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    Methylhydrazines

    BOXED WARNING

    Anemia, bone marrow suppression, herpes infection, infection, leukopenia, neutropenia, radiation therapy, requires a specialized care setting, requires an experienced clinician, thrombocytopenia, varicella, viral infection

    Administration of procarbazine requires an experienced clinician knowledgeable in the use of potent antineoplastic drugs and requires a specialized care setting such as a hospital or treatment facility with adequate clinical and laboratory facilities available for proper monitoring. Procarbazine is contraindicated in patients with severe bone marrow suppression (inadequate marrow reserve), as demonstrated by bone marrow aspiration. Consider the possibility of an inadequate marrow reserve in a patient with leukopenia, thrombocytopenia, or anemia. Patients with preexisting bone marrow suppression, including neutropenia and thrombocytopenia, should be allowed to recover their counts prior to procarbazine administration. Therapy should not be given to patients with neutrophil counts < 4000/mm3 or platelet counts < 100,000/mm3; bone marrow suppression occurs 2—8 weeks following procarbazine therapy. Use it cautiously in patients who have had previous myelosuppressive therapy such as chemotherapy or radiation therapy. These patients should be evaluated for sufficient bone marrow reserves prior to starting procarbazine therapy. Total blood cell counts should be monitored closely during therapy. Patients with an active infection should be treated prior to receiving procarbazine. Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy.

    DEA CLASS

    Rx

    DESCRIPTION

    Nonclassic alkylating agent; not cross-resistant with the other alkylating agents; has monoamine oxidase inhibitior (MAOI) activitiy; may cause disulfiram-like reactions.

    COMMON BRAND NAMES

    Matulane

    HOW SUPPLIED

    Matulane Oral Cap: 50mg

    DOSAGE & INDICATIONS

    For the treatment of Hodgkin's disease.
    NOTE: Dosage should be based on actual weight. If patient is obese or exhibits weight gain due to fluid retention, use ideal body weight.
    For the treatment of Hodgkin's disease as part of the BEACOPP regimen.
    Oral dosage
    Adults and Adolescents 15 years and older

    100 mg/m2/day PO on days 1 through 7 in combination with bleomycin (10 units/m2 IV on day 8), etoposide (100 mg/m2/day IV on days 1 through 3), doxorubicin (25 mg/m2 IV on day 1), cyclophosphamide (650 mg/m2 IV on day 1), vincristine (1.4 mg/m2 (Max: 2 mg) IV on day 8), and prednisone (40 mg/m2 PO on days 1 through 14). Cycles are repeated every 21 days for up to 8 cycles. Filgrastim was administered beginning on day 8 of each cycle and continued until the leukocyte count returned to normal in some clinical trials. The escalated dose BEACOPP regimen includes procarbazine 100 mg/m2/day PO on days 1 through 7 in combination with bleomycin (10 units/m2 IV on day 8), etoposide (200 mg/m2/day IV on days 1 through 3), doxorubicin (35 mg/m2 IV on day 1), cyclophosphamide (1,200 mg/m2 IV on day 1), vincristine (1.4 mg/m2 [Max: 2 mg] IV on day 8), and prednisone (40 mg/m2 PO on days 1 through 14). Cycles are repeated every 21 days for up to 8 cycles. Filgrastim was administered beginning on day 8 of each cycle and continued until the leukocyte count returned to normal in some clinical trials.The standard dose BEACOPP and escalated dose BEACOPP regimens have shown benefit for the treatment of advanced Hodgkin's disease in clinical trials. Escalated dose BEACOPP has shown a significantly better freedom from treatment failure at 10 years (82% vs. 70%, p < 0.0001) and overall survival at 10 years (86% vs. 80%, p = 0.0053) compared to standard dose BEACOPP. A regimen of four cycles of escalated dose BEACOPP followed by four cycles of standard dose BEACOPP has also been used in patients who achieve a complete response after the initial four cycles of escalated dose BEACOPP.

    As a single agent or in combination with other drugs.
    Oral dosage
    Adults

    As a single agent, 2 to 4 mg/kg/day PO for first week. Then, doses of 4 to 6 mg/kg daily until WBC falls below 4,000/mm3 or platelets fall below 100,000/mm3 or until maximum response is obtained. When the maximum response is obtained, a maintenance dose of 1 to 2 mg/kg/day PO may be used. When used as part of the MOPP regimen, the procarbazine dose is 100 mg/m2/day PO on days 1 through 14 of a 28-day cycle.

    Children and Adolescents

    50 to 100 mg/m2/day PO for 10 to 14 days of a 28-day cycle. The manufacturer recommends 50 mg/m2/day PO for the first week, then 100 mg/m2/day PO until maximum response is obtained or until leukopenia or thrombocytopenia occurs. When maximum response is obtained, the dose may be maintained at 50 mg/m2/day PO. In combination with other agents, procarbazine 100 mg/m2/day (Max dose: 150 mg) PO on days 1 through 15 has been used.

    For the treatment of non-Hodgkin's lymphoma (NHL)†, in combination with cyclophosphamide, etoposide, and prednisone.
    Oral dosage
    Adults

    50 mg PO once daily at bedtime as a component of PEP-C and 60 mg/m2/day PO on days 1 to 10 as a component of CEPP(B) have been studied. PEP-C resulted in an overall response rate (ORR) of 69% (complete response (CR) rate, 36%) in a retrospective analysis of 75 patients with recurrent lymphoma. The PEP-C regimen consisted of procarbazine 50 mg/day PO at bedtime plus prednisone 20 mg/day PO after breakfast, cyclophosphamide 50 mg/day PO after lunch, and etoposide 50 mg/day PO after dinner until a leukocyte count of less than 3 X 109/L (median duration of induction, 3 weeks; range, 2 weeks to 2 months) followed by a maintenance phase (resumed when leukocyte count is greater than 3 X 109/L) with PEP-C therapy titrated to maintain a white blood cell count of at least 3 X 109/L (e.g., PEP-C given 5 days/week, every other day, or twice or once weekly); the median time on therapy was 10 months (range, 3 weeks to 48 months). Most patients in this study had NHL (n = 66) and had received 2 or more previous therapies (80%); additionally, 47% of patients were refractory to the last treatment and 57% of patients were older than 60 years of age. The ORR was highest in patients with indolent lymphoma (follicular, n = 24 of 26 [88%]; marginal zone, n = 10 of 14 [71%]; small lymphocytic, n = 8 of 12 [67%]) compared with more aggressive lymphoma subtypes (diffuse large cell, n = 3 of 9 [33%]; T-cell, n = 3 of 5 [60%]). Serious toxicities with PEP-C therapy included grade 3 or 4 infection (n = 8) and thrombocytopenia (n = 8). In a randomized study of 75 patients with intermediate- or high-grade NHL, CEPP(B) led to an ORR of 72% (CR, 34%) The CEPP(B) regimen consisted of procarbazine 60 mg/m2/day PO on days 1 to 10 with cyclophosphamide 600 mg/m2 IV on days 1 and 8, etoposide 70 mg/m2/day IV on days 1 to 3, and prednisone 60 mg/m2/day orally on days 1 to 10 with or without bleomycin 15 units/m2 on days 1 and 15 repeated every 28 days; the median number of cycles received was 3 (range 1 to 6). The ORR was 70% (CR, 34%) in 61 evaluable patients with relapsed disease prior to CEPP(B) therapy; additionally, the median overall survival (OS) time was 12 months and the actuarial 5-year OS rate was 30% in relapsed patients. In this study, 8 patients had febrile neutropenia requiring hospitalization and 1 patient died after developing adult respiratory distress syndrome.

    For stem cell transplant preparation† prior to allogeneic transplantation in patients with severe aplastic anemia, in combination with cyclophosphamide and antithymocyte globulin.
    Oral dosage
    Adolescents and Adults 50 years and younger

    6.25 mg/kg/day orally in divided doses for 6 days (on days -8 to-3) plus cyclophosphamide (50 mg/kg/day IV for 4 days on days -5 to -2) and antithymocyte globulin (ATG) (1.25 mg/kg IV every other day for 3 doses on days -7, -5, and -3) or procarbazine 12.5 mg/kg PO on days -7, -5, and -3, cyclophosphamide (50 mg/kg/day IV on days -5 to -2), and rabbit antihuman thymocyte serum (0.2 mL/kg IV on days -6, -4, and -2) has been evaluated as a conditioning regimen prior to HLA-matched, allogeneic transplantation in patients with previously transfused, severe aplastic anemia. Following transplantation, patients received graft-versus-host disease (GVHD) prophylaxis with cyclosporine and/or methotrexate. In a retrospective analysis of 113 patients (aged 16 to 50 years) with severe aplastic anemia who received procarbazine, cyclophosphamide, and ATG prior to an HLA-matched, sibling donor allogeneic transplant, 16 patients (14.1%) experienced graft failure at a median follow-up of 30 months (range, 1 to 80 months). The estimated probability of rejection was 15%. Additionally, the overall survival (OS) rate was 89.5% and the estimated 6-year probability of disease-free survival was 89%. Grade 2 or higher acute GVHD developed in 10.5% of patients and chronic GVHD was reported in 11.9% of patients with sustained engraftment. In a clinical trial in 40 patients (aged 2 to 35 years) with previously transfused, severe aplastic anemia who received conditioning therapy with procarbazine, cyclophosphamide, and rabbit antihuman thymocyte serum prior to a HLA-matched allogeneic transplantation, 4 patients failed to engraft for an overall rejection rate of 10%. At a median follow-up of 59 months, the actuarial 1-year, 2-year, and 5-year OS rates were 75%, 64%, and 61%, respectively. Grade 2 to 4 acute GVHD was reported in 53% of engrafted patients and 11 of 31 long-term surviving patients (35%) experienced chronic GVHD.

