What is the recommended dose of terlipressin (a synthetic analogue of vasopressin) for acute variceal bleeding?

Terlipressin Dosing for Acute Variceal Bleeding

For acute esophageal variceal bleeding, administer terlipressin 2 mg IV every 4 hours for the first 48 hours until bleeding is controlled, then reduce to 1 mg IV every 4 hours for a total treatment duration of 2-5 days. 1, 2

Initial Dosing Phase (First 48 Hours)

• Start with 2 mg IV every 4 hours immediately when variceal bleeding is suspected, even before endoscopic confirmation 1, 2
• This higher initial dose is critical for achieving rapid portal pressure reduction and hemodynamic response 2
• Continue this dose until bleeding is controlled, typically for the first 48 hours 1

Maintenance Dosing Phase

• Reduce to 1 mg IV every 4 hours once hemorrhage is controlled after the initial 48-hour period 3, 1, 2
• Continue maintenance dosing for a total treatment duration of 2-5 days 3, 1, 2

Treatment Duration Considerations

The optimal duration depends on patient risk factors:

• Lower-risk patients (Child-Pugh class A or B with no active bleeding during endoscopy) may require only 2 days of total treatment after successful endoscopic hemostasis 1, 4
• Higher-risk patients (Child-Pugh class C or active bleeding during endoscopy) should receive the full 5 days of treatment 1
• Research demonstrates that 24 hours of terlipressin is as effective as 72 hours when used as adjunctive therapy to successful endoscopic variceal ligation, though this applies only to selected low-risk patients 4

Dose Adjustment for Poor Response

• In patients with inadequate response, the maintenance dose can be increased to 2 mg IV every 4 hours 1

Essential Combination Therapy

Terlipressin should never be used as monotherapy 1, 2. The standard approach requires three simultaneous components:

• Vasoactive therapy (terlipressin) started immediately 1, 2
• Endoscopic variceal ligation performed within 12 hours of presentation 1, 2
• Prophylactic antibiotics (ceftriaxone 1 g IV every 24 hours for up to 7 days) 3, 1, 2

This combination achieves 77% five-day hemostasis versus 58% with endoscopy alone 1

Mortality Benefit

Terlipressin is the only vasoactive drug proven to reduce bleeding-related mortality (relative risk 0.66,95% CI 0.49-0.88) 3, 2, 5, 6, making it superior to other vasoactive agents in this critical outcome despite comparable hemostasis rates 3

Important Safety Considerations and Contraindications

Absolute contraindications include 1, 2:

• Hypoxia or oxygen saturation <90%
• Worsening respiratory symptoms
• Ongoing coronary, peripheral, or mesenteric ischemia

Common adverse effects include 3, 1:

• Hyponatremia
• Myocardial ischemia due to coronary vasoconstriction
• Abdominal pain
• Diarrhea
• Respiratory failure

Adverse events occur 2.39-fold more frequently with terlipressin compared to octreotide 7, 2, and the incidence increases with longer treatment duration (24.32% with 5 days vs 10.8% with 2 days) 1

Alternative Dosing Strategy

Recent research suggests that continuous infusion at 4 mg/24 hours may be more effective than bolus dosing, achieving better portal pressure reduction at lower total doses with fewer adverse events 8. However, this approach is not yet incorporated into major guidelines and the standard bolus regimen remains the recommended approach 3, 1, 2.

Clinical Algorithm

1. Suspect variceal bleeding in any cirrhotic patient with upper GI bleeding 1
2. Immediately start terlipressin 2 mg IV every 4 hours AND antibiotic prophylaxis 1, 2
3. Perform endoscopy within 12 hours 1, 2
4. After 48 hours, reduce to 1 mg IV every 4 hours if bleeding controlled 1, 2
5. Continue for 2-5 days based on risk stratification 3, 1, 2
6. Consider early TIPS for high-risk patients (Child-Pugh C score 10-13 or Child-Pugh B with active bleeding despite therapy) 1, 2

Important Caveat: FDA-Approved Indication

Note that the FDA-approved dosing for terlipressin (TERLIVAZ) is 0.85 mg IV every 6 hours for hepatorenal syndrome, not variceal bleeding 9. The dosing regimen described above for variceal bleeding (2 mg every 4 hours initially) is based on international guidelines and is not FDA-approved for this indication in the United States 7.