TEMOZOLOMIDE

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Temozolomide is an alkylating agent that causes DNA methylation at O6 and N7 positions of guanine, leading to DNA damage and apoptosis. It is converted to the active metabolite MTIC under physiological conditions.

What the body does with it

Metabolism	Hydrolyzed spontaneously at physiologic pH to the active metabolite MTIC (monomethyl triazenoimidazole carboxamide). Metabolism occurs primarily in the liver via non-enzymatic processes; CYP450 enzymes do not play a significant role.
Excretion	Approximately 38% of total radioactivity is excreted in urine over 7 days (5.6% as unchanged temozolomide, 12% as AIC metabolite, 21% as other polar metabolites), and less than 1% is excreted in feces.
Half-life	1.8 hours (range 1.3–2.5 hours) for temozolomide; the active monomethyl triazeno imidazole carboxamide (MTIC) metabolite has a half-life of approximately 2.0 hours.
Protein binding	Approximately 15% bound to plasma proteins (primarily albumin); weak and reversible binding.
Volume of Distribution	0.4 L/kg (range 0.3–0.5 L/kg), indicating distribution primarily into total body water; crosses the blood-brain barrier achieving cerebrospinal fluid concentrations 30–40% of plasma levels.
Bioavailability	Oral: ~100% (rapid and complete absorption; food reduces peak concentration by 33% but does not affect AUC).
Onset of Action	Oral: Median time to peak plasma concentration (Tmax) is 1 hour (range 0.5–1.5 hours) after a single dose; clinical response (tumor shrinkage) typically observed within 2–4 weeks of continuous daily dosing.
Duration of Action	Plasma levels decline rapidly after absorption; clinical effect duration is linked to treatment cycle (e.g., 42–56 days for concomitant radiotherapy phase, then up to 6–12 cycles of maintenance therapy).

Classification & Brands

Dosing & administration

150 mg/m2 orally once daily for 5 consecutive days of a 28-day cycle; for first cycle, then increase to 200 mg/m2/day if tolerated.

Dosage form	CAPSULE
Renal impairment	No specific dose adjustment recommended for mild to moderate renal impairment (CrCl ≥36 mL/min). For severe impairment (CrCl <36 mL/min), not recommended due to lack of data.
Liver impairment	Child-Pugh class A: No adjustment. Child-Pugh class B: Use with caution; consider dose reduction. Child-Pugh class C: Not recommended.
Pediatric use	In pediatric patients (≥3 years), 150 mg/m2/day orally for 5 days of a 28-day cycle for first cycle, then increase to 200 mg/m2/day if tolerated. For refractory or recurrent disease, alternative dosing of 200 mg/m2/day for 5 days every 28 days may be used.
Geriatric use	No specific dose adjustment required; increased risk of myelosuppression, especially neutropenia and thrombocytopenia. Monitor blood counts closely.

Use during pregnancy

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

Clinical note

Valproic acid may decrease clearance Can cause severe myelosuppression and pneumocystis pneumonia prophylaxis is required.

Breastfeeding

Not recommended during breastfeeding. Temozolomide is excreted into human milk; M/P ratio unknown. Potential for severe adverse reactions in nursing infants including myelosuppression, immunosuppression, and carcinogenesis. Advise to discontinue breastfeeding during therapy and for at least 1 week after the last dose.

Teratogenic Risk

Pregnancy Category D. Temozolomide is teratogenic and embryotoxic in animal studies. First trimester exposure is associated with major congenital malformations including CNS, skeletal, and visceral defects. Second and third trimester exposure may cause intrauterine growth restriction, preterm birth, and fetal myelosuppression. Use is contraindicated in pregnancy unless no safer alternative exists.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Myelosuppression
Serious Effects

Absolute Contraindications

["Known hypersensitivity to temozolomide or dacarbazine","Severe myelosuppression (absolute neutrophil count <1.5 x 10^9/L, platelet count <100 x 10^9/L)"]

Clinical Precautions

Precautions

["Myelosuppression (neutropenia, thrombocytopenia, anemia) - dose-limiting","Pneumocystis jirovecii pneumonia risk during prolonged therapy","Hepatotoxicity - monitor LFTs","Fetal harm if used during pregnancy","Secondary malignancies (rare)"]

Clinical Tips & Counseling

Drug interactions

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