    Children 2 years and older

    12.5 mg/kg PO on days -7, -5, and -3 plus cyclophosphamide (50 mg/kg/day IV on days -5 to -2) and rabbit antihuman thymocyte serum (0.2 mL/kg IV on days -6, -4, and -2) has been evaluated as a conditioning regimen prior to HLA-matched, allogeneic transplantation in patients with previously transfused, severe aplastic anemia. Following transplantation, patients received graft-versus-host disease (GVHD) prophylaxis with methotrexate. In a clinical trial in 40 patients (aged 2 to 35 years) with previously transfused, severe aplastic anemia who received conditioning therapy with procarbazine, cyclophosphamide, and rabbit antihuman thymocyte serum prior to a HLA-matched allogeneic transplantation, 4 patients failed to engraft for an overall rejection rate of 10%. At a median follow-up of 59 months, the actuarial 1-year, 2-year, and 5-year OS rates were 75%, 64%, and 61%, respectively. Grade 2 to 4 acute GVHD was reported in 53% of engrafted patients and 11 of 31 long-term surviving patients (35%) experienced chronic GVHD.

    For the adjuvant treatment of high-grade malignant glioma†.
    In combination with lomustine and vincristine in adult patients.
    Oral dosage
    Adults

    60 or 100 mg/m2/day PO as part of the PCV regimen and radiotherapy (RT) has been studied. In a multicenter, randomized trial of 674 patients with grade 3 or 4 astrocytoma (GBM, 67%; AA, 17%;), procarbazine 100 mg/m2/day PO on days 1 to 10, in combination with lomustine 100 mg/m2 PO on day 1 and vincristine 1.5 mg/m2 (Max dose: 2 mg) IV on day 1, repeated every 6 weeks for up to 12 cycles (median of 3 cycles) led to no significant differences in median overall survival (OS) (10 vs. 9.5 months) or progression free survival (PFS) (6 months in each arm) with RT plus PCV compared with RT alone In a phase III study of 368 patients with newly diagnosed anaplastic oligodendrogliomas or anaplastic mixed oligoastrocytomas, procarbazine 60 mg/m2/day PO on days 8 to 21 plus lomustine 110 mg/m2 PO on day 1 and vincristine 1.4 mg/m2 (Max dose: 2 mg) IV on days 8 and 29, repeated every 6 weeks for 6 cycles (median of 3 cycles) improved PFS (23 vs. 13.2 months; HR = 0.68; 95% CI, 0.53 to 0.87; p = 0.0018) compared with RT alone; however, OS time was not significantly improved (40.3 vs. 30.6 months) with PCV.

    In combination with chemotherapy in pediatric patients.
    Oral dosage
    Children 21 months and older and Adolescents

    Regimens and dosages have varied. 75 mg/m2 PO as part of the 8-in-1 regimen or 4 mg/kg/day PO in combination with other chemotherapy agents have been studied. Procarbazine as part of the 8-in-1 regimen (vincristine 1.5 mg/m2 IV, lomustine 100 mg/m2 PO, hydroxyurea 3,000 mg/m2 PO, cisplatin 90 mg/m2 IV, cytarabine 300 mg/m2 IV, dacarbazine 150 mg/m2 IV, and methylprednisolone 300 mg/m2 IV) for 3 doses/day on day 1 repeated every 6 weeks for 8 cycles following induction then postoperative radiotherapy (RT) did not significantly improve progression-free survival (14 months in both arms) or overall survival (31 vs. 25 months) compared with vincristine, lomustine, and prednisone plus induction therapy with RT in 172 patients in a randomized phase III trial; additionally, the 5-year progression free survival (PFS) (33% vs. 26%) and overall survival (OS) (39% vs. 29%) rates were not significantly different between the 2 treatment arms. Patients treated in the 8-in-1 arm experienced more myelosuppression and hearing loss. In another study of 21 patients aged 1 to 47 months, procarbazine 4 mg/kg/day PO on days 1 to 7 plus carboplatin 15 mg/kg (450 mg/m2) IV on day 1, etoposide 5 mg/kg/day (150 mg/m2) IV on days 22 and 23, cisplatin 1 mg/kg/day (30 mg/m2) IV (with mannitol and saline) on days 22 and 23, vincristine 0.05 mg/kg (1.5 mg/m2) IV on day 43, and cyclophosphamide 50 mg/kg (1,500 mg/m2) IV (with uromitexan) on day 43 repeated for 7 cycles (over 16 months) or until disease progression or unacceptable toxicity led to 5-year PFS and OS rates of 35.3% and 58.8%, respectively. No patient received upfront RT.

    Infants and Children younger than 21 months

    100 mg/m2 PO as part of the 8-in-1 regimen or 4 mg/kg/day PO in combination with other chemotherapy drugs has been studied. Procarbazine as part of the 8-in-1 regimen (vincristine 1.5 mg/m2 IV, lomustine 70 mg/m2 PO, hydroxyurea 3,000 mg/m2 PO, cisplatin 90 mg/m2 IV, cytarabine 300 mg/m2 IV, dacarbazine 150 mg/m2 IV, and prednisone 300 mg/m2 PO) for 3 doses/day on day 1 starting within 6 weeks from surgery repeated once after 2 weeks and then given every 4 to 6 weeks for 8 additional cycles led to 3-year progression-free survival and overall survival rates of 36% and 51%, respectively, in 39 pediatric patients aged 1 to 23 months. The 8-in-1 regimen doses were calculated per kilogram in patients with body surface area of 0.45 m2 or less. Radiotherapy (RT) was scheduled following the 10 cycles of 8-in-1 therapy; however, only 2 patients received RT. Bone morrow suppression was frequently reported; additionally, 7 patients had hearing loss within the speech range contributing to the omission of cisplatin in 22% of maintenance cycles. No chemotherapy-related deaths were reported. In another study of 21 patients aged 1 to 47 months, procarbazine 4 mg/kg/day PO on days 1 to 7 plus carboplatin 15 mg/kg (450 mg/m2) IV on day 1, etoposide 5 mg/kg/day (150 mg/m2) IV on days 22 and 23, cisplatin 1 mg/kg/day (30 mg/m2) IV (with mannitol and saline) on days 22 and 23, vincristine 0.05 mg/kg (1.5 mg/m2) IV on day 43, and cyclophosphamide 50 mg/kg (1,500 mg/m2) IV (with uromitexan) on day 43 repeated for 7 cycles (over 16 months) or until disease progression or unacceptable toxicity led to 5-year PFS and OS rates of 35.3% and 58.8%, respectively. No patient received upfront RT.

    For the adjuvant treatment of medulloblastoma†, in combination with nitrogen mustard, vincristine, and prednisone.
    Oral dosage
    Children, Adolescents, and Adults 20 years and younger

    50 mg PO on day 1, 100 mg PO on day 2, and 100 mg/m2 PO on days 3 to 10 as a component of MOPP has been studied. Procarbazine plus nitrogen mustard 3 mg/m2 IV on days 1 and 8, vincristine 1.4 mg/m2 IV on days 1 and 8, and prednisone 40 mg/m2 PO on days 1 to 10 (MOPP regimen) repeated every 4 weeks for 12 cycles starting 4 weeks after completing radiotherapy (RT) did not significantly improve the 5-year event-free survival (EFS) (68% vs 57%) or overall survival (OS) (73.6% vs. 56.1%) rates compared with RT alone in 71 pediatric patients aged 1 to 20 years old in a randomized trial; however, the 5-year OS rate in patients 5 years of age or greater was 82% in the RT+MOPP arm compared with 50.1% in the RT alone arm (p = 0.02). Seven patients in the RT+MOPP arm required hospitalization for febrile neutropenia and one of these patients died.

