Gliadel
(carmustine)Dosage & Administration
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Gliadel Prescribing Information
GLIADEL Wafer is indicated for the treatment of patients with:
- newly-diagnosed high-grade glioma as an adjunct to surgery and radiation, and
- recurrent glioblastoma as an adjunct to surgery.
Recommended Dose
The recommended dose of GLIADEL Wafer is eight 7.7 mg wafers for a total of 61.6 mg implanted intracranially. The safety and effectiveness of repeat administration have not been studied.
Insertion Instructions
Following maximal tumor resection, confirmation of tumor pathology and establishment of hemostasis, place up to a maximum of eight GLIADEL Wafers to cover as much of the resection cavity as possible. Should the size and shape of the resected cavity not accommodate eight wafers, place the maximum number of wafers feasible within the cavity. Slight overlapping of the wafers is acceptable. Wafers broken in half may be used, but discard wafers broken in more than two pieces. Oxidized regenerated cellulose (Surgicel®) may be placed over the wafers to secure them against the cavity surface. After placement of the wafers, irrigate the resection cavity and close the dura in a water-tight fashion.
Preparation and Safe Handling
GLIADEL Wafers contain a cytotoxic drug. Follow applicable special handling and disposal procedures.1
Each wafer is packaged within two nested aluminum foil laminate pouches. The inner pouch is sterile and is designed to maintain product sterility and protect the product from moisture. The outside surface of the outer laminated aluminum foil pouch is a peelable overwrap and is not sterile.
Deliver GLIADEL Wafers to the operating room in their outer aluminum foil pouch, unopened. Do not open the pouch until the wafers are ready to be implanted. GLIADEL Wafers in unopened outer foil pouches are stable at room temperature for six hours at a time for up to three cycles within a 30-day period.
Exposure to carmustine can cause severe burning and hyperpigmentation of the skin. Use double gloves when handling GLIADEL Wafers. Discard the outer gloves into a biohazard waste container after use. Use a dedicated surgical instrument for wafer implantation. If repeat neurosurgical intervention is indicated, handle residual wafers or wafer remnants as potential cytotoxic agents.
Instructions for Opening Pouch Containing GLIADEL Wafer
Read all steps of the instructions prior to opening the pouch.
Instructions for opening the pouch containing GLIADEL Wafer can be viewed at the following website: http://gliadel.com/hcp/pouch-opening-instructions. Illustrations are also pictured below.
Figure 1: To remove the sterile inner pouch from the outer pouch, locate the folded corner and slowly pull in an outward motion.
Figure 2: Do NOT pull in a downward motion rolling knuckles over the pouch. This may exert pressure on the wafer and cause it to break.
Figure 3: The inner pouch is a multi-layered, silver colored, foil laminate. Remove the inner pouch by grabbing hold of the crimped edge of the inner pouch using a sterile instrument and pulling upward.
Figure 4: To open the inner pouch, gently hold the crimped edge and cut in an arc-like fashion around the wafer.
Figure 5: To remove the GLIADEL Wafer, gently grasp the wafer with the aid of forceps and place it onto a designated sterile field.
GLIADEL Wafer is an off-white to pale yellow round wafer. Each GLIADEL Wafer contains 7.7 mg of carmustine.
Pregnancy
Risk Summary
GLIADEL Wafer can cause fetal harm when administered to a pregnant woman. There are no available data on GLIADEL use in pregnant women. There have been no animal reproductive 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 based on body surface area (BSA) and embryotoxic in rabbits at exposures similar to exposures at the recommended human dose based on BSA (see Data). Advise pregnant women of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Animal Data
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 0.5 mg/kg/day or greater when given on gestation days 6 through 15. Carmustine caused fetal malformations (anophthalmia, micrognathia, omphalocele) at 1 mg/kg/day (about 0.12 times the recommended human dose, eight wafers of 7.7 mg carmustine/wafer, based on BSA). Carmustine was embryotoxic in rabbits at intravenous doses of 4 mg/kg/day (about 1.2 times the recommended human dose based on BSA). Embryotoxicity was characterized by increased embryo-fetal deaths, reduced numbers of litters, and reduced litter sizes.
Lactation
Risk Summary
No data are available regarding the presence of carmustine, the active component of GLIADEL Wafer, or its metabolites in human milk or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children from GLIADEL Wafers, advise women not to breastfeed following implantation with GLIADEL Wafers and for at least 7 days after implantation.
Females and Males of Reproductive Potential
Pregnancy Testing
Verify pregnancy status of females of reproductive potential prior to implantation with GLIADEL Wafer [see Use in Specific Populations (8.1)].
Contraception
GLIADEL Wafer can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Females
Advise females of reproductive potential to use effective contraception for 6 months after implantation of GLIADEL Wafer.
Males
Based on its mechanism of action, advise males with female partners of reproductive potential to use effective contraception for 3 months following implantation of GLIADEL Wafer [see Clinical Pharmacology (12.1), Nonclinical Toxicology (13.1)]
Infertility
Males
Carmustine caused testicular degeneration in animals. Advise male patients of the potential risk of infertility [see Nonclinical Toxicology (13.1)].
Pediatric Use
The safety and effectiveness of GLIADEL Wafer in pediatric patients have not been established.
Geriatric Use
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.
None.
Seizures
Seizures occurred in 37% of patients treated with GLIADEL Wafers for recurrent glioma in Study 2. New or worsening (treatment emergent) seizures occurred in 20% of patients; 54% of treatment emergent seizures occurred within the first 5 post-operative days [see Adverse Reactions (6.1)]. The median time to onset of the first new or worsened post-operative seizure was four days. Institute optimal anti-seizure therapy prior to surgery. Monitor patients for seizures postoperatively.
Intracranial Hypertension
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 (6.1)]. 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 high-grade glioma experienced wound healing abnormalities [see Adverse Reactions (6.1)]. Monitor patients post-operatively for impaired neurosurgical wound healing.
Meningitis
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.
Wafer Migration
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.
Embryo-Fetal Toxicity
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 based on body surface area (BSA) and embryotoxic in rabbits at exposures similar to the exposure at the recommended human dose based on BSA.
Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception for 6 months after implantation of GLIADEL Wafer. Advise males with female partners of reproductive potential to use effective contraception for 3 months following implantation of GLIADEL Wafers [see Use in Specific Populations (8.1, 8.3), Nonclinical Toxicology (13.1)].