Dosing and uses of Zolinza (vorinostat)
Adult dosage forms and strengths
capsule
- 100mg
Cutaneous T-cell Lymphoma
Indicated for treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent, or recurrent disease during or following 2 systemic therapies
400 mg PO qDay
May reduce to 300 mg qDay, and then to 300 mg qDay for 5 days/wk if intolerant
Monitor: CBC, electrolytes, serum glucose and creatinine q2week during first 2 months and monthly thereafter
Dosage modifications
Hepatic impairment
- Mild/moderate (Child-Pugh A or B): Use with caution
- Severe (Child-Pugh C): Contraindicated
Multiple Myeloma (Orphan)
Orphan designation for treatment of multiple myeloma
Sponsor
- Merck Research Laboratories; Merck & Co Inc; PO Box 2000, RY 33-212; Rahway, NJ 07065-0900
Melanoma (Orphan)
Orphan designation for treatment of advanced melanoma (stages IIb, IIc, III, and IV)
Sponsor
- Qameleon Therapeutics; Moslaan 32, 1433 WJ; Kudelstaart, Netherlands
Pediatric dosage forms and strengths
Safety and efficacy not established
Zolinza (vorinostat) adverse (side) effects
>10%
Diarrhea (52%)
Fatigue (52%)
Nausea (41%)
Dysguesia (28%)
Thrombocytopenia (26%)
Anorexia (24%)
Weight loss (20.9%)
Muscle spasms (19.8%)
Alopecia (18.6%)
Chills (16%)
Dry mouth (16%)
Increase serum Cr (16%)
Dizziness (15%)
Constipation (15%)
Vomiting (15%)
Anemia (14%)
Peripheral edema (12.8%)
Headache (11.6%)
Pruritus (11.6%)
Cough (10.5%)
Upper respiratory infection (10.5%)
Decreased appetite
Pyrexia
1-10%
Prolonged QT interval (3.5-6%)
Pulmonary embolism (4.7%)
Warnings
Contraindications
Severe hepatic Impairment
Cautions
Congenital long QT syndrome, drugs/conditions that prolong QT interval; correct hypokalemia or hypomagnesemia before commencing treatment
History of thromboembolic disease; potential for DVT/Pe
Potential for hyperglycemia; caution in diabetes
Dose related anemia and thrombocytopenia may occur; modify dose or discontinue if reduction in platelets or HgB
Concomitant valproic acid
May cause dizziness or fatigue
Concomitant coumarin-derived anticoagulants
Hepatic/renal impairment
Nausea, vomiting, or diarrhea
Avoid pregnancy
Drink at least 2 L of fluids daily
Pregnancy and lactation
Pregnancy category: d
Lactation: not known whether excreted in breast milk, do not nurse
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 of Zolinza (vorinostat)
Mechanism of action
Histone deacetylase inhibitor for enzymes HDAC1, HDAC2, HDAC3, and HDAC6, which in turn alters chromatin structure and transcription factor activation; as a result, cell growth is terminated and apoptosis occurs
Absorption
Peak plasma time: 4 hr
Peak plasma concentration (400 mg dose): 1.2±0.62 umol/L
Fasted state has quicker peak time, but lower AUC and peak concentration
Taken with a high fat meal increases extent of absorption by 33%
Bioavailability: 43%
Distribution
Protein Bound: 71%
Metabolism
Liver
Metabolites: Inactive
Elimination
Half-Life, Terminal: 2 hr
Excretion: Urine 52%
Administration
Oral Administration
Take with food
Drink at least 2 L of fluids daily
