It is recommended that procarbazine 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: Refer to individual protocols for specific dosage and interval information. Procarbazine is associated with a high emetic potential (Dupuis 2011); antiemetics are recommended to prevent nausea and vomiting (Dupuis 2013). 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: 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 (Kelly 2012). Manufacturer's labeling: Infants, Children, and Adolescents: Oral: 50 to 100 mg/m2/day once daily for 14 days of a 28-day cycle (Longo 1986)
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 (Kelly 2011)
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 (Ater 2012)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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 (Kintzel 1995).
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
(For additional information see "Procarbazine: Drug information")
Note: Procarbazine is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]). 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.
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, begin within 4 weeks after radiotherapy) for 6 cycles (van den Bent 2006; van den Bent 2013) or 75 mg/m2 days 8 to 21 every 6 weeks (in combination with lomustine and vincristine, followed by radiotherapy) for up to 4 cycles (Cairncross 2006; Cairncross 2013).
CNS tumors (low-grade gliomas) (off-label use): PCV regimen: Oral: 60 mg/m2 days 8 to 21 every 8 weeks (after radiotherapy; in combination with lomustine and vincristine) for 6 cycles (Buckner 2016)
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)
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/refractory (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)
Primary CNS lymphoma (off-label use): Oral:
R-MPV regimen: Induction: 100 mg/m2 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 (Morris 2013; Shah 2007) or autologous stem cell transplant (Omuro 2015). 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: 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 (Fritsch 2017)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution in patients with renal impairment as increased toxicity may occur. However, because predominantly inactive metabolites are excreted via the kidneys, dosage adjustment is not necessary (Kintzel 1995).
There are no dosage adjustments provided in the manufacturer's labeling; use with caution in patients with hepatic impairment as increased toxicity may occur. 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
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral, as hydrochloride:
Matulane: 50 mg [DSC]
Matulane: 50 mg [contains corn starch, fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow), methylparaben, propylparaben]
No
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 #10 (quinoline yellow), fd&c yellow #6 (sunset yellow), methylparaben, propylparaben]
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 (Dupuis 2011); antiemetics are recommended to prevent nausea and vomiting (Dupuis 2013).
Oral: May be given 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 (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).
Hazardous agent (NIOSH 2016 [group 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 2016; USP-NF 2020).
Protect from light.
Treatment of Hodgkin lymphoma [FDA approved in pediatrics (age not specified) and adults]; has also been used to treat CNS tumors (low grade gliomas)
Matulane may be confused with mitotane.
Procarbazine may be confused with dacarbazine
Matulane [US, Canada] may be confused with Materna brand name for vitamin with minerals [multiple international markets]
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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
Known hypersensitivity to procarbazine or any component of the formulation; inadequate bone marrow reserve
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. Withhold treatment for leukopenia (WBC <4,000/mm3) or thrombocytopenia (platelets <100,000/mm3). Monitor for infections due to neutropenia.
• CNS toxicity: Withhold treatment for CNS toxicity (eg, paresthesias, neuropathies, confusion). 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: Withhold treatment for hemorrhage or bleeding tendencies.
• Hypersensitivity: Generalized allergic reactions have been reported. Withhold treatment for hypersensitivity.
• 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.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment (toxicities may be increased).
• Renal impairment: Use with caution in patients with renal impairment (toxicities may be increased).
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.
Other warnings/precautions:
• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
In pediatric patients, undue toxicity characterized as tremors, coma, and convulsions have been reported rarely; monitor closely with use.
None known.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy
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. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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 (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: In the US, after receipt of the single dose COVID-19 adenovirus vector vaccine (Janssen), administer an additional 2nd dose using an mRNA COVID-19 vaccine, at least 28 days after the primary vaccine dose, in patients taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect 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 enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect 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
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such cytotoxic chemotherapy. If combined, monitor for reduced efficacy of cytotoxic chemotherapy. Risk D: Consider therapy modification
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect 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 enhance the adverse/toxic effect 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 enhance the adverse/toxic effect 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 enhance the adverse/toxic effect 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
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect 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 diminish the therapeutic effect 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 enhance the adverse/toxic effect of Levosulpiride. Risk C: Monitor therapy
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect 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
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect 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
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to 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
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect 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
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect 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
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect 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 combination
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
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.
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.
Females of reproductive potential should avoid becoming pregnant during treatment.
Azoospermia and infertility have been reported with procarbazine when used in combination with other chemotherapy agents.
Procarbazine may cause fetal harm if administered to a pregnant female. There are case reports of fetal malformations in the offspring of pregnant women exposed to procarbazine as part of a combination chemotherapy regimen.
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.
Procarbazine inhibits DNA, RNA, and protein synthesis by inhibiting transmethylation of methionine into transfer RNA; may also damage DNA directly through alkylation.
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
Time to peak, plasma: ≤1 hour
Excretion: Urine (70% as inactive metabolites [Kintzel 1995]; <5% as unchanged drug)
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.
Capsules (Matulane Oral)
50 mg (per each): $143.63
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