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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(proe KAR ba zeen)
Generic Available (U.S.)
No
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of Hodgkin's disease
Use: Unlabeled/Investigational
Treatment of non-Hodgkin's lymphoma, brain tumors
Pregnancy Risk Factor
D
Pregnancy Considerations
Animal studies have demonstrated teratogenic effects. There are no adequate and well-controlled studies in pregnant women. There are, however, case reports of fetal malformations in the offspring of pregnant women exposed to procarbazine as part of a combination chemotherapy regimen. Women of childbearing potential should avoid becoming pregnant during treatment.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to procarbazine or any component of the formulation; pre-existing bone marrow aplasia; ethanol ingestion; pregnancy
Warnings/Precautions
Boxed warnings:
• Experienced physician: See “Other warnings/precautions” below.
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Bone marrow suppression: May occur 2-8 weeks after treatment initiation; allow ≥1 month interval between radiation therapy or myelosuppressive chemotherapy and initiation of treatment. Withhold treatment for leukopenia (WBC <4000/mm3) or thrombocytopenia (platelets <100,000/mm3).
• CNS toxicity: Withhold treatment for CNS toxicity.
• Diarrhea: Withhold treatment for diarrhea.
• Disulfiram-like reaction: Avoid ethanol consumption, may cause disulfiram-like reaction.
• Hemolysis: May cause hemolysis and/or presence of Heinz inclusion bodies in erythrocytes.
• Hemorrhage: Withhold treatment for hemorrhage.
• Hypersensitivity: Withhold treatment for hypersensitivity.
• Infertility: May cause infertility.
• Secondary malignancies: Possibly carcinogenic; acute leukemia and lung cancer have been reported following use.
• Stomatitis: Withhold treatment for stomatitis.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
Other warnings/precautions:
• Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
• MAO inhibitor activity: Possesses MAO inhibitor activity and has potential for severe drug and food interactions; follow MAO-I diet.
Adverse Reactions
Most frequencies not defined.
Cardiovascular: Edema, flushing, hypotension, syncope, tachycardia
Central nervous system: Apprehension, ataxia, chills, coma, confusion, depression, dizziness, drowsiness, fatigue, fever, hallucination, headache, insomnia, lethargy, nervousness, nightmares, pain, seizure, slurred speech
Dermatologic: Alopecia, dermatitis, hyperpigmentation, petechiae, pruritus, purpura, rash, urticaria
Endocrine & metabolic: Gynecomastia (in prepubertal and early pubertal males)
Hematologic: Eosinophilia; hemolysis (in patients with G6PD deficiency); hemolytic anemia; myelosuppression (leukopenia, anemia, thrombocytopenia); pancytopenia
Gastrointestinal: Abdominal pain, anorexia, constipation, diarrhea, dysphagia, hematemesis, melena; nausea and vomiting ([60% to 90%], increasing the dose in a stepwise fashion over several days may minimize); stomatitis, xerostomia
Genitourinary: Azoospermia (reported with combination chemotherapy), hematuria, nocturia, polyuria, reproductive dysfunction (>10%)
Hepatic: Hepatic dysfunction, jaundice
Neuromuscular & skeletal: Arthralgia, falling, foot drop, myalgia, neuropathy, paresthesia, reflex diminished, tremor, unsteadiness, weakness
Ocular: Diplopia, inability to focus, nystagmus, papilledema, photophobia, retinal hemorrhage
Otic: Hearing loss
Respiratory: Cough, epistaxis, hemoptysis, hoarseness, pleural effusion, pneumonitis, pulmonary toxicity (<1%)
Miscellaneous: Allergic reaction, diaphoresis, herpes, infection, secondary malignancies (2% to 15%; reported with combination therapy)
Drug Interactions
Alpha-/Beta-Agonists (Direct-Acting): MAO Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Primarily with oral administration of phenylephrine. Exceptions: Dipivefrin. Risk D: Consider therapy modification
Alpha-/Beta-Agonists (Indirect-Acting): MAO Inhibitors may enhance the hypertensive effect of Alpha-/Beta-Agonists (Indirect-Acting). Risk X: Avoid combination
Alpha1-Agonists: MAO Inhibitors may enhance the hypertensive effect of Alpha1-Agonists. Risk X: Avoid combination
Alpha2-Agonists (Ophthalmic): MAO Inhibitors may enhance the hypertensive effect of Alpha2-Agonists (Ophthalmic). Risk X: Avoid combination
Altretamine: May enhance the orthostatic hypotensive effect of MAO Inhibitors. Risk C: Monitor therapy
Amphetamines: MAO Inhibitors may enhance the hypertensive effect of Amphetamines. Risk X: Avoid combination
Anilidopiperidine Opioids: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Management: Avoid use of fentanyl (and other anilidopiperidine opioids when possible) in patients who have used a monoamine oxidase inhibitor within the past 14 days due to reports of unpredictable but severe adverse effects. Risk X: Avoid combination
