MATULANE
Clinical safety rating
cautionComprehensive clinical and safety monograph for MATULANE (MATULANE).
Comprehensive clinical and safety monograph for MATULANE (MATULANE).
Treatment of advanced Hodgkin lymphoma (in combination with other drugs)Treatment of non-Hodgkin lymphoma (off-label)Treatment of brain tumors (off-label)
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.
| 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. |
| Molecular Weight | 284.32 |
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. |
| 1st trimester | Contraindicated due to teratogenicity; embryotoxic and fetotoxic in animal studies. |
| 2nd trimester | Contraindicated; risk of fetal harm. |
| 3rd trimester | Contraindicated; risk of fetal harm. |
Clinical note
Comprehensive clinical and safety monograph for MATULANE (MATULANE).
| Placental transfer | Crosses placenta; documented in animal studies and based on molecular weight. |
| Breastfeeding | Excreted into breast milk; risk of tumorigenicity and myelosuppression in nursing infant. Discontinue breastfeeding or avoid drug. |
| Lactation Rating | L5 - Contraindicated |
| 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. |
| Fetal Monitoring | If exposure occurs, perform detailed fetal ultrasound for structural anomalies. Monitor maternal CBC, LFTs, renal function, and signs of myelosuppression. Fetal monitoring for growth restriction and anemia via serial ultrasounds and Doppler studies. |
| Fertility Effects | Matulane is associated with gonadal toxicity, including azoospermia and ovarian failure. Risk of permanent infertility. Sperm banking or oocyte cryopreservation recommended before therapy. |
■ 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.
| Serious Effects |
PregnancyBreastfeedingHypersensitivity to procarbazineSevere bone marrow suppressionConcurrent use with alcohol (disulfiram-like reaction)
| 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. |
| Food/Dietary | Avoid tyramine-rich foods: aged cheeses (cheddar, Swiss), cured meats (salami, pepperoni), fermented soy products (tofu, miso), sauerkraut, pickled herring, broad bean pods, yeast extracts, red wine, beer, and draft beers. Also avoid alcohol completely due to additive CNS depression. |
| Clinical Pearls | Matulane (procarbazine) is a monoamine oxidase inhibitor (MAOI); concurrent use with sympathomimetics, tyramine-rich foods, or tricyclic antidepressants can precipitate hypertensive crisis. It is also a potent CNS depressant; avoid alcohol. Monitor for leukopenia and thrombocytopenia; nadir typically occurs 2-4 weeks after therapy. Discontinue if hypersensitivity pneumonitis occurs. |
| Patient Advice | Avoid foods high in tyramine such as aged cheeses, cured meats, fermented foods, and alcoholic beverages (especially beer and red wine) to prevent severe high blood pressure. · Do not take any over-the-counter medications, especially cold, sinus, or allergy medications, without consulting your doctor due to risk of drug interactions. · This drug may cause dizziness or drowsiness; avoid driving or operating machinery until you know how it affects you. · Report any signs of infection (fever, sore throat), unusual bleeding/bruising, or shortness of breath immediately. · Use effective contraception during treatment and for at least 1 month after stopping, as this drug can harm an unborn baby. |
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