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Please see FULL PRESCRIBING INFORMATION, INCLUDING BOXED WARNING

PRIMARY ENDPOINT

TERLIVAZ® demonstrated a significantly higher rate of Verified HRS Reversal, defined as improvement in renal function, avoidance of dialysis, and short-term survival1

Primary Endpoint Verified HRS Reversal Graph

Study: Multicomponent primary endpoint (Verified HRS Reversal) was defined as1:

  • 2 consecutive SCr values ≤1.5 mg/dL (at least 2 hours apart) by Day 14 or discharge
  • Survival without renal replacement therapy (eg, dialysis) for ≥10 days

HRS, hepatorenal syndrome; SCr, serum creatinine.

ADDITIONAL CONFIRM ENDPOINTS

TERLIVAZ demonstrated sustained reversal of HRS without RRT1,2,a

Sustained HRS Reversal Through Day 30 Graph

Study: Sustained reversal (secondary endpoint) was defined as the percentage of patients who maintained HRS reversal (SCr ≤1.5 mg/dL) without RRTa (eg, dialysis) through Day 30.1

HRS, hepatorenal syndrome; RRT, renal replacement therapy; SCr, serum creatinine.

aRRT (eg, dialysis): refers to any procedure to replace nonendocrine kidney function and includes intermittent hemodialysis, ultrafiltration, continuous hemofiltration, hemodialysis, peritoneal dialysis, and other dialysis and filtration techniques.

ADDITIONAL CONFIRM ENDPOINTS

Additional renal function assessment with TERLIVAZ2

HRS Reversal by Day 14 or Discharge Graph

Study: HRS reversal (secondary endpoint) was defined as the percent of patients who achieved SCr ≤1.5 mg/dL on at least one single measurement by Day 14 or discharge.2

Limitation of analysis: HRS reversal is a surrogate endpoint using a single SCr measurement of ≤1.5 mg/dL. Conclusions based on these data may be limited.

HRS, hepatorenal syndrome; SCr, serum creatinine.

ADDITIONAL CONFIRM ENDPOINTS

Nearly half of patients achieved complete or partial improvement in renal function with TERLIVAZ2

Complete Response - Partial Response Graph

Complete response (other prespecified endpoint) was defined as a return of SCr to a value within 0.3 mg/dL of the baseline value3

Complete Response - Partial Response Graph

Partial response (other prespecified endpoint) was defined as the regression of AKI stage with a reduction of SCr to ≥ 0.3 mg/dL above the baseline value3

AKI, acute kidney injury; SCr, serum creatinine.

HRS REVERSAL BY SCR: POOLED DATA FROM 3 PHASE III TRIALS OF TERLIPRESSIN: INTEGRATED ITT POPULATIONa

TERLIVAZ treatment earlier in disease progression was associated with a higher rate of HRS reversal4

HRS Reversal by SCr Graph

Limitation of analysis: HRS reversal is a surrogate endpoint using a single SCr measurement of ≤1.5 mg/dL. Conclusions based on these data may be limited.

Limitation of Use: Patients with SCr >5 mg/dL are unlikely to experience benefit.

OT-0401 (N=112) and REVERSE (N=196) are phase III, prospective, multicenter, randomized, double-blind, placebo-controlled trials with 1:1 randomization that evaluate the efficacy and safety of terlipressin for treatment of HRS-1. HRS reversal was a secondary endpoint in both trials and was defined as a decrease in SCr to ≤1.5 mg/dL during treatment without dialysis.5,6

Pooled data from 3 trials of TERLIVAZ.

HRS, hepatorenal syndrome; SCr, serum creatinine.

aThe integrated intent-to-treat (integrated ITT) population is the population created from the pooling of the 3 studies. The integrated ITT is defined as all randomized subjects. The primary endpoint for the summary of clinical efficacy was incidence of HRS reversal.

bHRS reversal was a secondary endpoint in all 3 trials and was defined as a decrease in SCr to ≤1.5 mg/dL on at least one single measurement during treatment without dialysis.

RRT INCIDENCE: POST HOC ANALYSIS OF PRESPECIFIED ENDPOINT FROM CONFIRM

TERLIVAZ was associated with a lower incidence of RRT7

RRT Incidence Through Days 14 and 30 Graph

44% relative reduction in RRT at Day 14 and 39% at Day 30 with TERLIVAZ.7

aThis post hoc analysis was done to show RRT incidence in patients in the ITT population who were alive through Day 90. The analysis was retrospective and based on a much smaller population than the full randomized population in the CONFIRM trial.

ITT, intent-to-treat; RRT, renal replacement therapy.