Antihypertensives: MAO Inhibitors may enhance the hypotensive effect of Antihypertensives. MAO Inhibitors may enhance the orthostatic hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Atomoxetine: MAO Inhibitors may enhance the neurotoxic (central) effect of Atomoxetine. Risk X: Avoid combination
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Beta2-Agonists: MAO Inhibitors may enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy
Bezafibrate: MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Risk X: Avoid combination
Buprenorphine: May enhance the adverse/toxic effect of MAO Inhibitors. Risk X: Avoid combination
BuPROPion: MAO Inhibitors may enhance the neurotoxic (central) effect of BuPROPion. Risk X: Avoid combination
BusPIRone: May enhance the adverse/toxic effect of MAO Inhibitors. Elevated blood pressure has been reported. Risk X: Avoid combination
CarBAMazepine: May enhance the adverse/toxic effect of MAO Inhibitors. Risk X: Avoid combination
Cardiac Glycosides: Antineoplastic Agents may decrease the absorption of Cardiac Glycosides. This may only affect digoxin tablets. Exceptions: Digitoxin. Risk C: Monitor therapy
COMT Inhibitors: May enhance the adverse/toxic effect of MAO Inhibitors. Risk D: Consider therapy modification
Cyclobenzaprine: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Dexmethylphenidate: MAO Inhibitors may enhance the hypertensive effect of Dexmethylphenidate. Risk X: Avoid combination
Dextromethorphan: MAO Inhibitors may enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Risk X: Avoid combination
Diethylpropion: MAO Inhibitors may enhance the hypertensive effect of Diethylpropion. Risk X: Avoid combination
Doxapram: MAO Inhibitors may enhance the hypertensive effect of Doxapram. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
HYDROmorphone: MAO Inhibitors may enhance the adverse/toxic effect of HYDROmorphone. Risk X: Avoid combination
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Levodopa: May enhance the adverse/toxic effect of MAO Inhibitors. Of particular concern is the development of hypertensive reactions when levodopa is used with nonselective MAOI. Risk D: Consider therapy modification
Linezolid: MAO Inhibitors may enhance the adverse/toxic effect of Linezolid. Risk X: Avoid combination
Lithium: MAO Inhibitors may enhance the adverse/toxic effect of Lithium. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Maprotiline: May enhance the adverse/toxic effect of MAO Inhibitors. Risk X: Avoid combination
Meperidine: MAO Inhibitors may enhance the serotonergic effect of Meperidine. This may cause serotonin syndrome. Risk X: Avoid combination
Methadone: MAO Inhibitors may enhance the adverse/toxic effect of Methadone. Management: Initial safety testing, where small incremental doses of methadone are given with the patient closely monitored (including vitals, etc.), is recommended if methadone is to be used with (or within 14 days of) an MAO inhibitor. Avoid transdermal selegiline. Risk D: Consider therapy modification
Methyldopa: MAO Inhibitors may enhance the adverse/toxic effect of Methyldopa. Risk X: Avoid combination
Methylphenidate: MAO Inhibitors may enhance the hypertensive effect of Methylphenidate. Risk X: Avoid combination
Mirtazapine: MAO Inhibitors may enhance the neurotoxic (central) effect of Mirtazapine. Risk X: Avoid combination
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Orthostatic Hypotension Producing Agents: MAO Inhibitors may enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Oxymorphone: May enhance the adverse/toxic effect of MAO Inhibitors. Risk X: Avoid combination
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Propoxyphene: May enhance the adverse/toxic effect of MAO Inhibitors. Specifically, the risk of serotonin syndrome or other serotonergic adverse events may be increased. Risk X: Avoid combination
Reserpine: MAO Inhibitors may enhance the adverse/toxic effect of Reserpine. Existing MAOI therapy can result in paradoxical effects of added reserpine (e.g., excitation, hypertension). Management: Monoamine oxidase inhibitors (MAOIs) should be avoided or used with great caution in patients who are also receiving reserpine. Risk D: Consider therapy modification
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk X: Avoid combination
Selective Serotonin Reuptake Inhibitors: MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk X: Avoid combination
Serotonin 5-HT1D Receptor Agonists: MAO Inhibitors may decrease the metabolism of Serotonin 5-HT1D Receptor Agonists. Management: If MAO inhibitor therapy is required, naratriptan, eletriptan or frovatriptan may be a suitable 5-HT1D agonist to employ. Exceptions: Eletriptan; Frovatriptan; Naratriptan. Risk X: Avoid combination