    For the first-line treatment of advanced non-small cell lung cancer (NSCLC)†, in combination with cyclophosphamide, doxorubicin, and methotrexate.
    Oral dosage
    Adults

    100 mg/m2/day PO for 10 days as part of the CAMP regimen (cyclophosphamide 300 mg/m2 IV, doxorubicin 20 mg/m2 IV, and methotrexate 15 mg/m2 IV on days 1 and 8 repeated every 28 days) has been studied in randomized clinical studies. The overall response rate (ORR) was 20.8% (partial response [PR], n = 11) in 53 evaluable patients who received CAMP compared with 38.2% (complete response [CR], n = 2; PR, n = 19) in 55 evaluable patients who received cisplatin and etoposide (p = 0.05) in a randomized trial that included 133 patients with previously untreated, advanced non-small cell lung cancer. In an analysis that adjusted for multiple prognostic factors, cisplatin and etoposide therapy was associated with better OS (hazard ratio = 0.7; 95% CI, 0.5 to 1; unadjusted p = 0.03). Grade 2 or less renal toxicity was reported significantly more often in the cisplatin and etoposide arm and there was 1 treatment-related death in this arm. In another randomized trial that evaluated the efficacy of 4 regimens: CAMP (n = 115); mitomycin-C, vinblastine, and cisplatin (MVP; n = 121); vindesine and cisplatin (VDA-P; n = 126); and etoposide and cisplatin (VP-P; n = 124), the ORR were 17%, 31%, 25%, and 20%, respectively, and the median OS times were 25.1, 22, 26, and 26.6 weeks, respectively. Additionally, no treatment was associated with improved survival in an analysis that adjusted for prognostic covariates. Fewer patients in the CAMP arm had severe or life-threatening gastrointestinal toxicity, infection, and hematological toxicity compared with the other treatment arms.

    †Indicates off-label use

    MAXIMUM DOSAGE

    The suggested maximum tolerated dose (MTD) for procarbazine is dependent on the disease state, performance status, and other chemotherapy agents or radiation therapy given in combination.

    Adults

    6 mg/kg/day PO as a single agent or 100 mg/m2/day PO in combination with other chemotherapy agents.

    Children

    100 mg/m2/day PO.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Although specific guidelines for dosage adjustments in hepatic impairment are not available; reduced doses are recommended to avoid excessive toxicity.

    Renal Impairment

    Although specific guidelines for dosage adjustments in renal impairment are not available; reduced doses are recommended to avoid excessive toxicity in patients with a BUN > 40 mg/dl and/or serum creatinine > 2 mg/dl.

    ADMINISTRATION

    CAUTION: Observe and exercise usual cautions for handling, preparing, and administering cytotoxic drugs.

    Oral Administration

    Procarbazine is given orally with or without food. If nausea and vomiting are a problem, procarbazine should be administered with fluids or food. The total daily dose may be given in divided doses to minimize GI toxicity.
    Procarbazine should be a gradually titrated up to the full dose over 3—4 days to avoid GI intolerance.

    STORAGE

    Matulane:
    - Storage information not listed

    CONTRAINDICATIONS / PRECAUTIONS

    Anemia, bone marrow suppression, herpes infection, infection, leukopenia, neutropenia, radiation therapy, requires a specialized care setting, requires an experienced clinician, thrombocytopenia, varicella, viral infection

    Administration of procarbazine requires an experienced clinician knowledgeable in the use of potent antineoplastic drugs and requires a specialized care setting such as a hospital or treatment facility with adequate clinical and laboratory facilities available for proper monitoring. Procarbazine is contraindicated in patients with severe bone marrow suppression (inadequate marrow reserve), as demonstrated by bone marrow aspiration. Consider the possibility of an inadequate marrow reserve in a patient with leukopenia, thrombocytopenia, or anemia. Patients with preexisting bone marrow suppression, including neutropenia and thrombocytopenia, should be allowed to recover their counts prior to procarbazine administration. Therapy should not be given to patients with neutrophil counts < 4000/mm3 or platelet counts < 100,000/mm3; bone marrow suppression occurs 2—8 weeks following procarbazine therapy. Use it cautiously in patients who have had previous myelosuppressive therapy such as chemotherapy or radiation therapy. These patients should be evaluated for sufficient bone marrow reserves prior to starting procarbazine therapy. Total blood cell counts should be monitored closely during therapy. Patients with an active infection should be treated prior to receiving procarbazine. Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy.

    Bleeding, diarrhea, peripheral neuropathy, stomatitis

    Prompt discontinuation of procarbazine therapy should be considered in the following situations: symptoms of central nervous system toxicity (e.g., confusion, paresthesias, or peripheral neuropathy), hypersensitivity reactions, stomatitis, diarrhea, and following bleeding or hemorrhage episodes.

    Intramuscular injections

    Intramuscular injections should not be administered to patients with platelet counts < 50,000/mm3 who are receiving procarbazine. IM injections may cause bleeding, bruising, or hematomas due to procarbazine-induced thrombocytopenia.

    Dental disease, dental work

    Myelosuppressive effects of procarbazine can increase the risk of infection or bleeding; therefore, dental work should be delayed until blood counts have returned to normal. Patients, especially those with dental disease, should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks.

    Alcoholism, hepatic disease, renal impairment

    Procarbazine should be used with caution in patients with alcoholism. Procarbazine may precipitate hepatic precoma in patients with cirrhosis. In addition, patients should be warned to avoid alcoholic beverages while receiving procarbazine therapy since there may be a disulfiram-like reaction. Preexisting hepatic disease or renal impairment/renal failure can cause accumulation of the drug worsening procarbazine's toxicity. Dosage reduction is recommended in patients with compromised renal (e.g., serum BUN > 40 mg/dl and/or serum creatinine > 2 mg/dl) or hepatic function (e.g., jaundice, serum bilirubin > 3 mg/dl). Renal and hepatic function should be evaluated prior to therapy; urinalysis, transaminase, alkaline phosphatase, and blood urea nitrogen/creatinine should be repeated at least weekly during therapy.

    Angina, cardiac arrhythmias, cardiac disease, cerebrovascular disease, coronary artery disease, hyperthyroidism, MAOI therapy, pheochromocytoma, thyroid disease

    Procarbazine has weak monoamine oxidase (MAO) inhibitor activity and can affect blood pressure. Do not use procarbazine along with MAOI therapy (see Drug Interactions). Cautious use of procarbazine is warranted in patients with a pheochromocytoma. Pheochromocytomas secrete pressor substances that may alter blood pressure during therapy. Patients with cardiac disease, coronary artery disease (e.g., angina), or cardiac arrhythmias may be aggravated by decreases in blood pressure. Patients who have undergone sympathectomy may be more sensitive to the hypotensive effects. Similarly, patients with cerebrovascular disease may aggravated cerebral ischemia as a result of reduced blood pressure. Patients with thyroid disease, specifically hyperthyroidism, may have increased sensitivity to the pressor amines.

    Tobacco smoking

    Patients should be advised to discontinue tobacco smoking during procarbazine therapy. Tobacco use during procarbazine therapy has been associated with an increased risk of secondary lung cancer. Results of a case-controlled study in patients with Hodgkin's disease receiving MOPP combination chemotherapy suggest an increased risk of lung cancer in a dose-dependent fashion, which is multiplied with exposure to tobacco smoke.

    G6PD deficiency

    Patients with G6PD deficiency are at increased risk for developing hemolysis during procarbazine therapy.

    Bipolar disorder, mania, Parkinson's disease, schizophrenia, seizure disorder

    Procarbazine can change the pattern of epileptiform seizures in patients with a seizure disorder. Parkinson's disease may be aggravated by procarbazine therapy. Patients with paranoid schizophrenia or other hyperexcitable personality states (e.g., mania, bipolar disorder) should use caution because the MAO inhibition by procarbazine may cause excessive CNS stimulation or swing manic-depressive patients into manic episodes.

    Infertility, male-mediated teratogenicity, pregnancy

    Procarbazine is a known teratogen and should not be used during pregnancy (FDA pregnancy risk category D). Both male and female patients should use barrier contraception when either is taking procarbazine because of the drug's effects on germ cell lines; procarbazine may cause male-mediated teratogenicity. Both male and female patients desiring to conceive should be counseled regarding the possibility of infertility and should discuss alternatives for adequate contraception during and after procarbazine therapy.

    Breast-feeding

    Although it is unknown whether procarbazine is excreted into breast milk, its use during breast-feeding is generally not recommended due to its carcinogenic and mutagenic effects.

    Children

    Procarbazine treatment should be individualized for use in children. Undue toxicity (e.g., tremors, coma, and seizures) has occurred in some cases. Very close clinical monitoring is required.

