MYCAPSSA may require increased dosages of MYCAPSSA [see Drug Interactions (‎7.1)].

Delayed-release capsules: 20 mg. White hard gelatin capsules imprinted with "OT" on one half of the capsule and "20" on the other half. Each capsule contains 20 mg octreotide, provided as octreotide acetate.

{ "type": "p", "children": [], "text": "Delayed-release capsules: 20 mg. White hard gelatin capsules imprinted with \"OT\" on one half of the capsule and \"20\" on the other half. Each capsule contains 20 mg octreotide, provided as octreotide acetate." }

Hypersensitivity to octreotide or any of the components of MYCAPSSA. Anaphylactoid reactions, including anaphylactic shock, have been reported in patients receiving octreotide [see Adverse Reactions (‎6.3)].

{ "type": "p", "children": [], "text": "Hypersensitivity to octreotide or any of the components of MYCAPSSA. Anaphylactoid reactions, including anaphylactic shock, have been reported in patients receiving octreotide [see Adverse Reactions (‎6.3)].\n" }

MYCAPSSA may inhibit gallbladder contractility and decrease bile secretion, which may lead to gallbladder abnormalities or sludge. Gallbladder-related adverse reactions have been reported in clinical trials in patients receiving MYCAPSSA. There have been postmarketing reports of cholelithiasis (gallstones) in patients taking somatostatin analogs resulting in complications, including cholecystitis, cholangitis, pancreatitis and requiring cholecystectomy [see Adverse Reactions (‎6)]. Monitor patients periodically. If complications of cholelithiasis are suspected, discontinue MYCAPSSA and treat appropriately.

MYCAPSSA alters the balance between the counter-regulatory hormones, insulin, glucagon, and growth hormone, which may result in hypoglycemia, or hyperglycemia, or diabetes mellitus. In clinical trials with MYCAPSSA, the following adverse reactions were reported: increased blood glucose (7%), hypoglycemia (4%), and diabetes mellitus (1%) [see Adverse Reactions (‎6.1)]. Blood glucose levels should be monitored when MYCAPSSA treatment is initiated, or when the dose is altered. Adjust antidiabetic treatment accordingly.

MYCAPSSA suppresses the secretion of thyroid-stimulating hormone, which may result in hypothyroidism. In clinical trials with MYCAPSSA, the following adverse reactions were reported: hypothyroidism (1%), increased TSH (1%), or decreased free T4 (1%) [see Adverse Reactions (‎6.1)]. Assess thyroid function periodically during treatment with MYCAPSSA.

Cardiac conduction abnormalities and other ECG changes including QT prolongation, axis shifts, early repolarization, low voltage, R/S transition, and early R wave progression, have occurred during treatment with octreotide. In MYCAPSSA clinical trials the following adverse reactions were reported: bradycardia (2%), conduction abnormalities (1%), and arrhythmias/tachycardia (2%) [see Adverse Reactions (‎6)]. These ECG changes may occur in patients with acromegaly. Dosage adjustments of concomitantly used drugs that have bradycardia effects (i.e. beta-blockers) may be necessary [see Drug Interactions (‎7.2)].

New onset steatorrhea, stool discoloration and loose stools have been reported in patients receiving somatostatin analogs, including octreotide. Somatostatin analogs reversibly inhibit secretion of pancreatic enzymes and bile acids, which may result in malabsorption of dietary fats and subsequent symptoms of steatorrhea, loose stools, abdominal bloating, and weight loss. If new occurrence or worsening of these symptoms are reported in patients receiving MYCAPSSA, evaluate patients for potential pancreatic exocrine insufficiency and manage accordingly.

Decreased vitamin B12 levels and abnormal Schilling’s tests have been observed in some patients receiving octreotide. Monitor vitamin B12 levels during treatment with MYCAPSSA.

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.

MYCAPSSA has been evaluated in patients with acromegaly in a placebo-controlled study [see Clinical Studies (‎14)] and an open-label baseline-controlled study. The data reflect exposure of 183 patients to MYCAPSSA for a mean duration of 29 weeks. In the overall study population, 56% were female and the average age of patients was 54.3 years. Adverse reactions occurring ≥ 5% and greater than placebo for the placebo-controlled study are presented in Table 1 and adverse reactions occurring ≥ 5% in the open-label study are presented in Table 2.

<div class="scrollingtable"><table> <caption> <span>Table 1: Adverse Reactions Occurring ≥ 5% and Greater than Placebo in a Placebo-Controlled Study with MYCAPSSA in Acromegaly Patients</span> </caption> <col/> <col/> <col/> <thead> <tr class="First Last"> <th class="Botrule Lrule Rrule Toprule" valign="bottom"></th><th align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> MYCAPSSA %<br/> (N=28)</th><th align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> PLACEBO %<br/> (N=28)</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Includes blood glucose increased, hyperglycemia and glycosylated hemoglobin increased</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Diarrhea</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">29</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">21</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Nausea</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">21</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">11</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Blood glucose increased<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">14</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">7</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Vomiting</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">14</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Abdominal discomfort</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">14</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">11</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Dyspepsia</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">11</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">4</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Sinusitis</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">11</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Osteoarthritis</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">11</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Urinary tract infection</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">7</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">4</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Pain</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">7</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Large intestine polyp</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">7</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">0</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Cholelithiasis</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">7</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">4</td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table> <caption> <span>Table 2: Adverse Reactions Occurring ≥ 5% in an Open-Label Study with MYCAPSSA in Acromegaly Patients</span> </caption> <col/> <col/> <thead> <tr class="First Last"> <th class="Botrule Lrule Rrule Toprule" valign="bottom"></th><th align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> MYCAPSSA %<br/> (N=155)</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>Includes blood glucose increased, hyperglycemia and impaired fasting glucose</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Headache</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">33</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Nausea</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">30</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Arthralgia</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">26</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Asthenia</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">22</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Hyperhidrosis</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">21</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Diarrhea</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">18</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Peripheral swelling</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">16</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Dyspepsia</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">8</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Abdominal pain upper</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">8</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Abdominal distension</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">7</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Nasopharyngitis</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">7</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Influenza</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">7</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Blood glucose increased<a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">6</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Vomiting</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">6</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Flatulence</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">6</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Back pain</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">6</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Abdominal pain</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">5</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Dizziness</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">5</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Fatigue</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">5</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Upper respiratory tract infection</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">5</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="bottom">Hypertension</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom">5</td> </tr> </tbody> </table></div>

Other Adverse Reactions

Gallbladder Abnormalities

In the placebo-controlled study, in patients treated with MYCAPSSA, acute cholecystitis occurred in 4% of patients.

In the open-label study, cholelithiasis occurred in 4.5% of patients and bile duct obstruction, bile duct stone, acute cholecystitis and jaundice occurred in 1% of patients each.

Hypoglycemia/Hyperglycemia

In the placebo-controlled study, 18% of patients treated with MYCAPSSA and 4% of patients treated with placebo developed at least one glucose value above the upper normal limit. All patients with abnormal glucose values were asymptomatic. Asymptomatic hypoglycemia was reported in 4% of patients.

In the open-label study 16% of patients developed a glucose value above the upper limit of normal. Asymptomatic hypoglycemia was reported in 4% and symptomatic hypoglycemia was reported in 1% of patients. Diabetes was reported in 1% of patients.

Hypothyroidism

In the open-label study, hypothyroidism, increased TSH, or decreased free T4 were reported in 1% of patients.

Cardiac

In the open-label study, bradycardia was reported in 2%, conduction abnormalities in 1%, and arrhythmias/tachycardia in 2% of patients.

Gastrointestinal

Gastrointestinal symptoms were the most commonly reported adverse reactions with MYCAPSSA.

