FDA Approved Cardiovascular & Renal

Terlipressin

also known as: Terlivaz, Glypressin, Lucassin, Variquel, Remestyp, Triglycyl lysine vasopressin

Terlivaz — the first and only FDA-approved drug for hepatorenal syndrome (HRS). FDA-approved September 2022 (Mallinckrodt) for adults with HRS with rapid reduction in kidney function, after a multi-decade regulatory history including four prior Complete Response Letters and the successful CONFIRM Phase 3 trial (NEJM 2021).

A synthetic triglycyl-lysine-vasopressin dodecapeptide prodrug developed in the 1960s by Ferring Pharmaceuticals and marketed outside the US for decades (Glypressin®, Lucassin®). The three N-terminal glycine residues act as a slow-release handle — endogenous endothelial endopeptidases cleave them sequentially to release lysine-vasopressin (lypressin) over approximately six hours per bolus dose, giving an intermittent-dosing alternative to continuous vasopressin infusion. Mallinckrodt's Terlivaz® received FDA approval on 14 September 2022 after priority review, fast-track designation, orphan designation, and four prior Complete Response Letters; approval was based on the CONFIRM Phase 3 trial (n=300, NEJM March 2021) showing improved Verified HRS Reversal (29.1% vs 15.8% placebo, p=0.012). Indication: improving kidney function in adults with HRS with rapid reduction in kidney function. Carries a boxed warning for serious / fatal respiratory failure.

Mechanism of action

Terlipressin itself has modest direct V1a receptor activity. The three N-terminal glycine residues are sequentially cleaved by endothelial endopeptidases to release lysine-vasopressin (lypressin) — a V1a-selective vasoconstrictor. V1a receptor activation in the splanchnic vasculature is the therapeutic mechanism in hepatorenal syndrome: splanchnic vasoconstriction reduces the pathologic splanchnic arterial vasodilation that underlies HRS, restoring effective arterial blood volume and renal perfusion. Selectivity for V1a over V2 is higher than for native vasopressin, reducing free-water-retention liability. The prodrug architecture allows intermittent IV bolus dosing (every 4–6 hours) rather than the continuous-infusion requirement of vasopressin itself.

Primary uses

  • Hepatorenal syndrome with rapid reduction in kidney function (FDA-approved)
  • Bleeding esophageal varices (international approvals — portal-pressure reduction)
  • Type 1 hepatorenal syndrome (international approvals — European guidelines)

Typical dosing

0.85–2 mg IV bolus every 6 hours (intravenous bolus)

Starting dose 0.85 mg IV every 6 hours. If serum creatinine has decreased <30% from baseline after 3 days, increase to 1.7 mg every 6 hours. Maximum 2 mg every 6 hours. Maximum treatment duration 14 days. Not recommended if serum creatinine >5 mg/dL (unlikely to benefit). Monitor SpO2 before and during treatment. Contraindicated in acute-on-chronic liver failure grade 3.

Regulatory status

FDA-approved September 14, 2022 (Terlivaz®, Mallinckrodt plc). Priority review, fast-track, and orphan drug designation. US indication: adults with hepatorenal syndrome with rapid reduction in kidney function. Long prior international approval history (Germany, Italy, Spain, UK, Australia, Canada, etc.) as Glypressin®, Lucassin®, Variquel®, and Remestyp®. US approval history included four Complete Response Letters before the CONFIRM Phase 3 success.

References

  1. [fda-pi] Terlivaz® (terlipressin) Prescribing Information. Mallinckrodt Pharmaceuticals. Initial US approval September 14, 2022.
  2. [clinical-trial] Wong F, Pappas SC, Curry MP, et al. "Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome (CONFIRM)." N Engl J Med, 2021;384(9):818-828.
  3. [news-release] Mallinckrodt plc. "Mallinckrodt Receives U.S. FDA Approval for Terlivaz® (terlipressin) for injection for the Treatment of Hepatorenal Syndrome (HRS)." September 14, 2022.

Related peptides

Vasopressin

Vasostrict — the endogenous antidiuretic hormone as an ICU vasopressor. FDA-approved April 2014 for adults with vasodilatory shock (post-cardiotomy, sepsis) who remain hypotensive despite fluids and catecholamines. Works through V1a receptors on vascular smooth muscle — a receptor axis pharmacologically distinct from catecholamine receptors, preserving its vasopressor effect when adrenergic receptors are desensitised.

Desmopressin

DDAVP — the classic V2-selective vasopressin analog. FDA-approved February 1978 for central diabetes insipidus; decades of label expansion added primary nocturnal enuresis, nocturia (Noctiva / Nocdurna), and hemostatic use in mild hemophilia A and type 1 von Willebrand disease. WHO Essential Medicines List.

Angiotensin II

Giapreza — the first new vasopressor class approved in decades. FDA-approved December 2017 (La Jolla Pharmaceutical) for catecholamine-resistant septic / distributive shock based on the ATHOS-3 trial (NEJM 2017, n=321). Engages a third vasoconstrictor pathway (RAAS / AT1) independent of catecholamines and vasopressin — useful when both of those axes are desensitised.
Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.