These Highlights Do Not Include All The Information Needed To Use Mycapssa®

Other Adverse Reactions

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.

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.

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:

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.

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.

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 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.

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.

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.

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)].

The following important adverse reactions are described below and elsewhere in the labeling:

• Cholelithiasis and Complications of Cholelithiasis [see Warnings and Precautions (‎5.1)]
• Hyperglycemia and Hypoglycemia [see Warnings and Precautions (‎5.2)]
• Thyroid Function Abnormalities [see Warnings and Precautions (‎5.3)]
• Cardiac Function Abnormalities [see Warnings and Precautions (‎5.4)]
• Decreased Vitamin B12 Levels and Abnormal Schilling's Tests [see Warnings and Precautions (‎5.5)]

• Proton Pump Inhibitors, H2-receptor Antagonists, or Antacids: may decrease bioavailability of MYCAPSSA and the MYCAPSSA dose may need to be increased (‎7).
• Cyclosporine: may have decreased bioavailability and require dose adjustment (7).
• Insulin and Antidiabetic Drugs: patients receiving insulin or antidiabetic drugs agents may require dose adjustment (‎7).
• Digoxin: exposure may be decreased and assessment of clinical response to digoxin should be performed (‎7).
• Lisinopril: bioavailability may be increased, monitor patient's blood pressure and adjust dose of lisinopril if needed (‎7).
• Levonorgestrel: counsel women to use an alternative non-hormonal method of contraception or a back-up method when MYCAPSSA is used with combined oral contraceptives (‎7).
• Bromocriptine: dose adjustment of bromocriptine may be necessary (‎7).
• Beta Blocker and Calcium Channel Blockers: dose adjustment of beta blockers or calcium channel blockers may be necessary (‎7).
• Drugs Metabolized by CYP 450 Enzymes: 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 (‎7).

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)].

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.

Important information:

• Each MYCAPSSA wallet contains twenty-eight 20-mg capsules. The number of wallets required in a 28-day period depends on your prescribed dose.

How to Use the MYCAPSSA Wallet

• 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.

To open the wallet:

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

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).

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

Figure A: How to Open the MYCAPSSA Wallet

How to Remove a Capsule from the MYCAPSSA Wallet

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.

• Place the tip of a thumb at the edge of a capsule's plastic cavity (see Figure B).
• Gently push the capsule until it is removed. Collect the removed capsule in your hand.
• Do not use two thumbs to push a capsule as this could damage it.
• Do 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.

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

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

Approved: 06/2020

In a single-dose PK study conducted in healthy volunteers, inhibition of GH (as measured by C_avg) 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)].

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)].

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

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.

MYCAPSSA may alter absorption of dietary fats in some patients. 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.

Cholelithiasis and Complications of Cholelithiasis: Monitor periodically. Discontinue if complications of cholelithiasis are suspected (‎5.1).

Hypoglycemia or Hyperglycemia: Monitor glucose and adjust antidiabetic treatment as needed (‎5.2).

Thyroid Function Abnormalities: Hypothyroidism may occur. Assess thyroid function periodically (5.3).

Cardiac Function: Bradycardia, arrhythmia, or conduction abnormalities may occur. Drugs that have bradycardia effects may need dosage adjustments (5.4, ‎7.2).

Decreased Vitamin B₁₂ Levels and Abnormal Schilling's Tests: Decreased vitamin B₁₂ levels and abnormal Schilling's tests have been observed in some patients receiving octreotide. Monitor vitamin B₁₂ levels during treatment (‎5.5).

• Take MYCAPSSA orally with a glass of water on an empty stomach, at least 1 hour before a meal or at least 2 hours after a meal (‎2.1).
• Initiate MYCAPSSA at a dosage of 40 mg daily, administered as 20 mg orally twice daily (‎2.2).
• Monitor insulin-like growth factor 1 (IGF-1) levels and patient's signs and symptoms every two weeks during the dose titration or as indicated (‎2.2).
• Titrate the MYCAPSSA dosage, based on IGF-1 levels and patient's signs and symptoms. Increase the dosage in increments of 20 mg (2.2).
• The maximum recommended dosage is 80 mg daily (‎2.2).
• Once the maintenance dosage of MYCAPSSA is achieved, monitor IGF-1 levels and patient's signs and symptoms monthly or as indicated (‎2.2).
• For patients with end-stage renal disease, initiate at a dosage of 20 mg orally once daily. Titrate and adjust the maintenance dosage based on IGF-1 levels, patient's signs and symptoms and tolerability (‎2.4).

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.

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.

• 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
• 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

Females and Males of Reproductive Potential: Advise premenopausal females of the potential for an unintended pregnancy (‎8.3).

