(proe KAR ba zeen)
Treatment of Hodgkin lymphoma
Hypersensitivity to procarbazine or any component of the formulation; inadequate bone marrow reserve
It is recommended that procarbazine hydrochloride be given only by or under the supervision of a physician experienced in the use of potent antineoplastic drugs. Adequate clinical and laboratory facilities should be available to patients for proper monitoring of treatment.
Note: Procarbazine is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Roila, 2010). The manufacturer suggests that an estimated lean body mass be used in obese patients and patients with rapid weight gain due to edema, ascites, or abnormal fluid retention.
Hodgkin lymphoma:
MOPP regimen: While procarbazine is approved as part of the MOPP regimen, the MOPP regimen is generally no longer used due to improved toxicity profiles with other combination regimens used in the treatment of Hodgkin lymphoma.
BEACOPP, standard or escalated regimen (off-label dosing): Oral: 100 mg/m2 days 1 to 7 every 21 days (in combination with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisone) for 8 cycles (Diehl, 2003)
Non-Hodgkin lymphomas (NHL; off-label use):
CEPP regimen: Oral: 60 mg/m2 days 1 to 10 every 28 days (in combination with cyclophosphamide, etoposide and prednisone) (Chao, 1990)
PEP-C regimen: Oral: 50 mg daily at bedtime (length of induction cycle depends on phase of treatment and blood counts; frequency may vary based on tolerance in maintenance cycle; in combination with prednisone, etoposide, and cyclophosphamide) (Coleman, 2008)
CNS tumors, anaplastic oligodendroglioma/oligoastrocytoma (off-label use):PCV regimen: Oral: 60 mg/m2 days 8 to 21 every 6 weeks (in combination with lomustine and vincristine) for 6 cycles (van den Bent, 2006) or 75 mg/m2 days 8-21 every 6 weeks (in combination with lomustine and vincristine) for up to 4 cycles (Cairncross, 2006).
Primary CNS lymphoma (off-label use): Oral: 100 mg/m2 for 7 days in cycles 1, 3, and 5 (in combination with methotrexate [high-dose], vincristine, methotrexate [intrathecal], leucovorin, dexamethasone, cytarabine [high-dose], and whole brain radiation) (DeAngelis, 2002).
Refer to adult dosing; use with caution.
Note: Procarbazine is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis, 2011). The manufacturer suggests that an estimated lean body mass be used in obese patients and patients with rapid weight gain due to edema, ascites, or abnormal fluid retention.
Hodgkin lymphoma:
MOPP regimen: While procarbazine is approved as part of the MOPP regimen, the MOPP regimen is generally no longer used due to improved toxicity profiles with other combination regimens used in the treatment of Hodgkin lymphoma.
BEACOPP regimen (off-label dosing): Oral: 100 mg/m2 days 0 to 6 of a 21-day treatment cycle (in combination with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisone) for 4 cycles (Kelley, 2011).
No dosage adjustment provided in manufacturer 's labeling; use with caution; may result in increased toxicity. However, because predominantly inactive metabolites are excreted via the kidneys, dosage adjustment is not necessary (Kintzel, 1995).
No dosage adjustment provided in manufacturer 's labeling; use with caution; may result in increased toxicity. The following adjustments have been reported in literature:
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
Oral: May be given as a single daily dose or in 2 to 3 divided doses. Procarbazine is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis, 2011; Roila, 2010).
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
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.