In the placebo-controlled study, gastrointestinal adverse reactions were reported in 68% of patients treated with MYCAPSSA. These adverse reactions were diarrhea, nausea, vomiting, abdominal discomfort, dyspepsia, large intestinal polyp, abdominal pain, constipation, and flatulence. The adverse reactions were mild to moderate, occurred mostly during the initial 3 months of treatment, and resolved on treatment within a median duration of 8 days.

In the open-label study, gastrointestinal adverse reactions were reported in 57% of patients. Gastrointestinal adverse reactions occurring in ≥ 1% of patients were nausea, diarrhea, dyspepsia, abdominal pain, abdominal distention, vomiting, flatulence, constipation, gastroesophageal reflux disease, abdominal discomfort, frequent bowel movement, gastritis, hemorrhoids, dry mouth, and gastrointestinal motility disorder. Large intestinal polyp was reported in 1 patient. The adverse reactions were mostly mild to moderate, occurred during the initial 2 months of treatment, and resolved on treatment within a median of 13 days. Ten patients discontinued treatment due to gastrointestinal adverse reactions.

As with all therapeutic peptides, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other octreotide acetate products may be misleading.

No antibodies to the octreotide peptide from MYCAPSSA were detected in 149 patients assessed in the open label study throughout 13 months of treatment.

The following adverse reactions have been identified during the post-approval use of octreotide acetate. 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.

<div class="scrollingtable"><table> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">Proton Pump Inhibitors, H2-receptor Antagonists, or Antacids</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Clinical Impact:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Concomitant administration of MYCAPSSA with esomeprazole resulted in a decrease in the bioavailability for MYCAPSSA [<span class="Italics">See <a href="#LINK_1de1bde2-c3c9-45a3-a44b-9a05f0d39b1c">Clinical Pharmacology (‎12.3)</a>]</span>. Drugs that alter the pH of the upper GI tract (e.g., other proton pump inhibitors (PPIs), H2-receptor antagonists, and antacids) may alter the absorption of MYCAPSSA and lead to a reduction in bioavailability.</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Intervention:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Co-administration of MYCAPSSA with PPIs, H2-blockers, or antacids may require increased doses of MYCAPSSA.</td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">Cyclosporine</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Clinical Impact:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Concomitant administration of MYCAPSSA with cyclosporine resulted in a decrease in cyclosporine bioavailability <span class="Italics">[see <a href="#LINK_1de1bde2-c3c9-45a3-a44b-9a05f0d39b1c">Clinical Pharmacology (‎12.3)</a>].</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Intervention:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Adjustment of cyclosporine dose to maintain therapeutic levels may be necessitated.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">Insulin and Antidiabetic Drugs</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Clinical Impact:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">MYCAPSSA inhibits the secretion of insulin and glucagon.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Intervention:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Monitor blood glucose levels in diabetic patients upon MYCAPSSA initiation and subsequent dose adjustment. Patients receiving insulin or antidiabetic drugs agents may require dose adjustment of these therapeutic agents.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">Digoxin</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Clinical Impact:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Concomitant administration of MYCAPSSA with digoxin resulted in a decrease in digoxin peak exposure <span class="Italics">[see <a href="#LINK_1de1bde2-c3c9-45a3-a44b-9a05f0d39b1c">Clinical Pharmacology (‎12.3)</a>].</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Intervention:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Digoxin has a narrow therapeutic ratio and careful assessment of clinical response should be performed when digoxin is concomitantly administered with MYCAPSSA.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">Lisinopril</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Clinical Impact:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Concomitant administration of MYCAPSSA increases lisinopril bioavailability <span class="Italics">[see <a href="#LINK_1de1bde2-c3c9-45a3-a44b-9a05f0d39b1c">Clinical Pharmacology (‎12.3)</a>]</span>.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Intervention:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Monitor patient's blood pressure and adjust the dosage of lisinopril if needed.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">Levonorgestrel</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Clinical Impact:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Concomitant administration of MYCAPSSA with levonorgestrel decreases levonorgestrel bioavailability <span class="Italics">[see <a href="#LINK_1de1bde2-c3c9-45a3-a44b-9a05f0d39b1c">Clinical Pharmacology (‎12.3)</a>]</span>.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Intervention:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Decreased bioavailability may potentially diminish the effectiveness of combined oral contraceptives (COCs) or increase breakthrough bleeding. Counsel women to use an alternative non-hormonal method of contraception or a back-up method when MYCAPSSA is used with COCs.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">Bromocriptine</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Clinical Impact:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Concomitant administration of MYCAPSSA with bromocriptine may increase the systemic exposure of bromocriptine <span class="Italics">[see <a href="#LINK_1de1bde2-c3c9-45a3-a44b-9a05f0d39b1c">Clinical Pharmacology (‎12.3)</a>].</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Intervention:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Dose adjustment of bromocriptine may be necessary.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">Beta Blocker and Calcium Channel Blockers</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Clinical Impact:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">MYCAPSSA may cause bradycardia in acromegaly patients.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Intervention:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Patients receiving beta blockers or calcium channel blockers may require dose adjustments of these therapeutic agents.</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"><span class="Bold">Drugs Metabolized by CYP 450 Enzymes</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Clinical Impact:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Limited published data indicate that somatostatin analogs including MYCAPSSA may decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes, which may be due to the suppression of GH. </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"><span class="Italics">Intervention:</span></td><td class="Botrule Lrule Rrule Toprule" valign="top">Concomitant use with other drugs mainly metabolized by CYP3A4 that have a narrow therapeutic index (e.g., quinidine) should be used with caution and increased monitoring may be required.</td> </tr> </tbody> </table></div>

Risk Summary

Available data from case reports with octreotide acetate use in pregnant women are insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with MYCAPSSA. No adverse developmental effects were observed with intravenous administration of octreotide to pregnant rats and rabbits during organogenesis at doses 7 and 13 times, respectively, the clinical dose based on octreotide injection body surface area. Transient growth retardation, with no impact on postnatal development, was observed in rat offspring from a pre- and post-natal study of octreotide at intravenous doses below the clinical dose based on octreotide injection body surface area (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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.

Data

Animal Data

In embryo-fetal development studies in rats and rabbits, pregnant animals received intravenous doses of octreotide up to 1 mg/kg/day during the period of organogenesis. A slight reduction in body weight gain was noted in pregnant rats at 0.1 and 1 mg/kg/day. There were no maternal effects in rabbits or embryo-fetal effects in either species up to the maximum dose tested. At 1 mg/kg/day in rats and rabbits, the dose multiple was approximately 7 and 13 times, respectively, the clinical dose based on octreotide injection body surface area.

In a pre- and post-natal development rat study at intravenous doses of 0.02-1 mg/kg/day, a transient growth retardation of the offspring was observed at all doses which was possibly a consequence of growth hormone inhibition by octreotide. The doses attributed to the delayed growth are below the clinical dose based on octreotide injection body surface area.

Risk Summary

There is no information available on the presence of octreotide in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Studies show that octreotide administered subcutaneously passes into the milk of lactating rats (see Data). When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for MYCAPSSA and any potential adverse effects on the breastfed child from MYCAPSSA or from the underlying maternal condition.

Data

Following a subcutaneous dose (1 mg/kg) of octreotide to lactating rats, transfer of octreotide into milk was observed at a low concentration compared to plasma (milk/plasma ratio of 0.009).

Discuss the potential for unintended pregnancy with premenopausal women as the therapeutic benefits of a reduction in GH levels and normalization of IGF-1 concentration in acromegalic females treated with octreotide may lead to improved fertility.

Safety and efficacy of MYCAPSSA in pediatric patients have not been established.

In post-marketing reports, serious adverse reactions, including hypoxia, necrotizing enterocolitis, and death, have been reported with octreotide injection use in pediatric patients, most notably in children under 2 years of age.

