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Procarbazine: Pediatric drug information

Procarbazine: Pediatric drug information
2025© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Procarbazine: Drug information" and "Procarbazine: Patient drug information"

For abbreviations, symbols, and age group definitions show table
ALERT: US Boxed Warning
Experienced physician:

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.

Brand Names: US
  • Matulane
Brand Names: Canada
  • Matulane
Therapeutic Category
  • Antineoplastic Agent, Miscellaneous
Dosing: Pediatric

Note: Refer to individual protocols for specific dosage and interval information. Procarbazine is associated with a high emetic potential (Ref); antiemetics are recommended to prevent nausea and vomiting (Ref). 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

Hodgkin lymphoma:

MOPP regimen: Note: 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 (Ref). Manufacturer's labeling: Infants, Children, and Adolescents: Oral: 50 to 100 mg/m2/day once daily for 14 days of a 28-day cycle (Ref)

BEACOPP regimen (high-risk): Limited data available: Children and Adolescents: 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 2 to 4 cycles (Ref)

CNS tumors; low-grade gliomas, WHO grades 1 and 2

CNS tumors; low-grade gliomas, WHO grades 1 and 2: Limited data available: TPCV regimen: Children <10 years: Oral: 50 mg/m2 every 6 hours for 4 doses (at hours 60, 66, 72, and 78) during a 42-day cycle (in combination with thioguanine, vincristine, and lomustine) for a total of 8 cycles (Ref)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

All patients: There are no dosage adjustments provided in the 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 (Ref).

Dosing: Liver Impairment: Pediatric

All patients: There are no dosage adjustments provided in the manufacturer's labeling; use with caution; may result in increased toxicity. The following adjustments have been reported in literature based primarily on experience in adult patients:

Floyd 2006:

Transaminases 1.6 to 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

Dosing: Adult

(For additional information see "Procarbazine: Drug information")

Dosage guidance:

Safety: Allow a 1-month interval (or longer, based on marrow recovery) between myelosuppressive radiation or chemotherapy prior to initiation of procarbazine.

Dosing: The manufacturer suggests that an estimated lean body mass be used in patients with obesity and patients with rapid weight gain due to edema, ascites, or abnormal fluid retention.

Clinical considerations: Procarbazine is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).

CNS tumors

CNS tumors (gliomas: anaplastic oligodendroglioma, oligoastrocytoma, low grade gliomas) (off-label use):

Anaplastic oligodendroglioma, oligoastrocytoma: PCV regimen: Oral: 60 mg/m2 on days 8 to 21 of a 42-day treatment cycle (in combination with lomustine and vincristine; to begin within 4 weeks after radiotherapy) for 6 cycles (Ref) or 75 mg/m2 on days 8 to 21 of a 42-day treatment cycle (in combination with lomustine and vincristine, followed by radiotherapy) for up to 4 cycles (Ref).

Low-grade gliomas: PCV regimen: Oral: 60 mg/m2 on days 8 to 21 of a 56-day treatment cycle (in combination with lomustine and vincristine; after radiotherapy) for 6 cycles (Ref).

Hodgkin lymphoma

Hodgkin lymphoma:

BEACOPP, standard or escalated regimen (off-label dosing): Oral: 100 mg/m2 on days 1 to 7 every 21 days (in combination with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisone) for 6 to 8 cycles (Ref). May consider a PET scan after cycle 2 to determine (based on response) if patient is appropriate for reducing the total number of cycles to 4 or 6 eBEACOPP cycles (Ref).

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.

Non-Hodgkin lymphomas, relapsed or refractory

Non-Hodgkin lymphomas, relapsed or refractory (off-label use):

CEPP regimen: Oral: 60 mg/m2 on days 1 to 10 every 28 days (in combination with cyclophosphamide, etoposide and prednisone) for up to 6 cycles (Ref).

PEP-C regimen: Oral: 50 mg once 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) (Ref).

Primary CNS lymphoma

Primary CNS lymphoma (off-label use):

R-MPV regimen: Induction: Oral: 100 mg/m2/day for 7 days in cycles 1, 3, and 5 (in combination with rituximab, high-dose methotrexate, leucovorin, and vincristine; each cycle is 14 days), followed by reduced-dose whole brain radiotherapy and cytarabine (Ref) or autologous stem cell transplant (Ref). Two additional cycles of R-MPV may be administered to patients with partial response after initial induction chemotherapy; refer to protocols for details.