Protect from light.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as hydrochloride:
Matulane: 50 mg
Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
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.Alpha-/Beta-Agonists (Indirect-Acting): MAO Inhibitors may enhance the hypertensive effect of Alpha-/Beta-Agonists (Indirect-Acting). While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Avoid combination
Alpha1-Agonists: MAO Inhibitors may enhance the hypertensive effect of Alpha1-Agonists. While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Avoid combination
Altretamine: May enhance the orthostatic hypotensive effect of MAO Inhibitors. Monitor therapy
Amphetamines: MAO Inhibitors may enhance the hypertensive effect of Amphetamines. While linezolid and tedizolid may interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Antidepressants (Serotonin Reuptake Inhibitor/Antagonist): MAO Inhibitors may enhance the adverse/toxic effect of Antidepressants (Serotonin Reuptake Inhibitor/Antagonist). While methylene blue and linezolid are expected to interact, specific recommendations for their use differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Apraclonidine: MAO Inhibitors may enhance the adverse/toxic effect of Apraclonidine. MAO Inhibitors may increase the serum concentration of Apraclonidine. Avoid combination
AtoMOXetine: MAO Inhibitors may enhance the neurotoxic (central) effect of AtoMOXetine. Avoid combination
Atropine (Ophthalmic): MAO Inhibitors may enhance the hypertensive effect of Atropine (Ophthalmic). Avoid combination
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Beta2-Agonists: MAO Inhibitors may enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy
Betahistine: MAO Inhibitors may increase the serum concentration of Betahistine. Monitor therapy
Bezafibrate: MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid combination
Blood Glucose Lowering Agents: MAO Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Brimonidine (Ophthalmic): MAO Inhibitors may enhance the adverse/toxic effect of Brimonidine (Ophthalmic). MAO Inhibitors may increase the serum concentration of Brimonidine (Ophthalmic). Monitor therapy
Brimonidine (Topical): MAO Inhibitors may enhance the adverse/toxic effect of Brimonidine (Topical). MAO Inhibitors may increase the serum concentration of Brimonidine (Topical). Monitor therapy
Buprenorphine: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
BuPROPion: MAO Inhibitors may enhance the hypertensive effect of BuPROPion. Avoid combination
BusPIRone: May enhance the adverse/toxic effect of MAO Inhibitors. Specifically, blood pressure elevations been reported. Avoid combination
CarBAMazepine: May enhance the adverse/toxic effect of MAO Inhibitors. Management: Avoid concurrent use of carbamazepine during, or within 14 days of discontinuing, treatment with a monoamine oxidase inhibitor. Avoid combination
Carbocisteine: Procarbazine may enhance the adverse/toxic effect of Carbocisteine. Specifically, procarbazine may enhance adverse effects of alcohol that is present in liquid formulations of carbocisteine-containing products. Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
Codeine: MAO Inhibitors may enhance the adverse/toxic effect of Codeine. Monitor therapy
COMT Inhibitors: May enhance the adverse/toxic effect of MAO Inhibitors. Consider therapy modification
Cyclobenzaprine: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Cyproheptadine: MAO Inhibitors may enhance the anticholinergic effect of Cyproheptadine. Cyproheptadine may diminish the serotonergic effect of MAO Inhibitors. Avoid combination
Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Dexmethylphenidate: MAO Inhibitors may enhance the hypertensive effect of Dexmethylphenidate. Avoid combination
Dextromethorphan: MAO Inhibitors may enhance the serotonergic effect of Dextromethorphan. This may cause serotonin syndrome. Avoid combination
Diethylpropion: MAO Inhibitors may enhance the hypertensive effect of Diethylpropion. Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Domperidone: MAO Inhibitors may enhance the adverse/toxic effect of Domperidone. MAO Inhibitors may diminish the therapeutic effect of Domperidone. Domperidone may diminish the therapeutic effect of MAO Inhibitors. Monitor therapy
Doxapram: MAO Inhibitors may enhance the hypertensive effect of Doxapram. Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
EPINEPHrine (Nasal): MAO Inhibitors may enhance the hypertensive effect of EPINEPHrine (Nasal). Monitor therapy
EPINEPHrine (Oral Inhalation): MAO Inhibitors may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Avoid combination
Epinephrine (Racemic): MAO Inhibitors may enhance the hypertensive effect of Epinephrine (Racemic). Monitor therapy
EPINEPHrine (Systemic): MAO Inhibitors may enhance the hypertensive effect of EPINEPHrine (Systemic). Monitor therapy
FentaNYL: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
HYDROcodone: MAO Inhibitors may enhance the adverse/toxic effect of HYDROcodone. Management: Consider alternatives to this combination when possible. Consider therapy modification
HYDROmorphone: MAO Inhibitors may enhance the adverse/toxic effect of HYDROmorphone. Avoid combination