Clinical studies of octreotide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In MYCAPSSA clinical studies, 39 patients (21%) were age 65 years or over and 1 patient was age 75 years or over. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

In patients with mild, moderate, or severe renal impairment there is no dose adjustment recommended for MYCAPSSA. There is a significant increase in octreotide exposure in patients with end stage renal disease (ESRD). Start patients with ESRD on MYCAPSSA 20 mg orally daily. Adjust the maintenance dose thereafter based on IGF-1 levels, patient's signs and symptoms, and tolerability [see Dosage and Administration (‎2.3) and Clinical Pharmacology (‎12.3)].

Patients with liver cirrhosis and patients with fatty liver disease showed prolonged elimination of octreotide following subcutaneous administration of drug [see Clinical Pharmacology (‎12.3)].

A limited number of accidental overdoses of injectable octreotide acetate in adults has been reported. The doses ranged from 2.4 mg/day to 6 mg/day administered by continuous infusion or subcutaneously 1.5 mg three times a day. Adverse reactions in some patients included arrhythmia, hypotension, cardiac arrest, brain hypoxia, pancreatitis, hepatic steatosis, hepatomegaly, lactic acidosis, flushing, diarrhea, lethargy, weakness, and weight loss.

{ "type": "p", "children": [], "text": "A limited number of accidental overdoses of injectable octreotide acetate in adults has been reported. The doses ranged from 2.4 mg/day to 6 mg/day administered by continuous infusion or subcutaneously 1.5 mg three times a day. Adverse reactions in some patients included arrhythmia, hypotension, cardiac arrest, brain hypoxia, pancreatitis, hepatic steatosis, hepatomegaly, lactic acidosis, flushing, diarrhea, lethargy, weakness, and weight loss." }

If overdose occurs, contact Poison Control (1-800-222-1222) for latest recommendations.

{ "type": "p", "children": [], "text": "If overdose occurs, contact Poison Control (1-800-222-1222) for latest recommendations." }

MYCAPSSA delayed release capsules contain octreotide acetate, a somatostatin analog. Octreotide is known chemically as L-cysteinamide, D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-N-[2-hydroxy-1-(hydroxy-methyl) propyl]-, cyclic (2→7)-disulfide; [R-(R*,R*)].

{ "type": "p", "children": [], "text": "MYCAPSSA delayed release capsules contain octreotide acetate, a somatostatin analog. Octreotide is known chemically as L-cysteinamide, D-phenylalanyl-L-cysteinyl-L-phenylalanyl-D-tryptophyl-L-lysyl-L-threonyl-N-[2-hydroxy-1-(hydroxy-methyl) propyl]-, cyclic (2→7)-disulfide; [R-(R*,R*)]." }

The molecular weight of octreotide is 1019.3 (free peptide, C49H66N10O10S2) and its amino acid sequence is:

{ "type": "p", "children": [], "text": "The molecular weight of octreotide is 1019.3 (free peptide, C49H66N10O10S2) and its amino acid sequence is:" }

MYCAPSSA (octreotide) delayed-release capsules are enteric-coated capsules for oral use. Each capsule contains 20 mg of octreotide (provided as octreotide acetate). Octreotide is present as a salt with 1.4 to 2.5 molar equivalents of acetate. The capsules contain the following inactive ingredients: polyvinylpyrrolidone (PVP-12), sodium caprylate, magnesium chloride, polysorbate 80, glyceryl monocaprylate, glyceryl tricaprylate, gelatin, gelatin capsules, and Acryl-EZE® (methacrylate). The capsule is printed with "OT 20" in Opacode® black ink.

{ "type": "p", "children": [], "text": "MYCAPSSA (octreotide) delayed-release capsules are enteric-coated capsules for oral use. Each capsule contains 20 mg of octreotide (provided as octreotide acetate). Octreotide is present as a salt with 1.4 to 2.5 molar equivalents of acetate. The capsules contain the following inactive ingredients: polyvinylpyrrolidone (PVP-12), sodium caprylate, magnesium chloride, polysorbate 80, glyceryl monocaprylate, glyceryl tricaprylate, gelatin, gelatin capsules, and Acryl-EZE® (methacrylate). The capsule is printed with \"OT 20\" in Opacode® black ink." }

Octreotide exerts pharmacologic actions similar to the natural hormone somatostatin, but is a more potent inhibitor of GH, glucagon, and insulin than somatostatin. Like somatostatin, it also suppresses luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH), decreases splanchnic blood flow, and inhibits release of serotonin, gastrin, vasoactive intestinal peptide, secretin, motilin, and pancreatic polypeptide.

In a single-dose PK study conducted in healthy volunteers, inhibition of GH (as measured by Cavg) was observed in all subjects receiving MYCAPSSA, as compared to their GH levels prior to MYCAPSSA.

In a study designed to assess the duration of MYCAPSSA-induced increased intestinal permeability, an increase in paracellular permeability was observed 2 hours after MYCAPSSA administration and returned to baseline by 5.5 hours after MYCAPSSA administration. MYCAPSSA-induced permeability is completely reversible within this timeframe.

MYCAPSSA maintained GH and IGF-1 levels in patients with acromegaly.

Single doses of octreotide acetate given subcutaneously have been shown to inhibit gallbladder contractility and to decrease bile secretion in normal volunteers. In clinical trials the incidence of gallstone or biliary sludge formation was markedly increased [see Warnings and Precautions (‎5.1)].

Octreotide acetate may cause clinically significant suppression of TSH [see Warnings and Precautions (‎5.3)].

Absorption

In healthy subjects, similar systemic exposure (AUC) was observed between a single dose oral administration of MYCAPSSA (20 mg octreotide acetate), and a single dose of subcutaneous Sandostatin IR (0.1 mg octreotide acetate). Peak octreotide levels (Cmax) were 33% lower following oral administration compared to the subcutaneous route. Absorption time was longer following oral administration compared to the subcutaneous route; peak concentrations were reached at a median of 1.67–2.5 hours after 20 mg MYCAPSSA administration compared to 0.5 hours for the subcutaneous administration.

In healthy subjects, after single-dose oral administration of MYCAPSSA, the systemic exposure of octreotide (Cmax, AUC0-24, and AUC0-inf) increased dose-proportionally at doses ranging from 3–40 mg.

In patients with acromegaly, there was a dose-related increase in the mean plasma octreotide concentrations after chronic administration of MYCAPSSA 40 mg (20 mg bid), 60 mg (40 mg AM / 20 mg PM), and 80 mg (40 mg AM / 40 mg PM) bid. Mean peak concentrations (Cmax) following chronic dosing were lower in patients with acromegaly (mean [CV%] = 2.51 ng/mL [80%] and 5.30 ng/mL [76%] at 20 and 40 mg bid, respectively) compared to single-dose peak concentrations observed in healthy subjects at the same dose (mean [CV%] = 3.62 [53%] and 8.21 ng/mL [88%] at 20 and 40 mg, respectively).

Effect of Food on Oral Absorption

In healthy subjects, data from a single-dose, crossover PK study of food effect demonstrated that administration of MYCAPSSA 20 mg capsules with food led to an approximate 90% decrease in the rate (Cmax) and extent of absorption (AUC0-t).

Distribution

In healthy volunteers, the distribution half-life (tα½) of octreotide acetate from plasma after subcutaneous administration was 0.2 h, the volume of distribution (Vdss) was estimated to be 13.6 L, and the total body clearance ranged from 7–10 L/hr. In blood, the distribution into the erythrocytes was found to be negligible and about 65% was bound in the plasma in a concentration-independent manner. Binding was mainly to lipoprotein and, to a lesser extent, to albumin.

In patients with acromegaly, the Vdss following subcutaneous administration was increased compared to healthy volunteers, estimated to be 21.6 L; mean peak concentrations were lower in acromegaly patients compared to healthy volunteers (2.8 ng/mL vs 5.2 ng/mL, respectively after 0.1 ng/mL dose).

Elimination

According to data obtained with the immediate-release octreotide subcutaneous injection, approximately 32% of the dose is excreted unchanged in the urine.

