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Paclitaxel (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 (ie, paclitaxel before cisplatin). Pharmacokinetic data from these patients demonstrated a decrease in paclitaxel clearance of approximately 33% when paclitaxel was administered following cisplatin.

The metabolism of paclitaxel is catalyzed by cytochrome P450 isoenzymes CYP2C8 and CYP3A4. Caution should be exercised when paclitaxel is concomitantly administered with known substrates (eg, midazolam, buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, and triazolam), inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin), and inducers (eg, rifampin and carbamazepine) of CYP3A4. (See CLINICAL PHARMACOLOGY.)

Caution should also be exercised when paclitaxel is concomitantly administered with known substrates (eg, repaglinide and rosiglitazone), inhibitors (eg, gemfibrozil), and inducers (eg, rifampin) of CYP2C8. (See CLINICAL PHARMACOLOGY.)

Potential interactions between paclitaxel, 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.

Hematology: Paclitaxel therapy should not be administered to patients with baseline neutrophil counts of less than 1500 cells/mm3. In order to monitor the occurrence of myelotoxicity, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving paclitaxel. Patients should not be re-treated with subsequent cycles of paclitaxel until neutrophils recover to a level >1500 cells/mm3 and platelets recover to a level >100,000 cells/mm3. In the case of severe neutropenia (<500 cells/mm3 for 7 days or more) during a course of paclitaxel therapy, a 20% reduction in dose for subsequent courses of therapy is recommended.

For patients with advanced HIV disease and poor-risk AIDS-related Kaposi's sarcoma, paclitaxel, at the recommended dose for this disease, can be initiated and repeated if the neutrophil count is at least 1000 cells/mm3.

OVERDOSAGE

There is no known antidote for paclitaxel 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).

CONTRAINDICATIONS

Paclitaxel Injection, USP is contraindicated in patients who have a history of hypersensitivity reactions to Paclitaxel Injection, USP or other drugs formulated in Cremophor® EL (polyoxyethylated castor oil).

Paclitaxel Injection, USP should not be used in patients with solid tumors who have baseline neutrophil counts of <1500 cells/mm3 or in patients with AIDS-related Kaposi's sarcoma with baseline neutrophil counts of <1000 cells/mm3.

REFERENCES

  1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.
  2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling occupational exposure to hazardous drugs. OSHA, 1999.
    http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html.
  3. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. 2006;63:1172-1193.
  4. Polovich M, White JM, Kelleher LO, eds. 2005. Chemotherapy and biotherapy guidelines and recommendations for practice. 2nd ed. Pittsburgh, PA: Oncology Nursing Society.

Brands listed are the trademarks of their respective owners.

SAGENT™

Mfd. for SAGENT Pharmaceuticals
Schaumburg, IL 60195 (USA)
Made in Romania
©2011 Sagent Pharmaceuticals, Inc.

June 2011

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