Isometheptene: MAO Inhibitors may enhance the adverse/toxic effect of Isometheptene. 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. Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. 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. Management: The concomitant use of nonselective monoamine oxidase inhibitors (MAOIs) and levodopa is contraindicated. Discontinue the nonselective MAOI at least two weeks prior to initiating levodopa. Monitor patients taking a selective MAOIs and levodopa. Consider therapy modification
Levonordefrin: MAO Inhibitors may enhance the hypertensive effect of Levonordefrin. Avoid combination
Levosulpiride: Benzamide Derivatives may enhance the adverse/toxic effect of Levosulpiride. Monitor therapy
Linezolid: MAO Inhibitors may enhance the adverse/toxic effect of Linezolid. Avoid combination
Lithium: MAO Inhibitors may enhance the adverse/toxic effect of Lithium. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification
MAO Inhibitors: May enhance the hypertensive effect of other MAO Inhibitors. MAO Inhibitors may enhance the serotonergic effect of other MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Maprotiline: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Meperidine: MAO Inhibitors may enhance the serotonergic effect of Meperidine. This may cause serotonin syndrome. Avoid combination
Mequitazine: MAO Inhibitors may enhance the anticholinergic effect of Mequitazine. Avoid combination
Metaraminol: MAO Inhibitors may enhance the hypertensive effect of Metaraminol. Monitor therapy
Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Methadone: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Monitor therapy
Methyldopa: MAO Inhibitors may enhance the adverse/toxic effect of Methyldopa. Avoid combination
Methylene Blue: MAO Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Avoid combination
Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination
Methylphenidate: MAO Inhibitors may enhance the hypertensive effect of Methylphenidate. Avoid combination
Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Monitor therapy
Mianserin: MAO Inhibitors may enhance the neurotoxic effect of Mianserin. Avoid combination
Mirtazapine: MAO Inhibitors may enhance the neurotoxic (central) effect of Mirtazapine. While methylene blue and linezolid are expected to interact, specific recommendations for their use differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Moclobemide: MAO Inhibitors may enhance the adverse/toxic effect of Moclobemide. Avoid combination
Morphine (Liposomal): MAO Inhibitors may enhance the adverse/toxic effect of Morphine (Liposomal). Avoid combination
Morphine (Systemic): MAO Inhibitors may enhance the adverse/toxic effect of Morphine (Systemic). Avoid combination
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nefopam: MAO Inhibitors may enhance the adverse/toxic effect of Nefopam. Avoid combination
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Norepinephrine: MAO Inhibitors may enhance the hypertensive effect of Norepinephrine. Monitor therapy
OxyCODONE: MAO Inhibitors may enhance the adverse/toxic effect of OxyCODONE. Management: Per Canadian labeling, use of oxycodone is contraindicated in patients who either are receiving MAO inhibitors or have used them within 14 days. Though not contraindicated in U.S. prescribing information, consider alternatives when possible. Consider therapy modification
OxyMORphone: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Pheniramine: May enhance the anticholinergic effect of MAO Inhibitors. Avoid combination
Pholcodine: May enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Pindolol: MAO Inhibitors may enhance the hypotensive effect of Pindolol. Management: Canadian labeling for pindolol states that concurrent use with a monoamine oxidase inhibitor is not recommended. Consider therapy modification
Pizotifen: MAO Inhibitors may enhance the anticholinergic effect of Pizotifen. Avoid combination
Reboxetine: MAO Inhibitors may enhance the adverse/toxic effect of Reboxetine. 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. Consider therapy modification
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Selective Serotonin Reuptake Inhibitors: MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. 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. Avoid combination
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: MAO Inhibitors may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tapentadol: May enhance the adverse/toxic effect of MAO Inhibitors. Specifically, the additive effects of norepinephrine may lead to adverse cardiovascular effects. Tapentadol may enhance the serotonergic effect of MAO Inhibitors. This could result in serotonin syndrome. Avoid combination
Tetrabenazine: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Tetrahydrozoline (Nasal): MAO Inhibitors may enhance the hypertensive effect of Tetrahydrozoline (Nasal). Avoid combination
Tianeptine: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination
TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Tricyclic Antidepressants: MAO Inhibitors may enhance the serotonergic effect of Tricyclic Antidepressants. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Avoid combination
Tryptophan: May enhance the adverse/toxic effect of MAO Inhibitors. Avoid combination
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). 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. Avoid combination
CBC with differential, platelet and reticulocyte count, urinalysis, liver function test, renal function test. Monitor for infections, CNS toxicity, and gastrointestinal toxicities.
Frequency not always defined.