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Serotonin/Norepinephrine Reuptake Inhibitors: MAO Inhibitors may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This may cause serotonin syndrome. Risk X: Avoid combination
Sibutramine: May enhance the serotonergic effect of Serotonin Modulators. This may cause serotonin syndrome. Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Tapentadol: May enhance the adverse/toxic effect of MAO Inhibitors. Risk X: Avoid combination
Tetrabenazine: May enhance the adverse/toxic effect of MAO Inhibitors. Risk X: Avoid combination
Tetrahydrozoline: MAO Inhibitors may enhance the hypertensive effect of Tetrahydrozoline. Risk X: Avoid combination
Tetrahydrozoline (Nasal): MAO Inhibitors may enhance the hypertensive effect of Tetrahydrozoline (Nasal). Risk X: Avoid combination
TraMADol: May enhance the neuroexcitatory and/or seizure-potentiating effect of MAO Inhibitors. TraMADol may enhance the serotonergic effect of MAO Inhibitors. Management: Consider alternatives to combined treatment with tramadol and monoamine oxidase inhibitors due to an increased risk of serotonin syndrome and seizures. Avoid transdermal selegiline. Risk D: Consider therapy modification
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Tricyclic Antidepressants: MAO Inhibitors may enhance the serotonergic effect of Tricyclic Antidepressants. This may cause serotonin syndrome. Risk X: Avoid combination
Tryptophan: May enhance the adverse/toxic effect of MAO Inhibitors. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Antineoplastic Agents may enhance the anticoagulant effect of Vitamin K Antagonists. Antineoplastic Agents may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May enhance the adverse/toxic effects of procarbazine; concurrent use not recommended.
Food: Concurrent ingestion of foods rich in tyramine may cause sudden and severe high blood pressure (hypertensive crisis). Avoid tyramine-containing foods with MAO-Is. Food's freshness is also an important concern; improperly stored or spoiled food can create an environment where tyramine concentrations may increase.
Herb/Nutraceuticals: Avoid supplements containing caffeine, tyrosine, tryptophan, or phenylalanine. Ingestion of large quantities may increase the risk of severe side effects (eg, hypertensive reactions, serotonin syndrome).
Storage
Protect from light.
Mechanism of Action
Mechanism of action is not clear, methylating of nucleic acids; inhibits DNA, RNA, and protein synthesis; may damage DNA directly and suppresses mitosis; metabolic activation required by host
Pharmacodynamics/Kinetics
Absorption: Rapid and complete
Distribution: Crosses blood-brain barrier; equilibrates between plasma and CSF
Metabolism: Hepatic and renal
Half-life elimination: 1 hour
Time to peak, plasma: 1 hour
Excretion: Urine and respiratory tract (<5% as unchanged drug, 70% as metabolites)
Dosage
Refer to individual protocols. Manufacturer states that the dose is based on patient's ideal weight if the patient is obese or has abnormal fluid retention. Other studies suggest that ideal body weight may not be necessary. Oral (may be given as a single daily dose or in 2-3 divided doses):
Children:
BMT aplastic anemia conditioning regimen (unlabeled use): 12.5 mg/kg/day every other day for 4 doses
Hodgkin's disease: MOPP/IC-MOPP regimens: 100 mg/m2/day for 14 days and repeated every 4 weeks
Neuroblastoma and medulloblastoma (unlabeled use): Doses as high as 100-200 mg/m2/day once daily have been used
Adults: Initial: 2-4 mg/kg/day in single or divided doses for 7 days then increase dose to 4-6 mg/kg/day until response is obtained or leukocyte count decreased <4000/mm3 or the platelet count decreased <100,000/mm3; maintenance: 1-2 mg/kg/day
Dosing in renal impairment: The FDA-approved labeling does not contain dosing adjustment guidelines; use with caution; may result in increased toxicity.
Dosing in hepatic impairment: The FDA-approved labeling does not contain dosing adjustment guidelines; use with caution; may result in increased toxicity. The following guidelines have been used by some clinicians:
Floyd, 2006:
Transaminases 1.6-6 times ULN: Administer 75% of dose
Transaminases >6 times ULN: Use clinical judgment
Serum bilirubin >5 mg/dL or transaminases >3 times ULN: Avoid use
King, 2001: Serum bilirubin >5 mg/dL or transaminases >180 units/L: Avoid use
Dosage: Combination Regimens
Brain tumors:
8 in 1 (Brain tumors)
MOPP (Medulloblastoma)
PCV (Brain Tumor Regimen)
Lymphoma, Hodgkin's disease:
BEACOPP-14 (Hodgkin's Lymphoma)
BEACOPP Escalated (Hodgkin's Lymphoma)
BEACOPP Standard (Hodgkin's Lymphoma)
Chlorambucil-VPP (Hodgkin's Lymphoma)
MOPP/ABVD
MOPP/ABV Hybrid
MOPP (Lymphoma, Hodgkin's Disease)
OPPA
Lymphoma, non-Hodgkin's:
CEPP(B)
COP-BLAM
COPP
Retinoblastoma: 8 in 1 (Retinoblastoma)
Administration: Oral
May be given as a single daily dose or in 2-3 divided doses.
