Proposed Mechanism of Action1
TERLIVAZ®:
- Is a synthetic vasopressin analogue
- Has twice the selectivity for vasopressin V1 receptors, targeting the splanchnic circulation, versus V2 receptors2
- Acts as a prodrug for lysine-vasopressin as well as having pharmacologic activity on its own
TERLIVAZ is thought to increase renal blood flow in HRS patients by:
- Reducing portal hypertension
- Reducing blood circulation in portal vessels
- Increasing effective arterial volume and mean arterial pressure (MAP)
Pharmacodynamics1
- After a single 0.85 mg dose in HRS patients, the following was seen within 5 minutes after dose and maintained for at least 6 hours:
- Increase in diastolic, systolic, and MAP
- Max change in BP and HR—1.2 to 2 hours post dose
- MAP—estimated maximum effect = increase of 16.2 mmHg
- Decrease in heart rate
- Estimated maximum effect for heart rate = decrease of 10.6 beats/minute
- Increase in diastolic, systolic, and MAP
Pharmacokinetics1
- Terminal half-life
- TERLIVAZ—0.9 hours
- Lysine-vasopressin—3 hours
HRS, hepatorenal syndrome.
Learn more about ordering TERLIVAZ for your appropriate patients
SEE DISTRIBUTORS AND ADDITIONAL RESOURCESINDICATION 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.
Reference:
- TERLIVAZ® (terlipressin). Prescribing Information. Bridgewater, NJ: Mallinckrodt Hospital Products Inc.
- Mattos AZ, Schacher FC, Mattos AA. Vasoconstrictors in hepatorenal syndrome—a critical review. Ann Hepatol. 2019;18(2):287-290. doi:10.1016/j.aohep.2018.12.002