HRS patients are faced with poor outcomes1-3
Hepatorenal syndrome (HRS) with rapid reduction in kidney function is an acute condition that occurs in patients with decompensated cirrhosis and ascites.4
Without treatment1,2
≤2 weeks
MEDIAN SURVIVAL TIME
>80%
MORTALITY
within 3 months
With treatment3,a,b
36.9%
IN-HOSPITAL
MORTALITY RATE
33%
30-DAY READMISSION RATE
41% of which were unplanned
30.5 days
MEAN LENGTH
OF STAY
aPatient identification based on ICD coding, which does not differentiate types of HRS.
bReason for discharge varied among patients and was not necessarily indicative of patient outcomes.
There is an unmet need for treating HRS with rapid reduction in kidney function1,4-9
Historical Treatment Options | ||
---|---|---|
Midodrine and Octreotide | Norepinephrine | |
FDA Approved to Treat HRS With Rapid Reduction in Kidney Function | No1 | No1 |
AASLD HRS Guidance Recommendation/Preference | 3rd preference4 | 2nd preference4 |
FDA-Established Efficacy for Treating HRS | No1,4 | No1,5 |
FDA-Established Safety for Treating HRS | No1 | No1 |
Typical Treatment Setting | Medical Floor6 | ICU5 |
Need for Dedicated Central Line | No7,8 | Yes5 |
Need for Cardiac Monitoringc | No7,8 | Yes9 |
Mechanism of Action | Midodrine: α-agonist that acts as a peripheral vasoconstrictor7 Octreotide: somatostatin analog that reduced splanchnic blood flow8 | Mixed α- and β-adrenergic receptor agonist that acts as a peripheral vasoconstrictor in the setting of HRS9 |
AASLD, American Association for the Study of Liver Diseases; ICU, intensive care unit.
cWhile the Prescribing Information for midodrine and octreotide does not require cardiac monitoring, HCPs should exercise their own medical judgment when making patient-specific treatment decisions.
Recent diagnostic criteria allow for earlier diagnosis and intervention, which may lead to better outcomes10,11
SEE HRS GUIDANCEINDICATION 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:
- Boyer T, Medicis JJ, Pappas SC, et al. A randomized, placebo-controlled, double-blind study to confirm the reversal of hepatorenal syndrome type 1 with terlipressin: the REVERSE trial design. Open Access J Clin Trials. 2012;4:39-49.
- Flamm SL, Brown K, Wadei HM, et al. The current management of hepatorenal syndrome—acute kidney injury in the United States and the potential of terlipressin. Liver Transpl. 2021;27:1191-1202.
- Jamil K, Huang X, Lovelace B, et al. The burden of illness of hepatorenal syndrome (HRS) in the United States: a retrospective analysis of electronic health records. J Med Econ. 2019;22:421-429.
- 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.
- European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406-460. Published correction appears in J Hepatol. 2018;69:1207.
- Tariq R, Singal AK. Management of hepatorenal syndrome: a review. J Clin Transl Hepatol. 2020;8:192-199.
- Midodrine hydrochloride. Prescribing Information. Morgantown, WV: Mylan Pharmaceuticals, Inc.; 2020.
- Sandostatin® (octreotide acetate). Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2021.
- LEVOPHED® (norepinephrine bitartrate). Prescribing Information. Lake Forest, IL: Hospira, Inc.; 2020.
- Wong F, Pappas S, Vargas HE, et al. The diagnosis of hepatorenal syndrome: how much does use of the 2015 revised consensus recommendations affect earlier treatment and serum creatinine at treatment start? (Poster SAT-141) J Hepatol. 2019;70:e692-e693.
- 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.