Introduction
Mycapssa® (octreotide) is an innovative oral formulation of the somatostatin analog octreotide, developed by Chiasma, Inc. It represents a significant advancement in acromegaly treatment as the first and only oral somatostatin receptor ligand (SRL) approved by the FDA. This formulation utilizes a proprietary transient permeability enhancer (TPE®) technology that facilitates the absorption of octreotide through the intestinal wall, eliminating the need for invasive injections that have been the standard of care for decades.
Mechanism of Action
Mycapssa contains octreotide, a cyclic octapeptide that mimics natural somatostatin pharmacologically. It exerts its therapeutic effects through high-affinity binding to somatostatin receptors (particularly subtypes 2 and 5). This binding inhibits the secretion of growth hormone (GH) from pituitary adenoma cells and reduces the production of insulin-like growth factor 1 (IGF-1) from the liver. The TPE® technology enables gastrointestinal absorption by transiently altering intestinal permeability through localized interactions with epithelial tight junctions.
Indications
Mycapssa is indicated for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with injectable octreotide or lanreotide. It is approved for:
- Maintenance of biochemical response (GH and IGF-1 levels)
- Symptom control in acromegaly
- Not indicated for initial therapy or patients who have not responded to injectable SRLs
Dosage and Administration
Standard dosing: 40 mg twice daily (approximately every 6-8 hours) with water on an empty stomach- At least 1 hour before or 2 hours after meals
- Capsules should be swallowed whole, not crushed or chewed
- May be increased to 60 mg twice daily if inadequate response after 3 weeks
- May be decreased to 20 mg twice daily if adverse reactions occur
- Renal impairment: No dose adjustment needed
- Hepatic impairment: Use with caution in moderate to severe impairment
- Elderly: No specific dose adjustment required
- Pediatrics: Safety and effectiveness not established
Pharmacokinetics
Absorption: Bioavailability approximately 0.88% (significantly higher than previous oral octreotide attempts)- Tmax: 2.1-3.0 hours
- Food effect: High-fat meal reduces exposure by approximately 85%
- Protein binding: 41-65% (primarily albumin and lipoprotein)
- Forms various metabolites with minimal activity
- Primarily fecal excretion (52%)
- Renal excretion (32% in urine)
Contraindications
- Hypersensitivity to octreotide or any component of the formulation
- Patients with known hypersensitivity to related somatostatin analogs
Warnings and Precautions
Gallbladder abnormalities: Monitor for cholelithiasis and biliary sludge formation Glucose metabolism: May alter glycemic control; monitor blood glucose levels Cardiac abnormalities: May cause bradycardia, conduction abnormalities, and arrhythmias Vitamin B12 deficiency: May alter absorption; monitor levels with long-term use Thyroid function: May cause hypothyroidism; monitor thyroid function tests Hepatic impairment: Use with caution in patients with moderate to severe impairmentDrug Interactions
Cyclosporine: Reduced cyclosporine concentrations; monitor levels Bromocriptine: Increased bromocriptine availability; may require dose adjustment Insulin and oral hypoglycemics: May alter requirements; monitor glucose closely Beta-blockers: Additive bradycardic effects CYP3A4 inhibitors/inducers: May alter octreotide concentrations Drugs that prolong QT interval: Potential additive effectsAdverse Effects
Common (≥10%):- Headache (18%)
- Nausea (16%)
- Arthralgia (16%)
- Diarrhea (15%)
- Blood glucose increased (14%)
- Abdominal pain (12%)
- Fatigue (11%)
- Vomiting (10%)
- Cholelithiasis (3%)
- Bradycardia (1%)
- Hepatitis
- Pancreatitis
- QT prolongation
- Hypothyroidism
Monitoring Parameters
Baseline:- GH and IGF-1 levels
- Gallbladder ultrasound
- ECG
- Fasting blood glucose/HbA1c
- Thyroid function tests
- Vitamin B12 levels
- Liver function tests
- GH and IGF-1 levels every 6 months
- Gallbladder ultrasound annually
- Regular glucose monitoring
- Thyroid function every 6-12 months
- Vitamin B12 annually
- Cardiac monitoring if symptoms develop
Patient Education
Administration:- Take exactly as prescribed, typically twice daily
- Take on empty stomach (1 hour before or 2 hours after meals)
- Swallow capsules whole with water
- Do not crush or chew capsules
- Maintain regular meal schedule to minimize gastrointestinal effects
- Report any symptoms of gallstones (abdominal pain, nausea, vomiting)
- Monitor blood sugar regularly if diabetic
- Report palpitations, dizziness, or fainting
- Keep all scheduled appointments for monitoring
- Inform all healthcare providers about Mycapssa use
- Do not discontinue without medical supervision
- Store at room temperature (20-25°C)
- Keep in original container with desiccant
- Protect from moisture
References
1. FDA Prescribing Information: Mycapssa (octreotide) capsules. 2020. 2. Melmed S, et al. A large, multicenter, randomized, double-blind, phase 3 study of oral octreotide capsules vs placebo for maintenance of biochemical response in acromegaly. J Clin Endocrinol Metab. 2021;106(5):e2005-e2015. 3. Fleseriu M, et al. Maintenance of acromegaly control in patients switched from injectable somatostatin receptor ligands to oral octreotide. J Clin Endocrinol Metab. 2020;105(10):e3785-e3797. 4. Samson SL, et al. Long-term efficacy and safety of oral octreotide in acromegaly: results from a phase 3 extension trial. Endocr Pract. 2022;28(1):34-42. 5. ClinicalTrials.gov: MPOWERED Trial (NCT02685709) and CHIASMA OPTIMAL Trial (NCT03252353).