R-MP regimen: Patients ≥65 years: Oral: 60 mg/m2 on days 2 to 11 every 42 days (in combination with rituximab, high-dose methotrexate, and leucovorin) for 3 cycles, followed by maintenance treatment (beginning on day 43 after the last R-MP induction cycle): 100 mg once daily for 5 days every 28 days for 6 maintenance cycles; administer maintenance even if not all 3 induction cycles were completed (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution in patients with kidney function impairment as increased toxicity may occur. Because predominantly inactive metabolites are excreted via the kidneys, dosage adjustment is not necessary (Ref). However, the following adjustments have been reported:

GFR ≥10 mL/minute: No dosage adjustment necessary (Ref).

GFR <10 mL/minute: Use is not recommended (Ref).

Hemodialysis: Use is not recommended (Ref).

Dosing: Liver Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution in patients with hepatic impairment as increased toxicity may occur. No need for dosage adjustment is expected (Ref). However, the following adjustments have been reported:

Floyd 2006:

Transaminases 1.6 to 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.

Adverse Reactions

The following adverse drug reactions are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Edema, flushing, hypotension, syncope, tachycardia

Dermatologic: Alopecia, dermatitis, diaphoresis, hyperpigmentation, pruritus, purpuric rash, skin rash, urticaria

Endocrine & metabolic: Gynecomastia (in prepubertal and early pubertal males)

Gastrointestinal: Abdominal pain, anorexia, constipation, diarrhea, dysphagia, hematemesis, melena, stomatitis, xerostomia

Genitourinary: Hematuria, nocturia, urinary frequency

Hematologic & oncologic: Anemia, bone marrow depression, eosinophilia, hemolytic anemia, leukopenia, pancytopenia, petechia, thrombocytopenia

Hepatic: Hepatic impairment, jaundice

Hypersensitivity: Hypersensitivity reaction

Infection: Herpes virus infection, infection

Nervous system: Apprehension, asthenia, ataxia, chills, coma, confusion, depression, dizziness, drowsiness, falling, fatigue, hallucination, headache, hyporeflexia, insomnia, lethargy, nervousness, neuropathy, nightmares, pain, paresthesia, seizure, slurred speech, tremor, unsteadiness

Neuromuscular & skeletal: Arthralgia, foot-drop, myalgia

Ophthalmic: Accommodation disturbance, diplopia, nystagmus disorder, papilledema, photophobia, retinal hemorrhage

Otic: Hearing loss

Respiratory: Cough, epistaxis, hemoptysis, hoarseness, pleural effusion, pneumonitis

Miscellaneous: Fever

Postmarketing:

Gastrointestinal: Nausea, vomiting

Nervous system: Mania (Carney 1982)

Contraindications

Known hypersensitivity to procarbazine or any component of the formulation; inadequate bone marrow reserve.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Hematologic toxicity (leukopenia and thrombocytopenia) occurs 2 to 8 weeks after treatment initiation. Allow ≥1 month interval between radiation therapy or myelosuppressive chemotherapy and initiation of procarbazine treatment.

• CNS toxicity: CNS toxicity (eg, paresthesias, neuropathies, confusion) has been observed. CNS depression may occur; use with caution with other agents associated with CNS depression.

• Disulfiram-like reaction: Avoid ethanol consumption during procarbazine therapy, as a disulfiram-like reaction may occur.

• Hemolysis: Procarbazine may cause hemolysis and/or presence of Heinz inclusion bodies in erythrocytes.

• Hemorrhage: Hemorrhage or bleeding may occur.

• Hypersensitivity: Generalized allergic reactions have been reported.

• Secondary malignancies: Procarbazine is possibly carcinogenic; acute myeloid leukemia and lung cancer have been reported following the use of procarbazine in combination with other chemotherapeutic agents.

Concurrent drug therapy issues:

• Monoamine oxidase inhibitor activity: Procarbazine may possess some monoamine oxidase inhibitor (MAOI) activity; the potential for serious drug and food interactions is unclear as there is no clinical evidence to support such interactions; following an MAOI diet (avoid tyramine-containing foods) is recommended.

Warnings: Additional Pediatric Considerations

In pediatric patients, undue toxicity characterized as tremors, coma, and convulsions have been reported rarely; monitor closely with use.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as hydrochloride:

Matulane: 50 mg [contains corn starch, fd&c yellow #6 (sunset yellow), methylparaben, propylparaben, quinoline yellow (d&c yellow #10)]

Generic Equivalent Available: US

No

Pricing: US

Capsules (Matulane Oral)

50 mg (per each): $178.22

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as hydrochloride:

Matulane: 50 mg [contains corn starch, fd&c yellow #6 (sunset yellow), methylparaben, propylparaben, quinoline yellow (d&c yellow #10)]

Extemporaneous Preparations

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.
Administration: Pediatric

Oral: Total daily dose may be administered as a single daily dose or in divided doses throughout the day to minimize GI toxicity. Procarbazine is associated with a high emetic potential (Ref); antiemetics are recommended to prevent nausea and vomiting (Ref).

