terlipressin (Rx)

Brand and Other Names:Terlivaz
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Dosing & Uses

AdultPediatric

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

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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

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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
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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.

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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
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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
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Images

No images available for this drug.
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Patient Handout

A Patient Handout is not currently available for this monograph.
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Formulary

FormularyPatient Discounts

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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.