    Vaccination

    Vaccination during chemotherapy, such as with procarbazine, or radiation therapy should be avoided because the antibody response is suboptimal. When chemotherapy is being planned, vaccination should precede the initiation of chemotherapy by >= 2 weeks. The administration of live vaccines to immunocompromised patients should be avoided. Those undergoing chemotherapy should not be exposed to others who have recently received the oral poliovirus vaccine (OPV). Measles-mumps-rubella (MMR) vaccination is not contraindicated for the close contacts, including health care professionals, of immunocompromised patients. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination. When exposed to a vaccine-preventable disease such as measles, severely immunocompromised children should be considered susceptible regardless of their vaccination history.

    ADVERSE REACTIONS

    Severe

    pancytopenia / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    hematemesis / Delayed / Incidence not known
    coma / Early / Incidence not known
    seizures / Delayed / Incidence not known
    pleural effusion / Delayed / Incidence not known
    retinal hemorrhage / Delayed / Incidence not known
    papilledema / Delayed / Incidence not known
    teratogenesis / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known

    Moderate

    leukopenia / Delayed / 10.0
    thrombocytopenia / Delayed / 10.0
    anemia / Delayed / 10.0
    eosinophilia / Delayed / Incidence not known
    stomatitis / Delayed / Incidence not known
    constipation / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    melena / Delayed / Incidence not known
    ataxia / Delayed / Incidence not known
    confusion / Early / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    nystagmus / Delayed / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    edema / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    pneumonitis / Delayed / Incidence not known
    infertility / Delayed / Incidence not known
    secondary malignancy / Delayed / Incidence not known
    photophobia / Early / Incidence not known
    hemoptysis / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    hematuria / Delayed / Incidence not known
    depression / Delayed / Incidence not known
    hallucinations / Early / Incidence not known

