Paclib Special Precautions

General: Paclitaxel has a low therapeutic index. Therapeutic response is not likely to occur without evidence of toxicity. It should also be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents.
Cardiovascular: Hypotension, hypertension and bradycardia have been reported but patients are usually asymptomatic and generally do not require treatment. Severe cases of conduction abnormalities have been reported in <1% of patients receiving paclitaxel. In severe cases, paclitaxel infusions may need to be interrupted or discontinued at the discretion of the physician. Cardiac function monitoring is recommended in patients with preexisting cardiac abnormalities and when paclitaxel is co-administered with doxorubicin in patients with metastatic breast cancer.
If patients develop significant cardiac function abnormalities during administration, appropriate therapy should be administered and continuous electrocardiographic monitoring should be performed during subsequent therapy with paclitaxel.
Hepatic: Patients with hepatic impairment may be at an increased risk of toxicity mainly grade III to IV myelosuppression. Increased myelosuppression may be observed in patients with moderate to severe hepatic impairment. Paclitaxel is not recommended in patients with severely impaired hepatic function (transaminase levels ≥10 x ULN or bilirubin levels >7.5 mg/dL or > 5 x ULN; see Dosage & Administration).
Neurologic: Peripheral neuropathy (dose-dependent) may occur frequently. Carefully monitor patient with pre-existing peripheral neuropathy and in severe cases, reduce all subsequent doses by 20% (see Dosage & Administration).
Hypersensitivity: Patients with a history of severe hypersensitivity reaction to products containing Cremophor EL should not be treated with paclitaxel (see Contraindications). Minor symptoms such as flushing, skin reactions, dyspnea, hypotension or tachycardia do not require interruption of therapy. However, immediate discontinuation of paclitaxel and aggressive symptomatic therapy should be done in cases of severe reactions such as hypotension requiring treatment, dyspnea requiring bronchodilators, angioedema, or generalized urticaria.
Injection Site Reaction: Erythema, tenderness, skin discoloration, or swelling at the injection site may occur. Recurrence of skin reactions at a previous site of extravasation (i.e., "recall" reactions) after paclitaxel administration at a different injection site has been reported rarely. More severe events such as phlebitis, cellulitis, induration, skin exfoliation, necrosis, and fibrosis have also been reported rarely (see Dosage & Administration).
Gastrointestinal: Exclude bowel perforation in patients receiving paclitaxel who complain of abdominal pain with other signs and symptoms.
Infectious Complications: Patients should be informed to take extra precautions to reduce the risk of infection or bleeding (e.g., avoiding people with infection, getting cut or bruised).
The risk-benefit should be considered when administering paclitaxel to patients with the following conditions: Varicella or recent exposure to such disease.
Herpes Zoster.
Infection.
Precaution must be taken in patients who have undergone therapies with cytotoxic drugs, including radiotherapy.
Effects on the Ability to Drive or Use Machines: The alcohol content in the product may impair the ability to perform hazardous activities requiring mental alertness following paclitaxel infusion, particularly when high doses of the drug are administered over short periods (e.g., 3 hours). Concomitant use with CNS depressants should be done with caution.
Hepatic and Renal Impairment: The use of paclitaxel in patients with impaired renal and hepatic function has not been fully established. Since paclitaxel is metabolized in the liver, dose reduction is recommended in patients with moderate to severe liver failure. Dose reduction may not be necessary in patients with renal failure. (See Dosage & Administration).
Carcinogenicity, Mutagenicity, Fertility: There is no study on the carcinogenic potential of paclitaxel. Paclitaxel has been shown to be clastogenic in vitro (chromosome aberrations in human lymphocytes) and in vivo (micronucleus test in mice) mammalian test system but was not mutagenic in the Ames test or the CHO/HGPRT gene mutation assay.
Reproduction studies in rats and rabbits showed evidence of maternal toxicity, embryotoxicity and fetotoxicity during organogenesis at IV doses of 1 mg/kg (6 mg/m² or systemic exposures approximately equivalent to 0.04 times the maximum recommended human dose on a mg/m² basis) and 3 mg/kg (33 mg/m² or systemic exposures approximately equivalent to 0.2 times the maximum recommended human dose on a mg/m² basis), respectively. These resulted in intrauterine mortality, increased resorptions, increased fetal deaths and reduced fertility. Paclitaxel produced low fertility in rats at an IV dose of 1 mg/kg (6 mg/m²).
Use in Children: The safety and efficacy of paclitaxel in children have not been established. In a clinical trial in children, high dose paclitaxel (350 to 420 mg/m² or more than two times the recommended dose) infused over 3 hours caused CNS toxicity (rarely associated with death). The toxicity is attributed to the high dose alcohol content (vehicle) given over a short infusion time. Concomitant use of antihistamines may intensify this effect.
Use in Elderly: The safety and efficacy of paclitaxel in elderly patients have not been clearly established. However, most of the patients treated for refractory metastatic ovarian carcinoma are older than 60 years. There is no evidence of age-related differences in the safety or dose tolerance between young and old patients. However, clinical studies show that severe myelosuppression, severe neuropathy and cardiovascular events were more frequent in elderly patients. Estimates of efficacy appeared similar between elderly and younger patients but comparative efficacy could not be determined due to a small number of elderly patients studied.