HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use zolinza safely and effectively. See full prescribing information for zolinza.
zolinza (vorinostat) capsule for oral use
Initial U.S. Approval: 2006
INDICATIONS AND USAGE
ZOLINZA is a histone deacetylase (HDAC) inhibitor indicated for:
Treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. ( 1)
DOSAGE AND ADMINISTRATION
400 mg orally once daily with food. ( 2.1)
If patient is intolerant to therapy, the dose may be reduced to 300 mg orally once daily with food. If necessary, the dose may be further reduced to 300 mg once daily with food for 5 consecutive days each week. ( 2.2, 5)
DOSAGE FORMS AND STRENGTHS
Capsules: 100 mg ( 3)
CONTRAINDICATIONS
None ( 4)
WARNINGS AND PRECAUTIONS
Pulmonary embolism and deep vein thrombosis have been reported. Monitor patient for pertinent signs and symptoms. ( 5.1)
Dose-related thrombocytopenia and anemia have occurred and may require dose modification or discontinuation. ( 2.2, 5.2, 6)
Gastrointestinal disturbances (e.g., nausea, vomiting and diarrhea) have been reported. Patients may require antiemetics, antidiarrheals and fluid and electrolyte replacement (to prevent dehydration). ( 5.3, 6, 17.1)
Hyperglycemia has been observed. Adjustment of diet and/or therapy for increased glucose may be necessary. ( 5.4, 5.6)
QTc prolongation has been observed. Monitor electrolytes and ECGs at baseline and periodically during treatment. ( 5.5, 5.6)
Monitor blood cell counts and chemistry tests, including electrolytes, glucose and serum creatinine, every 2 weeks during the first 2 months of therapy and monthly thereafter. ( 5.6)
Severe thrombocytopenia and gastrointestinal bleeding have been reported with concomitant use of ZOLINZA and other HDAC inhibitors (e.g., valproic acid). Monitor platelet count. ( 5.7, 7.2)
Fetal harm can occur when administered to a pregnant woman. Women should be apprised of the potential harm to the fetus. ( 5.8)
ADVERSE REACTIONS
The most common adverse reactions (incidence ≥20%) are diarrhea, fatigue, nausea, thrombocytopenia, anorexia and dysgeusia. ( 6)
To report SUSPECTED ADVERSE REACTIONS, contact Merck & Co., Inc. at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
DRUG INTERACTIONS
Coumarin-derivative anticoagulants: Prolongation of prothrombin time and International Normalized Ratio have been observed with concomitant use. Monitor carefully. ( 7.1)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling
Revised: 03/2007
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FULL PRESCRIBING INFORMATION: CONTENTS*
* Sections or subsections omitted from the full prescribing information are not listed
1. INDICATIONS AND USAGE
2. DOSAGE AND ADMINISTRATION
2.1 Dosing Information
2.2 Dose Modifications
2.3 Dosing in Special Populations
3. DOSAGE FORMS AND STRENGTHS
4. CONTRAINDICATIONS
5. WARNINGS AND PRECAUTIONS
5.1 Thromboembolism
5.2 Hematologic
5.3 Gastrointestinal
5.4 Hyperglycemia
5.5 QTc Prolongation
5.6 Monitoring: Laboratory Tests
5.7 Other Histone Deacetylase (HDAC) Inhibitors
5.8 Pregnancy
6. ADVERSE REACTIONS
6.1 Clinical Trials Experience
7. DRUG INTERACTIONS
7.1 Coumarin-Derivative Anticoagulants
7.2 Other HDAC Inhibitors
8. USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Use in Patients with Hepatic Impairment
8.7 Use in Patients with Renal Impairment
10. OVERDOSAGE
11. DESCRIPTION
12. CLINICAL PHARMACOLOGY
12.1 Mechanism Of Action
12.3 Pharmacokinetics
13. NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility
14. CLINICAL STUDIES
15. REFERENCES
16. HOW SUPPLIED/STORAGE AND HANDLING
17. PATIENT COUNSELING INFORMATION
17.1 Instructions
17.2 FDA-Approved Patient LabelingFULL PRESCRIBING INFORMATION
1. INDICATIONS AND USAGE
ZOLINZA1 is indicated for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies.
2. DOSAGE AND ADMINISTRATION
2.1 Dosing Information
The recommended dose is 400 mg orally once daily with food.
Treatment may be continued as long as there is no evidence of progressive disease or unacceptable toxicity.
ZOLINZA capsules should not be opened or crushed [see How Supplied/Storage and Handling (16)].
2.2 Dose Modifications
If a patient is intolerant to therapy, the dose may be reduced to 300 mg orally once daily with food. The dose may be further reduced to 300 mg once daily with food for 5 consecutive days each week, as necessary.
2.3 Dosing in Special Populations
No information is available in patients with renal or hepatic impairment [see Pharmacokinetics (12.3)].
3. DOSAGE FORMS AND STRENGTHS
100 mg white, opaque, hard gelatin capsules with “568” over “100 mg” printed within radial bar in black ink on the capsule body.
4. CONTRAINDICATIONS
None
5. WARNINGS AND PRECAUTIONS
5.1 Thromboembolism
As pulmonary embolism and deep vein thrombosis have been reported as adverse reactions, physicians should be alert to the signs and symptoms of these events, particularly in patients with a prior history of thromboembolic events [see Adverse Reactions (6)].
5.2 Hematologic
Treatment with ZOLINZA can cause dose-related thrombocytopenia and anemia. If platelet counts and/or hemoglobin are reduced during treatment with ZOLINZA, th