In healthy subjects, there was no effect of route of administration on octreotide elimination, and comparable mean elimination half-lives (t½) of 2.3 hours and 2.7 hours were demonstrated between subcutaneous injection and oral octreotide treatments, respectively.

In patients with acromegaly, elimination after chronic dosing was slightly slower than that seen in healthy volunteers, with mean apparent half-life values at steady state ranging from 3.2–4.5 hours across doses (20 mg, 40 mg, 60 mg, and 80 mg). Elimination is complete approximately 48 hours after the last dose in patients who have achieved steady-state plasma levels. Minimal accumulation (approximately 10%) was observed in patients after repeat administration of MYCAPSSA.

Specific Populations

Geriatric Patients

In patients 65 years of age and older, after subcutaneous administration of octreotide acetate, the half-life of octreotide increased significantly (46%) and clearance of octreotide decreased significantly (26%).

Patients with Renal Impairment

Exposure in patients with severe renal impairment was not substantially different from that of the matched controls. Following oral administration of a single dose of 20 mg MYCAPSSA to patients with severe renal impairment (eGFR 15–29 mL/min/1.73m2) and patients with end-stage renal disease (ESRD) requiring dialysis, patients with ESRD on dialysis had a 46% decrease in clearance with a corresponding 87% increase in AUC and 85% increase in t½ compared to matched healthy subjects. ESRD patients had higher mean plasma concentrations than did those with severe renal impairment with higher mean values for Cmax (9.30 ng/mL compared to 6.13 ng/mL in the matched controls), AUC0–t (68.0 h∙ng/mL compared to 32.2 h∙ng/mL in the matched controls), AUCinf (69.5 h∙ng/mL compared to 32.4 h∙ng/mL in the matched controls), and t½ (7.09 hr compared to 3.84 hr in the matched controls), consistent with the known effect of renal impairment on octreotide exposure [see Use in Specific Populations (‎8.6)].

Patients with Hepatic Impairment

In patients with liver cirrhosis, after subcutaneous administration of octreotide acetate, prolonged elimination of drug was observed, with octreotide acetate t½ increasing from 1.9–3.7 hr and total body clearance decreasing from 7–10 L/hr to 5.9 L/hr, whereas patients with fatty liver disease showed t½ increased to 3.4 hr and total body clearance of 8.2 L/hr.

Drug Interactions

Limited published data indicate that somatostatin analogs including MYCAPSSA may decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes, which may be due to the suppression of GH [see Drug Interactions (‎7.2)].

Octreotide has been associated with alterations in nutrient absorption, so it may have an effect on absorption of orally administered drugs.

<div class="scrollingtable"><table> <caption> <span>Table 3 Effect of Co-administered Drugs on MYCAPSSA Systemic Exposure</span> </caption> <col/> <col/> <col/> <col/> <thead> <tr class="First"> <th align="center" class="Botrule Lrule Rrule Toprule" rowspan="3" valign="top"> Co-administered drug and dosing regimen</th><th align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"> MYCAPSSA</th> </tr> <tr> <th align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="top"> Dose (mg)</th><th align="center" class="Botrule Rrule" colspan="2" valign="top"> Mean Ratio (ratio with/without co-administered drug) No Effect=1.0</th> </tr> <tr class="Last"> <th align="center" class="Botrule Lrule Rrule Toprule" valign="top"> Change in AUC</th><th align="center" class="Botrule Lrule Rrule Toprule" valign="top"> Change in C<span class="Sub">max</span></th> </tr> </thead> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top">Esomeprazole 40 mg QD on days 2-7</td><td class="Botrule Lrule Rrule Toprule" valign="top">20 mg on Day 1 and 20 mg on Day 7</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">0.59<span class="Sup">1</span> <br/> (0.40 – 0.88)<span class="Sup">2</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">0.55<span class="Sup">1</span> <br/> (0.40 – 0.75)<span class="Sup">2</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top">Metoclopramide 20 mg</td><td class="Botrule Lrule Rrule Toprule" valign="top">40 mg</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">0.91<br/> (0.61 – 1.35)</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">0.95<br/> (0.62 – 1.44)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top">Loperamide 4 mg</td><td class="Botrule Lrule Rrule Toprule" valign="top">40 mg</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">0.97<br/> (0.65 – 1.44)<span class="Sup">2</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.91<br/> (0.59 – 1.39)<span class="Sup">2</span> </p> </td> </tr> <tr class="Last"> <td class="Toprule" colspan="4" valign="top"> <p class="First"> <span class="Sup">1</span>Clinically significant <span class="Italics">[see Dosage and Administration (</span>‎<span class="Italics"><a href="#LINK_c2cb8905-6247-4365-8dc1-d64a1b998547">2</a></span><span class="Italics">) and Drug Interactions (</span>‎<span class="Italics"><a href="#LINK_6067c4ed-c48f-4f9f-9f45-e62928309b92">7.1</a></span><span class="Italics">, </span>‎<span class="Italics"><a href="#LINK_a3b445d1-ed55-42ee-834a-b21ec4ebf79a">7.2</a></span><span class="Italics">)]<br/> </span><span class="Italics"><span class="Sup">2</span>Mean ratio with 90% CI (with/without co-administered drug, e.g., 1= no change, 0.6 = 40% decrease,1.3=1.3-fold increase in exposure)</span> </p> </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table> <caption> <span>Table 4 Effect of MYCAPSSA on Systemic Exposure of Co-administered Drugs</span> </caption> <col/> <col/> <col/> <col/> <thead> <tr class="First"> <th align="center" class="Botrule Lrule Rrule Toprule" rowspan="3" valign="top"> Co-administered drug and dosing regimen</th><th align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"> MYCAPSSA</th> </tr> <tr> <th align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="top"> Dose (mg)<span class="Sup">1</span></th><th align="center" class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"> Mean Ratio (ratio with/without co-administered drug) No Effect=1.0</th> </tr> <tr class="Last"> <th align="center" class="Botrule Lrule Rrule Toprule" valign="top"> Change in AUC</th><th align="center" class="Botrule Lrule Rrule Toprule" valign="top"> Change in C<span class="Sub">max</span></th> </tr> </thead> <tbody> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top">Cyclosporine 300 mg</td><td class="Botrule Lrule Rrule Toprule" valign="top">20 mg</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">0.38<span class="Sup">2</span> <br/> (0.31 – 0.46)<span class="Sup">3</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">0.29<span class="Sup">2</span> <br/> (0.22 – 0.37)<span class="Sup">3</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top">Digoxin 0.5 mg</td><td class="Botrule Lrule Rrule Toprule" valign="top">40 mg</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">1.0<br/> (0.94 – 1.13)<span class="Sup">3</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">0.63<span class="Sup">2</span> <br/> (0.55 – 0.72)<span class="Sup">3</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top">Lisinopril 20 mg</td><td class="Botrule Lrule Rrule Toprule" valign="top">40 mg</td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">1.40<span class="Sup">2</span> <br/> (1.21 – 1.61)<span class="Sup">3</span></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top">1.50<span class="Sup">2</span> <br/> (1.32 – 1.71)<span class="Sup">3</span></td> </tr> <tr> <td class="Lrule Rrule Toprule" valign="top">Ethinyl Estradiol 0.06 mg</td><td class="Lrule Rrule Toprule" valign="top">40 mg</td><td align="center" class="Lrule Rrule Toprule" valign="top">0.94<br/> (0.86 – 1.03)<span class="Sup">3</span></td><td align="center" class="Lrule Rrule Toprule" valign="top">0.92<br/> (0.83 – 1.01)<span class="Sup">3</span></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top">Levonorgestrel 0.3 mg</td><td class="Botrule Lrule Rrule" valign="top">40 mg</td><td align="center" class="Botrule Lrule Rrule" valign="top">0.76<span class="Sup">2</span> <br/> (0.67 – 0.86)<span class="Sup">3</span></td><td align="center" class="Botrule Lrule Rrule" valign="top">0.62<span class="Sup">2</span> <br/> (0.54 – 0.71)<span class="Sup">3</span></td> </tr> <tr class="Last"> <td class="Toprule" colspan="4" valign="top"><span class="Sup">1</span>Single dose<br/> <span class="Sup">2</span>Clinically significant <span class="Italics">[see Dosage and Administration (</span>‎<span class="Italics"><a href="#LINK_c2cb8905-6247-4365-8dc1-d64a1b998547">2</a></span><span class="Italics">) and Drug Interactions (</span>‎<span class="Italics"><a href="#LINK_6067c4ed-c48f-4f9f-9f45-e62928309b92">7.1</a></span><span class="Italics">, </span>‎<span class="Italics"><a href="#LINK_a3b445d1-ed55-42ee-834a-b21ec4ebf79a">7.2</a></span><span class="Italics">)]<br/> <span class="Sup">3</span>Mean ratio with 90% CI (with/without co-administered drug, e.g., 1= no change, 0.6 = 40% decrease, 1.5=1.5-fold increase in exposure)</span></td> </tr> </tbody> </table></div>