    Mild

    vomiting / Early / 10.0
    nausea / Early / 10.0
    infection / Delayed / Incidence not known
    abdominal pain / Early / Incidence not known
    xerostomia / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    diarrhea / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    hyporeflexia / Delayed / Incidence not known
    headache / Early / Incidence not known
    dizziness / Early / Incidence not known
    drowsiness / Early / Incidence not known
    tremor / Early / Incidence not known
    syncope / Early / Incidence not known
    hoarseness / Early / Incidence not known
    cough / Delayed / Incidence not known
    azoospermia / Delayed / Incidence not known
    gynecomastia / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known
    flushing / Rapid / Incidence not known
    skin hyperpigmentation / Delayed / Incidence not known
    rash (unspecified) / Early / Incidence not known
    diaphoresis / Early / Incidence not known
    alopecia / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    diplopia / Early / Incidence not known
    epistaxis / Delayed / Incidence not known
    purpura / Delayed / Incidence not known
    petechiae / Delayed / Incidence not known
    nocturia / Early / Incidence not known
    increased urinary frequency / Early / Incidence not known
    musculoskeletal pain / Early / Incidence not known
    arthralgia / Delayed / Incidence not known
    myalgia / Early / Incidence not known
    insomnia / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    nightmares / Early / Incidence not known
    fatigue / Early / Incidence not known
    lethargy / Early / Incidence not known
    weakness / Early / Incidence not known
    fever / Early / Incidence not known
    chills / Rapid / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Major) Ingestion of certain products should be minimized while receiving procarbazine therapy, as the drug has some MAO inhibiting actions. Caffeine may produce hypertension or hypertensive crisis or induce cardiac arrhythmias if administered to patients taking drugs with strong MAOI properties. All preparations containing caffeine should be used sparingly such as teas, coffee, chocolate, cola, guarana, or 'stay awake' products. Some non-prescription medicines also contain caffeine and should not be taken without health care professional advice. Following discontinuation of procarbazine, dietary restrictions should continue for at least 2 weeks due to the slow recovery from the enzyme-inhibiting effects.
    Acetaminophen; Butalbital; Caffeine: (Major) Ingestion of certain products should be minimized while receiving procarbazine therapy, as the drug has some MAO inhibiting actions. Caffeine may produce hypertension or hypertensive crisis or induce cardiac arrhythmias if administered to patients taking drugs with strong MAOI properties. All preparations containing caffeine should be used sparingly such as teas, coffee, chocolate, cola, guarana, or 'stay awake' products. Some non-prescription medicines also contain caffeine and should not be taken without health care professional advice. Following discontinuation of procarbazine, dietary restrictions should continue for at least 2 weeks due to the slow recovery from the enzyme-inhibiting effects.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Major) Ingestion of certain products should be minimized while receiving procarbazine therapy, as the drug has some MAO inhibiting actions. Caffeine may produce hypertension or hypertensive crisis or induce cardiac arrhythmias if administered to patients taking drugs with strong MAOI properties. All preparations containing caffeine should be used sparingly such as teas, coffee, chocolate, cola, guarana, or 'stay awake' products. Some non-prescription medicines also contain caffeine and should not be taken without health care professional advice. Following discontinuation of procarbazine, dietary restrictions should continue for at least 2 weeks due to the slow recovery from the enzyme-inhibiting effects. (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Acetaminophen; Caffeine; Dihydrocodeine: (Major) Ingestion of certain products should be minimized while receiving procarbazine therapy, as the drug has some MAO inhibiting actions. Caffeine may produce hypertension or hypertensive crisis or induce cardiac arrhythmias if administered to patients taking drugs with strong MAOI properties. All preparations containing caffeine should be used sparingly such as teas, coffee, chocolate, cola, guarana, or 'stay awake' products. Some non-prescription medicines also contain caffeine and should not be taken without health care professional advice. Following discontinuation of procarbazine, dietary restrictions should continue for at least 2 weeks due to the slow recovery from the enzyme-inhibiting effects. (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Major) Ingestion of certain products should be minimized while receiving procarbazine therapy, as the drug has some MAO inhibiting actions. Caffeine may produce hypertension or hypertensive crisis or induce cardiac arrhythmias if administered to patients taking drugs with strong MAOI properties. All preparations containing caffeine should be used sparingly such as teas, coffee, chocolate, cola, guarana, or 'stay awake' products. Some non-prescription medicines also contain caffeine and should not be taken without health care professional advice. Following discontinuation of procarbazine, dietary restrictions should continue for at least 2 weeks due to the slow recovery from the enzyme-inhibiting effects.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Major) Ingestion of certain products should be minimized while receiving procarbazine therapy, as the drug has some MAO inhibiting actions. Caffeine may produce hypertension or hypertensive crisis or induce cardiac arrhythmias if administered to patients taking drugs with strong MAOI properties. All preparations containing caffeine should be used sparingly such as teas, coffee, chocolate, cola, guarana, or 'stay awake' products. Some non-prescription medicines also contain caffeine and should not be taken without health care professional advice. Following discontinuation of procarbazine, dietary restrictions should continue for at least 2 weeks due to the slow recovery from the enzyme-inhibiting effects.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Acetaminophen; Codeine: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Acetaminophen; Dextromethorphan: (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Acetaminophen; Dextromethorphan; Doxylamine: (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Acetaminophen; Guaifenesin; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Acetaminophen; Oxycodone: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Acetaminophen; Pentazocine: (Major) Patients receiving concurrent pentazocine and MAOI inhbitors may be at increased risk for developing serotonin syndrome; pentazocine should be used cautiously in patients receiving other drugs with MAOI activity, such as procarbazine.
    Acetaminophen; Propoxyphene: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Acetaminophen; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Acetaminophen; Tramadol: (Major) Avoid use of tramadol concurrently or within 14 days of discontinuing a drug with monamine oxidase inhibitor (MAOI)-like activity, such as procarbazine. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during treatment initiation and dose increases. International recommendations contraindicate the use of tramadol within 14 days of an MAOI. There is an increased risk of seizures and serotonin syndrome in patients receiving these drugs currently. In animal studies, an increased number of deaths was noted with the combination due to interference with detoxification mechanisms.
    Acrivastine; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Aldesleukin, IL-2: (Moderate) The safety and efficacy of aldesleukin, IL 2 in combination with any antineoplastic agents have not been established. Hypersensitivity reactions have been reported in patients receiving combination regimens containing sequential high dose aldesleukin, IL 2 and dacarbazine. Aldesleukin, IL 2 can decrease dacarbazine serum concentrations by increasing the volume of distribution of dacarbazine by 36 percent via an unknown mechanism.
    Alfentanil: (Major) In theory, the use of alfentanil in a patient taking procarbazine may increase the risk of serotonergic symptoms. Procarbazine has MAOI activity; the manufacturer of alfentanil does not recommend its use within 14 day of an MAO Inhibitor. Alfentanil belongs to the same group of opiate agonists, phenylpiperidines, as meperidine, a known serotonin reuptake inhibitor. Caution is advised until more data are available.
    Alprazolam: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Amide local anesthetics: (Major) Patients taking procarbazine should not be given local anesthetics containing sympathomimetic vasoconstrictors; coadministration may invoke a severe hypertensive reaction. Procarbazine should be discontinued for at least 10 days prior to elective surgery.
    Amitriptyline; Chlordiazepoxide: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Amoxapine: (Major) In general, drugs with MAOI activity, such as procarbazine, should not be used with tricyclic antidepressants. Severe hypertensive crises, serotonin syndrome, or increased anticholinergic effects can result from concomitant use. Combining procarbazine with other medications possessing serotonergic or combined serotonergic/noradrenergic effects (such as amoxapine, maprotiline, mirtazapine, trazodone) may also cause an excess of serotonergic or noradrenergic activity. Tricyclic antidepressants can, in some cases, be used concomitantly with MAOIs if tricyclic antidepressant therapy is in effect prior to beginning therapy with a MAOI; tricyclic antidepressants should never be added to an existing MAOI regime. Under careful monitoring for signs or symptoms of hypertension, add the MAOI gradually, starting at a low dose. Patients should also be monitored closely for signs or symptoms of serotonin syndrome (characterized by hyperthermia, diaphoresis, shivering, tremor, myoclonus, seizures, ataxia, delirium, restlessness). Strict adherence to diet restrictions should be emphasized and the patient should not be receiving other sympathomimetics.
    Amphetamine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Amphetamine; Dextroamphetamine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Armodafinil: (Severe) Armodafinil has not been evaluated for drug interactions with drugs with MAO inhibiting activity (e.g., procarbazine). Other CNS stimulants may induce severe cardiovascular and cerebrovascular responses if administered in combination with drugs with MAO inhibitor activity. The manufacturer recommends caution during coadministration of armodafinil with MAO inhibitors.
    Articaine; Epinephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Ingestion of certain products should be minimized while receiving procarbazine therapy, as the drug has some MAO inhibiting actions. Caffeine may produce hypertension or hypertensive crisis or induce cardiac arrhythmias if administered to patients taking drugs with strong MAOI properties. All preparations containing caffeine should be used sparingly such as teas, coffee, chocolate, cola, guarana, or 'stay awake' products. Some non-prescription medicines also contain caffeine and should not be taken without health care professional advice. Following discontinuation of procarbazine, dietary restrictions should continue for at least 2 weeks due to the slow recovery from the enzyme-inhibiting effects.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Ingestion of certain products should be minimized while receiving procarbazine therapy, as the drug has some MAO inhibiting actions. Caffeine may produce hypertension or hypertensive crisis or induce cardiac arrhythmias if administered to patients taking drugs with strong MAOI properties. All preparations containing caffeine should be used sparingly such as teas, coffee, chocolate, cola, guarana, or 'stay awake' products. Some non-prescription medicines also contain caffeine and should not be taken without health care professional advice. Following discontinuation of procarbazine, dietary restrictions should continue for at least 2 weeks due to the slow recovery from the enzyme-inhibiting effects. (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Major) Ingestion of certain products should be minimized while receiving procarbazine therapy, as the drug has some MAO inhibiting actions. Caffeine may produce hypertension or hypertensive crisis or induce cardiac arrhythmias if administered to patients taking drugs with strong MAOI properties. All preparations containing caffeine should be used sparingly such as teas, coffee, chocolate, cola, guarana, or 'stay awake' products. Some non-prescription medicines also contain caffeine and should not be taken without health care professional advice. Following discontinuation of procarbazine, dietary restrictions should continue for at least 2 weeks due to the slow recovery from the enzyme-inhibiting effects. (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Aspirin, ASA; Oxycodone: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Atomoxetine: (Severe) Procarbazine is a weak monoamine oxidase inhibitor (MAOI). The use of atomoxetine with monoamine oxidase inhibitors (MAOIs) is contraindicated. Atomoxetine should not be taken with any MAOI, or within 2 weeks after discontinuing a MAOI and vice versa. Atomoxetine is one of the selective norepinephrine reuptake inhibitors (SNRIs). Since norepinephrine is deaminated by monoamine oxidase, administration of drugs that inhibit this enzyme concurrently with atomoxetine can lead to serious reactions. These reactions may include confusion, seizures, and severe hypertension as well as less severe symptoms.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Concurrent use of methylene blue and MAOIs or drugs that possess MAOI-like activity (e.g., procarbazine) should generally be avoided due to the potential for serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving serotonergic agents such as selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clompiramine. It is not known if patients receiving intravenous methylene blue with other serotonergic psychiatric agents are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Atropine; Difenoxin: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Atropine; Diphenoxylate: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Barbiturates: (Moderate) Use procarbazine and barbiturates together with caution; additive CNS depression may occur.
    Belladonna; Opium: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Benzodiazepines: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Concurrent use of methylene blue and MAOIs or drugs that possess MAOI-like activity (e.g., procarbazine) should generally be avoided due to the potential for serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving serotonergic agents such as selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clompiramine. It is not known if patients receiving intravenous methylene blue with other serotonergic psychiatric agents are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Benzonatate: (Moderate) These drugs should be prescribed with caution. It may be advisable to avoid the use of benzonatate, which is structurally similar to local anesthetic agents, in patients receiving MAOIs. Consider alternatives to benzonatate. Procarbazine is a drug with monoamine oxidase inhibitor (MAOI) activity. Use of a drug with MAOI activity with local anesthetics may increase the risk of hypotension or CNS-related effects. If co-use is medically necessary, observe the patient for additive effects such as low blood pressure, sedation, dizziness, mental confusion, or other side effects.
    Benzphetamine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Beta-agonists: (Major) Procarbazine has MAOI activity and the cardiovascular effects of beta-2 agonists may be potentiated by concomitant use of MAOIs. Although no data are available, procarbazine may interact similarly. Close observation for such effects is prudent, particularly if beta-agonists are administered within two weeks of stopping the MAOI.
    Brompheniramine; Carbetapentane; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Brompheniramine; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Bupropion: (Severe) There is an increased risk of hypertensive reactions when bupropion is co-administered with monoamine oxidase inhibitors (MAOIs), and the combination is contraindicated. Therefore, concurrent use of bupropion and medications with MAO activity, such as procarbazine, should be avoided.
