ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension)(十六)
concomitantly with medicines known to inhibit (e.g., ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir) or induce (e.g., rifampicin, carbamazepine, phenytoin, efavirenz, and nevirapine) either CYP2C8 or CYP3A4.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category D [see Warnings and Precautions (5.8)].
There are no adequate and well-controlled studies in pregnant women using ABRAXANE. Based on its mechanism of action and findings in animals, ABRAXANE can cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving ABRAXANE.
Administration of paclitaxel formulated as albumin-bound particles to rats during pregnancy, on gestation days 7 to 17 at doses of 6 mg/m2 (approximately 2% of the daily maximum recommended human dose on a mg/m2 basis) caused embryofetal toxicities, as indicated by intrauterine mortality, increased resorptions (up to 5-fold), reduced numbers of litters and live fetuses, reduction in fetal body weight and increase in fetal anomalies. Fetal anomalies included soft tissue and skeletal malformations, such as eye bulge, folded retina, microphthalmia, and dilation of brain ventricles. A lower incidence of soft tissue and skeletal malformations were also exhibited at 3 mg/m2 (approximately 1% of the daily maximum recommended human dose on a mg/m2 basis).
8.3 Nursing Mothers
It is not known whether paclitaxel is excreted in human milk. Paclitaxel and/or its metabolites were excreted into the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
8.4 Pediatric Use
The safety and effectiveness of ABRAXANE in pediatric patients have not been eva luated.
8.5 Geriatric Use
Of the 229 patients in the randomized study who received ABRAXANE for the treatment of metastatic breast cancer, 13% were at least 65 years of age and < 2% were 75 years or older. No toxicities occurred notably more frequently among patients who received ABRAXANE.
Of the 514 patients in the randomized study who received ABRAXANE and carboplatin for the first-line treatment of non-small cell lung cancer, 31% were 65 years or older and 3.5% were 75 years or older. Myelosuppression, peripheral neuropathy, and arthralgia were more frequent in patients 65 years or older compared to patients younger than 65 years old. No overall difference in effectiveness, as measured by response rates, was observed between patients 65 years or older compared to patients younger than 65 years old.
Of the 431 patients in the randomized study who received ABRAXANE and gemcitabine for the first-line treatment of pancreatic adenocarcinoma, 41% were 65 years or older and 10% were 75 years or older. No overall differences in effectiveness were observed between patients who were 65 years of age or older and younger patients. Diarrhea, decreased appetite, dehydration and epistaxis were more frequent in patients 65 years or older compared with patients younger than 65 years old. Clinical studies of |
