m Disorders
Infection viral 17 (11) 0
Respiratory System
Upper respiratory tract infection 13 (8) 0
Pharyngitis 12 (8) 0
Sinusitis 10 (6) 0
Coughing 8 (5) 0
Skin and Appendages
Rash 13 (8) 0
Pruritus 12 (8) 2 (1)
Urinary System
Urinary tract infection 12 (8) 0
Micturition increased frequency 9 (6) 0
Vision
Diplopia 8 (5) 0
Vision abnormal* 8 (5)
TABLE 9: Adverse Hematologic Effects (Grade 3 to 4) in the Anaplastic Astrocytoma Trial in Adults TEMODAR*
*
Change from Grade 0 to 2 at baseline to Grade 3 or 4 during treatment.
Hemoglobin 7/158 (4%)
Lymphopenia 83/152 (55%)
Neutrophils 20/142 (14%)
Platelets 29/156 (19%)
WBC 18/158 (11%)
TEMODAR for injection delivers equivalent temozolomide dose and exposure to both temozolomide and 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide (MTIC) as the corresponding TEMODAR capsules. Adverse reactions probably related to treatment that were reported from the 2 studies with the intravenous formulation (n=35) that were not reported in studies using the TEMODAR capsules were: pain, irritation, pruritus, warmth, swelling, and erythema at infusion site as well as the following adverse reactions: petechiae and hematoma.
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of TEMODAR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug exposure.
TEMODAR Capsules: allergic reactions, including anaphylaxis, have been reported. Erythema multiforme has been reported, which resolved after discontinuation of TEMODAR and, in some cases, recurred upon rechallenge. Cases of toxic epidermal necrolysis and Stevens-Johnson syndrome have been reported.
There have been reported cases of hepatotoxicity, including elevations of liver enzymes, hyperbilirubinemia, cholestasis, and hepatitis.
Opportunistic infections including Pneumocystis carinii pneumonia (PCP) have also been reported. Cases of interstitial pneumonitis/pneumonitis, alveolitis, and pulmonary fibrosis have been reported. Prolonged pancytopenia, which may result in aplastic anemia, has been reported, and in some cases has resulted in a fatal outcome.
7 DRUG INTERACTIONS
7.1 Valproic Acid
Administration of valproic acid decreases oral clearance of temozolomide by about 5%. The clinical implication of this effect is not known [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category D. See Warnings and Precautions section.
TEMODAR can cause fetal harm when administered to a pregnant woman. Five consecutive days of oral temozolomide administration of 0.38 and 0.75 times the highest recommended human dose (75 and 150 mg/m2) in rats and rabbits, respectively, during the period of organogenesis caused numerous malformations of the external and internal soft tissues and skeleton in both species. Doses equivalent to 0.75 times the highest recommended human dose (150 mg/m2) caused embryolethality in rats and rabbits as indicated by increased resorptions. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient |