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.

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

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)].

MYCAPSSA delayed-release 20 mg capsules are white hard gelatin capsules imprinted with "OT" on one half of the capsule and "20" on the other half.

The capsules are supplied as:

• Take MYCAPSSA orally with a glass of water on an empty stomach, at least 1 hour before a meal or at least 2 hours after a meal.
• Swallow MYCAPSSA capsules whole. Do not crush or chew the capsules.

• If IGF-1 levels remain above the upper normal limit after treatment with the maximum recommended dosage of 80 mg daily or the patient cannot tolerate treatment with MYCAPSSA, consider discontinuing MYCAPSSA and switching patient to another somatostatin analog.
• Withdraw MYCAPSSA therapy periodically to assess disease activity. If IGF-1 levels increase and signs and symptoms recur, resume MYCAPSSA therapy.

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.

Mycapssa_®

(octreotide) delayed-release capsules

20 mg*

2

28 Capsules

*Each capsule contains octreotide 20 mg (provided as octreotide acetate).

Acetate composition varies. See prescribing information.

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.

• Initiate MYCAPSSA at a dosage of 40 mg daily, administered as 20 mg orally twice daily.
• Monitor insulin-like growth factor 1 (IGF-1) levels and patient's signs and symptoms every two weeks during the dose titration or as indicated.
• Titrate the MYCAPSSA dosage based on IGF-1 levels and patient's signs and symptoms. Increase the dosage in increments of 20 mg daily.
• For MYCAPSSA dosages of 60 mg daily, administer as 40 mg in the morning and 20 mg in the evening.
• For MYCAPSSA dosages of 80 mg daily, administer as 40 mg twice daily.
• The maximum recommended dosage of MYCAPSSA is 80 mg daily.
• Once the maintenance dosage of MYCAPSSA is achieved, monitor IGF-1 levels and patient's signs and symptoms monthly or as indicated.

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.

NDC 69880-120-28

Mycapssa_®

(octreotide) delayed-release capsules

20 mg*

Rx only

*Each capsule contains octreotide 20 mg (provided

as octreotide acetate). Acetate composition varies.

See prescribing information.

Keep out of reach of children.

1

PRESS

& HOLD

HERE

PULL OUT HERE

❶

PRESS

❷

PULL

OPENING AND CLOSING INSTRUCTIONS

• 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

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.

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.

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)].

Other Adverse Reactions

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.

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.

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:

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.

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.

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 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.

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.

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.

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)].

The following important adverse reactions are described below and elsewhere in the labeling:

• Cholelithiasis and Complications of Cholelithiasis [see Warnings and Precautions (‎5.1)]
• Hyperglycemia and Hypoglycemia [see Warnings and Precautions (‎5.2)]
• Thyroid Function Abnormalities [see Warnings and Precautions (‎5.3)]
• Cardiac Function Abnormalities [see Warnings and Precautions (‎5.4)]
• Decreased Vitamin B12 Levels and Abnormal Schilling's Tests [see Warnings and Precautions (‎5.5)]

• Proton Pump Inhibitors, H2-receptor Antagonists, or Antacids: may decrease bioavailability of MYCAPSSA and the MYCAPSSA dose may need to be increased (‎7).
• Cyclosporine: may have decreased bioavailability and require dose adjustment (7).
• Insulin and Antidiabetic Drugs: patients receiving insulin or antidiabetic drugs agents may require dose adjustment (‎7).
• Digoxin: exposure may be decreased and assessment of clinical response to digoxin should be performed (‎7).
• Lisinopril: bioavailability may be increased, monitor patient's blood pressure and adjust dose of lisinopril if needed (‎7).
• Levonorgestrel: counsel women to use an alternative non-hormonal method of contraception or a back-up method when MYCAPSSA is used with combined oral contraceptives (‎7).
• Bromocriptine: dose adjustment of bromocriptine may be necessary (‎7).
• Beta Blocker and Calcium Channel Blockers: dose adjustment of beta blockers or calcium channel blockers may be necessary (‎7).
• Drugs Metabolized by CYP 450 Enzymes: 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 (‎7).

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)].

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.

Important information:

• Each MYCAPSSA wallet contains twenty-eight 20-mg capsules. The number of wallets required in a 28-day period depends on your prescribed dose.

How to Use the MYCAPSSA Wallet

• 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.

To open the wallet:

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

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).

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

Figure A: How to Open the MYCAPSSA Wallet

How to Remove a Capsule from the MYCAPSSA Wallet

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.

• Place the tip of a thumb at the edge of a capsule's plastic cavity (see Figure B).
• Gently push the capsule until it is removed. Collect the removed capsule in your hand.
• Do not use two thumbs to push a capsule as this could damage it.
• Do 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.

