What is the recommended subcutaneous dosage of telripressin (Terlipressin) for hepatorenal syndrome?

Terlipressin Subcutaneous Dosing for Hepatorenal Syndrome

Terlipressin is not administered subcutaneously—it must be given intravenously only, either as bolus injections or continuous infusion. There is no approved or recommended subcutaneous formulation or dosing regimen for this medication in hepatorenal syndrome.

Correct Intravenous Dosing Regimens

Initial Dosing Options

Start with 1 mg IV bolus every 4-6 hours (total 4 mg/day) through a peripheral IV line, always combined with albumin. 1, 2 This is the standard approach recommended by the American Association for the Study of Liver Diseases and does not require ICU monitoring. 2

Alternative initial dosing strategies include:

• 0.5-1 mg IV bolus every 4-6 hours for the first 3 days per European Association for the Study of the Liver guidelines, though 1 mg is more commonly used 1, 2
• 2 mg/day as continuous IV infusion, which provides equal efficacy with lower total daily doses and fewer ischemic side effects compared to bolus dosing 3, 1, 2

Mandatory Albumin Co-Administration

Always administer albumin concurrently: 1 g/kg IV on day 1 (maximum 100 g), followed by 20-40 g/day until treatment completion. 1, 2 Terlipressin without albumin is significantly less effective than the combination. 2

Dose Escalation Protocol

If serum creatinine fails to decrease by ≥25-30% from baseline by day 3-4, increase to 2 mg IV every 4-6 hours (total 8 mg/day). 1, 2 The maximum dose is 12 mg/day regardless of administration method. 1, 4

A sustained increase in mean arterial pressure of ≥5-10 mmHg by day 3 predicts treatment response and supports continuing therapy. 1, 2

Treatment Duration

Continue treatment for up to 14 days maximum, or discontinue 24 hours after serum creatinine decreases to <1.5 mg/dL. 3, 2 If there is no response by day 3-4, consider discontinuation or switching to norepinephrine. 3

Critical Safety Monitoring

**Do not initiate terlipressin if SpO₂ <90%—this is an absolute contraindication.** 2 Other absolute contraindications include serum creatinine >5 mg/dL and active coronary, peripheral, or mesenteric ischemia. 2

Monitor for:

• Ischemic complications (cardiac, peripheral, mesenteric) occur in approximately 12% of patients 2
• Respiratory failure occurred in 30% of patients in the CONFIRM trial, especially those with concomitant organ failure 3, 5
• Vital signs including pulse oximetry every 2-4 hours in patients with ACLF grade <3 2

Common Pitfalls to Avoid

Avoid excessive albumin administration before terlipressin initiation, as this increases risk of respiratory failure. 2 Monitor volume status carefully throughout treatment.

Do not fail to escalate the dose on day 4 when creatinine reduction is inadequate—dose escalation is essential for improving outcomes. 2

Alternative Vasoconstrictor if Terlipressin Unavailable or Fails

Switch to norepinephrine 0.5 mg/hour continuous infusion, titrated up to 3 mg/hour to achieve MAP increase >10 mmHg above baseline. 1, 4 Norepinephrine demonstrates similar response rates of 39-70% compared to terlipressin. 3, 4 However, norepinephrine requires ICU monitoring, which significantly increases cost. 3

Predictors of Treatment Response

Favorable prognostic factors include:

• Baseline bilirubin <10 mg/dL 3, 2
• Baseline serum creatinine <5 mg/dL 3, 2
• Lower ACLF stage 3
• Presence of systemic inflammatory response syndrome, alcohol-associated hepatitis, or sepsis 3

For every 1 mg/dL reduction in creatinine with vasoconstrictor therapy, there is a 27% reduction in relative risk of mortality. 2, 4