What is the recommended dose of terlipressin (glypressin) for managing oesophageal bleed?

Terlipressin Dosing for Esophageal Variceal Bleeding

For management of esophageal variceal bleeding, terlipressin should be administered at an initial dose of 2 mg IV every 4 hours for the first 48 hours until bleeding is controlled, followed by a maintenance dose of 1 mg IV every 4 hours for a total treatment duration of 2-5 days. 1, 2

Standard Dosing Regimen

• Initial phase (first 48 hours): 2 mg IV every 4 hours until bleeding is controlled 1
• Maintenance phase: 1 mg IV every 4 hours 1
• Total treatment duration: 2-5 days 1, 2

Alternative Administration Method: Continuous Infusion

Recent evidence suggests continuous infusion may be more effective with fewer side effects:

• Continuous infusion at 4 mg/24 hours (compared to bolus injections) 3
• Benefits of continuous infusion include:
  • Greater reduction in hepatic venous pressure gradient 3
  • Lower rebleeding rates (1.8% vs 14.5% with bolus dosing) 3
  • Fewer adverse events (36.3% vs 56.4% with bolus dosing) 3
  • Lower total daily dose requirement (4.25 mg vs 7.42 mg/24h) 3

Duration of Therapy

While the standard duration is 2-5 days, emerging evidence suggests shorter courses may be effective:

• A randomized controlled trial found that 24 hours of terlipressin was as effective as 72 hours when used as adjunctive therapy to successful endoscopic variceal band ligation 4
• Another study showed 12-hour terlipressin therapy had similar outcomes to 72-hour therapy (rebleeding rates of 4.6% vs 4%) 5

Efficacy and Comparative Effectiveness

• Terlipressin is the only vasoactive drug proven to reduce bleeding-related mortality 2
• Initial hemostasis rates are high (88-98%) 6, 7
• Efficacy is comparable to other vasoactive agents like octreotide and somatostatin in terms of hemostasis and survival 2, 6

Adverse Effects and Precautions

• Common adverse effects include: 1

  • Abdominal pain
  • Nausea
  • Respiratory failure
  • Diarrhea
  • Dyspnea

• Terlipressin is contraindicated in patients with: 1

  • Hypoxia or worsening respiratory symptoms
  • Ongoing coronary, peripheral, or mesenteric ischemia
  • Oxygen saturation <90% 1

Clinical Pearls

• Terlipressin should be initiated as soon as variceal bleeding is suspected, even before diagnostic endoscopy 2
• Endoscopic therapy (preferably endoscopic variceal ligation) should be performed as soon as possible, ideally within 12 hours of presentation 2
• Prophylactic antibiotics should be administered concurrently 2
• For high-risk patients (Child-Pugh class C or Child-Pugh class B with active bleeding despite vasoactive therapy), early TIPS placement should be considered 2

Dosing Adjustment Considerations

• In patients with poor response, the maintenance dose can be increased to 2 mg IV every 4 hours 1
• For patients at higher risk of adverse effects, continuous infusion at a lower total daily dose may be preferable 3
• In patients with hepatorenal syndrome, dose adjustment may be needed based on serum creatinine levels 1