Studies in laboratory animals have demonstrated no mutagenic potential of octreotide acetate.

No carcinogenicity studies have been conducted with MYCAPSSA. No carcinogenic potential was demonstrated in mice treated subcutaneously with octreotide acetate for 85–99 weeks at doses up to 2000 mcg/kg/day (8 times the clinical dose based on octreotide injection body surface area). In a 116-week subcutaneous study in rats administered octreotide acetate, a 27% and 12% incidence of injection-site sarcomas or squamous cell carcinomas was observed in males and females, respectively, at the highest dose level of 1250 mcg/kg/day (10 times the clinical dose based on octreotide injection body surface area) compared to an incidence of 8% to 10% in the vehicle-control groups. The increased incidence of injection-site tumors was most probably caused by irritation and the high sensitivity of the rat to repeated subcutaneous injections at the same site. There was also a 15% incidence of uterine adenocarcinomas in the 1250 mcg/kg/day females compared to 7% in the saline-control females and 0% in the vehicle-control females. The presence of endometritis coupled with the absence of corpora lutea, the reduction in mammary fibroadenomas, and the presence of uterine dilatation suggest that the uterine tumors were associated with estrogen dominance in the aged female rats, which does not occur in humans.

No fertility studies in animals have been conducted with MYCAPSSA. Injectable octreotide acetate did not impair fertility in rats at doses up to 1000 mcg/kg/day, which represents 7 times the clinical dose based on octreotide injection body surface area.

The efficacy of MYCAPSSA was established in a 9 month, randomized, double-blind, placebo-controlled study (NCT03252353) that enrolled 56 patients with acromegaly.

{ "type": "p", "children": [], "text": "The efficacy of MYCAPSSA was established in a 9 month, randomized, double-blind, placebo-controlled study (NCT03252353) that enrolled 56 patients with acromegaly." }

In the overall study population, 54% were female and the average age of patients was 55 years. 91% of patients were Caucasian, 5% Asian, 2% Black, and 2% Other. The percentage of patients with previous pituitary surgery was 88%. The baseline IGF-1 levels (the average of 2 assessments measured within 2 weeks of randomization) was 0.80 times ULN (range: 0.5–1.1 times ULN) in the patients treated with MYCAPSSA and 0.84 times ULN (range: 0.3–1.1 times ULN) in patients treated with the placebo.

{ "type": "p", "children": [], "text": "In the overall study population, 54% were female and the average age of patients was 55 years. 91% of patients were Caucasian, 5% Asian, 2% Black, and 2% Other. The percentage of patients with previous pituitary surgery was 88%. The baseline IGF-1 levels (the average of 2 assessments measured within 2 weeks of randomization) was 0.80 times ULN (range: 0.5–1.1 times ULN) in the patients treated with MYCAPSSA and 0.84 times ULN (range: 0.3–1.1 times ULN) in patients treated with the placebo." }

In this study, patients initiated MYCAPSSA treatment twice daily 1 month after their last injection of somatostatin analogs. The starting dose was 40 mg (20 mg in the morning and 20 mg in the evening). Dose increase was allowed during dose titration to 60 mg (40 mg in the morning and 20 mg in the evening) and to a maximal dose of 80 mg daily (40 mg in the morning and 40 mg in the evening) until patients were deemed adequately controlled based on biochemical results and/or clinical judgement. Patients then maintained their target dose until end of treatment.

{ "type": "p", "children": [], "text": "In this study, patients initiated MYCAPSSA treatment twice daily 1 month after their last injection of somatostatin analogs. The starting dose was 40 mg (20 mg in the morning and 20 mg in the evening). Dose increase was allowed during dose titration to 60 mg (40 mg in the morning and 20 mg in the evening) and to a maximal dose of 80 mg daily (40 mg in the morning and 40 mg in the evening) until patients were deemed adequately controlled based on biochemical results and/or clinical judgement. Patients then maintained their target dose until end of treatment." }

The primary efficacy endpoint was somatostatin dose-adjusted proportion of patients who maintain their biochemical response, defined as an IGF-1 levels less than or equal to the ULN at the end of 9 months of treatment. 58% of patients treated with MYCAPSSA vs. 19% of patients treated with placebo maintained their biochemical response.

{ "type": "p", "children": [], "text": "The primary efficacy endpoint was somatostatin dose-adjusted proportion of patients who maintain their biochemical response, defined as an IGF-1 levels less than or equal to the ULN at the end of 9 months of treatment. 58% of patients treated with MYCAPSSA vs. 19% of patients treated with placebo maintained their biochemical response." }

25% of patients treated with MYCAPSSA required discontinuation of MYCAPSSA and treatment with other somatostatin analogs at some point during the 9-month study. Criteria for somatostatin analog rescue were IGF-1 levels ≥ 1.3 times ULN and exacerbation of acromegaly signs and symptoms on two consecutive assessments while treated for at least 2 weeks with 80 mg/day or other reasons such as adverse reactions or patient's decision.

{ "type": "p", "children": [], "text": "25% of patients treated with MYCAPSSA required discontinuation of MYCAPSSA and treatment with other somatostatin analogs at some point during the 9-month study. Criteria for somatostatin analog rescue were IGF-1 levels ≥ 1.3 times ULN and exacerbation of acromegaly signs and symptoms on two consecutive assessments while treated for at least 2 weeks with 80 mg/day or other reasons such as adverse reactions or patient's decision." }

Storage

Until first use, store unopened wallets of MYCAPSSA refrigerated at 2° to 8°C (36° to 46°F). Do not freeze.

After first use, opened wallets may be stored at 20° to 25°C (68° to 77°F) for up to 1 month.

Cholelithiasis and Complications of Cholelithiasis

Advise patients to contact their healthcare provider if they experience signs or symptoms of gallstones (cholelithiasis) or complications of cholelithiasis (e.g., cholecystitis, cholangitis and pancreatitis) [see Warnings and Precautions (‎5.1)].

Hypoglycemia and Hyperglycemia

Advise patients to contact their healthcare provider if they have problems with blood sugar levels, either hyperglycemia or hypoglycemia [see Warnings and Precautions (‎5.2)].

Thyroid Function Abnormalities

Inform patients that their thyroid function will be assessed periodically during treatment [see Warnings and Precautions (‎5.3)].

Cardiac Function Abnormalities

Inform patients to contact the health care provider in case they notice irregular heartbeat [see Warnings and Precautions (‎5.4)].

Steatorrhea and Malabsorption of Dietary Fats

Advise patients to contact their healthcare provider if they experience new or worsening symptoms of steatorrhea, stool discoloration, loose stools, abdominal bloating, weight loss [see Warnings and Precautions (5.5)].