Monitoring Parameters
CBC with differential, platelet and reticulocyte count, urinalysis, liver function test, renal function test.
Dietary Considerations
Avoid tyramine-containing foods/beverages. Some examples include aged or matured cheese, air-dried or cured meats (including sausages and salamis), fava or broad bean pods, tap/draft beers, Marmite concentrate, sauerkraut, soy sauce and other soybean condiments.
Patient Education
Avoid alcohol; may cause acute disulfiram reaction (headache, respiratory difficulties, nausea, vomiting, sweating, thirst, hypotension, and flushing). Avoid tyramine-containing foods; could cause serious hypertensive effects. Maintain adequate hydration unless instructed to restrict fluid intake. You will be more sensitive to infection. May cause considerable nausea or vomiting, mental depression, nervousness, insomnia, nightmares, dizziness, confusion, lethargy, rash, hair loss or hyperpigmentation (reversible), loss of libido, sterility, or amenorrhea. Report persistent fever, chills, or sore throat; unusual bleeding, blood in urine, stool (black stool), or vomitus; unresolved depression; mania; hallucinations; nightmares; disorientation; seizures; chest pain or palpitations; respiratory difficulty; or vision changes.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation), stomatitis, and dysphagia.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness, nervousness, insomnia, confusion, mania, depression, and hallucinations are common
Mental Health: Effects on Psychiatric Treatment
May cause myelosuppression; use caution with clozapine and carbamazepine; procarbazine possesses MAO inhibitor activity; avoid with antidepressants, narcotics, phenothiazines, and foods containing tyramine
Nursing: Physical Assessment/Monitoring
Use of CNS depressants increases risk of adverse reactions. Emetic potential is high; antiemetic is generally required. Monitor for neurotoxicity, nausea and vomiting, pneumonitis, arthralgia, and paresthesia. Instruct patient about dietary and alcohol cautions (procarbazine has some MAO inhibitory effects; can result in life-threatening hypertension with tyramine; alcohol may cause disulfiram-like reaction).
Oncology: Emetic Potential
High (>90%)
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral, as hydrochloride:
Matulane®: 50 mg
Extemporaneously Prepared
Hazardous agent: Use appropriate precautions for handling and disposal.
A 10 mg/mL oral suspension may be prepared using capsules, glycerin, and strawberry syrup. Empty the contents of ten 50 mg capsules into a mortar. Add 2 mL glycerin and mix to a thick uniform paste. Add 10 mL strawberry syrup in incremental proportions; mix until uniform. Transfer the mixture to an amber glass bottle and rinse mortar with small amounts of strawberry syrup; add rinses to the bottle in sufficient quantity to make 50 mL. Label “shake well” and “protect from light”. Stable for 7 days at room temperature.
Matulane® data on file, Sigma Tau Pharmaceuticals, Inc.
References
Floyd J, Mirza I, Sachs B, et al, "Hepatotoxicity of Chemotherapy," Semin Oncol, 2006, 33(1):50-67.
King PD and Perry MC, “Hepatotoxicity of Chemotherapy,” Oncologist, 2001, 6(2):162-76.
Longo DL, Young RC, Wesley M, et al, “Twenty Years of MOPP Therapy for Hodgkin's Disease,” J Clin Oncol, 1986, 4(9):1295-306.
Rodriguez LA, Prados M, Silver P, et al, “Re-evaluation of Procarbazine for the Treatment of Recurrent Malignant Central Nervous System Tumors,” Cancer, 1989, 64(12):2420-3.
Shulman KI and Walker SE, “A Reevaluation of Dietary Restrictions for Irreversible Monoamine Oxidase Inhibitors,” Psychiatr Ann, 2001, 31(6):378-84.
Shulman KI and Walker SE, “Refining the MAOI Diet: Tyramine Content of Pizzas and Soy Products,” J Clin Psychiatry, 1999, 60(3):191-3.
Spivack SD, “Procarbazine,” Ann Intern Med, 1974, 81:795-800.
Toth B, “A Review of the Antineoplastic Action of Certain Hydrazines and Hydrazine-Containing Natural Products,” In Vivo, 1996, 10(1):65-96.
Walker SE, Shulman KI, Tailor SA, et al, “Tyramine Content of Previously Restricted Foods in Monoamine Oxidase Inhibitor Diets,” J Clin Psychopharmacol, 1996, 16(5):383-8.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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