    Bupropion; Naltrexone: (Severe) There is an increased risk of hypertensive reactions when bupropion is co-administered with monoamine oxidase inhibitors (MAOIs), and the combination is contraindicated. Therefore, concurrent use of bupropion and medications with MAO activity, such as procarbazine, should be avoided.
    Buspirone: (Severe) Simultaneous use of buspirone with drugs that possess monoamine oxidase inhibitor activity, such as procarbazine, can increase blood pressure, so it is recommended that this combination be avoided. When switching drug therapy, there should be a 14-day delay after discontinuing a drug with MAOI-like actions before initiating a serotonergic drug like buspirone treatment.
    Caffeine: (Major) Ingestion of certain products should be minimized while receiving procarbazine therapy, as the drug has some MAO inhibiting actions. Caffeine may produce hypertension or hypertensive crisis or induce cardiac arrhythmias if administered to patients taking drugs with strong MAOI properties. All preparations containing caffeine should be used sparingly such as teas, coffee, chocolate, cola, guarana, or 'stay awake' products. Some non-prescription medicines also contain caffeine and should not be taken without health care professional advice. Following discontinuation of procarbazine, dietary restrictions should continue for at least 2 weeks due to the slow recovery from the enzyme-inhibiting effects.
    Caffeine; Ergotamine: (Major) Ingestion of certain products should be minimized while receiving procarbazine therapy, as the drug has some MAO inhibiting actions. Caffeine may produce hypertension or hypertensive crisis or induce cardiac arrhythmias if administered to patients taking drugs with strong MAOI properties. All preparations containing caffeine should be used sparingly such as teas, coffee, chocolate, cola, guarana, or 'stay awake' products. Some non-prescription medicines also contain caffeine and should not be taken without health care professional advice. Following discontinuation of procarbazine, dietary restrictions should continue for at least 2 weeks due to the slow recovery from the enzyme-inhibiting effects.
    Carbamazepine: (Moderate) Myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution. Dosage adjustments may be necessary. Monitor patient closely. Carbamazepine may potentially accelerate the hepatic metabolism of dacarbazine, DTIC.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Carbetapentane; Guaifenesin; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Carbetapentane; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Carbetapentane; Phenylephrine; Pyrilamine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Carbetapentane; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Carbidopa; Levodopa: (Major) Concomitant use of levodopa and drugs with monoamine oxidase inhibitor (MAOI) activity (e.g., procarbazine) can result in hypertensive crisis. Simultaneous use of these agents should be avoided if possible.
    Carbidopa; Levodopa; Entacapone: (Major) Concomitant use of levodopa and drugs with monoamine oxidase inhibitor (MAOI) activity (e.g., procarbazine) can result in hypertensive crisis. Simultaneous use of these agents should be avoided if possible. (Major) Patients should not receive COMT-inhibitors in combination with agents with non-selective MAO inhibiting activity like procarbazine. MAO and COMT are the two major enzymes involved in the metabolism of catecholamines. It is theoretically possible that the combination of COMT-inhibitors and a non-selective MAOI would result in inhibition of the majority of pathways responsible for normal catecholamine metabolism. Typically, at least 14-days should elapse between the discontinuation of the non-selective MAOI and the use of entacapone or tolcapone to avoid potential interactions.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Carbinoxamine; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Carbinoxamine; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Carmustine, BCNU: (Minor) Pretreatment with procarbazine may increase the cytotoxicity of carmustine. Procarbazine acts as a methylating agent and reduces the cell's ability to repair DNA damage formed by carmustine. When these drugs are given in combination, it has been suggested that procarbazine should be administered prior to carmustine.
    Celecoxib: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Cetirizine; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Chlophedianol; Guaifenesin; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Chlordiazepoxide: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Chlordiazepoxide; Clidinium: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Chlorpheniramine; Codeine: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Chlorpheniramine; Dextromethorphan: (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Chlorpheniramine; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Chlorpheniramine; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Clonazepam: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Clorazepate: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
    Codeine: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Codeine; Guaifenesin: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Codeine; Phenylephrine; Promethazine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Moderate) CNS depressants, such promethazine, can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously. (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Codeine; Promethazine: (Moderate) CNS depressants, such promethazine, can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously. (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    COMT inhibitors: (Major) Patients should not receive COMT-inhibitors in combination with agents with non-selective MAO inhibiting activity like procarbazine. MAO and COMT are the two major enzymes involved in the metabolism of catecholamines. It is theoretically possible that the combination of COMT-inhibitors and a non-selective MAOI would result in inhibition of the majority of pathways responsible for normal catecholamine metabolism. Typically, at least 14-days should elapse between the discontinuation of the non-selective MAOI and the use of entacapone or tolcapone to avoid potential interactions.
    Desloratadine; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Dexmethylphenidate: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Dextroamphetamine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Dextromethorphan: (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Dextromethorphan; Guaifenesin: (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Dextromethorphan; Promethazine: (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions. (Moderate) CNS depressants, such promethazine, can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Dextromethorphan; Quinidine: (Major) Dextromethorphan should be used cautiously, if at all, in patients receiving drugs with MAOI like activity, such as procarbazine. Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with procarbazine, with the potential for severe reactions.
    Diazepam: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Diclofenac: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diclofenac; Misoprostol: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diethylpropion: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Diflunisal: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Diphenhydramine; Ibuprofen: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diphenhydramine; Naproxen: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Diphenhydramine; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Dobutamine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Dopamine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Echinacea: (Major) Echinacea possesses immunostimulatory activity and may theoretically reduce the response to drugs that alter immune system activity like antineoplastic drugs. Although documentation is lacking, coadministration of echinacea with immunosuppressants is not recommended by some resources.
    Entacapone: (Major) Patients should not receive COMT-inhibitors in combination with agents with non-selective MAO inhibiting activity like procarbazine. MAO and COMT are the two major enzymes involved in the metabolism of catecholamines. It is theoretically possible that the combination of COMT-inhibitors and a non-selective MAOI would result in inhibition of the majority of pathways responsible for normal catecholamine metabolism. Typically, at least 14-days should elapse between the discontinuation of the non-selective MAOI and the use of entacapone or tolcapone to avoid potential interactions.
    Ephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Epinephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Esomeprazole; Naproxen: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Estazolam: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Ester local anesthetics: (Major) Patients taking procarbazine should not be given local anesthetics containing sympathomimetic vasoconstrictors; coadministration may invoke a severe hypertensive reaction. Procarbazine should be discontinued for at least 10 days prior to elective surgery.
    Ethanol: (Severe) A disulfiram-like reaction can occur in patients who drink ethanol while they are receiving procarbazine. Patients should be counseled to avoid alcohol-containing products while receiving procarbazine therapy.
    Etodolac: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Famotidine; Ibuprofen: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
    Fenoprofen: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Fentanyl: (Major) In theory, procarbazine potentiates the CNS depression and hypotension caused by opiate agonists such as fentanyl. Procarbazine has MAOI activity; the manufacturers of fentanyl do not recommend its use within 14 days of an MAO Inhibitor. Caution is advised until more data are available.
    Fexofenadine; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Flucytosine: (Minor) Flucytosine can cause significant hematologic toxicity. It should be used cautiously with all antineoplastic agents, especially those that cause bone marrow depression.
    Flurazepam: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Flurbiprofen: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Food: (Major) Foods with a high tyramine content should be minimized while receiving procarbazine therapy as procarbazine has MAOI activity.
    General anesthetics: (Major) Patients receiving drugs that possess MAOI properties, such as procarbazine, may have an increased risk of hypotension after administration of general anesthetics. Procarbazine should be discontinued for at least 10 days prior to elective surgery.
    Green Tea: (Severe) Green tea catechins inhibit Catechol-O-methyltransferase (COMT) in animals. Monoamine oxidase (MAO) and COMT are the two major enzymes involved in the metabolism of catecholamines. Procarbazine has non-selective MAO inhibiting activity. It may be prudent to avoid the combination of green tea and monoamine oxidase inhibitors (MAOIs) including procarbazine. In addition, some, but not all, green tea products contain caffeine; caffeine interacts with MAOIs. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Guaifenesin; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Guaifenesin; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Guarana: (Moderate) Caffeine, an active constituent of guarana, interacts with MAOIs (including drugs with MAOI activity such as procarbazine). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Guarana should be avoided during and for 1 to 2 weeks after discontinuation of any MAOI.
    Hydrocodone; Ibuprofen: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Hydrocodone; Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Hydrocodone; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Hydromorphone: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Concurrent use of methylene blue and MAOIs or drugs that possess MAOI-like activity (e.g., procarbazine) should generally be avoided due to the potential for serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving serotonergic agents such as selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clompiramine. It is not known if patients receiving intravenous methylene blue with other serotonergic psychiatric agents are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Ibuprofen: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ibuprofen; Oxycodone: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Ibuprofen; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Indomethacin: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Isoniazid, INH: (Major) In theory, concurrent use of isoniazid, INH with other drugs that possess MAO-inhibiting activity, such as procarbazine, may result in hypertensive crises, fever, delirium, circulatory collapse, seizures, coma, or death, and the combination should be avoided if possible. Similar severe adverse events have occurred after combining other MAOIs. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity. Procarbazine is an antineoplastic agent that is also a weak MAOI. A washout period between treatment with isoniazid and procarbazine may be necessary, but specific recommendations are not available.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) In theory, concurrent use of isoniazid, INH with other drugs that possess MAO-inhibiting activity, such as procarbazine, may result in hypertensive crises, fever, delirium, circulatory collapse, seizures, coma, or death, and the combination should be avoided if possible. Similar severe adverse events have occurred after combining other MAOIs. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity. Procarbazine is an antineoplastic agent that is also a weak MAOI. A washout period between treatment with isoniazid and procarbazine may be necessary, but specific recommendations are not available.
    Isoniazid, INH; Rifampin: (Major) In theory, concurrent use of isoniazid, INH with other drugs that possess MAO-inhibiting activity, such as procarbazine, may result in hypertensive crises, fever, delirium, circulatory collapse, seizures, coma, or death, and the combination should be avoided if possible. Similar severe adverse events have occurred after combining other MAOIs. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity. Procarbazine is an antineoplastic agent that is also a weak MAOI. A washout period between treatment with isoniazid and procarbazine may be necessary, but specific recommendations are not available.
    Isoproterenol: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Ketoprofen: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Ketorolac: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Lansoprazole; Naproxen: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Levodopa: (Major) Concomitant use of levodopa and drugs with monoamine oxidase inhibitor (MAOI) activity (e.g., procarbazine) can result in hypertensive crisis. Simultaneous use of these agents should be avoided if possible.
    Levomethadyl: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Levorphanol: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Linezolid: (Severe) Concurrent use of linezolid with procarbazine or use of linezolid within 2 weeks of taking procarbazine is contraindicated due to the risk of severe hypertensive crisis. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Linezolid should not be used concurrently with other drugs that possess MAOI-like activity, such as procarbazine.
    Lisdexamfetamine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Live Vaccines: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
    Lomustine, CCNU: (Minor) Pretreatment with procarbazine may increase the cytotoxicity of lomustine. Procarbazine acts as a methylating agent and reduces the cell's ability to repair DNA damage formed by lomustine. When these drugs are given in combination, it has been suggested that procarbazine should be administered prior to lomustine.
    Loratadine; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Lorazepam: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Maprotiline: (Major) Concurrent use of drugs with MAO-inhibiting activity, such as procarbazine, with maprotiline can cause hyperpyrexia, hypertension, or seizures. The combination should be avoided whenever possible and is considered contraindicated.
