paclitaxel
Taxol

Available forms
Available by prescription only
Injection: 30 mg/5 ml

Indications and dosages
 First-line and subsequent therapy for the treatment of advanced carcinoma of the ovary. Adults (previously untreated): 175 mg/m² over 3 hours every 3 weeks followed by cisplatin 75 mg/m²; or, 135 mg/m² over 24 hours in combination with cisplatin 75 mg/m² every 3 weeks.
Adults (previously treated): 135 or 175 mg/m² I.V. over 3 hours q 3 weeks.
 Breast carcinoma after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy (prior therapy should have included an anthracycline unless clinically contraindicated); adjuvant treatment of node-positive breast cancer administered sequentially to standard doxorubicin-containing combination chemotherapy. Adults: 175 mg/m² I.V. over 3 hours q 3 weeks.
 AIDS-related Kaposi’s sarcoma. Adults: 135 mg/m² I.V. over 3 hours q 3 weeks, or 100 mg/m² I.V. over 3 hours q 2 weeks.
 Initial treatment of advanced non-small-cell lung cancer for patients who aren’t candidates for curative surgery or radiation. Adults: 135 mg/m² I.V. infusion over 24 hours; follow with cisplatin 75 mg/m². Repeat cycle every 3 weeks.
≡ Dosage adjustment. Subsequent courses shouldn’t be repeated until neutrophil count is at least 1,500 cells/mm³ and platelet count is at least 100,000 cells/mm³.

Pharmacodynamics
Antineoplastic action: Prevents depolymerization of cellular microtubules, thus inhibiting the normal reorganization of the microtubule network necessary for mitosis and other vital cellular functions.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: About 89% to 98% bound to serum proteins.
Metabolism: Possibly metabolized in liver.
Excretion: Not fully understood.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or polyoxyethylated castor oil, a vehicle used in drug solution. Also contraindicated in patients with baseline neutrophil counts below 1,500/mm³. Use cautiously in patients who have received radiation therapy.

Interactions
Drug-drug. Cisplatin: Myelosuppression may be greater when cisplatin is given before rather than after paclitaxel. Consider this effect before therapy.
CNS depressants, antihistamines, opiates: May increase the potential for CNS depression. Monitor patient.
Cyclosporine, dexamethasone, diazepam, etoposide, ketoconazole, quinidine, teniposide, verapamil, vincristine: Inhibits paclitaxel metabolism. Use together cautiously.

Adverse reactions
CNS: peripheral neuropathy.
CV: bradycardia, hypotension, abnormal ECG.
GI: nausea, vomiting, diarrhea, mucositis.
Hematologic: neutropenia, leukopenia, thrombocytopenia, anemia, bleeding.
Hepatic: liver dysfunction.
Musculoskeletal: myalgia, arthralgia.
Skin: alopecia, cellulitis at injection site.
Other: hypersensitivity reactions (anaphylaxis), phlebitis, infections.

Effects on lab test results
• May increase alkaline phosphatase, AST, and triglyceride levels.
• May decrease hemoglobin, hematocrit, and neutrophil, WBC, and platelet counts.

Overdose and treatment
Primary complications of overdose include bone marrow suppression, peripheral neurotoxicity, and mucositis.
 No specific antidote for overdose is known.

Special considerations
• Severe hypersensitivity reactions characterized by dyspnea, hypotension, angioedema, and generalized urticaria have occurred in 2% of patients receiving paclitaxel. To reduce risk or severity of these reactions, pretreat patients with corticosteroids (such as dexamethasone), antihistamines (such as diphenhydramine), and H₂-receptor antagonists (such as cimetidine or ranitidine).
• One commercially available formulation contains metabisulfite. Use cautiously in patients who have allergies to sulfites.
• Don’t rechallenge patients who experience severe hypersensitivity reactions to drug.
• In patients who experience severe neutropenia (neutrophil count below 500 cells/mm³ for 1 week or longer) or severe peripheral neuropathy during drug therapy, reduce dosage by 20% for subsequent courses. Risk and severity of neurotoxicity and hematologic toxicity increase with dose, especially above 190 mg/m².
• Bone marrow toxicity is the most frequent and dose-limiting toxicity. Frequent blood count monitoring is needed during therapy. Packed RBC or platelet transfusions may be needed in severe cases. Take bleeding precautions as appropriate.
• Use caution during drug preparation and administration; wear gloves. If solution contacts skin, wash immediately and thoroughly with soap and water. If drug contacts mucous membranes, flush thoroughly with water. Mark all waste materials with CHEMOTHERAPY HAZARD labels.
• Concentrate must be diluted before infusion. Compatible solutions include normal saline solution, D₅W, dextrose 5% in normal saline solution injection, and 5% dextrose in lactated Ringer’s injection. Dilute to a final concentration of 0.3 to 1.2 mg/ml. Diluted solutions are stable for 27 hours at room temperature.
• Prepare and store infusion solutions in glass containers. Undiluted concentrate shouldn’t contact polyvinyl chloride I.V. bags or tubing. Store diluted solution in glass or polypropylene bottles, or use polypropylene or polyolefin bags. Administer through polyethylene-lined administration sets, and use an in-line filter with a microporous membrane not exceeding 0.22 microns.
• Monitor patient continuously for 30 minutes after starting infusion. Closely monitor patient throughout infusion.
• If patient develops significant conduction abnormalities during drug administration, provide appropriate therapy and monitor cardiac function continuously during subsequent drug therapy.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Because of potential for serious adverse reactions in breast-fed infants, women should discontinue breast-feeding during therapy.
Pediatric patients
• Safety and effectiveness in children haven’t been established.

Patient education
• Advise woman of childbearing age to avoid becoming pregnant during therapy because of potential harm to fetus.
• Warn patient that alopecia occurs in almost all patients.
• Teach patient to recognize and immediately report signs and symptoms of peripheral neuropathy, such as tingling, burning, and numbness in limbs. Although mild symptoms are common, severe symptoms occur infrequently. Dosage reduction may be needed.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use