NDC 69880-120 Mycapssa

Octreotide

NDC Product Code 69880-120

NDC CODE: 69880-120

Proprietary Name: Mycapssa What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Octreotide What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Product Characteristics

Color(s):
WHITE (C48325 - IMPRINTED BLACK)
Shape: CAPSULE (C48336)
Size(s):
22 MM
Imprint(s):
OT20
Score: 1

NDC Code Structure

NDC 69880-120-28

Package Description: 4 BLISTER PACK in 1 DOSE PACK > 7 CAPSULE, DELAYED RELEASE in 1 BLISTER PACK

NDC Product Information

Mycapssa with NDC 69880-120 is a a human prescription drug product labeled by Chiasma Inc.. The generic name of Mycapssa is octreotide. The product's dosage form is capsule, delayed release and is administered via oral form.

Labeler Name: Chiasma Inc.

Dosage Form: Capsule, Delayed Release - A solid dosage form in which the drug is enclosed within either a hard or soft soluble container made from a suitable form of gelatin, and which releases a drug (or drugs) at a time other than promptly after administration. Enteric-coated articles are delayed release dosage forms.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Mycapssa Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • OCTREOTIDE 20 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • POVIDONE K12 (UNII: 333AG72FWJ)
  • SODIUM CAPRYLATE (UNII: 9XTM81VK2B)
  • MAGNESIUM CHLORIDE (UNII: 02F3473H9O)
  • POLYSORBATE 80 (UNII: 6OZP39ZG8H)
  • GLYCERYL MONOCAPRYLATE (UNII: TM2TZD4G4A)
  • TRICAPRILIN (UNII: 6P92858988)
  • GELATIN, UNSPECIFIED (UNII: 2G86QN327L)
  • METHACRYLIC ACID - ETHYL ACRYLATE COPOLYMER (1:1) TYPE A (UNII: NX76LV5T8J)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • TRIETHYL CITRATE (UNII: 8Z96QXD6UM)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • SODIUM BICARBONATE (UNII: 8MDF5V39QO)
  • TALC (UNII: 7SEV7J4R1U)
  • SODIUM LAURYL SULFATE (UNII: 368GB5141J)
  • SHELLAC (UNII: 46N107B71O)
  • FERROSOFERRIC OXIDE (UNII: XM0M87F357)
  • PROPYLENE GLYCOL (UNII: 6DC9Q167V3)
  • AMMONIA (UNII: 5138Q19F1X)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.
  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Somatostatin Analog - [EPC] (Established Pharmacologic Class)
  • Somatostatin Receptor Agonists - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Chiasma Inc.
Labeler Code: 69880
FDA Application Number: NDA208232 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 07-06-2020 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Mycapssa Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

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

2.1 Important Administration Instructions

  • 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.

2.2 Recommended Dosage, Titration, And Monitoring

  • 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.

2.3 Dosage Interruptions And Modifications

  • 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.

2.4 Recommended Dosage In Patients With End Stage Renal Disease

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)].

2.5 Dosage Modifications With Concomitant Use Of Proton Pump Inhibitors, H2-Receptor Antagonists, Or Antacids

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

3 Dosage Forms And Strengths

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.

4 Contraindications

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)].

5.1 Cholelithiasis And Complications Of Cholelithiasis

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.

5.2 Hyperglycemia And Hypoglycemia

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.

5.3 Thyroid Function Abnormalities

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.

5.4 Cardiac Function Abnormalities

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)].

5.5 Decreased Vitamin B12 Levels And Abnormal Schilling's Tests

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.