Administration: Adult

Oral: May be administered as a single daily dose or in 2 to 3 divided doses. Some protocols administered in the evening; refer to specific protocol for details. Procarbazine is associated with a moderate or high emetic potential in adults; antiemetics are recommended to prevent nausea and vomiting (Ref).

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2024 [table 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).

Storage/Stability

Protect from light.

Use

Treatment of Hodgkin lymphoma [FDA approved in pediatrics (age not specified) and adults]; has also been used to treat CNS tumors (low grade gliomas)

Medication Safety Issues
Sound-alike/look-alike issues:

Matulane may be confused with mitotane.

Procarbazine may be confused with dacarbazine.

International issues:

Matulane [US, Canada] may be confused with Materna brand name for vitamin with minerals [multiple international markets]

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program

5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Alcohol (Ethyl): Procarbazine may increase adverse/toxic effects of Alcohol (Ethyl). A disulfiram-like reaction may occur. Alcohol (Ethyl) may increase CNS depressant effects of Procarbazine. Risk X: Avoid

Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor

Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor

Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor

Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor

ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor

ARIPiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid

BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of BCG Products. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Blonanserin: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Blonanserin. Specifically, the risk of seizures may be increased. Risk C: Monitor

Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor

Brivudine: May increase adverse/toxic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Bromperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Bromperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

BuPROPion: May increase neuroexcitatory and/or seizure-potentiating effects of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor

Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid

Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor

Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid

ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor

Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Cladribine. Risk X: Avoid

Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

CloZAPine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor

CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor

CNS Depressants: Procarbazine may increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Cytotoxic Chemotherapy) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor

COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor

Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Denosumab: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification

Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

DroPERidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid

Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor

FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Iloperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor

Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification

Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification

Isocarboxazid: Procarbazine may increase adverse/toxic effects of Isocarboxazid. Risk X: Avoid

Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider Therapy Modification

Lenograstim: Antineoplastic Agents may decrease therapeutic effects of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification

Levosulpiride: Benzamide Derivatives may increase adverse/toxic effects of Levosulpiride. Risk C: Monitor

Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Lipegfilgrastim: Antineoplastic Agents may decrease therapeutic effects of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider Therapy Modification

Loxapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Methotrimeprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Methotrimeprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid

Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid

Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor

Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor

OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor

Palifermin: May increase adverse/toxic effects of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider Therapy Modification

Paliperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pidotimod. Risk C: Monitor

Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Pimozide: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor

Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid

Piperacillin: May increase hypokalemic effects of Antineoplastic Agents. Risk C: Monitor

Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor

Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification

Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

QUEtiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification

RisperiDONE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor

Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid

Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification

Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid

Sertindole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification

Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor

Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor

Sulpiride: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor

Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid

Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid

Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Tertomotide. Risk X: Avoid

Thioridazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor

Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid

Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor

Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid

Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may decrease therapeutic effects of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid

Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting chemotherapy when possible. Patients vaccinated less than 14 days before or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification

Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Ziprasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Zoster Vaccine (Live/Attenuated): Immunosuppressants (Cytotoxic Chemotherapy) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid

Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Food Interactions

Ethanol: Ethanol may cause a disulfiram reaction. Management: Avoid ethanol.

Food: Concurrent ingestion of foods rich in tyramine, dopamine, tyrosine, phenylalanine, tryptophan, or caffeine may cause sudden and severe high blood pressure (hypertensive crisis or serotonin syndrome). Management: Avoid tyramine-containing foods (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). Food’s freshness is also an important concern; improperly stored or spoiled food can create an environment in which tyramine concentrations may increase. Avoid foods containing dopamine, tyrosine, phenylalanine, tryptophan, or caffeine.

Dietary Considerations

Avoid tyramine-containing foods/beverages. Some examples include aged or matured cheese; air-dried, smoked, pickled, or cured meats (including sausages and salamis); fava or broad bean pods; tap/draft beers; ripe bananas; Marmite concentrate; sauerkraut; and soy sauce and other soybean condiments.

