TEMOZOLOMIDE capsule

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

TEMOZOLOMIDE (UNII: YF1K15M17Y) (TEMOZOLOMIDE - UNII:YF1K15M17Y)

Available from:

Areva Pharmaceuticals

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Temozolomide Capsules are indicated for the treatment of adults with newly diagnosed glioblastoma, concomitantly with radiotherapy and then as maintenance treatment. Temozolomide Capsules are indicated for the: - adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma; - treatment of adults with refractory anaplastic astrocytoma. Temozolomide is contraindicated in patients with a history of serious hypersensitivity reactions to: - temozolomide or any other ingredients in Temozolomide capsules and - dacarbazine, since both temozolomide and dacarbazine are metabolized to the same active metabolite 5-(3-methyltriazen-1-yl)-imidazole-4-carboxamide. Reactions to Temozolomide have included anaphylaxis [see Adverse Reactions (6.2)]. Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1)] . Temozolomide can cause fetal harm when administered to a pregnant woman. Available postmarketing reports describe cases of spontaneous abortions and congenital malformations, including polymalformations with central nervous system, facial, cardiac, skeletal, and genitourinary system anomalies with exposure to Temozolomide during pregnancy. These cases report similar adverse developmental outcomes to those observed in animal studies. Administration of Temozolomide to rats and rabbits during the period of organogenesis caused numerous external, internal, and skeletal malformations at doses less than the maximum human dose based on body surface area (see Data) . Advise pregnant women of 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 Five consecutive days of oral administration of Temozolomide at doses of 75 and 150 mg/m 2 (0.38 and 0.75 times the human dose of 200 mg/m 2 ) in rats and rabbits, respectively, during the period of organogenesis (Gestation Days 8-12) caused numerous malformations of the external and internal organs and skeleton in both species. In rabbits, Temozolomide at the 150 mg/m 2 dose (0.75 times the human dose of 200 mg/m 2 ) caused embryolethality as indicated by increased resorptions. There are no data on the presence of Temozolomide or its metabolites in human milk, the effects on a breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions, including myelosuppression from Temozolomide in the breastfed children, advise women not to breastfeed during treatment with Temozolomide and for 1 week after the final dose. Temozolomide can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating Temozolomide [see Use in Specific Population (8.1)]. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with Temozolomide and for 6 months after the last dose. Males Because of the potential for embryofetal toxicity and genotoxic effects on sperm cells, advise male patients with pregnant partners or female partners of reproductive potential to use condoms during treatment with Temozolomide and for 3 months after the last dose [see Use in Specific Population (8.1), Nonclinical Toxicology (13.1)]. Advise male patients not to donate semen during treatment with Temozolomide and for 3 months after the last dose. Infertility Temozolomide may impair male fertility [see Nonclinical Toxicology (13.1)] . Limited data from male patients show changes in sperm parameters during treatment with Temozolomide; however, no information is available on the duration or reversibility of these changes. Safety and effectiveness of Temozolomide have not been established in pediatric patients. Safety and effectiveness of Temozolomide capsules were assessed, but not established, in 2 open-label studies in pediatric patients aged 3 to 18 years. In one study, 29 patients with recurrent brain stem glioma and 34 patients with recurrent high-grade astrocytoma were enrolled. In a second study conducted by the Children’s Oncology Group (COG), 122 patients were enrolled, including patients with medulloblastoma/PNET (29), high grade astrocytoma (23), low grade astrocytoma (22), brain stem glioma (16), ependymoma (14), other CNS tumors (9), and non-CNS tumors (9). The adverse reaction profile in pediatric patients was similar to adults. In MK-7365-051, 15% of patients with newly diagnosed glioblastoma were 65 years and older. This study did not include sufficient numbers of patients aged 65 years and older to determine differences in effectiveness from younger patients. No overall differences in safety were observed between patients ≥65 years and younger patients. The CATNON trial did not include sufficient numbers of patients aged 65 years and older to determine differences in safety or effectiveness when compared to younger patients. In MK-7365-0006, 4% of patients with refractory anaplastic astrocytoma were 70 years and older. This study did not include sufficient numbers of patients aged 70 years and older to determine differences in effectiveness from younger patients. Patients 70 years and older had a higher incidence of Grade 4 neutropenia (25%) and Grade 4 thrombocytopenia (20%) in the first cycle of therapy than patients less than 70 years of age [see Warnings and Precautions (5.1)and Adverse Reactions (6.1)]. In the entire safety database for which hematologic data exist (N=932), 7% (4/61) and 10% (6/63) of patients >70 years experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively. For patients ≤70 years, 7% (62/871) and 6% (48/879) experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively. Pancytopenia, leukopenia, and anemia also occurred. No dosage adjustment is recommended for patients with creatinine clearance (CLcr) of 36 to 130 mL/min/m 2 [see Clinical Pharmacology (12.3)]. The recommended dose of Temozolomide has not been established for patients with severe renal impairment (CLcr <36 mL/min/m 2 ) or for patients with end-stage disease on dialysis. No dosage adjustment is recommended for patients with mild to moderate hepatic impairment (Child Pugh class A and B) [see Clinical Pharmacology (12.3)]. The recommended dose of Temozolomide has not been established for patients with severe hepatic impairment (Child Pugh class C).

