TEMODAR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TEMODAR (TEMODAR).

How it works

Temozolomide is a prodrug that undergoes rapid nonenzymatic conversion at physiological pH to the active alkylating agent MTIC (monomethyl triazenoimidazole carboxamide). MTIC methylates DNA at the O6 position of guanine, leading to DNA mismatch repair-dependent cytotoxicity and apoptosis.

What the body does with it

Metabolism	Metabolized via nonenzymatic hydrolysis to MTIC and further to the inactive metabolites AIC (aminoimidazole carboxamide) and methylhydrazine; also undergoes minor hepatic metabolism via CYP450 isoenzymes (CYP1A1, CYP2A6, CYP2E1, and CYP3A4) with no significant drug interactions.
Excretion	Renal: ~38% of total dose recovered in urine over 7 days, primarily as unchanged temozolomide (5.6%) and metabolites (including AIC, a major metabolite). Fecal excretion is minimal (<1%). Biliary excretion is negligible.
Half-life	Terminal elimination half-life is approximately 1.8 hours. Clinically, the short half-life supports once-daily dosing; no accumulation occurs with repeated doses. The active metabolite MTIC has a half-life of about 2 hours.
Protein binding	Approximately 15% bound to plasma proteins, primarily albumin. Low binding minimizes drug interactions via protein displacement.
Volume of Distribution	Mean Vd is 0.4 L/kg (range 0.1-1.1 L/kg). This moderate distribution indicates partial tissue penetration, including crossing the blood-brain barrier (CSF concentration ~30% of plasma).
Bioavailability	Oral bioavailability is nearly 100% (mean 100%, range 96-104%). Food reduces peak concentration by 33% and delays absorption but does not affect AUC; thus, temozolomide can be taken with or without food.
Onset of Action	Oral: Clinical response (tumor shrinkage) typically observed after 2-4 weeks of continuous daily dosing. Intravenous: Not applicable as no IV formulation; oral only.
Duration of Action	Duration of therapeutic effect is sustained over the treatment cycle (42 days for concomitant phase with radiotherapy, then 28-day cycles). Each daily dose provides systemic exposure for ~12 hours; myelosuppression nadir occurs at 21-28 days post-cycle.

Classification & Brands

Dosing & administration

150-200 mg/m² orally once daily for 5 consecutive days of a 28-day cycle for anaplastic astrocytoma; 75 mg/m² orally daily for 42 days with radiotherapy for glioblastoma.

Dosage form	POWDER
Renal impairment	No dose adjustment required for GFR ≥30 mL/min; temozolomide is contraindicated in severe renal impairment (CrCl <36 mL/min) as per manufacturer.
Liver impairment	For mild to moderate hepatic impairment (Child-Pugh A/B), standard dose; severe (Child-Pugh C) has not been studied; use with caution.
Pediatric use	In pediatric patients (≥3 years), 150 mg/m² orally once daily for 5 days per 28-day cycle; may escalate to 200 mg/m² if tolerated. For high-grade glioma with radiotherapy, 90 mg/m² daily during RT.
Geriatric use	No specific geriatric dose adjustment; monitor for myelosuppression, especially in patients >70 years due to increased risk of neutropenia and thrombocytopenia.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TEMODAR (TEMODAR).

Breastfeeding	No human data; temozolomide is excreted in rat milk. M/P ratio unknown. Theoretical risk of infant neutropenia, thrombocytopenia, carcinogenesis. Contraindicated during breastfeeding; discontinue nursing or drug.
Teratogenic Risk	Teratogenic in animals (rat, rabbit) at doses below human therapeutic levels. First trimester: high risk of major malformations (central nervous system, skeletal). Second and third trimesters: risk of fetal growth restriction, low birth weight, and potential neurodevelopmental deficits. All trimesters: increased risk of fetal death. Avoid use in pregnancy unless no safer alternative.

Warnings & precautions

■ FDA Black Box Warning

TEMODAR can cause myelosuppression, including prolonged pancytopenia, which may result in aplastic anemia. Geriatric patients and women have been shown in clinical trials to have a higher risk of developing myelosuppression. Prescribe with caution and monitor blood counts frequently.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to temozolomide or any component of the formulation (including dacarbazine, which shares a metabolite); severe myelosuppression; pregnancy (can cause fetal harm).

Clinical Precautions

Precautions

Myelosuppression (monitor CBC weekly; may require dose reduction or discontinuation); Pneumocystis jirovecii pneumonia (prophylaxis required during concomitant radiotherapy); hepatotoxicity; secondary malignancies (myelodysplastic syndrome, acute myeloid leukemia); embryo-fetal toxicity; hypersensitivity reactions including Stevens-Johnson syndrome; seizures with brain tumors.

Clinical Tips & Counseling

Drug interactions

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TEMODAR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TEMODAR (TEMODAR).

How it works

What the body does with it

Metabolism	Metabolized via nonenzymatic hydrolysis to MTIC and further to the inactive metabolites AIC (aminoimidazole carboxamide) and methylhydrazine; also undergoes minor hepatic metabolism via CYP450 isoenzymes (CYP1A1, CYP2A6, CYP2E1, and CYP3A4) with no significant drug interactions.
Excretion	Renal: ~38% of total dose recovered in urine over 7 days, primarily as unchanged temozolomide (5.6%) and metabolites (including AIC, a major metabolite). Fecal excretion is minimal (<1%). Biliary excretion is negligible.
Half-life	Terminal elimination half-life is approximately 1.8 hours. Clinically, the short half-life supports once-daily dosing; no accumulation occurs with repeated doses. The active metabolite MTIC has a half-life of about 2 hours.
Protein binding	Approximately 15% bound to plasma proteins, primarily albumin. Low binding minimizes drug interactions via protein displacement.
Volume of Distribution	Mean Vd is 0.4 L/kg (range 0.1-1.1 L/kg). This moderate distribution indicates partial tissue penetration, including crossing the blood-brain barrier (CSF concentration ~30% of plasma).
Bioavailability	Oral bioavailability is nearly 100% (mean 100%, range 96-104%). Food reduces peak concentration by 33% and delays absorption but does not affect AUC; thus, temozolomide can be taken with or without food.
Onset of Action	Oral: Clinical response (tumor shrinkage) typically observed after 2-4 weeks of continuous daily dosing. Intravenous: Not applicable as no IV formulation; oral only.
Duration of Action	Duration of therapeutic effect is sustained over the treatment cycle (42 days for concomitant phase with radiotherapy, then 28-day cycles). Each daily dose provides systemic exposure for ~12 hours; myelosuppression nadir occurs at 21-28 days post-cycle.

Classification & Brands

Dosing & administration

150-200 mg/m² orally once daily for 5 consecutive days of a 28-day cycle for anaplastic astrocytoma; 75 mg/m² orally daily for 42 days with radiotherapy for glioblastoma.

Dosage form	POWDER
Renal impairment	No dose adjustment required for GFR ≥30 mL/min; temozolomide is contraindicated in severe renal impairment (CrCl <36 mL/min) as per manufacturer.
Liver impairment	For mild to moderate hepatic impairment (Child-Pugh A/B), standard dose; severe (Child-Pugh C) has not been studied; use with caution.
Pediatric use	In pediatric patients (≥3 years), 150 mg/m² orally once daily for 5 days per 28-day cycle; may escalate to 200 mg/m² if tolerated. For high-grade glioma with radiotherapy, 90 mg/m² daily during RT.
Geriatric use	No specific geriatric dose adjustment; monitor for myelosuppression, especially in patients >70 years due to increased risk of neutropenia and thrombocytopenia.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TEMODAR (TEMODAR).

Breastfeeding	No human data; temozolomide is excreted in rat milk. M/P ratio unknown. Theoretical risk of infant neutropenia, thrombocytopenia, carcinogenesis. Contraindicated during breastfeeding; discontinue nursing or drug.
Teratogenic Risk	Teratogenic in animals (rat, rabbit) at doses below human therapeutic levels. First trimester: high risk of major malformations (central nervous system, skeletal). Second and third trimesters: risk of fetal growth restriction, low birth weight, and potential neurodevelopmental deficits. All trimesters: increased risk of fetal death. Avoid use in pregnancy unless no safer alternative.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to temozolomide or any component of the formulation (including dacarbazine, which shares a metabolite); severe myelosuppression; pregnancy (can cause fetal harm).