Is terlipressin given intramuscularly, and what are the recommended intravenous dosing regimens for acute variceal bleeding and type 1 hepatorenal syndrome?

Terlipressin Administration Route and Dosing

Terlipressin is administered intravenously only—never intramuscularly—and can be given through a peripheral IV line without requiring central venous access or ICU monitoring. 1

Route of Administration

• Terlipressin must be given intravenously through a peripheral line, eliminating the need for central venous catheterization 1
• The medication does not require ICU-level monitoring for administration, making it suitable for general medical ward use 1
• There is no intramuscular formulation or indication for terlipressin 1

Dosing for Acute Variceal Bleeding

Standard Regimen

• Initial phase (first 48 hours): 2 mg IV every 4 hours until bleeding is controlled 2
• Maintenance phase: 1 mg IV every 4 hours after initial control 2
• Total duration: 2-5 days, with vasoactive therapy continued after endoscopic hemostasis to prevent early rebleeding 1, 2

Key Clinical Considerations

• Start immediately when variceal bleeding is suspected, even before diagnostic endoscopy 1, 2
• Shorter duration (2 days) may be sufficient in selected patients with Child-Pugh class A or B cirrhosis without active bleeding during endoscopy 2
• Longer duration (up to 5 days) is recommended for Child-Pugh class C cirrhosis or active bleeding during endoscopy 2
• Never use as monotherapy—must be combined with endoscopic band ligation (within 12 hours) and prophylactic antibiotics 2

Alternative: Continuous Infusion

• Continuous infusion achieves equal efficacy with lower total daily doses and fewer adverse events compared to bolus dosing 1, 3, 4
• Starting dose: 2 mg/day as continuous IV infusion, with dose escalation based on response 1, 4
• This method provides more stable portal pressure reduction and reduces ischemic complications 3, 4

Dosing for Type 1 Hepatorenal Syndrome (HRS-AKI)

FDA-Approved Regimen (CONFIRM Trial Protocol)

• Initial dose: 1 mg IV bolus every 6 hours for days 1-3 1
• Dose escalation: Increase to 2 mg IV every 6 hours on day 4 if serum creatinine has not decreased by ≥30% from baseline 1
• Maximum duration: Up to 14 days 1
• Discontinuation criteria: Can stop 24 hours after creatinine decreases to <1.5 mg/dL 1

Alternative Dosing Protocols

• Some guidelines recommend 1 mg IV every 4-6 hours initially, with escalation to 2 mg every 4-6 hours if inadequate response 1
• Continuous infusion (starting at 2 mg/day) is equally effective with lower total daily doses and fewer complications 1, 4

Mandatory Albumin Co-Administration

• Terlipressin must always be combined with albumin for HRS-AKI treatment 1, 5
• Day 1: 1 g/kg IV (maximum 100 g) 5
• Subsequent days: 20-40 g/day IV until treatment completion 1, 5
• Critical caveat: Reassess volume status after 1-2 days to avoid excessive albumin administration, which significantly increases respiratory failure risk (14% vs 5% placebo) 1

Absolute Contraindications

• SpO₂ <90% on room air or supplemental oxygen 1
• Ongoing coronary, peripheral, or mesenteric ischemia 1
• Known significant vascular disease 1

High-Risk Situations Requiring Caution

• ACLF grade 3 (≥3 organ failures)—increased risk of respiratory failure 1
• Serum creatinine >5 mg/dL—unlikely to benefit from treatment 1
• MELD score ≥35 in transplant-listed patients—risks may outweigh benefits 1

Monitoring Requirements

• Vital signs including pulse oximetry every 2-4 hours (not continuous monitoring) 1
• Daily serum creatinine to assess response 1
• Monitor for mean arterial pressure increase of 5-10 mm Hg, which predicts treatment response 1
• Assess for ischemic complications (arrhythmia, angina, splanchnic/digital ischemia) 1

Common Adverse Events

• Respiratory failure occurs in 14-30% of patients, particularly with ACLF-3 or excessive albumin 1
• Ischemic complications occur in approximately 12% of patients 1
• Other common effects include abdominal pain, nausea, diarrhea, and dyspnea 1
• Discontinue immediately if cardiac or ischemic symptoms develop, even if symptoms subside 1