What are the adverse effects of octreotide (somatostatin analog)?

Adverse Effects of Octreotide

Octreotide is generally well-tolerated with gastrointestinal symptoms and injection site reactions being the most common adverse effects, though serious complications including gallstone formation, glycemic disturbances, and cardiac effects require monitoring. 1

Common Adverse Effects (Occurring in ≥10% of Patients)

Gastrointestinal Effects

• Diarrhea and loose stools are the most frequently reported gastrointestinal adverse effects 1
• Nausea and abdominal discomfort/cramping occur commonly, though these typically abate with continued therapy 2, 3
• Steatorrhea (fat malabsorption) develops due to inhibition of pancreatic exocrine function 1
• Abdominal distension, bloating, and flatulence are reported 2

Cardiovascular Effects

• Bradycardia and cardiac conduction abnormalities are common, occurring in >10% of patients 1
• These effects result from octreotide's inhibitory action on various hormonal systems 1

Metabolic Effects

• Both hyperglycemia and hypoglycemia can occur, requiring insulin dose adjustments in diabetic patients 1
• This bidirectional effect on glucose reflects octreotide's complex actions on insulin, glucagon, and growth hormone secretion 2

Local Reactions

• Pain at the injection site is frequently reported with subcutaneous administration 1, 2

Less Common but Clinically Important Adverse Effects (<10%)

Hepatobiliary Complications

• Gallstone formation (cholelithiasis) occurs in 22-33% of patients on long-term therapy 1
• The mechanism involves altered fat absorption and decreased gallbladder motility 3
• In pediatric patients receiving octreotide LAR 40 mg monthly, gallstone incidence reached 33%, higher than the 22-24% seen in adults 4
• This may influence treatment selection and requires monitoring 1

Cardiovascular Complications

• Arrhythmias including complete atrioventricular block have been reported 1, 4
• Hypotension can occur, particularly in overdose situations 4

Gastrointestinal Pathology

• Active gastritis with mucosal damage has been documented in patients on chronic therapy (>2 years) 5
• Focal atrophy of gastric mucosa was found in 7 of 9 patients studied 5

Nutritional Deficiencies

• Vitamin B12 deficiency develops with long-term use, becoming abnormally low in 40% of patients after 2 years 5
• Fat-soluble vitamin deficiencies (vitamins A and D) can occur due to steatorrhea 6
• These require monitoring and supplementation during chronic therapy 6

Neurological Effects

• Headache, dizziness, fatigue, and lethargy have been reported 1, 4

Hematologic Effects

• Neutropenia has been reported, though rare, with rapid onset after initiation and resolution upon discontinuation 7
• This is not currently listed in standard adverse effect profiles but represents a potentially serious complication 7

Pancreatic Effects

• Pancreatitis has been reported, though the causal relationship remains unclear given patient comorbidities 1, 4

Serious Adverse Events in Overdose

In overdose situations (2,400-6,000 mcg/day), the following have been documented 4:

• Complete atrioventricular block and cardiac arrest
• Brain hypoxia
• Hepatitis steatosis and hepatomegaly
• Lactic acidosis
• Pancreatitis

Special Population Considerations

Pediatric Patients

• Serious adverse events including hypoxia, necrotizing enterocolitis, and death have been reported in children, particularly those under 2 years of age 4
• The relationship to octreotide is uncertain as most had serious underlying comorbidities 4
• Higher gallstone incidence (33%) compared to adults 4

Patients with Renal or Hepatic Impairment

• Half-life may be prolonged in severe renal failure requiring dialysis or in liver cirrhosis, necessitating dose adjustments 4

Clinical Monitoring Recommendations

Monitor for gallstone formation, vitamin B12 and fat-soluble vitamin levels, and glucose control during long-term therapy. 6, 5 Cardiac monitoring is prudent given the bradycardia and conduction abnormality risks 1. While gastrointestinal symptoms are common initially, they typically improve with continued use 2, 3.

Comparative Safety Profile

Octreotide demonstrates superior safety compared to terlipressin/vasopressin, with a 2.39-fold lower rate of adverse events in variceal hemorrhage management 1. This favorable safety profile makes octreotide the vasoactive drug of choice in this setting 1.