Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 0.85mg/vial
Hepatorenal Syndrome
Indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function
Days 1-3: 0.85 mg slow IV bolus q6hr
Day 4
- Adjust dose based on changes from baseline serum creatinine (SCr)
- SCr decreased by ≥30% from baseline: Continue at 0.85 mg IV q6hr
- SCr decreased by <30% from baseline: Increase to 1.7 mg IV q6hr
- SCr at or above baseline: Discontinue
-
Days 4-14
- Continue until 24 hr after second consecutive SCr of ≤1.5 mg/dL at least 2 hr apart OR for a maximum of 14 days
Dosage Modifications
Renal impairment
- Adjust dose according to SCr improvement from baseline as described above
Hepatic impairment
- No dose adjustment required
Dosing Considerations
Limitation of use: Patients with serum creatinine >5 mg/dL unlikely to benefit
Monitoring
-
Before initiating
- Obtain baseline oxygen saturation (SpO2)
- Assess acute-on-chronic liver failure (ACLF) Grade and volume status
- Record last available serum creatinine (SCr) value (baseline SCr)
-
During treatment
- Monitor oxygen saturation using continuous pulse oximetry; do not use in patients experiencing hypoxia until hypoxia resolves
- Treatment day 4 and afterwards: Assess SCr level vs baseline or previous measurement to adjust dose according to prescribing information
Safety and efficacy not established
Adverse Effects
>10%
Abdominal pain (19.5%)
Nausea (16%)
Respiratory failure (15.5%)
Diarrhea (13%)
Dyspnea (12.5%)
1-10%
Fluid overload (8.5%)
Pleural effusion (5.5%)
Sepsis (5.5%)
Bradycardia (5%)
Ischemia-related events (4.5%)
Postmarketing Reports
Headache
Hyponatremia
Skin necrosis and gangrene
Warnings
Black Box Warnings
Serious or fatal respiratory failure
- 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 (eg, SpO2) before initiating
- Do not initiate in patients experiencing hypoxia (eg, SpO2 <90%) until oxygenation levels improve
- Monitor for hypoxia using continuous pulse oximetry during treatment and discontinue if SpO2 decreases below 90%
Contraindications
Patients experiencing hypoxia or worsening respiratory symptoms
Patients with ongoing coronary, peripheral, or mesenteric ischemia
Cautions
May cause fetal harm when administered to pregnant females; terlipressin induces uterine contractions and endometrial ischemia in both humans and animals
May cause cardiac, cerebrovascular, peripheral, or mesenteric ischemia; avoid with history of severe cardiovascular conditions, cerebrovascular, and ischemic disease; discontinue signs or symptoms suggestive of ischemic adverse reactions occur
Serious or fatal respiratory failure
- May cause serious or fatal respiratory failure
- Obtain baseline SpO2 and do not initiate in hypoxic patients
- Monitor for changes in respiratory status using continuous pulse oximetry and regular clinical assessments
- Discontinue if hypoxia or increased respiratory symptoms occur
- Fluid overload may increase risk; manage intravascular volume overload by reducing or discontinuing albumin and/or other fluids and judicious diuretic use
- Temporarily interrupt, reduce, or discontinue treatment until volume status improves
- Avoid use in patients with ACLF Grade 3 because they are at significant risk for respiratory failure
Ineligibility for liver transplant
- Terlipressin-related adverse reactions (respiratory failure, ischemia) may make patients ineligible for liver transplantation (if listed)
- For patient with high prioritization for liver transplantation (eg, MELD ≥35), benefits of terlipressin may not outweigh risks
Pregnancy & Lactation
Pregnancy
May cause fetal harm, based on its mechanism of action and findings in published literature
In small, published studies, administration of a single IV dose to pregnant females during the first trimester induced uterine contractions and endometrial ischemia
Limited published data are not sufficient to determine drug-associated risk for major birth defects or miscarriage
Inform pregnant patients of potential risk to fetus
Animal studies
- Administration to pregnant guinea pigs at doses lower than the maximum recommended human dose of 4 mg/day caused a marked decrease in uterine and placental blood flow
- In rabbits, it is both embryotoxic and teratogenic (increased resorptions, increased implantation loss, fetal anomalies and fetal deformities)
Lactation
Data are not available regarding presence in human or animal milk, effects on breastfed infants, or effect on milk production
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Synthetic vasopressin analogue with twice the selectivity for vasopressin V1 receptors versus V2 receptors
Acts as both a prodrug of lysine-vasopressin, as well as having pharmacologic activity on its own
Thought to increase renal blood flow in patients with hepatorenal syndrome by reducing portal hypertension and blood circulation in portal vessels and increasing effective arterial volume and mean arterial pressure (MAP)
Absorption
Peak plasma concentration (steady-state): 70.5 ng/mL
Average plasma concentration (steady-state): 14.2 ng/mL
AUC24h (steady-state): 123 ng⋅hr/mL
Distribution
Vd: 6.3 L; 1370 L (lysine-vasopressin)
Metabolism
Metabolized by cleavage of N-terminal glycyl residues of terlipressin by various tissue peptidases, resulting in release of pharmacologically active metabolite lysine-vasopressin
Once formed, lysine-vasopressin is metabolized by body tissue via various peptidase-mediated routes
Terlipressin is not metabolized in blood or plasma
Owing to the ubiquitous nature of peptidases in body tissue, it is unlikely that metabolism will be affected by disease state or other drugs
Elimination
Half-life: 0.9 hr; 3 hr (lysine-vasopressin)
Excretion: Urine <1%; <0.1% (lysine-vasopressin) in healthy subjects
Clearance
- 27.4 L/hr (terlipressin); 318 L/hr (lysine-vasopressin)
- Clearance increases with increased body weight
- Body weight has no effect on lysine-vasopressin clearance
Administration
IV Compatibilities
0.9% NaCl
IV Preparation
Reconstitute each vial with 5 mL 0.9% NaCl to prepare 0.85 mg/5mL solution
Inspected visually for particulate matter and discoloration
IV Administration
Administer through peripheral or central line by slow IV bolus (over 2 minutes)
Dedicated central line not required
Flush line after administration
Storage
Unopened vials
- Refrigerate vials in carton at 2-8ºC (36-46ºF)
- Store in original carton to protect from light before reconstitution
Reconstituted vial
- Refrigerate at 2-8ºC (36-46ºF) for up to 48 hr
- Do not freeze
- Reconstituted solution does not need protection from light
Images
Formulary
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