. This enhancement may represent edema and inflammation caused by Gliadel® Wafer or tumor progression.
Therapeutic Interactions
Interactions of Gliadel® Wafer with other drugs have not been formally eva luated.
The short-term and long-term toxicity profiles of Gliadel® Wafer when given in conjunction with chemotherapy have not been fully explored. Gliadel® Wafer, when given in conjunction with radiotherapy does not appear to have any short-term or chronic toxicities.
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® Wafer in pediatric patients have not been established.
ADVERSE REACTIONS
Adverse reactions for the trials are described in the tables below.
Primary Surgery
The following data are the most frequently occurring adverse events observed in 5% or more of the newly-diagnosed malignant glioma patients during the trial.
COMMON ADVERSE EVENTS OBSERVED IN ≥ 5% OF PATIENTS RECEIVING Gliadel® WAFER AT INITIAL SURGERY Body System
Adverse Event Gliadel® Wafer
[N=120]
n (%) Placebo
[N=120]
n (%)
*Adverse events coded to the COSTART term "aggravation reaction" were usually events involving tumor/disease progression or general deterioration of condition (e.g. condition/health/Karnofsky/neurological/physical deterioration).
Body as a Whole
Aggravation reaction* 98 (82) 95 (79)
Headache 33 (28) 44 (37)
Asthenia 26 (22) 18 (15)
Infection 22 (18) 24 (20)
Fever 21 (18) 21 (18)
Pain 16 (13) 18 (15)
Abdominal pain 10 (8) 2 (2)
Back pain 8 (7) 4 (3)
Face edema 7 (6) 6 (5)
Abscess 6 (5) 3 (3)
Accidental injury 6 (5) 8 (7)
Chest pain 6 (5) 0
Allergic reacti |