Reproductive Considerations

Patients who could become pregnant should avoid pregnancy during treatment. In general, patients who could become pregnant should use effective contraception during systemic anti-cancer therapy and for 3 to 6 months after the last dose. Patients with partners who could become pregnant should use effective contraception during treatment and for 3 to 6 months after the last dose of systemic anti-cancer therapy (ESMO [Peccatori 2013]).

Procarbazine is associated with a high risk of azoospermia and infertility (ESMO [Lambertini 2020]). Azoospermia and infertility have been reported with procarbazine when used in combination with other chemotherapy agents.

Recommendations are available for fertility preservation of male and female patients to be treated with anticancer agents (ASCO [Oktay 2018], Klipstein 2020).

Pregnancy Considerations

Outcome data following maternal use of procarbazine during pregnancy are available (NTP 2013). Procarbazine may cause fetal harm if administered during pregnancy. There are case reports of fetal malformations in the offspring of pregnant patients exposed to procarbazine as part of a combination chemotherapy regimen.

The European Society for Medical Oncology (ESMO) has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach. In general, if chemotherapy is indicated, it should be avoided in the first trimester and there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (ESMO [Peccatori 2013]).

A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (877-635-4499).

Monitoring Parameters

CBC with differential, platelet and reticulocyte count (at least every 3 to 4 days); also urinalysis (weekly), liver function test (prior to therapy and weekly), renal function test (prior to therapy and weekly), alkaline phosphatase (weekly). Monitor for infections, CNS toxicity, and gastrointestinal toxicities.

Mechanism of Action

Procarbazine inhibits DNA, RNA, and protein synthesis by inhibiting transmethylation of methionine into transfer RNA; may also damage DNA directly through alkylation.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Rapid and complete.

Distribution: Crosses the blood-brain barrier and distributes into CSF.

Metabolism: Primarily hepatic. Oxidized to active metabolites methylazoxy-procarbazine and benzylazoxy-procarbazine, then further metabolized to inactive metabolites (Kintzel 1995).

Half-life elimination: ~1 hour (Perry 2012).

Time to peak, plasma: ≤1 hour (Perry 2012).

Excretion: Urine (70% as inactive metabolites [Kintzel 1995]; <5% as unchanged drug).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Natulan;
  • (AR) Argentina: Alapidium | Natulan | Procarbazina eczane | Xolgan;
  • (AU) Australia: Matulane;
  • (BE) Belgium: Natulan;
  • (BG) Bulgaria: Natulan;
  • (BR) Brazil: Natulanar;
  • (CH) Switzerland: Natulan;
  • (CN) China: Natulan;
  • (CZ) Czech Republic: Natulan;
  • (DE) Germany: Natulan | Natulan abacus;
  • (EE) Estonia: Hodpro | Natulan | P-carzine;
  • (EG) Egypt: Natulan;
  • (ES) Spain: Natulan;
  • (FI) Finland: Natulan;
  • (FR) France: Natulan;
  • (GB) United Kingdom: Natulan | Procarbazine;
  • (GR) Greece: Natulan;
  • (HK) Hong Kong: Natulan;
  • (HU) Hungary: Natulan;
  • (IE) Ireland: Natulan;
  • (IL) Israel: Natulan;
  • (IN) India: Indicarb | Neozine | P-carzine;
  • (IT) Italy: Natulan;
  • (JP) Japan: Natulan | Procarbazine Hcl Chugai | Procarbazine hydrochloride typ;
  • (KR) Korea, Republic of: Matulane | Natulan;
  • (LB) Lebanon: Natulan;
  • (LT) Lithuania: Hodpro | Natulan | Natuzine | P-carzine | Procarbazine;
  • (LV) Latvia: Natulan;
  • (MA) Morocco: Natulan | Zinocarb;
  • (MY) Malaysia: Natulan | P-carzine;
  • (NL) Netherlands: Natulan;
  • (NO) Norway: Natulan | Natulan orifarm;
  • (NZ) New Zealand: Natulan;
  • (PK) Pakistan: P-carbazine;
  • (PL) Poland: Hodpro | Natulan;
  • (PR) Puerto Rico: Matulane;
  • (RU) Russian Federation: Natulan;
  • (SE) Sweden: Natulanar;
  • (SI) Slovenia: Natulan;
  • (SK) Slovakia: Natulan;
  • (TH) Thailand: Natulan;
  • (TN) Tunisia: Natulan;
  • (TR) Turkey: Natulan;
  • (TW) Taiwan: Natulan;
  • (UA) Ukraine: Glocarbazin | Natulan | Procarbazine;
  • (UY) Uruguay: Natulan;
  • (ZA) South Africa: Natulan
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