6 Adverse Reactions

  • 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)]

6.1 Clinical Studies Experience

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.Table 1: Adverse Reactions Occurring ≥ 5% and Greater than Placebo in a Placebo-Controlled Study with MYCAPSSA in Acromegaly PatientsMYCAPSSA % (N=28)PLACEBO % (N=28)Diarrhea2921Nausea2111Blood glucose increasedIncludes blood glucose increased, hyperglycemia and glycosylated hemoglobin increased147Vomiting140Abdominal discomfort1411Dyspepsia114Sinusitis110Osteoarthritis110Urinary tract infection74Pain70Large intestine polyp70Cholelithiasis74Table 2: Adverse Reactions Occurring ≥ 5% in an Open-Label Study with MYCAPSSA in Acromegaly PatientsMYCAPSSA % (N=155)Headache33Nausea30Arthralgia26Asthenia22Hyperhidrosis21Diarrhea18Peripheral swelling16Dyspepsia8Abdominal pain upper8Abdominal distension7Nasopharyngitis7Influenza7Blood glucose increasedIncludes blood glucose increased, hyperglycemia and impaired fasting glucose6Vomiting6Flatulence6Back pain6Abdominal pain5Dizziness5Fatigue5Upper respiratory tract infection5Hypertension5

Other

Other Adverse Reactions

Gallbladder AbnormalitiesIn 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/HyperglycemiaIn 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.

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

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

GastrointestinalGastrointestinal 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.

Risk SummaryAvailable 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 DataIn 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 SummaryThere 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.

DataFollowing 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).

AbsorptionIn 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 AbsorptionIn 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).

DistributionIn 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).

EliminationAccording 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 PatientsIn 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 ImpairmentExposure 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 ImpairmentIn 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 InteractionsLimited 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.Table 3 Effect of Co-administered Drugs on MYCAPSSA Systemic ExposureCo-administered drug and dosing regimenMYCAPSSADose (mg)Mean Ratio (ratio with/without co-administered drug) No Effect=1.0Change in AUCChange in CmaxEsomeprazole 40 mg QD on days 2-720 mg on Day 1 and 20 mg on Day 70.59Clinically significant [see Dosage and Administration (‎2) and Drug Interactions (‎7.1, ‎7.2)] (0.40 – 0.88)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)0.55 (0.40 – 0.75)Metoclopramide 20 mg40 mg0.91 (0.61 – 1.35)0.95 (0.62 – 1.44)Loperamide 4 mg40 mg0.97 (0.65 – 1.44)30.91 (0.59 – 1.39)3Table 4 Effect of MYCAPSSA on Systemic Exposure of Co-administered DrugsCo-administered drug and dosing regimenMYCAPSSADose (mg)Single dose unless otherwise noted.Mean Ratio (ratio with/without co-administered drug) No Effect=1.0Change in AUCChange in CmaxCyclosporine 300 mg20 mg0.38Clinically significant [see Dosage and Administration (‎2) and Drug Interactions (‎7.1, ‎7.2)] (0.31 – 0.46)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)0.29 (0.22 – 0.37)Digoxin 0.5 mg40 mg1.0 (0.94 – 1.13)0.63 (0.55 – 0.72)Lisinopril 20 mg40 mg1.40 (1.21 – 1.61)1.50 (1.32 – 1.71)Ethinyl Estradiol 0.06 mg40 mg0.94 (0.86 – 1.03)0.92 (0.83 – 1.01)Levonorgestrel 0.3 mg40 mg0.76 (0.67 – 0.86)0.62 (0.54 – 0.71)

Cholelithiasis and Complications of CholelithiasisAdvise 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 HyperglycemiaAdvise 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 AbnormalitiesInform patients that their thyroid function will be assessed periodically during treatment [see Warnings and Precautions (‎5.3)].

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

Decreased Vitamin B12 Levels and Abnormal Schilling's TestsInform patients that Vitamin B12 levels may be monitored during the treatment [see Warnings and Precautions (‎5.5)].

Females and Males of Reproductive PotentialInform female patients that treatment with MYCAPSSA may result in unintended pregnancy [see Use in Specific Populations (‎8.3)].

Rx ONLYManufactured by MW Encap Ltd., Scotland, UK.Copyright © Chiasma 2020Revised: 06/2020

6.2 Immunogenicity

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.