P values are nominal.

RRT IN TRANSPLANT: POST HOC ANALYSIS OF PRESPECIFIED ENDPOINTS FROM CONFIRM

TERLIVAZ was associated with a lower incidence of RRT before and after liver transplant2,8

RRT Incidence Pre-Liver Transplant Graph, RRT Incidence Post-Liver Transplant Graph

ITT, intent-to-treat; RRT, renal replacement therapy.

These post hoc analyses were done to show RRT incidence in patients in the ITT population who received a liver transplant. The analyses were retrospective and based on a much smaller population than the full randomized population in the CONFIRM trial. Those who did not receive a liver transplant were excluded.

Learn more about safety

SEE ADVERSE EVENTS
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INDICATION AND LIMITATION OF USE

TERLIVAZ is indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function.

  • Patients with a serum creatinine >5 mg/dL are unlikely to experience benefit.

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS OR FATAL RESPIRATORY FAILURE

  • TERLIVAZ® may cause serious or fatal respiratory failure. Patients with volume overload or with acute-on-chronic liver failure (ACLF) Grade 3 are at increased risk. Assess oxygenation saturation (e.g., SpO2) before initiating TERLIVAZ.
  • Do not initiate TERLIVAZ in patients experiencing hypoxia (e.g., SpO2 <90%) until oxygenation levels improve. Monitor patients for hypoxia using continuous pulse oximetry during treatment and discontinue TERLIVAZ if SpO2 decreases below 90%.

Contraindications

TERLIVAZ is contraindicated:

  • In patients experiencing hypoxia or worsening respiratory symptoms.
  • In patients with ongoing coronary, peripheral, or mesenteric ischemia.

Warnings and Precautions

  • Serious or Fatal Respiratory Failure: Obtain baseline oxygen saturation and do not initiate TERLIVAZ in hypoxic patients. Monitor patients for changes in respiratory status using continuous pulse oximetry and regular clinical assessments. Discontinue TERLIVAZ in patients experiencing hypoxia or increased respiratory symptoms.

    Manage intravascular volume overload by reducing or discontinuing the administration of albumin and/or other fluids and through judicious use of diuretics. Temporarily interrupt, reduce, or discontinue TERLIVAZ treatment until patient volume status improves. Avoid use in patients with ACLF Grade 3 because they are at significant risk for respiratory failure.

  • Ineligibility for Liver Transplant: TERLIVAZ-related adverse reactions (respiratory failure, ischemia) may make a patient ineligible for liver transplantation, if listed. For patients with high prioritization for liver transplantation (e.g., MELD ≥35), the benefits of TERLIVAZ may not outweigh its risks.

  • Ischemic Events: TERLIVAZ may cause cardiac, cerebrovascular, peripheral, or mesenteric ischemia. Avoid use of TERLIVAZ in patients with a history of severe cardiovascular conditions or cerebrovascular or ischemic disease. Discontinue TERLIVAZ in patients who experience signs or symptoms suggestive of ischemic adverse reactions.

  • Embryo-Fetal Toxicity: TERLIVAZ may cause fetal harm when administered to a pregnant woman. If TERLIVAZ is used during pregnancy, the patient should be informed of the potential risk to the fetus.

Adverse Reactions

  • The most common adverse reactions (≥10%) include abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea.

Please see full Prescribing Information, including Boxed Warning.

References:

  1. TERLIVAZ® (terlipressin). Prescribing Information. Bridgewater, NJ: Mallinckrodt Hospital Products Inc.
  2. Data on File. Ref-05035. Mallinckrodt Pharmaceuticals.
  3. Wong F, Pappas SC, Curry MP, et al. Terlipressin plus albumin for the treatment of type 1 hepatorenal syndrome. N Engl J Med. 2021;384:818-828.
  4. Data on File. Ref-05858. Mallinckrodt Pharmaceuticals.
  5. Sanyal AJ, Boyer T, Garcia-Tsao G, et al. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterol. 2008;134:1360-1368.
  6. Boyer T, Sanyal AJ, Wong F, et al. Terlipressin plus albumin is more effective than albumin alone in improving renal function in patients with cirrhosis and hepatorenal syndrome type 1. Gastroenterol. 2016;150:1579-1589.
  7. Data on File. Ref-05872. Mallinckrodt Pharmaceuticals.
  8. Data on File. Ref-05870. Mallinckrodt Pharmaceuticals.
  9. Sanyal A, Boyer TD, Frederick RT, et al. Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomized clinical studies. Aliment Pharmacol Ther. 2017;45:1390-1402.