What are the adverse effects of octreotide?

Adverse Effects of Octreotide

The most common adverse effects of octreotide are gastrointestinal symptoms (diarrhea, nausea, steatorrhea), injection site pain, and gallstone formation, with the latter occurring in 22-33% of patients on long-term therapy. 1

Gastrointestinal Adverse Effects

Most Frequent GI Symptoms

• Diarrhea and loose stools are the most frequently reported gastrointestinal adverse effects, typically occurring early in treatment and usually resolving within 3 months. 1, 2
• Steatorrhea (fat malabsorption) develops due to inhibition of pancreatic exocrine function, though it is generally mild. 3, 1
• Abdominal discomfort, nausea, bloating, and flatulence are common but typically transient. 4, 5
• Despite steatorrhea, patients with dumping syndrome receiving long-term therapy experience approximately 1% weight gain. 3

Serious GI Complications

• Gastritis with mucosal damage has been documented in long-term users, with moderate to severe active gastritis found in 100% of patients in one study after 2+ years of therapy. 6

Hepatobiliary Adverse Effects

Gallstone Formation (Cholelithiasis)

• Gallstone formation occurs in 22-33% of adult patients on long-term therapy, typically developing during the first year of treatment. 1, 2
• Pediatric patients have a higher incidence at 33% compared to adults. 1, 7
• Most octreotide-associated gallstones are small, cholesterol-based, and asymptomatic, not requiring surgical intervention. 8
• The mechanism involves inhibition of gallbladder emptying, hepatic bile secretion, and sphincter of Oddi motility, leading to bile stasis and cholesterol precipitation. 8
• Gallstone formation is not dose-related. 2

Cardiovascular Adverse Effects

• Bradycardia and cardiac conduction abnormalities occur in >10% of patients. 1
• In overdose situations, arrhythmias, complete atrioventricular block, hypotension, and cardiac arrest have been reported. 7

Metabolic and Endocrine Effects

Glucose Dysregulation

• Both hyperglycemia and hypoglycemia can occur, requiring insulin dose adjustments in diabetic patients. 1
• This bidirectional effect on glucose reflects octreotide's inhibition of both insulin and glucagon secretion. 4, 5

Vitamin Deficiencies

• Vitamin B-12 concentrations decline significantly during long-term therapy, becoming abnormally low in approximately 40% of patients after 2 years. 6
• Fat-soluble vitamin deficiencies (vitamins A and D) can occur secondary to steatorrhea. 1

Local Adverse Effects

• Pain, burning, or discomfort at the injection site is common with subcutaneous administration. 4, 5
• This is a major limitation to long-term use of short-acting formulations requiring multiple daily injections. 3

Serious Pediatric Adverse Events

• In children under 2 years of age, serious adverse events including hypoxia, necrotizing enterocolitis, and death have been reported in postmarketing surveillance, though causality has not been established due to serious underlying comorbidities. 7
• Safety and efficacy have not been demonstrated in pediatric patients under age 6 years. 7

Treatment Efficacy and Discontinuation

• In long-term studies of dumping syndrome, 47% of patients discontinued octreotide therapy due to side effects or lack of efficacy. 3
• Only 5 of 103 acromegalic patients (4.9%) discontinued treatment due to adverse events in a large multicenter trial. 2

Clinical Monitoring Recommendations

• Careful monitoring is essential to prevent fluid retention when initiating octreotide, particularly in patients with high stomal outputs who may experience significant fluid retention. 3
• Periodic gallbladder ultrasound evaluations may be considered, though results typically do not influence management of asymptomatic patients. 8
• Glucose monitoring is necessary due to potential for both hyper- and hypoglycemia. 1
• Vitamin B-12 levels should be monitored during chronic therapy. 6

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

Formulation Considerations

• Long-acting formulations are preferred by patients due to less frequent administration and associated improvements in quality of life, despite short-acting formulations being more effective for some symptoms like hypoglycemia. 3