6.3 Postmarketing Experience

  • 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, thrombocytopeniaCardiac: myocardial infarction, cardiac arrest, atrial fibrillationEar and labyrinth: deafnessEndocrine: diabetes insipidus, adrenal insufficiency in patients 18 months of age and under, pituitary apoplexyEye: glaucoma, visual field defect, scotoma, retinal vein thrombosisGastrointestinal: intestinal obstruction, peptic/gastric ulcer, abdomen enlargedGeneral and administration site: generalized edema, facial edemaHepatobiliary: gallbladder polyp, fatty liver, hepatitisImmune: anaphylactoid reactions including anaphylactic shockInfections and infestations: appendicitisLaboratory abnormalities: increased liver enzymes, CK increased, creatinine increasedMetabolism and nutrition: diabetes mellitusMusculoskeletal: arthritis, joint effusion, Raynaud's syndromeNervous System: convulsions, aneurysm, intracranial hemorrhage, hemiparesis, paresis, suicide attempt, paranoia, migraines, Bell's palsy, aphasiaRenal and urinary: renal failure, renal insufficiencyReproductive and breast: gynecomastia, galactorrhea, libido decrease, breast carcinomaRespiratory: status asthmaticus, pulmonary hypertension, pulmonary nodule, pneumothorax aggravatedSkin and subcutaneous tissue: urticaria, cellulitis, petechiaeVascular: orthostatic hypotension, hematuria, gastrointestinal hemorrhage, arterial thrombosis of the arm

7.1 Effects Of Other Drugs On Mycapssa

Proton Pump Inhibitors, H2-receptor Antagonists, or AntacidsClinical Impact:Concomitant administration of MYCAPSSA with esomeprazole resulted in a decrease in the bioavailability for MYCAPSSA [See Clinical Pharmacology (‎12.3)]. 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.Intervention:Co-administration of MYCAPSSA with PPIs, H2-blockers, or antacids may require increased doses of MYCAPSSA.

7.2 Effects Of Mycapssa On Other Drugs

CyclosporineClinical Impact:Concomitant administration of MYCAPSSA with cyclosporine resulted in a decrease in cyclosporine bioavailability [see Clinical Pharmacology (‎12.3)].Intervention:Adjustment of cyclosporine dose to maintain therapeutic levels may be necessitated.Insulin and Antidiabetic DrugsClinical Impact:MYCAPSSA inhibits the secretion of insulin and glucagon.Intervention: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.DigoxinClinical Impact:Concomitant administration of MYCAPSSA with digoxin resulted in a decrease in digoxin peak exposure [see Clinical Pharmacology (‎12.3)].Intervention:Digoxin has a narrow therapeutic ratio and careful assessment of clinical response should be performed when digoxin is concomitantly administered with MYCAPSSA.LisinoprilClinical Impact:Concomitant administration of MYCAPSSA increases lisinopril bioavailability [see Clinical Pharmacology (‎12.3)].Intervention:Monitor patient's blood pressure and adjust the dosage of lisinopril if needed.LevonorgestrelClinical Impact:Concomitant administration of MYCAPSSA with levonorgestrel decreases levonorgestrel bioavailability [see Clinical Pharmacology (‎12.3)].Intervention: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.BromocriptineClinical Impact:Concomitant administration of MYCAPSSA with bromocriptine may increase the systemic exposure of bromocriptine [see Clinical Pharmacology (‎12.3)].Intervention:Dose adjustment of bromocriptine may be necessary.Beta Blocker and Calcium Channel BlockersClinical Impact:MYCAPSSA may cause bradycardia in acromegaly patients.Intervention:Patients receiving beta blockers or calcium channel blockers may require dose adjustments of these therapeutic agents.Drugs Metabolized by CYP 450 EnzymesClinical Impact: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. Intervention: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.

8.3 Females And Males Of Reproductive Potential

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.

8.4 Pediatric Use

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.

8.5 Geriatric Use

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.

8.6 Renal Impairment

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)].

