Octreotide acetate

Usage

Octreotide acetate is primarily prescribed for the management of:

• Acromegaly: A hormonal disorder caused by excessive growth hormone production. Octreotide mimics the inhibitory effects of somatostatin, thereby reducing growth hormone and insulin-like growth factor 1 (IGF-1) levels.

• Carcinoid Syndrome: A syndrome associated with carcinoid tumors that release hormones like serotonin, causing symptoms such as flushing, diarrhea, and wheezing. Octreotide controls these symptoms by inhibiting hormone release.

• VIPomas (Vasoactive Intestinal Peptide-secreting tumors): These tumors secrete VIP, leading to profuse watery diarrhea. Octreotide reduces diarrhea by inhibiting VIP secretion.

• Esophageal Variceal Bleeding: Octreotide can be used to control bleeding from esophageal varices by reducing portal venous pressure. Although other treatment modalities like endoscopic band ligation remain the preferred first line treatment, octreotide can be used as an adjunct or temporizing measure until definitive treatment can be achieved.

Pharmacological Classification: Octreotide is classified as a somatostatin analog.

Mechanism of Action: Octreotide binds to somatostatin receptors, particularly subtypes 2 and 5, which are expressed on various endocrine cells and tissues. This binding leads to the inhibition of hormone secretion (e.g., growth hormone, serotonin, VIP, insulin, glucagon) and reduces blood flow to the splanchnic circulation.

Alternate Names

• International Nonproprietary Name (INN): Octreotide
• No significant regional name variations exist.

Brand Names: Sandostatin, Sandostatin LAR Depot.

How It Works

Pharmacodynamics: Octreotide mimics the actions of somatostatin, leading to:

• Suppression of growth hormone, IGF-1, serotonin, VIP, insulin, glucagon, and other hormones.
• Reduction of gastrointestinal motility and secretion.
• Decrease in splanchnic blood flow.

Pharmacokinetics:

• Absorption: Subcutaneous administration has rapid absorption. Intramuscular (IM) administration of the depot formulation (Sandostatin LAR) provides sustained release.
• Metabolism: Primarily hepatic, with some peptide degradation.
• Elimination: Mainly renal excretion, with some biliary elimination.

Mode of Action: Binds to somatostatin receptors (primarily subtypes 2 and 5), inhibiting intracellular signaling cascades that lead to hormone release.

Dosage

Standard Dosage

Adults:

• Subcutaneous: Acromegaly: Initial 50 mcg three times daily; titrate to achieve target GH/IGF-1 levels (GH < 5 ng/mL or IGF-1 within normal limits). Carcinoid tumors: 100-600 mcg/day initially, divided two to four times daily; maintenance dose is often around 300-450 mcg/day. VIPomas: 200-300 mcg/day initially, divided two to four times daily; titrate as needed.
• IM (Sandostatin LAR Depot): Acromegaly and carcinoid tumors: After initial subcutaneous stabilization, 20 mg every 4 weeks. Dose can be adjusted based on response (10-30 mg/month).

Children:

Dosing needs to be individualized based on weight, age, and the specific condition. Pediatric use should be carefully monitored due to limited experience in this population.

Special Cases:

• Elderly Patients: Start with a lower dose and titrate cautiously, monitoring for adverse effects. Decreased clearance and increased half-life warrant adjustments.
• Patients with Renal Impairment: Dose adjustment may be required as renal clearance is the primary route of elimination.
• Patients with Hepatic Dysfunction: Reduced clearance may necessitate lower doses.
• Patients with Comorbid Conditions: Close monitoring is crucial, especially in patients with diabetes, gallstones, or cardiovascular diseases. Dosage adjustment might be needed.

Clinical Use Cases

• Esophageal Variceal Bleeding: IV bolus followed by continuous infusion. Dosing is determined based on the clinical situation and response.
• other clinical use cases are limited as the main use case of octreotide are for acromegaly and carcinoid tumor and vipoma.

