Terlipressin vs Vasopressin in Bleeding Esophageal Varices
Vasopressin is no longer recommended for acute variceal hemorrhage due to significant cardiovascular adverse events, while terlipressin remains a viable option outside the United States, though octreotide is preferred based on superior safety profile. 1
Why Vasopressin Should Not Be Used
Vasopressin has been abandoned in clinical practice for variceal bleeding due to its unacceptable side effect profile. 1 The drug causes:
- Significant increase in peripheral vascular resistance 1
- Reduction in cardiac output and coronary blood flow 1
- High risk of mesenteric or myocardial ischemia 1
- Requires continuous IV infusion due to short half-life 1
The serious cardiovascular complications have led to vasopressin being discontinued for this indication in Europe and most clinical settings. 2
Terlipressin as the Vasopressin Alternative
Terlipressin is a synthetic vasopressin analogue designed to overcome vasopressin's limitations. 1 Key advantages include:
- Longer half-life allowing intermittent bolus dosing (every 4-6 hours) rather than continuous infusion 1, 3
- Fewer adverse effects compared to vasopressin 1
- Only vasoactive drug proven to reduce bleeding-related mortality (RR 0.66; 95% CI 0.49-0.88) 1, 3
- Effective in controlling bleeding with positive impact on survival 1
Standard Terlipressin Dosing
- Initial 48 hours: 2 mg IV every 4 hours until bleeding controlled 1
- Maintenance: 1 mg IV every 4 hours 1
- Duration: 2-5 days 1
Critical Safety Concerns with Terlipressin
Despite being safer than vasopressin, terlipressin still carries significant risks that limit its use:
Adverse events occur 2.39-fold more frequently with terlipressin compared to octreotide or somatostatin. 1, 4 Specific complications include:
- Hyponatremia 1
- Myocardial ischemia due to coronary artery vasoconstriction 1
- Abdominal pain 1
- Chest pain 1
- Diarrhea 1
Absolute Contraindications
Terlipressin must not be used in patients with: 1
- Hypoxia or worsening respiratory symptoms
- Ongoing coronary ischemia
- Peripheral vascular ischemia
- Mesenteric ischemia
Why Octreotide is Now Preferred Over Terlipressin
The 2024 AGA guidelines explicitly recommend octreotide as the vasoactive drug of choice based on its superior safety profile. 1, 4
Evidence Supporting Octreotide Preference
- No significant differences in efficacy: Meta-analyses show equivalent mortality, hemostasis rates, early rebleeding, late rebleeding, blood transfusion requirements, and hospital stay between terlipressin and octreotide 1, 4
- Terlipressin less effective for rapid control: In a meta-analysis of 3,344 patients from 30 RCTs, terlipressin was less effective than octreotide for bleeding control within 24 hours 1, 4
- Higher complication risk: Terlipressin has higher risk of complications than somatostatin analogues 1
Octreotide Dosing
Regulatory Status Consideration
Terlipressin is NOT FDA-approved for variceal bleeding in the United States, though it is used as standard therapy outside the US. 1, 4 This further supports octreotide as the preferred agent in US practice.
Clinical Algorithm for Drug Selection
For acute esophageal variceal bleeding:
- First-line: Octreotide (50 μg bolus, then 50 μg/hr infusion) 1, 4
- Alternative (outside US): Terlipressin (2 mg IV q4h initially, then 1 mg q4h) - only if no cardiovascular contraindications 1
- Never use: Vasopressin due to unacceptable cardiovascular toxicity 1
Always combine vasoactive therapy with: 1, 4
- Prophylactic antibiotics (ceftriaxone 1g IV q24h)
- Endoscopic variceal ligation when feasible
Common Pitfall to Avoid
Do not assume terlipressin is superior because it is the only agent proven to reduce mortality in meta-analysis. 3 This mortality benefit must be weighed against the 2.39-fold increase in adverse events compared to octreotide, which shows equivalent efficacy in all other outcomes with better tolerability. 1, 4 The most recent 2024 AGA guideline explicitly prioritizes safety profile in selecting octreotide over terlipressin. 1