Changes in Vitamin B12 Levels

Inform patients that Vitamin B12 levels may be monitored during the treatment [see Warnings and Precautions (‎5.5)].

Females and Males of Reproductive Potential

Inform female patients that treatment with MYCAPSSA may result in unintended pregnancy [see Use in Specific Populations (‎8.3)].

Rx ONLY

{ "type": "p", "children": [], "text": "Rx ONLY" }

Manufactured by MW Encap Ltd., Scotland, UK.

{ "type": "p", "children": [], "text": "Manufactured by MW Encap Ltd., Scotland, UK." }

Mycapssa is a registered trademark owned by the Chiesi Group. ©2024 Chiesi USA. All rights reserved.

{ "type": "p", "children": [], "text": " Mycapssa is a registered trademark owned by the Chiesi Group. ©2024 Chiesi USA. All rights reserved." }

<div class="scrollingtable"><table> <col/> <col/> <col/> <col/> <col/> <thead> <tr class="First Last"> <th align="center" class="Botrule Lrule Rrule Toprule" colspan="5" valign="top"> Patient Information<br/> MYCAPSSA® [my (as in sky)-cap-sah]<br/> (octreotide)<br/> delayed-release capsules, for oral use</th> </tr> </thead> <tfoot> <tr class="First Last"> <td colspan="4" valign="top">This Patient Information has been approved by the U.S. Food and Drug Administration.</td><td align="right" valign="top">Approved: 07/2024      </td> </tr> </tfoot> <tbody> <tr class="First"> <td class="Lrule Rrule" colspan="5" valign="top"><span class="Bold">What is MYCAPSSA?</span></td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="5" valign="top"> <ul class="Disk"> <li>MYCAPSSA is an oral prescription medicine used in the long-term maintenance treatment of acromegaly in people for whom initial treatment with octreotide or lanreotide has been effective and tolerated.</li> <li>It is not known if MYCAPSSA is safe and effective in children.</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5" valign="top"><span class="Bold">Do not take MYCAPSSA if you</span>:</td> </tr> <tr> <td class="Lrule Rrule" colspan="5" valign="top"> <ul class="Disk"> <li>are allergic to octreotide acetate or any of the ingredients in MYCAPSSA. MYCAPSSA can cause a serious allergic reaction including anaphylactic shock. Stop taking MYCAPSSA right away and get emergency help if you have any of these symptoms:</li> </ul> </td> </tr> <tr> <td class="Lrule" valign="top"></td><td valign="top"></td><td valign="top"> <ul class="Disk"> <li>swelling of your tongue, throat, lips, eyes or face</li> <li>severe itching of the skin with rash or raised bumps</li> <li>chest pain</li> </ul> </td><td valign="top"></td><td class="Rrule" valign="top"> <ul class="Disk"> <li>trouble swallowing or breathing</li> <li>feeling faint</li> <li>rapid heart beat</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="5" valign="top">See the end of this leaflet for a complete list of ingredients in MYCAPSSA.</td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5" valign="top"><span class="Bold">Before you take MYCAPSSA, tell your healthcare provider about all of your medical conditions, including if you:</span></td> </tr> <tr> <td class="Lrule Rrule" colspan="5" valign="top"> <ul class="Disk"> <li>have liver cirrhosis or liver problems</li> <li>have kidney problems</li> <li>are pregnant or plan to become pregnant. It is not known if MYCAPSSA will harm your unborn baby. MYCAPSSA may increase your chance of becoming pregnant.</li> <li>are breastfeeding or plan to breastfeed. It is not known if MYCAPSSA passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take MYCAPSSA.</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="5" valign="top"><span class="Bold">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements.</td> </tr> <tr> <td class="Lrule Rrule" colspan="5" valign="top">MYCAPSSA may affect the way other medicines work, and other medicines may affect how MYCAPSSA works.</td> </tr> <tr> <td class="Lrule Rrule" colspan="5" valign="top"><span class="Bold">Especially tell your healthcare provider</span> if you take oral contraceptives. Use an alternative non-hormonal method of contraception or a back-up method while taking MYCAPSSA.</td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="5" valign="top">Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.</td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5" valign="top"><span class="Bold">How should I take MYCAPSSA?</span></td> </tr> <tr> <td class="Lrule Rrule" colspan="5" valign="top"> <ul class="Disk"> <li> <span class="Bold">Read the detailed "Instructions for Use" at the end of this Patient Information about the right way to take MYCAPSSA.</span> </li> <li>Take MYCAPSSA exactly as your healthcare provider tells you to take it.</li> <li>Take MYCAPSSA with a glass of water on an empty stomach.</li> <li>Take MYCAPSSA at least 1 hour before a meal or at least 2 hours after a meal (for example, you could take your morning dose 1 hour before breakfast and your evening dose at bedtime).</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="5" valign="top">Swallow the capsules whole. Do not crush or chew the capsules before swallowing.</td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5" valign="top"><span class="Bold">What are the possible side effects of MYCAPSSA?</span></td> </tr> <tr> <td class="Lrule" valign="top"></td><td class="Rrule" colspan="4" valign="top"> <ul class="Disk"> <li> <span class="Bold">gallbladder problems.</span> MYCAPSSA may cause problems with the gallbladder. Tell your healthcare provider if you have sudden pain in your upper right stomach (abdomen), sudden pain in your right shoulder or between your shoulder blades, yellowing of your skin or the whites of your eyes, fever with chills, nausea</li> <li> <span class="Bold">blood sugar problems.</span> MYCAPSSA may cause you to have high blood sugar (hyperglycemia), low blood sugar (hypoglycemia), or diabetes. Tell your healthcare provider if you have problems with high or low blood sugar. Your healthcare provider will check your blood sugar when you start taking MYCAPSSA or when your dose is changed.</li> <li> <span class="Bold">thyroid problems</span>. MYCAPSSA may keep your thyroid from releasing thyroid hormones leading to hypothyroidism. Your thyroid function will be checked regularly during your treatment with MYCAPSSA.</li> <li> <span class="Bold">heart rhythm problems</span>. Tell your healthcare provider if you have an irregular heartbeat (your heart is not beating normally).</li> <li> <span class="Bold">fatty stool</span>. MYCAPSSA may cause your body to have issues with absorbing dietary fats. Tell your healthcare provider if you have any new or worsening symptoms including fatty stools, changes in the color of your stools, loose stools, stomach (abdominal) bloating or weight loss.</li> <li> <span class="Bold">low vitamin B12 levels in your blood.</span> Your healthcare provider may check your vitamin B12 levels during treatment with MYCAPSSA.</li> </ul> </td> </tr> <tr> <td class="Lrule Rrule" colspan="5" valign="top"><span class="Bold">The most common side effects of MYCAPSSA include:</span></td> </tr> <tr> <td class="Lrule" valign="top"></td><td colspan="2" valign="top"> <ul class="Disk"> <li>headache</li> <li>nausea</li> <li>diarrhea</li> </ul> </td><td class="Rrule" colspan="2" valign="top"> <ul class="Disk"> <li>joint pain</li> <li>weakness</li> <li>sweating a lot</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="5" valign="top">These are not all the possible side effects of MYCAPSSA. For more information, ask your healthcare provider or pharmacist.</td> </tr> <tr> <td colspan="5" valign="top"><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></td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5" valign="top"><span class="Bold">How should I store MYCAPSSA?</span></td> </tr> <tr> <td class="Lrule Rrule" colspan="5" valign="top"> <ul class="Disk"> <li> <span class="Bold">Before first use,</span> store unopened wallets of MYCAPSSA in a refrigerator between 36°F to 46°F (2°C to 8°C).</li> <li> <span class="Bold">Do not</span> freeze.</li> <li> <span class="Bold">After first use,</span> store opened wallets at room temperature between 68°F to 77°F (20°C to 25°C) for up to 1 month.</li> </ul> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="5" valign="top"><span class="Bold">Keep MYCAPSSA and all medicines out of the reach of children.</span></td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5" valign="top"><span class="Bold">General information about the safe and effective use of MYCAPSSA.</span></td> </tr> <tr> <td class="Lrule Rrule" colspan="5" valign="top">Medicines are sometimes prescribed for purposes other than those listed in a Patient Information. Do not use MYCAPSSA for a condition for which it was not prescribed. Do not give MYCAPSSA to other people, even if they have the same symptoms you have. It may harm them.</td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="5" valign="top">You can ask your pharmacist or healthcare provider for information about MYCAPSSA that is written for health professionals.</td> </tr> <tr> <td class="Lrule Rrule Toprule" colspan="5" valign="top"><span class="Bold">What are the ingredients in MYCAPSSA?</span></td> </tr> <tr> <td class="Lrule Rrule" colspan="5" valign="top"><span class="Bold">Active ingredient</span>: octreotide acetate</td> </tr> <tr> <td class="Lrule Rrule" colspan="5" valign="top"><span class="Bold">Inactive ingredients</span>: polyvinylpyrrolidone (PVP-12), sodium caprylate, magnesium chloride, polysorbate 80, glyceryl monocaprylate, glyceryl tricaprylate, gelatin, gelatin capsules, and Acryl-EZE<span class="Sup">®</span> (methacrylate).