    Meclofenamate Sodium: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Mefenamic Acid: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Meloxicam: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Meperidine: (Severe) Meperidine is contraindicated in patients receiving or who have received procarbazine, a weak monoamine oxidase inhibitor (MAOI), in the preceding 2 to 3 weeks. Severe reactions, such as excitation; agitation; sweating; hyperthermia; rigidity; hypertension; severe respiratory depression; coma; and vasculatory collapse, possibly resulting in death, can occur. These reactions may stem from accumulation of serotonin; meperidine blocks the neuronal reuptake of serotonin.
    Meperidine; Promethazine: (Severe) Meperidine is contraindicated in patients receiving or who have received procarbazine, a weak monoamine oxidase inhibitor (MAOI), in the preceding 2 to 3 weeks. Severe reactions, such as excitation; agitation; sweating; hyperthermia; rigidity; hypertension; severe respiratory depression; coma; and vasculatory collapse, possibly resulting in death, can occur. These reactions may stem from accumulation of serotonin; meperidine blocks the neuronal reuptake of serotonin. (Moderate) CNS depressants, such promethazine, can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Mepivacaine; Levonordefrin: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Methadone: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Methamphetamine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Concurrent use of methylene blue and MAOIs or drugs that possess MAOI-like activity (e.g., procarbazine) should generally be avoided due to the potential for serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving serotonergic agents such as selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clompiramine. It is not known if patients receiving intravenous methylene blue with other serotonergic psychiatric agents are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Methylene Blue: (Major) Concurrent use of methylene blue and MAOIs or drugs that possess MAOI-like activity (e.g., procarbazine) should generally be avoided due to the potential for serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A). Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving serotonergic agents such as selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or clompiramine. It is not known if patients receiving intravenous methylene blue with other serotonergic psychiatric agents are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Methylphenidate: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Midazolam: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Midodrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Mirtazapine: (Severe) Use of mirtazapine concurrently with drugs that exhibit MAO-inhibition, such as procarbazine, is contraindicated. If combined, there is a possibility of developing serious reactions such as hyperpyrexia, hypertension, or seizures. An interval of 14 days is recommended between cessation of MAOI therapy and initiation of mirtazapine therapy and vice versa.
    Monoamine oxidase inhibitors: (Severe) Procarbazine is a weak monoamine oxidase inhibitor. Avoid concomitant administration with other monoamine oxidase inhibitors because of the possibility of severe hyperpyretic or hypertensive crises, convulsions, or death. In general, at least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other.
    Morphine: (Moderate) In theory, monoamine oxidase inhibitors (MAOIs) potentiate the CNS depression and hypotension caused by opiate agonists such as morphine. Procarbazine is a weak inhibitor of MAO; the manufacturers of morphine do not recommend its use within 14 days of an MAO Inhibitor. Caution is advised until more data are available.
    Morphine; Naltrexone: (Moderate) In theory, monoamine oxidase inhibitors (MAOIs) potentiate the CNS depression and hypotension caused by opiate agonists such as morphine. Procarbazine is a weak inhibitor of MAO; the manufacturers of morphine do not recommend its use within 14 days of an MAO Inhibitor. Caution is advised until more data are available.
    Nabumetone: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Naproxen: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Naproxen; Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Naproxen; Sumatriptan: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Nonsteroidal antiinflammatory drugs: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Norepinephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Oxaprozin: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Oxazepam: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Oxycodone: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Oxymorphone: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
    Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
    Pemoline: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
    Pentazocine: (Major) Patients receiving concurrent pentazocine and MAOI inhbitors may be at increased risk for developing serotonin syndrome; pentazocine should be used cautiously in patients receiving other drugs with MAOI activity, such as procarbazine.
    Pentazocine; Naloxone: (Major) Patients receiving concurrent pentazocine and MAOI inhbitors may be at increased risk for developing serotonin syndrome; pentazocine should be used cautiously in patients receiving other drugs with MAOI activity, such as procarbazine.
    Phendimetrazine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Phenothiazines: (Moderate) CNS depressants, such as phenothiazines, can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Phentermine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Phentermine; Topiramate: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Phenylephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Phenylephrine; Promethazine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. (Moderate) CNS depressants, such promethazine, can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Piroxicam: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Prilocaine; Epinephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Promethazine: (Moderate) CNS depressants, such promethazine, can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Propoxyphene: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Pseudoephedrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Quazepam: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Racepinephrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Rasagiline: (Major) Concurrent use of rasagiline and procarbazine may increase the risk of a hypertensive crisis. Procarbazine is an antineoplastic agent which exhibits weak monoamine oxidase (MAO) inhibitor activity and rasagiline is a selective monoamine oxidase inhibitor (MAOI) type B. Monoamine oxidase type A is the primary enzyme in the gastrointestinal tract, and is responsible for the breakdown of dietary amines such as tyramine. When monoamine oxidase is inhibited by an MAOI, tyramine is absorbed systemically and may result in a hypertensive crisis. Although rasagiline is a selective MAOI-B, there is a risk of hypertension during ingestion of substances high in tyramine or during concurrent use of other drugs with MAOI activity such as procarbazine, since the MAOI-B selectivity of rasagiline decreases with increasing dosages.
    Remifentanil: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Reserpine: (Severe) Administration of reserpine to patients receiving monoamine oxidase inhibitors (MAOIs), such as procarbazine, can cause hypertension and increased excitation. These effects presumably are due to the sudden increases in catecholamine levels. Administration of MAOIs to patients receiving reserpine can potentiate the adverse CNS depressant effects.
    Ritodrine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Rofecoxib: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Sedating H1-blockers: (Moderate) Use procarbazine and sedating H1-blockers together with caution; additive central nervous system depression may occur.
    Selective serotonin reuptake inhibitors: (Major) Procarbazine is a weak monoamine oxidase inhibitor (MAOI). Although procarbazine appears to be less likely than other MAOIs to produce serious drug interactions, clinicians should avoid the use of selective serotonin reuptake inhibitors (SSRIs) in patients receiving MAOIs. Fatalities have been reported when fluoxetine was administered to patients receiving MAOIs. Confusion, seizures, severe hypertension, and other, less severe symptoms have also been reported with this drug combination. Non-selective MAOIs inhibit both MAO types A and B. Since serotonin is metabolized by MAO type A, it is thought that this drug interaction may lead to serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. At least 2 weeks should elapse between the discontinuation of MAOI therapy and the start of therapy with an SSRI except fluoxetine. At least 5 weeks should elapse between the discontinuation of fluoxetine therapy and commencement of MAOI therapy. This 5-week period is needed because of the long half-lives of fluoxetine and its principle metabolite norfluoxetine.
    Serotonin norepinephrine reuptake inhibitors: (Major) Concurrent use of procarbazine and serotonin norepinephrine reuptake inhibitors (SNRIs) should be avoided if possible. Procarbazine is a weak monoamine oxidase inhibitor (MAOI). Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with an SNRI can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. If combination therapy is necessary, patients should be monitored for the emergence of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
    Sibutramine: (Major) Procarbazine possesses weak non-selective MAO-inhibiting activity and concurrent use with sibutramine should be avoided if possible.The concomitant use of sibutramine with MAOIs is contraindicated. Sibutramine is a serotonin reuptake inhibitor. Since serotonin is deaminated by monoamine oxidase-A, concurrent administration of sibutramine with drugs that inhibit this enzyme such as MAOIs can lead to serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. There should be at least a 2-week interval between discontinuation of MAOI therapy and initiation of sibutramine therapy. Similarly, there should be at least a 2-week interval after stopping sibutramine therapy and the start of MAOI therapy.
    Sipuleucel-T: (Major) Concomitant use of sipuleucel-T and antineoplastic agents should be avoided. Concurrent administration of antineoplastic agents with the leukapheresis procedure that occurs prior to sipuleucel-T infusion has not been studied. Sipuleucel-T stimulates the immune system and patients receiving antineoplastic agents may have a diminished response to sipuleucel-T. When appropriate, consider discontinuing or reducing the dose of antineoplastic agents prior to initiating therapy with sipuleucel-T.
    Sodium Oxybate: (Severe) Although procarbazine appears to be less likely than other MAOIs to produce serious drug interactions, clinicians should minimize the use of sympathomimetics, such as sodium oxybate, in patients receiving procarbazine. Sympathomimetics should not be used within 14 days after the use of a MAOI.
    Sufentanil: (Moderate) Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Sulindac: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Sympathomimetics: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents.
    Tapentadol: (Major) Procarbazine has MAO-inhibiting activity. Coadministration with MAO inhibitors may result in excessive concentrations of norepinephrine and/or serotonin, increasing the risk of adverse cardiovascular effects and serotonin syndrome. Until further data are available examining the potential interaction between procarbazine and tapentadol, extreme caution and careful observation of the patient are advised if these two drugs are used concurrently.
    Tedizolid: (Major) Caution is warranted with concurrent use of tedizolid and drugs that possess MAOI-like activity, such as procarbazine, because of the theoretical possibility of severe hyperpyretic or hypertensive crises, convulsions, or death. Tedizolid is an antibiotic that is also a weak reversible, non-selective MAO inhibitor and most potential drug interactions with tedizolid are related to this action of the drug.
    Temazepam: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Tobacco: (Major) A pharmacodynamic interaction may occur between tobacco smoke and procarbazine. Tobacco smoking during procarbazine therapy has been associated with an increased risk of secondary lung cancer. Results of a case-controlled study in patients with Hodgkin's disease receiving MOPP combination chemotherapy suggest an increased risk of lung cancer in a dose-dependent fashion, which is multiplied with exposure to tobacco smoke. Patients should be advised to discontinue tobacco smoking during procarbazine therapy.
    Tolcapone: (Major) Patients should not receive COMT-inhibitors in combination with agents with non-selective MAO inhibiting activity like procarbazine. MAO and COMT are the two major enzymes involved in the metabolism of catecholamines. It is theoretically possible that the combination of COMT-inhibitors and a non-selective MAOI would result in inhibition of the majority of pathways responsible for normal catecholamine metabolism. Typically, at least 14-days should elapse between the discontinuation of the non-selective MAOI and the use of entacapone or tolcapone to avoid potential interactions.
    Tolmetin: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Tramadol: (Major) Avoid use of tramadol concurrently or within 14 days of discontinuing a drug with monamine oxidase inhibitor (MAOI)-like activity, such as procarbazine. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during treatment initiation and dose increases. International recommendations contraindicate the use of tramadol within 14 days of an MAOI. There is an increased risk of seizures and serotonin syndrome in patients receiving these drugs currently. In animal studies, an increased number of deaths was noted with the combination due to interference with detoxification mechanisms.
    Trandolapril; Verapamil: (Minor) The absorption of verapamil can also be reduced by the cyclophosphamide, vincristine, procarbazine, prednisone (COPP) chemotherapeutic drug regimen.
    Trazodone: (Major) Due to the risk of serotonin syndrome, concurrent use of trazodone and medications with MAO-like activity, such as procarbazine, should be avoided if possible. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Triazolam: (Minor) CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously.
    Tricyclic antidepressants: (Major) In general, drugs with MAOI activity, such as procarbazine, should not be used with tricyclic antidepressants. Severe hypertensive crises, serotonin syndrome, or increased anticholinergic effects can result from concomitant use. Tricyclic antidepressants can, in some cases, be used concomitantly with MAOIs if tricyclic antidepressant therapy is in effect prior to beginning therapy with a MAOI; tricyclic antidepressants should never be added to an existing MAOI regime. Under careful monitoring for signs or symptoms of hypertension, add the MAOI gradually, starting at a low dose. Patients should also be monitored closely for signs or symptoms of serotonin syndrome (characterized by hyperthermia, diaphoresis, shivering, tremor, myoclonus, seizures, ataxia, delirium, restlessness). Strict adherence to diet restrictions should be emphasized and the patient should not be receiving other sympathomimetics. Most references suggest avoiding this drug interaction entirely if clomipramine or imipramine are being administered.
    Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
    Valdecoxib: (Major) Due to the thrombocytopenic effects of procarbazine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants, NSAIDs, platelet inhibitors, including aspirin, strontium-89 chloride, and thrombolytic agents. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
    Verapamil: (Minor) The absorption of verapamil can also be reduced by the cyclophosphamide, vincristine, procarbazine, prednisone (COPP) chemotherapeutic drug regimen.
    Vilazodone: (Major) Due to the risk of serotonin syndrome, concurrent use of vilazodone and medications with MAO-like activity, such as procarbazine, should be avoided if possible. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Vortioxetine: (Major) Due to the risk of serotonin syndrome, concurrent use of vortioxetine and medications with MAO-like activity, such as procarbazine, should be avoided if possible. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Patients receiving procarbazine in combination with vortioxetine should be monitored for the emergence of serotonin syndrome or other adverse effects. If serotonin syndrome is suspected, vortioxetine and concurrent serotonergic agents should be discontinued.

