Paclitaxel Disease Interactions

Because of their cytotoxic effects on rapidly proliferating tissues, antineoplastic agents frequently can, to varying extent, induce myelosuppression. The use of these drugs may be contraindicated in patients with known infectious diseases. All patients should be instructed to immediately report any signs or symptoms suggesting infection such as fever, sore throat, or local infection during antineoplastic therapy. Close clinical monitoring of hematopoietic function is recommended.

Severe conduction abnormalities, some requiring pacemaker placement, have been reported during paclitaxel therapy. Therapy with paclitaxel should be administered cautiously in patients with or predisposed to conduction disorders. Clinical monitoring of cardiac function is recommended during subsequent paclitaxel therapy.

Paclitaxel is extensively metabolized by the liver. Patients with moderate to severe hepatic impairment may be at increased risk for hepatotoxicity. Additionally, myelotoxicity of paclitaxel may be exacerbated in patients with serum total bilirubin >2 times ULN. Therapy with paclitaxel should be administered cautiously and at a reduced dosage in patients with compromised hepatic function.

Paclitaxel induces dose-dependent myelosuppression, primarily affecting neutrophils. Anemia characterized as a red blood cell count <11 g/dl has been reported in 78% of patients administered paclitaxel. Thrombocytopenia is uncommon and rarely severe. Therapy with paclitaxel should be administered cautiously in patients whose bone marrow reserve may be severely depressed and should be withheld when neutrophil counts fall below 1500/mm3 and/or platelet counts fall below 100,000/mm3. Paclitaxel injection should not be used in patients with solid tumors with baseline neutrophil counts less than 1500/mm3 or in patients with AIDS-related Kaposi's sarcoma with baseline neutrophil counts of less than 1000/mm3. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitoring of hematopoietic function is recommended.

Dose-dependent peripheral neuropathy has been reported in 60% of patients during paclitaxel therapy. Severe peripheral neuropathy is rare and requires a 20% reduction in dosage of paclitaxel. Therapy with paclitaxel should be administered cautiously in patients with or predisposed to peripheral neuropathy.

Anaphylaxis and severe hypersensitivity reactions characterized by dyspnea and hypotension requiring treatment, angioedema, and generalized urticaria have occurred in patients receiving paclitaxel. It is recommended that all patients should be pretreated with corticosteroids, diphenhydramine, and H2 antagonists. Patients who have developed severe hypersensitivity reactions should not be rechallenged with paclitaxel injection.