</td> </tr> <tr> <td class="Lrule Rrule" colspan="5" valign="top">Chiesi Farmaceutici S.p.A.,<br/> Parma, Italy</td> </tr> <tr class="Last"> <td class="Lrule Rrule" colspan="5" valign="top">For more information about MYCAPSSA call the medical information department at 1-888-661-9260 or us.medical@chiesi.com or go to <a href="http://www.mycapssa.com/">www.MYCAPSSA.com</a> and select patient information.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<col/>\n<col/>\n<col/>\n<col/>\n<col/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"5\" valign=\"top\"> Patient Information<br/>\n MYCAPSSA® [my (as in sky)-cap-sah]<br/>\n (octreotide)<br/>\n delayed-release capsules, for oral use</th>\n</tr>\n</thead>\n<tfoot>\n<tr class=\"First Last\">\n<td colspan=\"4\" valign=\"top\">This Patient Information has been approved by the U.S. Food and Drug Administration.</td><td align=\"right\" valign=\"top\">Approved: 07/2024      </td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"First\">\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\"><span class=\"Bold\">What is MYCAPSSA?</span></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"5\" valign=\"top\">\n<ul class=\"Disk\">\n<li>MYCAPSSA is an oral prescription medicine used in the long-term maintenance treatment of acromegaly in people for whom initial treatment with octreotide or lanreotide has been effective and tolerated.</li>\n<li>It is not known if MYCAPSSA is safe and effective in children.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\" valign=\"top\"><span class=\"Bold\">Do not take MYCAPSSA if you</span>:</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\">\n<ul class=\"Disk\">\n<li>are allergic to octreotide acetate or any of the ingredients in MYCAPSSA. MYCAPSSA can cause a serious allergic reaction including anaphylactic shock. Stop taking MYCAPSSA right away and get emergency help if you have any of these symptoms:</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"></td><td valign=\"top\"></td><td valign=\"top\">\n<ul class=\"Disk\">\n<li>swelling of your tongue, throat, lips, eyes or face</li>\n<li>severe itching of the skin with rash or raised bumps</li>\n<li>chest pain</li>\n</ul>\n</td><td valign=\"top\"></td><td class=\"Rrule\" valign=\"top\">\n<ul class=\"Disk\">\n<li>trouble swallowing or breathing</li>\n<li>feeling faint</li>\n<li>rapid heart beat</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"5\" valign=\"top\">See the end of this leaflet for a complete list of ingredients in MYCAPSSA.</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\" valign=\"top\"><span class=\"Bold\">Before you take MYCAPSSA, tell your healthcare provider about all of your medical conditions, including if you:</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\">\n<ul class=\"Disk\">\n<li>have liver cirrhosis or liver problems</li>\n<li>have kidney problems</li>\n<li>are pregnant or plan to become pregnant. It is not known if MYCAPSSA will harm your unborn baby. MYCAPSSA may increase your chance of becoming pregnant.</li>\n<li>are breastfeeding or plan to breastfeed. It is not known if MYCAPSSA passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take MYCAPSSA.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\"><span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span> including prescription and over-the-counter medicines, vitamins, and herbal supplements.</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\">MYCAPSSA may affect the way other medicines work, and other medicines may affect how MYCAPSSA works.</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\"><span class=\"Bold\">Especially tell your healthcare provider</span> if you take oral contraceptives. Use an alternative non-hormonal method of contraception or a back-up method while taking MYCAPSSA.</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"5\" valign=\"top\">Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\" valign=\"top\"><span class=\"Bold\">How should I take MYCAPSSA?</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\">\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">Read the detailed \"Instructions for Use\" at the end of this Patient Information about the right way to take MYCAPSSA.</span>\n</li>\n<li>Take MYCAPSSA exactly as your healthcare provider tells you to take it.</li>\n<li>Take MYCAPSSA with a glass of water on an empty stomach.</li>\n<li>Take MYCAPSSA at least 1 hour before a meal or at least 2 hours after a meal (for example, you could take your morning dose 1 hour before breakfast and your evening dose at bedtime).</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"5\" valign=\"top\">Swallow the capsules whole. Do not crush or chew the capsules before swallowing.</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\" valign=\"top\"><span class=\"Bold\">What are the possible side effects of MYCAPSSA?</span></td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"></td><td class=\"Rrule\" colspan=\"4\" valign=\"top\">\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">gallbladder problems.</span> MYCAPSSA may cause problems with the gallbladder. Tell your healthcare provider if you have sudden pain in your upper right stomach (abdomen), sudden pain in your right shoulder or between your shoulder blades, yellowing of your skin or the whites of your eyes, fever with chills, nausea</li>\n<li>\n<span class=\"Bold\">blood sugar problems.</span> MYCAPSSA may cause you to have high blood sugar (hyperglycemia), low blood sugar (hypoglycemia), or diabetes. Tell your healthcare provider if you have problems with high or low blood sugar. Your healthcare provider will check your blood sugar when you start taking MYCAPSSA or when your dose is changed.</li>\n<li>\n<span class=\"Bold\">thyroid problems</span>. MYCAPSSA may keep your thyroid from releasing thyroid hormones leading to hypothyroidism. Your thyroid function will be checked regularly during your treatment with MYCAPSSA.</li>\n<li>\n<span class=\"Bold\">heart rhythm problems</span>. Tell your healthcare provider if you have an irregular heartbeat (your heart is not beating normally).</li>\n<li>\n<span class=\"Bold\">fatty stool</span>. MYCAPSSA may cause your body to have issues with absorbing dietary fats. Tell your healthcare provider if you have any new or worsening symptoms including fatty stools, changes in the color of your stools, loose stools, stomach (abdominal) bloating or weight loss.</li>\n<li>\n<span class=\"Bold\">low vitamin B12 levels in your blood.</span> Your healthcare provider may check your vitamin B12 levels during treatment with MYCAPSSA.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\"><span class=\"Bold\">The most common side effects of MYCAPSSA include:</span></td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\"></td><td colspan=\"2\" valign=\"top\">\n<ul class=\"Disk\">\n<li>headache</li>\n<li>nausea</li>\n<li>diarrhea</li>\n</ul>\n</td><td class=\"Rrule\" colspan=\"2\" valign=\"top\">\n<ul class=\"Disk\">\n<li>joint pain</li>\n<li>weakness</li>\n<li>sweating a lot</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"5\" valign=\"top\">These are not all the possible side effects of MYCAPSSA. For more information, ask your healthcare provider or pharmacist.</td>\n</tr>\n<tr>\n<td colspan=\"5\" valign=\"top\"><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></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\" valign=\"top\"><span class=\"Bold\">How should I store MYCAPSSA?</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\">\n<ul class=\"Disk\">\n<li>\n<span class=\"Bold\">Before first use,</span> store unopened wallets of MYCAPSSA in a refrigerator between 36°F to 46°F (2°C to 8°C).</li>\n<li>\n<span class=\"Bold\">Do not</span> freeze.</li>\n<li>\n<span class=\"Bold\">After first use,</span> store opened wallets at room temperature between 68°F to 77°F (20°C to 25°C) for up to 1 month.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"5\" valign=\"top\"><span class=\"Bold\">Keep MYCAPSSA and all medicines out of the reach of children.</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\" valign=\"top\"><span class=\"Bold\">General information about the safe and effective use of MYCAPSSA.</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\">Medicines are sometimes prescribed for purposes other than those listed in a Patient Information. Do not use MYCAPSSA for a condition for which it was not prescribed. Do not give MYCAPSSA to other people, even if they have the same symptoms you have. It may harm them.</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"5\" valign=\"top\">You can ask your pharmacist or healthcare provider for information about MYCAPSSA that is written for health professionals.</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\" colspan=\"5\" valign=\"top\"><span class=\"Bold\">What are the ingredients in MYCAPSSA?</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\"><span class=\"Bold\">Active ingredient</span>: octreotide acetate</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\"><span class=\"Bold\">Inactive ingredients</span>: polyvinylpyrrolidone (PVP-12), sodium caprylate, magnesium chloride, polysorbate 80, glyceryl monocaprylate, glyceryl tricaprylate, gelatin, gelatin capsules, and Acryl-EZE<span class=\"Sup\">®</span> (methacrylate).</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\">Chiesi Farmaceutici S.p.A.,<br/>\n Parma, Italy</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Rrule\" colspan=\"5\" valign=\"top\">For more information about MYCAPSSA call the medical information department at 1-888-661-9260 or us.medical@chiesi.com or go to <a href=\"http://www.mycapssa.com/\">www.MYCAPSSA.com</a> and select patient information.</td>\n</tr>\n</tbody>\n</table></div>" }

Read this Instructions for Use before you start taking MYCAPSSA 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 medical condition or treatment. Talk to your healthcare provider or pharmacist if you have any questions about how to use MYCAPSSA.

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Important information:

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

{ "type": "ul", "children": [ "Each MYCAPSSA wallet contains twenty-eight 20-mg capsules. The number of wallets required in a 28-day period depends on your prescribed dose." ], "text": "" }

How to Use the MYCAPSSA Wallet

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{ "type": "ul", "children": [ "Each MYCAPSSA wallet has a locking mechanism that helps to keep the medicine away from children.", "Become familiar with using the MYCAPSSA wallet so you will know how to use it the right way." ], "text": "" }

To open the wallet:

{ "type": "p", "children": [], "text": "\nTo open the wallet:\n" }

Step 1. With your left thumb, gently press the tip of the release button on the left side of the wallet (see Figure A).

{ "type": "p", "children": [], "text": "\nStep 1.\tWith your left thumb, gently press the tip of the release button on the left side of the wallet (see Figure A).\n" }

Step 2. While holding the release button, grasp the medicine card at the notch on the right side and pull it out (see Figure A).

{ "type": "p", "children": [], "text": "\nStep 2.\tWhile holding the release button, grasp the medicine card at the notch on the right side and pull it out (see Figure A).\n" }

Step 3. Unfold the medicine card (see Figure A).

{ "type": "p", "children": [], "text": "\nStep 3. Unfold the medicine card (see Figure A).\n" }

Figure A: How to Open the MYCAPSSA Wallet

{ "type": "p", "children": [], "text": "\nFigure A: How to Open the MYCAPSSA Wallet\n" }

How to Remove a Capsule from the MYCAPSSA Wallet

{ "type": "p", "children": [], "text": "\nHow to Remove a Capsule from the MYCAPSSA Wallet\n" }

Capsules need to be removed carefully, because if they are cracked or broken they may not be as effective. Follow these instructions to easily remove capsules without damaging them.

{ "type": "p", "children": [], "text": "Capsules need to be removed carefully, because if they are cracked or broken they may not be as effective. Follow these instructions to easily remove capsules without damaging them." }

{ "type": "ul", "children": [ "Place the tip of a thumb at the edge of a capsule's plastic cavity (see Figure B).\n", "Gently push the capsule until it is removed. Collect the removed capsule in your hand.", "\nDo not use two thumbs to push a capsule as this could damage it.", "\nDo not press the middle of a capsule. This could also damage it.", "If a capsule is cracked or broken, throw it away (discard it) and remove another capsule." ], "text": "" }

Figure B: How to Remove a Capsule from the Medicine Card Inside the MYCAPSSA Wallet

{ "type": "p", "children": [], "text": "\nFigure B: How to Remove a Capsule from the Medicine Card Inside the MYCAPSSA Wallet\n" }

This Instructions for Use has been approved by the U.S. Food and Drug Administration. Approved: 01/2024

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Always take with a glass of water on an empty stomach at least 1 hour before a meal or at least 2 hours after a meal.

{ "type": "p", "children": [], "text": "Always take with a glass of water on an empty stomach at least\n1 hour before a meal or at least 2 hours after a meal." }

Mycapssa® (octreotide) delayed-release capsules

{ "type": "p", "children": [], "text": "Mycapssa®\n\n(octreotide) delayed-release capsules" }

20 mg*

{ "type": "p", "children": [], "text": "20 mg*" }

28 Capsules

{ "type": "p", "children": [], "text": "28 Capsules" }

*Each capsule contains octreotide 20 mg (provided as octreotide acetate). Acetate composition varies. See prescribing information.

{ "type": "p", "children": [], "text": "*Each capsule contains octreotide 20 mg (provided as octreotide acetate).\nAcetate composition varies. See prescribing information." }

NDC 10122-550-28

{ "type": "p", "children": [], "text": "NDC 10122-550-28" }

Mycapssa® (octreotide) delayed-release capsules

{ "type": "p", "children": [], "text": "Mycapssa®\n\n(octreotide) delayed-release capsules" }

20 mg*

{ "type": "p", "children": [], "text": "20 mg*" }

Rx only

{ "type": "p", "children": [], "text": "Rx only" }

*Each capsule contains octreotide 20 mg (provided as octreotide acetate). Acetate composition varies. See prescribing information. Keep out of reach of children.

{ "type": "p", "children": [], "text": "*Each capsule contains octreotide 20 mg (provided\nas octreotide acetate). Acetate composition varies.\nSee prescribing information.\nKeep out of reach of children." }

1 PRESS & HOLD HERE

{ "type": "p", "children": [], "text": "1\nPRESS\n& HOLD\nHERE" }

PULL OUT HERE

{ "type": "p", "children": [], "text": "PULL OUT HERE" }

❶ PRESS

{ "type": "p", "children": [], "text": "❶\nPRESS" }

❷ PULL

{ "type": "p", "children": [], "text": "❷\nPULL" }

OPENING AND CLOSING INSTRUCTIONS

{ "type": "p", "children": [], "text": "OPENING AND CLOSING INSTRUCTIONS" }

{ "type": "ul", "children": [ "Use left thumb to push the button gently", "While holding the button down, pull out the medication card", "Press out to take capsule(s)", "Slide medication card back to lock" ], "text": "" }

28 capsules

{ "type": "p", "children": [], "text": "28 capsules" }

Always take with a glass of water on an empty stomach at least 1 hour before a meal or at least 2 hours after a meal.

{ "type": "p", "children": [], "text": "Always take with a glass of water on an empty stomach at least\n1 hour before a meal or at least 2 hours after a meal." }