ctions to PLATINOL-AQ have been reported. These reactions have occurred within minutes of administration to patients with prior exposure to PLATINOL-AQ, and have been alleviated by administration of epinephrine, corticosteroids, and antihistamines.
PLATINOL-AQ can commonly cause ototoxicity which is cumulative and may be severe. Audiometric testing should be performed prior to initiating therapy and prior to each subsequent dose of drug (see ADVERSE REACTIONS).
Certain genetic variants in the thiopurine S-methyltransferase (TPMT) gene are associated with increased risk of ototoxicity in children administered conventional doses of cisplatin (see CLINICAL PHARMACOLOGY). Children who do not have one of these TPMT gene variants remain at risk for ototoxicity. All pediatric patients receiving cisplatin should have audiometric testing at baseline, prior to each subsequent dose, of drug and for several years post therapy.
PLATINOL-AQ can cause fetal harm when administered to a pregnant woman. PLATINOL-AQ is mutagenic in bacteria and produces chromosome aberrations in animal cells in tissue culture. In mice PLATINOL-AQ is teratogenic and embryotoxic. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Patients should be advised to avoid becoming pregnant.
The carcinogenic effect of PLATINOL-AQ was studied in BD IX rats. PLATINOL-AQ was administered intraperitoneally (i.p.) to 50 BD IX rats for 3 weeks, 3 X 1 mg/kg body weight per week. Four hundred and fifty-five days after the first application, 33 animals died, 13 of them related to malignancies: 12 leukemias and 1 renal fibrosarcoma.
The development of acute leukemia coincident with the use of PLATINOL-AQ has been reported. In these reports, PLATINOL-AQ was generally given in combination with other leukemogenic agents.
Injection site reactions may occur during the administration of PLATINOL-AQ (see ADVERSE REACTIONS). Given the possibility of extravasation, it is recommended to closely monitor the infusion site for possible infiltration during drug administration. A specific treatment for extravasation reactions is unknown at this time.
PRECAUTIONS
Peripheral blood counts should be monitored weekly. Liver function should be monitored periodically. Neurologic examination should also be performed regularly (see ADVERSE REACTIONS).
Drug Interactions
Plasma levels of anticonvulsant agents may become subtherapeutic during cisplatin therapy.
In a randomized trial in advanced ovarian cancer, response duration was adversely affected when pyridoxine was used in combination with altretamine (hexamethylmelamine) and PLATINOL-AQ.
Carcinogenesis, Mutagenesis, Impairment of Fertility
See WARNINGS.
Pregnancy
Pregnancy Category D
See WARNINGS.
Nursing Mothers
Cisplatin has been reported to be found in human milk; patients receiving PLATINOL-AQ should not breast-feed.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Variants in the thiopurine S-methyltransferase (TPMT) gene are associated with an increased risk of ototoxicity in children treated with cisplatin (see CLINICAL PHARMACOLOGY).
All children should have audiometric monitoring performed prior to initiation of therapy prior to each subsequent dose, and for several years post therapy. Advanced testing methods may allow for earlier detection of he |
