Mycapssa

MYCAPSSA- octreotide capsule, delayed release
Chiasma Inc.

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 DOSAGE AND ADMINISTRATION

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 WARNINGS AND PRECAUTIONS

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 Patients

	MYCAPSSA % (N=28)	PLACEBO % (N=28)
* Includes blood glucose increased, hyperglycemia and glycosylated hemoglobin increased
Diarrhea	29	21
Nausea	21	11
Blood glucose increased *	14	7
Vomiting	14	0
Abdominal discomfort	14	11
Dyspepsia	11	4
Sinusitis	11	0
Osteoarthritis	11	0
Urinary tract infection	7	4
Pain	7	0
Large intestine polyp	7	0
Cholelithiasis	7	4

Table 2: Adverse Reactions Occurring ≥ 5% in an Open-Label Study with MYCAPSSA in Acromegaly Patients

	MYCAPSSA % (N=155)
* Includes blood glucose increased, hyperglycemia and impaired fasting glucose
Headache	33
Nausea	30
Arthralgia	26
Asthenia	22
Hyperhidrosis	21
Diarrhea	18
Peripheral swelling	16
Dyspepsia	8
Abdominal pain upper	8
Abdominal distension	7
Nasopharyngitis	7
Influenza	7
Blood glucose increased *	6
Vomiting	6
Flatulence	6
Back pain	6
Abdominal pain	5
Dizziness	5
Fatigue	5
Upper respiratory tract infection	5
Hypertension	5