"Sabahaddin Akman, owner of the Istanbul, Turkey, firm Ozay Pharmaceuticals, has pleaded guilty to charges of smuggling misbranded and adulterated cancer treatment drugs into the United States.
Akman pleaded guilty in the U.S. District Court"...
Fifty-four percent (54%) of patients treated with GLIADEL Wafers for recurrent glioma in Study 2 experienced new or worsened seizures within the first five post-operative days [see ADVERSE REACTIONS]. The median time to onset of the first new or worsened post-operative seizure was 4 days. Optimize anti-seizure therapy prior to surgery. Monitor patients for seizures postoperatively.
Brain edema occurred in 23% of patients with newly diagnosed glioma treated with GLIADEL Wafers in Study 1. Additionally, one GLIADEL-treated patient experienced intracerebral mass effect unresponsive to corticosteroids which led to brain herniation (see ADVERSE REACTIONS). Monitor patients closely for intracranial hypertension related to brain edema, inflammation, or necrosis of the brain tissue surrounding the resection. In refractory cases, consider re-operation and removal of GLIADEL Wafers or Wafer remnants.
Impaired Neurosurgical Wound Healing
Impaired neurosurgical wound healing including wound dehiscence, delayed wound healing, and subdural, subgleal, or wound effusions occur with GLIADEL Wafer treatment. In Study 1, 16% of GLIADEL Wafer-treated patients with newly diagnosed glioma experienced impaired intracranial wound healing and 5% had cerebrospinal fluid leaks. In Study 2, 14% of GLIADEL Wafer-treated patients with recurrent glioma experienced wound healing abnormalities [see ADVERSE REACTIONS]. Monitor patients post-operatively for impaired neurosurgical wound healing.
Meningitis occurred in 4% of patients with recurrent glioma receiving GLIADEL Wafers in Study 2. Two cases of meningitis were bacterial; one patient required removal of the Wafers four days after implantation; the other developed meningitis following reoperation for recurrent tumor. One case was diagnosed as chemical meningitis and resolved following steroid treatment.
In one case the cause was unspecified, but meningitis resolved following antibiotic treatment. Monitor postoperatively for signs of meningitis and central nervous system infection.
GLIADEL Wafer migration can occur. To reduce the risk of obstructive hydrocephalus due to wafer migration into the ventricular system, close any communication larger than the diameter of a Wafer between the surgical resection cavity and the ventricular system prior to Wafer implantation. Monitor patients for signs of obstructive hydrocephalus.
GLIADEL Wafers can cause fetal harm when administered to a pregnant woman. Carmustine, the active component of GLIADEL Wafer, is embryotoxic and teratogenic in rats at exposures less than the exposure at the recommended human dose on a mg/m² basis and embryotoxic in rabbits at exposures similar to the exposure at the recommended human dose on a mg/m² basis. Advise females of reproductive potential to avoid pregnancy after implantation of GLIADEL Wafers. If the patient becomes pregnant after GLIADEL Wafer implantation, warn the patient about the potential hazard to the fetus [see Use In Specific Populations].
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 carcinogenic in rats and mice when delivered by intraperitoneal injection at doses lower than those delivered by GLIADEL Wafer at the recommended dose. There were increases in tumor incidence in all treated animals. 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).
In male rats carmustine caused testicular degeneration at intraperitoneal doses of 8 mg/kg/week for eight weeks (about 1.3 times the recommended human dose on a mg/m² basis).
Use In Specific Populations
Pregnancy Category D
GLIADEL Wafer can cause fetal harm when administered to a pregnant woman. There have been no studies with GLIADEL Wafer; however, carmustine, the active component of GLIADEL Wafer, is embryotoxic and teratogenic in rats at exposures less than the exposure at the recommended human dose on a mg/m² basis and embryotoxic in rabbits at exposures similar to exposures at the recommended human dose on a mg/m² basis. 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 a fetus.
There are no studies assessing the reproductive toxicity of GLIADEL Wafer; however, carmustine, the active component of GLIADEL Wafer, is embryotoxic and teratogenic in rats at intraperitoneal doses of 0.5mg/kg/day or greater when given on gestation days 6 through 15. Carmustine caused fetal malformations (anophthalmia, micrognathia, omphalocele) at 1.0 mg/kg/day (about 0.12 the recommended human dose, eight wafers of 7.7 mg carmustine/wafer, on a mg/m² basis). Carmustine was embryotoxic in rabbits at intravenous 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.
It is not known if carmustine, the active component of GLIADEL Wafer, is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from carmustine, a decision should be made whether to discontinue nursing or not to administer the drug, taking into account the importance of the drug to the mother.
The safety and effectiveness of GLIADEL Wafer in pediatric patients have not been established.
Clinical trials of GLIADEL Wafer did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients.
Females and Males of Reproductive Potential
GLIADEL Wafer can cause fetal harm when administered during pregnancy (see Use In Specific Populations). Counsel patients on pregnancy planning and prevention. Advise female patients of reproductive potential to use effective contraception after implantation of GLIADEL Wafer. Advise patients to inform their healthcare provider if they become pregnant, or if pregnancy is suspected, while taking GLIADEL.
Carmustine caused testicular degeneration in animals. Advise male patients of the potential risk of infertility, and to seek counseling on fertility and family planning options prior to implantation of GLIADEL Wafer. (see Nonclinical Toxicology)This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 9/4/2013
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