    PREGNANCY AND LACTATION

    Pregnancy

    Although it is unknown whether procarbazine is excreted into breast milk, its use during breast-feeding is generally not recommended due to its carcinogenic and mutagenic effects.

    MECHANISM OF ACTION

    Mechanism of Action: Procarbazine must be activated by chemical decomposition or by microsomal oxidation via the hepatic cytochrome P-450 enzyme system to exert its cytotoxic effects. Several active metabolites can form including species capable of binding to DNA and free radicals. Procarbazine's exact mechanism(s) of action is not clear, but the drug appears to have several sites of action in the cell. Hydrogen peroxide and formaldehyde are generated from the procarbazine activation and are thought to interact with DNA, resulting in cytotoxicity. Procarbazine and its metabolites are capable of causing chromatid and single DNA strand breaks in animal models. The number of breaks depends on the dose and time elapsed after treatment. Procarbazine also inhibits DNA, RNA, and protein synthesis. Procarbazine may inhibit the incorporation of thymidine, deoxycytidine, formate, adenine, and 4-amino-5-imidazolecarboxamide into DNA, prevent the utilization of orotic acid in RNA synthesis, and prevent the utilization of leucine in the synthesis of proteins. However, the major mechanism of procarbazine cytotoxicity may be methylation of DNA due to the high levels of O6-methylguanine, a known mutagenic and carcinogenic adduct, reported in animal models. The drug appears to be most active during the G2 phase. Resistance to procarbazine develops rapidly after exposure to the drug. One mechanism of resistance to procarbazine is O6-alkylguanine-DNA alkyltransferase (AGAT)-mediated repair of O6-methylguanine. Other mechanisms of drug resistance are possible.Procarbazine exhibits weak monoamine oxidase (MAO) inhibitor activity; it appears the risk for serious drug interactions is not as great for procarbazine as for traditional MAOIs like phenelzine or tranylcypromine. When MAO is blocked, octopamine (a false neurotransmitter) accumulates diluting the usual potent neurotransmitters. This resulting sympathetic blockade lowers blood pressure, thus producing an antihypertensive action. Conversely, inhibition of MAO in the GI tract and liver can cause systemic absorption of large amounts of tyramine, which can result in hypertension because of excessive release of norepinephrine.

    PHARMACOKINETICS

    Procarbazine is given orally. The plasma half-life of procarbazine is about 7 minutes indicating rapid and extensive hepatic metabolism. Data in humans show that the methylazoxy isomer is the major plasma metabolite present after a single 250 mg oral dose of procarbazine. The plasma concentration of this metabolite peaks at approximately 90 minutes and seems to have an initial plasma half-life of 60 minutes. Other metabolites present at lesser serum concentrations than the methylazoxy isomer are azoprocarbazine and the benzylazoxy isomer. Procarbazine may induce its own metabolism as evidenced by a significant increase in azoprocarbazine concentrations following day 14 of dosing. It is unclear if procarbazine enzyme induction results in clinically significant drug interactions with other drugs. Procarbazine metabolites are eliminated renally; N-isopropylterephthalamic acid is the major urinary metabolite, which is inactive. Approximately 70% of a procarbazine dose is excreted in the urine within 24 hours. There is minimal fecal excretion (4—12% over 96 hours).

    Oral Route

    Procarbazine is rapidly and completely absorbed across the GI tract following oral administration. Procarbazine undergoes significant first-pass metabolism via the cytochrome P450 system or mitochondrial monoamine oxidase enzymatic conversion to form azoprocarbazine, which is then further metabolized intracellularly to cytotoxic metabolites. Following oral administration, equilibration between the plasma and CSF occurs within 15—30 minutes.

    Intravenous Route

    Procarbazine is not given intravenously. Intravenous administration of procarbazine results in significantly less clinical activity and a different spectrum of toxicity, demonstrating the importance of the first-pass metabolism for activation of procarbazine. In addition, procarbazine is not stable in aqueous solution and breaks down, albeit slowly, in the presence of light to the biologically inactive hydrazone.