Onxol (Paclitaxel) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Drug Interactions

In a Phase 1 trial using escalating doses of paclitaxel (110 to 200 mg/m²) and cisplatin (50 or 75 mg/m²) given as sequential infusions, myelosuppression was more profound when paclitaxel was given after cisplatin than with the alternate sequence (i.e. paclitaxel before cisplatin). Pharmacokinetic data from these patients demonstrated a decrease in paclitaxel clearance of approximately 33% when paclitaxel injection was administered following cisplatin.

The metabolism of paclitaxel is catalyzed by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. In the absence of formal clinical drug interaction studies, caution should be exercised when administering ONXOL concomitantly with known substrates or inhibitors of the cytochrome P450 isoenzymes CYP2C8 and CYP3A4. (See “ CLINICAL PHARMACOLOGY ” section.)

Potential interactions between ONXOL, a substrate of CYP3A4 and protease inhibitors (ritonavir, saquinavir, indinavir, and nelfinavir), which are substrates and/or inhibitors of CYP3A4 have not been evaluated in clinical trials.

Reports in the literature suggest that plasma levels of doxorubicin (and its active metabolite doxorubicinol) may be increased when paclitaxel and doxorubicin are used in combination.

OVERDOSAGE

There is no known antidote for ONXOL overdosage. The primary anticipated complications of overdosage would consist of bone marrow suppression, peripheral neurotoxicity and mucositis. Overdoses in pediatric patients may be associated with acute ethanol toxicity (See PRECAUTIONS: Pediatric Use section).

CONTRAINDICATIONS

ONXOL is contraindicated in patients who have a history of hypersensitivity reactions to ONXOL or other drugs formulated in polyoxyl 35 castor oil.

ONXOL should not be used in patients with solid tumors who have baseline neutrophil counts of <1,500 cells/mm³ or in patients with AIDS-related Kaposi’s sarcoma with baseline neutrophil counts of <1,000 cells/mm³.

References

1. Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs. NIH Publication No. 83-2621. For sale by the Superintendent of Documents, US Government Printing Office, Washington, DC 20402.

2. AMA Council Report. Guidelines for Handling Parenteral Antineoplastics. JAMA 1985; 253(11):1590-1592.

3. National Study Commission on Cytotoxic Exposure – Recommendations for Handling Cytotoxic Agents. Available from Louis P. Jeffrey, Chairman, National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, Massachusetts, 02115.

4. Clinical Oncological Society of Australia. Guidelines and Recommendations for Safe Handling of Antineoplastic Agents. Med J Australia 1983; 1:426-428.

5. Jones RB, et al: Safe Handling of Chemotherapeutic Agents: A Report from the Mount Sinai Medical Center. CA-A Cancer Journal for Clinicians 1983; Sept./Oct. 258-263.

6. American Society of Hospital Pharmacists Technical Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs. Am J Hosp Pharm 1990; 47:1033-1049.

7. Controlling Occupational Exposure of Hazardous Drugs (OSHA WORK-PRACTICE GUIDELINES). Am J Health – Syst-Pharm 1996; 53:1669-1685.

IVEX-2^® is the registered trademark of the Millipore Corporation.
Chemo Dispensing Pin™ is a trademark of B. Braun Medical Incorporated.

ONXOL^® is a registered trademark of IVAX Research Inc.

Mfd for: IVAX Research, Inc., Miami, FL 33137
Mfd by: Mayne Pharma Pty Ltd., Mulgrave, Victoria, Australia 3170
Dist. by: IVAX Pharmaceuticals, Inc., Miami, FL 33137
L5130
Rev. 06/05
481407