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

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

Approved: 06/2020

In a single-dose PK study conducted in healthy volunteers, inhibition of GH (as measured by C_avg) 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)].

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)].

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

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.

MYCAPSSA may alter absorption of dietary fats in some patients. 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.

Cholelithiasis and Complications of Cholelithiasis: Monitor periodically. Discontinue if complications of cholelithiasis are suspected (‎5.1).

Hypoglycemia or Hyperglycemia: Monitor glucose and adjust antidiabetic treatment as needed (‎5.2).

Thyroid Function Abnormalities: Hypothyroidism may occur. Assess thyroid function periodically (5.3).

Cardiac Function: Bradycardia, arrhythmia, or conduction abnormalities may occur. Drugs that have bradycardia effects may need dosage adjustments (5.4, ‎7.2).

Decreased Vitamin B₁₂ Levels and Abnormal Schilling's Tests: Decreased vitamin B₁₂ levels and abnormal Schilling's tests have been observed in some patients receiving octreotide. Monitor vitamin B₁₂ levels during treatment (‎5.5).

• Take MYCAPSSA orally with a glass of water on an empty stomach, at least 1 hour before a meal or at least 2 hours after a meal (‎2.1).
• Initiate MYCAPSSA at a dosage of 40 mg daily, administered as 20 mg orally twice daily (‎2.2).
• Monitor insulin-like growth factor 1 (IGF-1) levels and patient's signs and symptoms every two weeks during the dose titration or as indicated (‎2.2).
• Titrate the MYCAPSSA dosage, based on IGF-1 levels and patient's signs and symptoms. Increase the dosage in increments of 20 mg (2.2).
• The maximum recommended dosage is 80 mg daily (‎2.2).
• Once the maintenance dosage of MYCAPSSA is achieved, monitor IGF-1 levels and patient's signs and symptoms monthly or as indicated (‎2.2).
• For patients with end-stage renal disease, initiate at a dosage of 20 mg orally once daily. Titrate and adjust the maintenance dosage based on IGF-1 levels, patient's signs and symptoms and tolerability (‎2.4).

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.

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.

• 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
• 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

Females and Males of Reproductive Potential: Advise premenopausal females of the potential for an unintended pregnancy (‎8.3).

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.

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

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)].

MYCAPSSA delayed-release 20 mg capsules are white hard gelatin capsules imprinted with "OT" on one half of the capsule and "20" on the other half.

The capsules are supplied as:

• Take MYCAPSSA orally with a glass of water on an empty stomach, at least 1 hour before a meal or at least 2 hours after a meal.
• Swallow MYCAPSSA capsules whole. Do not crush or chew the capsules.

• If IGF-1 levels remain above the upper normal limit after treatment with the maximum recommended dosage of 80 mg daily or the patient cannot tolerate treatment with MYCAPSSA, consider discontinuing MYCAPSSA and switching patient to another somatostatin analog.
• Withdraw MYCAPSSA therapy periodically to assess disease activity. If IGF-1 levels increase and signs and symptoms recur, resume MYCAPSSA therapy.

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.

Mycapssa_®

(octreotide) delayed-release capsules

20 mg*

2

28 Capsules

*Each capsule contains octreotide 20 mg (provided as octreotide acetate).

Acetate composition varies. See prescribing information.

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.

• Initiate MYCAPSSA at a dosage of 40 mg daily, administered as 20 mg orally twice daily.
• Monitor insulin-like growth factor 1 (IGF-1) levels and patient's signs and symptoms every two weeks during the dose titration or as indicated.
• Titrate the MYCAPSSA dosage based on IGF-1 levels and patient's signs and symptoms. Increase the dosage in increments of 20 mg daily.
• For MYCAPSSA dosages of 60 mg daily, administer as 40 mg in the morning and 20 mg in the evening.
• For MYCAPSSA dosages of 80 mg daily, administer as 40 mg twice daily.
• The maximum recommended dosage of MYCAPSSA is 80 mg daily.
• Once the maintenance dosage of MYCAPSSA is achieved, monitor IGF-1 levels and patient's signs and symptoms monthly or as indicated.

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.

NDC 69880-120-28

Mycapssa_®

(octreotide) delayed-release capsules

20 mg*

Rx only

*Each capsule contains octreotide 20 mg (provided

as octreotide acetate). Acetate composition varies.

See prescribing information.

Keep out of reach of children.

1

PRESS

& HOLD

HERE

PULL OUT HERE

❶

PRESS

❷

PULL

OPENING AND CLOSING INSTRUCTIONS

• 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

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.

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.

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)].