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Vorinostat (Monograph)

Brand name: Zolinza
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Jul 28, 2023. Written by ASHP.

Introduction

Vorinostat, a histone deacetylase (HDAC) inhibitor, is an antineoplastic agent.

Uses for Vorinostat

Cutaneous T-cell Lymphoma

Treatment of skin manifestations of cutaneous T-cell lymphoma (CTCL) in patients who have progressive, persistent, or recurrent disease during or after 2 prior systemic therapies.

Designated an orphan drug by the US Food and Drug Administration (FDA) for use in this condition.

Vorinostat Dosage and Administration

General

Pretreatment Screening

Patient Monitoring

Dispensing and Administration Precautions

Other General Considerations

Administration

Oral Administration

Administer orally with food. Swallow capsules whole; do not open or crush.

Dosage

Adults

Cutaneous T-cell Lymphoma
Oral

400 mg once daily.

In patients who do not tolerate a dosage of 400 mg once daily (e.g., because of anemia or thrombocytopenia), reduce dosage to 300 mg once daily. If needed, may further reduce dosage to 300 mg once daily for 5 consecutive days each week.

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment (bilirubin concentration 1–3 times the ULN or AST concentration exceeding the ULN): reduce starting dosage to 300 mg orally once daily with food.

Severe hepatic impairment (bilirubin concentration > 3 times the ULN): not studied.

Renal Impairment

No specific dosage recommendations at this time. However, vorinostat is not eliminated renally.

Geriatric Use

No specific dosage recommendations in geriatric patients.

Cautions for Vorinostat

Contraindications

Warnings/Precautions

Warnings

Thromboembolism

Risk of PE and DVT. Monitor for signs and symptoms of such events, especially in patients with prior history of thromboembolic events.

Hematologic Effects

Risk of dose-related thrombocytopenia and anemia. Monitor CBC every 2 weeks for the first 2 months of therapy and monthly thereafter. Adjust dosage or discontinue therapy if thrombocytopenia or anemia occurs.

GI Effects

Risk of nausea, vomiting, and diarrhea; may require antiemetic and/or antidiarrheal agents. Administer fluid and electrolyte replacement to prevent dehydration. Adequately control preexisting nausea, vomiting, and diarrhea before initiating therapy.

Hyperglycemia

Risk of hyperglycemia. Monitor serum glucose concentrations every 2 weeks for first 2 months, then monthly; monitoring especially important in patients with known or possible diabetes mellitus. Adjust diet and/or antidiabetic therapy, if needed.

Electrolyte Abnormalities

Monitor blood chemistries (including serum electrolyte [i.e., potassium, magnesium, calcium] and creatinine concentrations) every 2 weeks for the first 2 months of therapy and monthly thereafter. Monitor serum potassium and magnesium more frequently in symptomatic patients (e.g., patients who develop nausea, vomiting, diarrhea, fluid imbalance, or cardiac symptoms). Correct hypokalemia or hypomagnesemia before initiation of therapy.

Interactions with other Histone Deacetylase (HDAC) Inhibitors

Concomitant use with other HDAC inhibitors (e.g., valproic acid) may result in severe thrombocytopenia and GI bleeding. Monitor platelet count every 2 weeks during the first 2 months.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity demonstrated in animals. Females of reproductive potential: Perform pregnancy testing within 7 days before starting treatment; use effective contraception during treatment and for ≥6 months after stopping therapy. If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard. Males with female partners of reproductive potential: Use effective contraception during treatment and for ≥3 months after stopping therapy.

Specific Populations

Pregnancy

May cause fetal harm.

Lactation

Not known whether distributed into human milk. Discontinue breast-feeding during therapy and for ≥1 week after stopping therapy.

Females and Males of Reproductive Potential

May reduce female fertility.

Advise females of reproductive potential to use effective contraception during and for ≥6 months after stopping therapy.

Advise males with female partners of reproductive potential to use effective contraception during and for ≥3 months after stopping therapy.

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.

Geriatric use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

Hepatic Impairment

Systemic exposure increased by 50% in mild or moderate hepatic impairment, and by 66% in severe hepatic impairment.

Risk of grade 3 or 4 thrombocytopenia increased in hepatic impairment.

Appropriate dosage not established in patients with severe hepatic impairment.

Renal Impairment

Not studied in patients with renal impairment, but renal excretion not a significant route of elimination.

Common Adverse Effects

Adverse effects (≥20% of patients): diarrhea, fatigue, nausea, dysgeusia, thrombocytopenia, anorexia.

Drug Interactions

Not metabolized by CYP isoenzymes. Pharmacokinetic interactions unlikely with drugs that are CYP enzyme inducers or inhibitors.

Does not inhibit CYP isoenzymes in vitro at therapeutic serum concentrations. Pharmacokinetic interactions with drugs metabolized by these isoenzymes unlikely.

Not a substrate of P-glycoprotein (P-gp) and does not inhibit P-gp at therapeutic concentrations. Pharmacokinetic interactions unlikely via this pathway.

Specific Drugs

Drug

Interaction

Comments

Coumarin-derivative anticoagulants

Possible prolongation of PT and INR

Carefully monitor PT and INR

HDAC inhibitors (e.g., valproic acid)

Possibility of severe thrombocytopenia and GI bleeding

Monitor platelet count every 2 weeks for the first 2 months

Vorinostat Pharmacokinetics

Absorption

Bioavailability

Following administration of a single 400-mg oral dose to adult cancer patients in the fasted state, median time to peak plasma concentrations was about 1.5 hours (0.5–10 hours).

Food

Administration with a high-fat meal increases extent and decreases rate of absorption; median time to peak plasma concentrations was 4 hours (range: 2–10 hours).

Distribution

Plasma Protein Binding

About 71% (mainly to plasma proteins).

Elimination

Metabolism

Extensively metabolized to inactive metabolites, principally by glucuronidation and hydrolysis followed by β-oxidation. Not metabolized by CYP isoenzymes.

Elimination Route

Excreted principally (about 35–52%) in urine as the 2 major, inactive metabolites.

Only a small portion (<1%) of a dose is excreted in urine as unchanged drug.

Half-life

About 2 hours.

Stability

Storage

Oral

Capsules

20–25°C (excursions permitted between 15–30°C).

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Vorinostat

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

100 mg

Zolinza

Merck

AHFS DI Essentials™. © Copyright 2024, Selected Revisions July 28, 2023. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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