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Please see FULL PRESCRIBING INFORMATION, INCLUDING BOXED WARNING

Earlier diagnosis can lead to better outcomes, as recommended by AASLD Guidance1-4

AASLD Guidance for Diagnosis and Treatment of HRS1*

AASLD Algorithm for Diagnosis and Treatment of HRS1 Image

Treatment1*

Vasoconstrictor Therapy
(in combination with albumin)

  • Preferred drug: terlipressine
  • In settings where terlipressin is not available, NE should be given
  • If neither can be administered, a trial of midodrine in combination with octreotide may be considered
  • When treating with vasoconstrictor therapy, albumin should be infused at 1 g/kg on Day 1 of therapy, then followed by 40-50 g/day and continued for the duration of therapy

Other treatment options, such as RRT and transplant, could be considered for certain patients.

AASLD, American Association for the Study of Liver Diseases; AIN, acute interstitial nephritis; AKI, acute kidney injury; ATN, acute tubular necrosis; HRS, hepatorenal syndrome; NE, norepinephrine; NGAL, neutrophil gelatinase-associated lipocalin; RRT, renal replacement therapy; SCr, serum creatinine; UTI, urinary tract infection; UTO, urinary tract obstruction.

aClinical assessment includes evaluation for prerenal (eg, overdiuresis, dehydration) or structural (eg, shock, nephrotoxins, obstructive uropathy) etiologies. Urinary sediments and biomarkers (particularly NGAL) may indicate ATN, whereas fractional excretion of sodium <1% may suggest HRS.

bRisk-factor management includes the withdrawal of nephrotoxic drugs, reduction or withdrawal of diuretics, detection, and treatment of infections, if present, and volume replacement (if severely volume-depleted) using 5% albumin or crystalloids, preferentially balanced, initially.

cPatients experiencing a further rise in serum creatinine despite risk factor management may immediately proceed to the next step, namely albumin challenge. Some members of the writing group advocate taking into account the absolute creatinine value in addition to the change in creatinine to expedite this step to allow earlier institution of vasoconstrictors in patients with a high (eg, >1.5 mg/dL) creatinine.

dThese patients are expected to have ascites, commonly refractory, and almost always hyponatremia.

eTERLIVAZ (terlipressin) was not evaluated in comparison to other treatments in a head-to-head clinical study.

*Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Biggins SW, Angeli P, Garcia-Tsao G, Ginès P, Ling SC, Nadim MK, Wong F, Kim WR. Copyright © 2021 American Association for the Study of Liver Diseases.
Reproduced with permission of John Wiley & Sons, Inc.

Terlipressin is recommended by AASLD Guidance and ACG Guidelines for the treatment of HRS

SEE THE RECOMMENDATIONS
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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. Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74:1014-1048.
  2. Boyer TD, Sanyal AJ, Garcia-Tsao G, et al. Predictors of response to terlipressin plus albumin in hepatorenal syndrome (HRS) type 1: relationship of serum creatinine to hemodynamics. J Hepatol. 2011;55:315-321.
  3. Piano S, Schmidt HH, Ariza X, et al. Association between grade of acute on chronic liver failure and response to terlipressin and albumin in patients with hepatorenal syndrome. Clin Gastroenterol Hepatol. 2018;16:1792-1800.
  4. Solé C, Pose E, Solà E, Ginès P. Hepatorenal syndrome in the era of acute kidney injury. Liver Int. 2018;38:1891-1901.
  5. TERLIVAZ® (terlipressin). Prescribing Information. Bedminster, NJ: Mallinckrodt Hospital Products Inc.