Product summary:

Temozolomide is a hazardous drug. Follow applicable special handling and disposal procedures. 1 Temozolomide capsules USP Temozolomide capsules USP are supplied in amber glass bottles with child-resistant caps containing the following capsule strengths: Temozolomide capsules USP 5 mg: have opaque white bodies with green caps. The capsule body is imprinted with the dosage strength. They are supplied as follows: 5-count – NDC 59923-703-05 14-count – NDC 59923-704-14 Temozolomide capsules USP 20 mg: have opaque white bodies with yellow caps. The capsule body is imprinted with the dosage strength. They are supplied as follows: 5-count – NDC 59923-705-05 14-count – NDC 59923-706-14 Temozolomide capsules USP 100 mg: have opaque white bodies with pink caps. The capsule body is imprinted with the dosage strength. They are supplied as follows: 5-count – NDC 59923-707-05 14-count – NDC 59923-708-14 Temozolomide capsules USP 140 mg: have opaque white bodies with blue caps. The capsule body is imprinted with the dosage strength. They are supplied as follows: 5-count – NDC 59923-709-05 14-count – NDC 59923-710-14 Temozolomide capsules USP 180 mg: have opaque white bodies with orange caps. The capsule body is imprinted with the dosage strength. They are supplied as follows: 5-count – NDC 59923-711-05 14-count – NDC 59923-712-14 Temozolomide capsules USP 250 mg: have opaque white bodies with white caps. The capsule body is imprinted with the dosage strength. They are supplied as follows: 5-count – NDC 59923-713-05 Store Temozolomide capsules USP at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

TEMOZOLOMIDE- TEMOZOLOMIDE CAPSULE
AREVA PHARMACEUTICALS
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
TEMOZOLOMIDE
CAPSULES USP SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION
FOR TEMOZOLOMIDE
CAPSULES USP.
TEMOZOLOMIDE CAPSULES USP, FOR ORAL USE
INITIAL U.S. APPROVAL: 1999
RECENT MAJOR CHANGES
Indications and Usage (
1.2) 09/2023
Dosage and Administration ( 2.1, 2.2, 2.3,
2.4) 09/2023
Contraindications (
4) 09/2023
Warnings and Precautions ( 5.1, 5.2, 5.4, 5.5,
5.6) 09/2023
INDICATIONS AND USAGE
Temozolomide Capsules USP is an alkylating drug indicated for the
treatment of adults with:
Newly diagnosed glioblastoma concomitantly with radiotherapy and then
as maintenance treatment. (
1.1)
Anaplastic astrocytoma. ( 1.2)
Adjuvant treatment of adults with newly diagnosed anaplastic
astrocytoma. ( 1.2)
Treatment of adults with refractory anaplastic astrocytoma. ( 1.2)
DOSAGE AND ADMINISTRATION
Newly Diagnosed Glioblastoma:
75 mg/m
once daily for 42 to 49 days concomitant with focal radiotherapy
followed by initial
maintenance dose of 150 mg/m
once daily for Days 1 to 5 of each 28-day cycle for 6 cycles. May
increase maintenance dose to 200 mg/m
for cycles 2 – 6 based on toxicity. ( 2.1)
Provide _Pneumocystis_Pneumonia (PCP) prophylaxis during concomitant
phase and continue in
patients who develop lymphopenia until resolution to Grade 1 or less.
( 2.1)
Adjuvant Treatment of Newly Diagnosed Anaplastic Astrocytoma:
Beginning 4 weeks after the end of radiotherapy, administer
Temozolomide Capsules USP orally in a
single dose on days 1-5 of a 28-day cycle for 12 cycles. The
recommended dosage for Cycle 1 is 150
mg/m
per day and for Cycles 2 to 12 is 200 mg/m
if patient experienced no or minimal toxicity in
Cycle 1. ( 2.2)
Refractory Anaplastic Astrocytoma: Initial dose of 150 mg/m
once daily on Days 1 to 5 of each 28-day
cycle. ( 2.2)
DOSAGE FORMS AND STRENGTHS
Capsules: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, and 250 mg ( 3)
CONTRAINDICATIONS
His