Dosage Adjustments

Adjustments are required based on the patient’s response, renal/hepatic function, and the presence of any comorbid conditions.

Side Effects

Common Side Effects

• Nausea
• Diarrhea
• Abdominal pain
• Gallstones or gallbladder sludge
• Headache
• Injection site reactions
• Hyperglycemia or hypoglycemia
• Bradycardia

Rare but Serious Side Effects

• Pancreatitis
• Hepatic dysfunction
• Cardiac conduction abnormalities
• Hypothyroidism

Long-Term Effects

• Gallbladder disease
• Cholelithiasis
• Steatorrhea
• Vitamin B12 deficiency
• Cardiac conduction disorders

Adverse Drug Reactions (ADR)

• Severe bradycardia
• Anaphylaxis
• Acute pancreatitis
• Hepatic failure

Contraindications

• Hypersensitivity to octreotide or any of its components.
• Severe liver disease (relative contraindication).
• Severe biliary tract obstruction

Drug Interactions

• CYP450 Interactions: Octreotide has minimal CYP450 interaction.
• Other Interactions:
  • Cyclosporine: Reduced cyclosporine levels.
  • Insulin/oral hypoglycemic agents: May alter glucose control.
  • Beta-blockers: Additive bradycardic effects.
  • Diuretics: May require dose adjustments due to fluid/electrolyte imbalance.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Category B (No adequate human studies). Use only if clearly needed.
• Breastfeeding: Octreotide is present in breast milk. The developmental benefits of breastfeeding should be weighed against potential infant risks. Breastfeeding is generally not recommended.

Drug Profile Summary

• Mechanism of Action: Somatostatin analog, inhibits hormone release.
• Side Effects: GI disturbances, gallstones, bradycardia, hyper-/hypoglycemia.
• Contraindications: Hypersensitivity, severe liver disease.
• Drug Interactions: Cyclosporine, insulin, beta-blockers, diuretics.
• Pregnancy & Breastfeeding: Category B; not recommended during breastfeeding.
• Dosage: Varies based on indication; SC or IM depot formulation.
• Monitoring Parameters: GH, IGF-1, tumor markers, liver function tests, glucose, ECG.

Popular Combinations

No routinely recommended combinations exist. Concomitant medications are used to manage specific symptoms (e.g., antidiarrheals).

Precautions

• Monitor liver and gallbladder function.
• Monitor blood glucose regularly.
• Caution in patients with pre-existing cardiac conduction abnormalities.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Octreotide acetate?

A: Dosage varies by indication. Refer to the detailed dosage section above.

Q2: How is Octreotide acetate administered?

A: Subcutaneous injection for immediate release; intramuscular injection for the depot formulation (Sandostatin LAR).

Q3: What are the common side effects of Octreotide acetate?

A: Nausea, diarrhea, abdominal pain, gallstones, headache, injection site reactions.

Q4: What are the contraindications to using Octreotide acetate?

A: Hypersensitivity to octreotide, severe liver disease.

Q5: Can Octreotide acetate be used during pregnancy?

A: Category B; use only if clearly needed.

Q6: Can Octreotide acetate be used during breastfeeding?

A: Not recommended, as it is excreted in breast milk.

Q7: How does Octreotide acetate affect blood glucose levels?

A: It can cause both hyperglycemia and hypoglycemia, so close monitoring is essential.

Q8: Does Octreotide acetate interact with other medications?

A: Yes, it can interact with cyclosporine, insulin, beta-blockers, and diuretics.

Q9: What monitoring parameters are important during Octreotide acetate therapy?

A: GH, IGF-1, liver function tests, glucose levels, ECG (especially if on concomitant beta-blocker therapy).

Q10: What is the role of Octreotide in the management of esophageal variceal bleeding?

A: Octreotide can reduce portal hypertension and thus variceal bleeding, though band ligation remains first line. It can be administered as a bolus followed by continuous intravenous infusion.