MATULANE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MATULANE (MATULANE).

How it works

Matulane (procarbazine) is a prodrug that undergoes metabolic activation to generate cytotoxic alkylating metabolites. It inhibits DNA, RNA, and protein synthesis through methylation of nucleic acids and proteins, and may also inhibit monoamine oxidase.

What the body does with it

Metabolism	Procarbazine is metabolized primarily by the liver via oxidation by CYP450 enzymes and other oxidases to active metabolites. It also undergoes some metabolism by monoamine oxidase (MAO) in the liver and other tissues.
Excretion	Primarily renal (approximately 50-60% as unchanged drug and metabolites) and fecal (approximately 10-20%); minor biliary excretion.
Half-life	Terminal elimination half-life is approximately 7-10 hours (range 5-15 hours) in adults; context: prolonged in hepatic or renal impairment.
Protein binding	Approximately 10-20% bound to plasma proteins (mainly albumin); minimal binding.
Volume of Distribution	Approximately 3-4 L/kg; indicates extensive tissue distribution including brain (penetrates CNS).
Bioavailability	Oral bioavailability is nearly complete (close to 100%) after oral administration.
Onset of Action	Oral administration: clinical effect (antitumor response) may be observed within 2-4 weeks of continuous therapy.
Duration of Action	Duration of action is variable; myelosuppression may persist for up to 2-4 weeks after drug discontinuation. Half-life contributes to prolonged exposure.

Classification & Brands

Dosing & administration

200-300 mg orally once daily for 10-14 days as part of MOPP regimen; maintenance dose: 50-100 mg orally once daily after hematologic recovery.

Dosage form	CAPSULE
Renal impairment	GFR ≥50 mL/min: no adjustment; GFR 10-50 mL/min: reduce dose to 50-75%; GFR <10 mL/min: avoid use or reduce to 50% and monitor.
Liver impairment	Child-Pugh A: 100% of dose; Child-Pugh B: reduce by 50%; Child-Pugh C: avoid use.
Pediatric use	Based on BSA: 100 mg/m2 orally once daily for 14 days as part of MOPP; or 50 mg/m2 orally on days 1-14.
Geriatric use	Start at lower end of dosing range (e.g., 200 mg daily) due to increased risk of myelosuppression and renal/hepatic impairment; monitor CBCs closely.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for MATULANE (MATULANE).

Breastfeeding	Procarbazine is excreted into breast milk. M/P ratio not reported. Due to potential for carcinogenicity and adverse effects in the nursing infant, breastfeeding is contraindicated during matulane therapy and for at least 2 weeks after last dose.
Teratogenic Risk	Matulane (procarbazine) is a known teratogen. First trimester exposure is associated with major congenital malformations. Second and third trimester exposure carries risk of intrauterine growth restriction, fetal bone marrow suppression, and potential carcinogenesis. Use contraindicated in pregnancy.

Warnings & precautions

■ FDA Black Box Warning

Procarbazine is carcinogenic, mutagenic, and teratogenic. It should be used only by physicians experienced in cancer chemotherapy. Patients receiving procarbazine should be carefully monitored for hematologic toxicity.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to procarbazine; concomitant use with MAO inhibitors, tricyclic antidepressants, or other drugs with MAO-inhibiting activity; severe bone marrow depression; pregnancy.

Clinical Precautions

Precautions

Bone marrow suppression (leukopenia, thrombocytopenia, anemia) requires dose adjustment; discontinue if toxicity is severe. CNS effects (drowsiness, depression, confusion) may occur. Disulfiram-like reaction with alcohol. Hypertensive crisis can occur with tyramine-rich foods or sympathomimetics due to MAO inhibition. Monitor for secondary malignancies. Fetal harm can occur; avoid pregnancy.

Clinical Tips & Counseling

Drug interactions

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MATULANE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MATULANE (MATULANE).

How it works

What the body does with it

Metabolism	Procarbazine is metabolized primarily by the liver via oxidation by CYP450 enzymes and other oxidases to active metabolites. It also undergoes some metabolism by monoamine oxidase (MAO) in the liver and other tissues.
Excretion	Primarily renal (approximately 50-60% as unchanged drug and metabolites) and fecal (approximately 10-20%); minor biliary excretion.
Half-life	Terminal elimination half-life is approximately 7-10 hours (range 5-15 hours) in adults; context: prolonged in hepatic or renal impairment.
Protein binding	Approximately 10-20% bound to plasma proteins (mainly albumin); minimal binding.
Volume of Distribution	Approximately 3-4 L/kg; indicates extensive tissue distribution including brain (penetrates CNS).
Bioavailability	Oral bioavailability is nearly complete (close to 100%) after oral administration.
Onset of Action	Oral administration: clinical effect (antitumor response) may be observed within 2-4 weeks of continuous therapy.
Duration of Action	Duration of action is variable; myelosuppression may persist for up to 2-4 weeks after drug discontinuation. Half-life contributes to prolonged exposure.

Classification & Brands

Dosing & administration

200-300 mg orally once daily for 10-14 days as part of MOPP regimen; maintenance dose: 50-100 mg orally once daily after hematologic recovery.

Dosage form	CAPSULE
Renal impairment	GFR ≥50 mL/min: no adjustment; GFR 10-50 mL/min: reduce dose to 50-75%; GFR <10 mL/min: avoid use or reduce to 50% and monitor.
Liver impairment	Child-Pugh A: 100% of dose; Child-Pugh B: reduce by 50%; Child-Pugh C: avoid use.
Pediatric use	Based on BSA: 100 mg/m2 orally once daily for 14 days as part of MOPP; or 50 mg/m2 orally on days 1-14.
Geriatric use	Start at lower end of dosing range (e.g., 200 mg daily) due to increased risk of myelosuppression and renal/hepatic impairment; monitor CBCs closely.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for MATULANE (MATULANE).

Breastfeeding	Procarbazine is excreted into breast milk. M/P ratio not reported. Due to potential for carcinogenicity and adverse effects in the nursing infant, breastfeeding is contraindicated during matulane therapy and for at least 2 weeks after last dose.
Teratogenic Risk	Matulane (procarbazine) is a known teratogen. First trimester exposure is associated with major congenital malformations. Second and third trimester exposure carries risk of intrauterine growth restriction, fetal bone marrow suppression, and potential carcinogenesis. Use contraindicated in pregnancy.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to procarbazine; concomitant use with MAO inhibitors, tricyclic antidepressants, or other drugs with MAO-inhibiting activity; severe bone marrow depression; pregnancy.