What is the recommended dosage and administration of terlipressin (glypressin) for managing upper gastrointestinal (GI) bleeding?

Terlipressin Administration for Upper GI Bleeding

The recommended dosage of terlipressin for upper GI bleeding is 2 mg IV every 4 hours for the first 48 hours, followed by 1 mg IV every 4 hours for a total treatment duration of 2-5 days. 1, 2, 3

Initial Management and Dosing

• Terlipressin should be initiated as soon as variceal bleeding is suspected, even before endoscopic confirmation 1, 2, 4
• Initial dose: 2 mg IV every 4 hours for the first 48 hours until bleeding is controlled 1, 3
• Maintenance dose: 1 mg IV every 4 hours for a total treatment duration of 2-5 days 1, 3
• Treatment should be administered for 3-5 days to prevent early rebleeding 1

Efficacy and Mechanism

• Terlipressin is the only vasoactive drug proven to reduce bleeding-related mortality (relative risk 0.66,95% CI 0.49-0.88) compared to placebo 2, 4
• Terlipressin reduces portal pressure by decreasing splanchnic blood flow 2, 5
• Initial hemostasis rates with terlipressin are high, with studies showing control of bleeding in 88-98% of cases 6, 7

Alternative Administration Methods

• Recent evidence suggests that continuous infusion of terlipressin (4 mg/24h) may be more effective than bolus administration in reducing portal pressure, with fewer adverse events and at a lower total daily dose 5
• Continuous infusion resulted in significantly higher hepatic venous pressure gradient response at 24 hours compared to bolus dosing (85.4% vs. 58.2%, p=0.002) 5

Duration of Therapy

• Standard duration is 2-5 days 1, 2
• Some studies suggest shorter courses may be effective:
  • A 24-hour course was found to be as effective as a 72-hour course when used as adjunctive therapy to successful endoscopic variceal band ligation 8
  • A 12-hour course showed similar results to 72-hour therapy in preventing rebleeding after endoscopic therapy 9
• However, current guidelines still recommend 2-5 days of treatment 1, 3

Combination with Other Treatments

• Terlipressin should be used in combination with:
  • Endoscopic therapy (preferably endoscopic variceal band ligation) which should be performed within 12 hours of admission 1, 2
  • Antibiotic prophylaxis (ceftriaxone 1g/24h or norfloxacin 400mg twice daily) for up to 7 days 1, 2
  • Volume replacement with crystalloids to maintain hemodynamic stability 1
  • Restrictive transfusion strategy with a hemoglobin threshold of 7 g/dl and a target of 7-9 g/dl 1

Adverse Effects and Precautions

• Common adverse events include abdominal pain, chest pain, diarrhea, and hyponatremia 1, 4
• Terlipressin has more adverse events compared to octreotide or somatostatin 1
• Consider octreotide in patients with cardiac conditions due to fewer cardiovascular side effects 2
• Avoid nephrotoxic drugs, large volume paracentesis, beta-blockers, vasodilators, and other hypotensive drugs during the course of acute variceal hemorrhage 1

Special Considerations

• For high-risk patients (Child-Pugh class C with score <14 or Child-Pugh class B with active bleeding), early pre-emptive TIPS (within 24-72h) should be considered 1, 2
• In case of uncontrolled bleeding despite terlipressin and endoscopic therapy, rescue TIPS should be used 1
• Balloon tamponade should only be used as a temporary "bridge" (maximum 24 hours) until definitive treatment can be instituted 1