Class: Histone deacetylase inhibitor
- Capsules, oral 100 mg
Inhibits enzymatic activity of histone deacetylases (HDACs) at nanomolar concentrations. These enzymes catalyze the removal of acetyl groups from the lysine residue of proteins, including histones and transcription factors.
When administered with high-fat meal, C max is 1.2 mcM and T max is 4 h. The extent of absorption is increased 33% when taken with a high-fat meal.
Plasma protein binding is approximately 71%.
Metabolism involves glucuronidation and hydrolysis followed by beta-oxidation.
Less than 1% of an administered dose is recovered unchanged in the urine. Total urinary recovery of vorinostat and 2 inactive metabolites averages 52%. Mean terminal half-life is 2 h.
Special PopulationsRenal Function Impairment
Not evaluated; renal excretion does not play a role in the elimination of vorinostat.Hepatic Function Impairment
An ongoing pharmacokinetic study showed higher incidence and severity of adverse reactions in patients with severe hepatic dysfunction.Elderly
Age does not appear to have a meaningful effect on vorinostat pharmacokinetics.Children
Not evaluated in patients younger than 18 y.Gender
Gender does not appear to have a meaningful effect on vorinostat pharmacokinetics.Race
Race does not appear to have a meaningful effect on vorinostat pharmacokinetics.
Indications and Usage
Treatment of cutaneous manifestation in patients with cutaneous T-cell lymphoma who have progressive, persistent, or recurrent disease during or following 2 systemic therapies.
Severe hepatic impairment.
Dosage and AdministrationAdults
PO 400 mg once daily with food, continued as long as there is no evidence of progressive disease or unacceptable toxicity. If a patient is intolerant to therapy, the dosage may be reduced to 300 mg once daily with food; the dosage may be further reduced to 300 mg once daily with food for 5 consecutive days each week, as necessary.
- Should be taken with food and at least 8 oz of liquid.
- Capsules should not be opened or crushed.
Store between 59° and 86°F.
Drug InteractionsCoumarin-derivative anticoagulants (eg, warfarin)
Prolongation of PT and INR may be prolonged.Other HDAC inhibitors (eg, valproic acid)
The risk of GI bleeding and severe thrombocytopenia may be increased. Monitor platelet count every 2 wk for the first 2 mo.
Fatigue (52%); dizziness (15%); headache (12%); pyrexia (11%).
Alopecia (19%); pruritus (12%).
Diarrhea (52%); nausea (41%); dysgeusia (28%); anorexia (24%); dry mouth (16%); constipation, vomiting (15%); decreased appetite (14%).
Thrombocytopenia (26%); anemia (14%).
Increased serum glucose (69%); proteinuria (51%); increased serum creatinine (46%); increased blood creatinine (16%).
Decreased weight (21%).
Muscle spasms (20%).
Cough, upper respiratory tract infection (11%); pulmonary embolism (5%).
Chills (16%); peripheral edema (13%); squamous cell carcinoma (4%).
Monitor CBC and blood chemistry, including electrolytes, glucose, and serum creatinine, every 2 wk during the first 2 mo of therapy and every month thereafter. Perform ECGs during treatment.
Category D .
Safety and efficacy not established.
Not evaluated; use with caution.
Contraindicated in patients with severe hepatic impairment; use with caution in patients with mild or moderate hepatic impairment.
GI disturbances, including diarrhea, nausea, and vomiting, may occur. Antiemetic and antidiarrheal medications may be needed.
Dose-related thrombocytopenia and anemia may occur.
May occur. Monitor serum glucose.
Although not studied, QTc prolongation has been reported.
Pulmonary embolism and deep vein thrombosis may occur.
No information is available.
- Advise patients to read the patient information leaflet before using vorinostat the first time and with each refill.
- Instruct patients to take vorinostat exactly as prescribed and not to change the dose or discontinue therapy unless advised by their health care provider.
- Instruct patients to take the medicine with food and to drink at least 8 oz of liquid when taking the capsule.
- Instruct patients to drink at least 2 L/day of fluid to prevent dehydration.
- Advise patients to swallow capsule whole and not to open or crush capsule.
- Instruct patients to report excessive diarrhea or vomiting to their health care provider.
- Instruct patients to seek immediate medical attention if unusual bleeding occurs.
- Advise patients that if a dose is missed to take it as soon as they remember. If it is almost time for the next dose, tell them to skip the missed dose and go back to the regular dosing schedule. Advise patients not to take 2 doses at the same time.
- Advise patients to keep all appointments and that blood cell counts, blood sugar, and other chemistries will be monitored every 2 wk for the first 2 mo of treatment then every month thereafter.
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