8.7 Hepatic Impairment

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)].

10 Overdosage

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.

11 Description

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.

12.1 Mechanism Of Action

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.

12.2 Pharmacodynamics

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)].

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

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.

14 Clinical Studies

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 higher than 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.

16 How Supplied/Storage And Handling

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:NDC NumberPackage Size69880-120-28Wallet of 28 capsules

Storage And Handling

StorageUntil 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.

17 Patient Counseling Information

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

Spl Patient Package Insert

  • Patient Information MYCAPSSA® [my (as in sky)-cap-sah] (octreotide) delayed-release capsules, for oral useThis Patient Information has been approved by the U.S. Food and Drug Administration.Approved: 06/2020      What is MYCAPSSA?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.It is not known if MYCAPSSA is safe and effective in children.Do not take MYCAPSSA if you: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:swelling of your tongue, throat, lips, eyes or facesevere itching of the skin with rash or raised bumpschest paintrouble swallowing or breathingfeeling faintrapid heart beatSee the end of this leaflet for a complete list of ingredients in MYCAPSSA.Before you take MYCAPSSA, tell your healthcare provider about all of your medical conditions, including if you:have liver cirrhosis or liver problemshave kidney problemsare 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.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.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.MYCAPSSA may affect the way other medicines work, and other medicines may affect how MYCAPSSA works.Especially tell your healthcare provider if you take oral contraceptives. Use an alternative non-hormonal method of contraception or a back-up method while taking MYCAPSSA.Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.How should I take MYCAPSSA?Read the detailed "Instructions for Use" at the end of this Patient Information about the right way to take MYCAPSSA.Take MYCAPSSA exactly as your healthcare provider tells you to take it.Take MYCAPSSA with a glass of water on an empty stomach.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).Swallow the capsules whole. Do not crush or chew the capsules before swallowing.What are the possible side effects of MYCAPSSA?gallbladder problems. 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, nauseablood sugar problems. 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.thyroid problems. MYCAPSSA may keep your thyroid from releasing thyroid hormones leading to hypothyroidism. Your thyroid function will be checked regularly during your treatment with MYCAPSSA.heart rhythm problems. Tell your healthcare provider if you have an irregular heartbeat (your heart is not beating normally).low vitamin B12 levels in your blood. Your healthcare provider may check your vitamin B12 levels during treatment with MYCAPSSA.The most common side effects of MYCAPSSA include:headachenauseadiarrheajoint painweaknesssweating a lotThese are not all the possible side effects of MYCAPSSA. For more information, ask your healthcare provider or pharmacist.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should I store MYCAPSSA?Before first use, store unopened wallets of MYCAPSSA in a refrigerator between 36°F to 46°F (2°C to 8°C).Do not freeze.After first use, store opened wallets at room temperature between 68°F to 77°F (20°C to 25°C) for up to 1 month.Keep MYCAPSSA and all medicines out of the reach of children.General information about the safe and effective use of MYCAPSSA.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.You can ask your pharmacist or healthcare provider for information about MYCAPSSA that is written for health professionals.What are the ingredients in MYCAPSSA?Active ingredient: octreotide acetateInactive ingredients: polyvinylpyrrolidone (PVP-12), sodium caprylate, magnesium chloride, polysorbate 80, glyceryl monocaprylate, glyceryl tricaprylate, gelatin, gelatin capsules, and Acryl-EZE® (methacrylate).Chiasma, Inc. Needham, MA 02494For more information about MYCAPSSA call the product information department at 1-844-312-2462 or go to www.MYCAPSSA.com and select patient information.

Instructions For Use Mycapssa® [My (As In Sky)-Cap-Sah] (Octreotide) Delayed-Release Capsules, For Oral Use

  • 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 WalletEach 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 WalletHow to Remove a Capsule from the MYCAPSSA WalletCapsules 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 WalletThis Instructions for Use has been approved by the U.S. Food and Drug Administration. Approved: 06/2020

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