Cardiovascular: Edema, flushing, hypotension, syncope, tachycardia
Central nervous system: Apprehension, ataxia, chills, coma, confusion, depression, dizziness, drowsiness, falling, fatigue, hallucination, headache, hyporeflexia, insomnia, lethargy, nervousness, neuropathy, nightmares, pain, paresthesia, seizure, slurred speech, unsteadiness
Dermatologic: Alopecia, dermatitis, diaphoresis, hyperpigmentation, pruritus, skin rash, urticaria
Endocrine & metabolic: Gynecomastia (in prepubertal and early pubertal males)
Gastrointestinal: Nausea and vomiting (60% to 90%; increasing the dose in a stepwise fashion over several days may minimize), abdominal pain, anorexia, constipation, diarrhea, dysphagia, hematemesis, melena, stomatitis, xerostomia
Genitourinary: Reduced fertility (>10%), azoospermia (reported with combination chemotherapy), hematuria, nocturia
Hematologic & oncologic: Malignant neoplasm (2% to 15%; secondary; nonlymphoid; reported with combination therapy), anemia, bone marrow depression, eosinophilia, hemolysis (in patients with G6PD deficiency), hemolytic anemia, pancytopenia, petechia, purpura, thrombocytopenia
Hepatic: Hepatic insufficiency, jaundice
Hypersensitivity: Hypersensitivity reaction
Infection: Herpes virus infection, increased susceptibility to infection
Neuromuscular & skeletal: Arthralgia, foot-drop, myalgia, tremor, weakness
Ophthalmic: Accommodation disturbance, diplopia, nystagmus, papilledema, photophobia, retinal hemorrhage
Otic: Hearing loss
Renal: Polyuria
Respiratory: Cough, epistaxis, hemoptysis, hoarseness, pleural effusion, pneumonitis, pulmonary toxicity (<1%)
Miscellaneous: Fever
Concerns related to adverse effects:
- Bone marrow suppression: Hematologic toxicity (leukopenia and thrombocytopenia) may occur 2-8 weeks after treatment initiation. Allow ≥1 month interval between radiation therapy or myelosuppressive chemotherapy and initiation of procarbazine treatment. Withhold treatment for leukopenia (WBC <4000/mm3) or thrombocytopenia (platelets <100,000/mm3). Monitor for infections due to neutropenia.
- CNS toxicity: Withhold treatment for CNS toxicity.
- Disulfiram-like reaction: Avoid ethanol consumption, may cause disulfiram-like reaction.
- Gastrointestinal toxicities: Procarbazine is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis, 2011; Roila, 2010). May cause diarrhea and stomatitis; withhold treatment for diarrhea or stomatitis.
- Hemolysis: May cause hemolysis and/or presence of Heinz inclusion bodies in erythrocytes.
- Hemorrhage: Withhold treatment for hemorrhage.
- Hypersensitivity: Withhold treatment for hypersensitivity.
- Infertility: Azoospermia and infertility have been reported with procarbazine when used in combination with other chemotherapy agents.
- Secondary malignancies: Possibly carcinogenic; acute myeloid leukemia and lung cancer have been reported following use.
Disease-related concerns:
- Hepatic impairment: Use with caution in patients with hepatic impairment.
- Renal impairment: Use with caution in patients with renal impairment.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
- MAO inhibitor activity: Possesses MAO inhibitor activity and has potential for severe drug and food interactions; follow MAOI diet (avoid tyramine-containing foods).
Special handling:
- Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
Other warnings/precautions:
- Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
D
Adverse events were observed in animal reproduction studies. There are case reports of fetal malformations in the offspring of pregnant women exposed to procarbazine as part of a combination chemotherapy regimen. Women of reproductive potential should avoid becoming pregnant during treatment.
Inhibits DNA, RNA, and protein synthesis by inhibiting transmethylation of methionine into transfer RNA; may also damage DNA directly through alkylation.
Rapid and complete
Crosses the blood-brain barrier and distributes into CSF, liver, kidney, intestine, and skin
Oxidized to active metabolites methylazoxy-procarbazine and benzylazoxy-procarbazine, then further metabolized to inactive metabolites (Kintzel 1995)
Urine (70% as inactive metabolites [Kintzel 1995]; <5% as unchanged drug)
≤1 hour
~1 hour
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience fatigue, lack of appetite, dry mouth, hair loss, abdominal pain, constipation, headache, muscle pain, joint pain, or insomnia. Have patient report immediately to prescriber signs of infection, signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any bleeding that is very bad or that will not stop), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), shortness of breath, severe dizziness, passing out, tachycardia, edema, illogical thinking, severe nausea, vomiting, diarrhea, burning or numbness feeling, vision changes, hearing impairment, seizures, change in balance, loss of strength and energy, mouth sores, dysphagia, involuntary eye movements, mood changes, or hallucinations (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.