Patients undergoing craniotomy for malignant glioma and implantation of GLIADEL® Wafer should be monitored closely for known complications of craniotomy, including seizures, intracranial infections, abnormal wound healing, and brain edema. Cases of intracerebral mass effect unresponsive to corticosteroids have been described in patients treated with GLIADEL® Wafer, including one case leading to brain herniation.

Pregnancy

There are no studies assessing the reproductive toxicity of GLIADEL® Wafer. Carmustine, the active component of GLIADEL® Wafer, can cause fetal harm when administered to a pregnant woman. Carmustine has been shown to be embryotoxic and teratogenic in rats at i.p. doses of 0.5, 1, 2, 4, or 8 mg/kg/day when given on gestation days 6 through 15. Carmustine caused fetal malformations (anophthalmia, micrognathia, omphalocele) at 1.0 mg/kg/day (about 1/6 the recommended human dose (eight wafers of 7.7 mg carmustine/wafer) on a mg/m2 basis). Carmustine was embryotoxic in rabbits at i.v. doses of 4.0 mg/kg/day (about 1.2 times the recommended human dose on a mg/m2 basis). Embryotoxicity was characterized by increased embryo-fetal deaths, reduced numbers of litters, and reduced litter sizes.

There are no studies of GLIADEL® Wafer in pregnant women. If GLIADEL® Wafer is used during pregnancy, or if the patient becomes pregnant after GLIADEL® Wafer implantation, the patient must be warned of the potential hazard to the fetus.

General

Communication between the surgical resection cavity and the ventricular system should be avoided to prevent the wafers from migrating into the ventricular system and causing obstructive hydrocephalus. If a communication larger than the diameter of a wafer exists, it should be closed prior to wafer implantation.

Computed tomography and magnetic resonance imaging of the head may demonstrate enhancement in the brain tissue surrounding the resection cavity after implantation of GLIADEL® Wafers. This enhancement may represent edema and inflammation caused by GLIADEL® Wafer or tumor progression.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, mutagenicity or impairment of fertility studies have been conducted with GLIADEL® Wafer. Carcinogenicity, mutagenicity and impairment of fertility studies have been conducted with carmustine, the active component of GLIADEL® Wafer. Carmustine was given three times a week for six months, followed by 12 months observation, to Swiss mice at i.p. doses of 2.5 and 5.0 mg/kg (about 1/5 and 1/3 the recommended human dose (eight wafers of 7.7 mg carmustine/wafer) on a mg/m2 basis) and to SD rats at i.p. dose of 1.5 mg/kg (about 1/4 the recommended human dose on a mg/m2 basis). There were increases in tumor incidence in all treated animals, predominantly subcutaneous and lung neoplasms. Mutagenesis: Carmustine was mutagenic in vitro (Ames assay, human lymphoblast HGPRT assay) and clastogenic both in vitro (V79 hamster cell micronucleus assay) and in vivo (SCE assay in rodent brain tumors, mouse bone marrow micronucleus assay). Impairment of Fertility: Carmustine caused testicular degeneration at i.p. doses of 8 mg/kg/week for eight weeks (about 1.3 times the recommended human dose on a mg/m2 basis) in male rats.

Pregnancy

Pregnancy Category D: see WARNINGS.

Nursing Mothers

It is not known if either carmustine, carboxyphenoxypropane, or sebacic acid is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from carmustine in nursing infants, it is recommended that patients receiving GLIADEL® Wafer discontinue nursing.

Pediatric Use

The safety and effectiveness of GLIADEL® in pediatric patients have not been established.

Bookmark this page: