Procarbazine

'Procarbazine is oral, cell cycle-phase specific antineoplastic (antineoplastic) agent used in the treatment of Hodgkin''s disease, non-Hodgkin''s lymphomas, brain tumors, and lung cancers. It has been described as a nonclassic alkylating agent and is not cross-resistant with the other alkylating agents. Today, Procarbazine is used almost exclusively for Hodgkin''s disease. It originally was synthesized as a monoamine oxidase inhibitor, and this activity, as well as a disulfiram-like reaction, are part of its unusual adverse effect profile. It was approved by the FDA in 1969. it must be activated by the cytochrome P-450 system to exert its cytotoxic effects. Several active metabolites can form. it''s exact mechanism(s) of action is not clear, but the drug appears to have several sites of action in the cell. The drug appears to be most active during S and G1 phase. The cytotoxic effects of it are evident only in cells that are rapidly proliferating and actively synthesizing DNA.'

Brands

P CARBAZINE NATULAN

Adult Dose

Dose: 50 to 250 mg/ sq.meter
Single Dose: 150 (150)
Frequency: 24 hourly
Route: PO
Instructions: In div.doses.For 14 days in each treatment cycle

Neonatal

Dose: Not used in this age group
Single Dose:
Frequency:
Route:
Instructions:

Paedriatic

Dose: 100 to 150 mg/sq.meter
Single Dose: 120 (125)
Frequency: 24 hourly
Route: Oral
Instructions: For 14 days

Characteristics

Procarbazine also known as Ibenzmethyzim. . It is of Synthetic origin and belongs to Amide. It belongs to DNA Strand Breakage pharmacological group on the basis of mechanism of action and also classified in Antineoplastic Agent, Alkylating Agent pharmacological group.The Molecular Weight of Procarbazine is 257.80. Its pKa is 6.8.

Contraindications

Procarbazine is contraindicated in conditions like Bone marrow depression,Pregnancy,Severe liver impairment,Breast feeding,Adjunct in treatment of opioid dependance.

Effects

The severe or irreversible adverse effects of Procarbazine, which give rise to further complications include Azoospermia, Cessation of menstrual function, Teratogenic effect.Procarbazine produces potentially life-threatening effects which include Bone marrow suppression, Thrombocytopenia, Carcinogenicity, Myelogenous leukemia. which are responsible for the discontinuation of Procarbazine therapy.The signs and symptoms that are produced after the acute overdosage of Procarbazine include Convulsions, Coma, Tremor.The symptomatic adverse reactions produced by Procarbazine are more or less tolerable and if they become severe, they can be treated symptomatically, these include Dizziness, Ataxia, Alopecia, Anorexia, Diarrhea, Fever, Myalgia, Insomnia, Nervousness, Chills, Stomatitis, Lethargy, Coma, Diplopia, Arthralgia, Nausea and vomiting, Thrombocytopenia, Influenza like syndrome, Convulsions, Photophobia, Nystagmus, Retinal hemorrhage, nervousness.

Indications

'Procarbazine is primarily indicated in conditions like Brain tumors, Hodgkin''s disease, Lung cancer, Malignant melanoma, Myeloma, Non-hodgkin''s lymphoma, Polycythemia rubravera.'

Interactions

Procarbazine is known to interact with other drugs, the details of drug interactions is as follows:DrugDetailsSeverityOnsetManagementAmitriptyline (HCl)Administration of Amitriptyline and procarbazine can cause nausea,vomitiing,flushing,dizziness,tremor,hyperthermia and hypertensive crises,seizures,coma and death may also occur.MajorThis combination should not be used or a gap of atleast 14 days should be given after discontinuing any of these drugs to start the other.CarbamazepineCoadministration enhances the excessive serotonergic activity in CNS i.e. serotonin syndrome and may produce adverse effects like tremor,dizziness,myoclonus,diaphoresis,hyperthermia and coma.MajorCoadministration in general must not be used.If necessary 14 days gap must be given and both drugs started at low doses.DoxapramBoth agents acts synergistically in inducing sympathomimetic effect. Procarbazine increases the storage of norepinephrine in adrenergic neurons and doxapram enhance liberation or reduce reuptake of catecholamines thus precipitate severe hypertensionMajorCoadministration is considered contraindicated. There should be gap of atleast 14 days between discontinuing of therapy with procarbazine and initiation of treatment with doxapram.EphedrineBoth agents act synergistically affecting the sympathomimetic activity in this way that procarbazine enhances the storage of norepinephrine in adrenergic neuron and ephedrine increases its liberation result in severe hypertension and hyperpyrexia.MajorBoth agents should not be used in combination.if necessary 14 days discontinuation of procarbazine must take before initiastion of ephedrine therapy.GuanethidineProcarbazine deplete catecholamines and inhibit their breakdown by increasing storage at agrenergic neurons thus antagonize hypotensive effect of guanethidine. ModerateThis combination should be avoided or give a gap of atleast 2 weeks before or after use of any of these drugs.LevodopaLevodopa exacerbate the hypertensive crises associated with procarbazine by enhancing peripheral availability of catecholamine and by decreasing degradation and increasing synthesis of dopamine.MajorCombination should be considered contraindicated. Coadministration of carbidopa prevents hypertensive crises by inhibiting peripheral conversion of levodopa to dopamine. There should b gap of at least 14 days between stopping therapy with procarbazine and initiating treatment with levodopa.LoratadineMaprotiline (HCl)coadministration produce significant adverse reactions due to excessive serotonergic activity in the CNS i.e. serotonin syndrome.MajorCoadministration of these agents is considered contraindicated.There should be a gap of at least 14 days between initiation of treatment with maprotiline and discontinuation of maprotiline.MethotrexateCoadministration results renal impairment because procabazine have transient effect on kidneys which alter the excreation of methotrexate.ModerateAn interval of 72 hours is recommended between administration of final dose of procarbazine.MethyldopaThe combined use of methyldopa and procarbazine may increases sympathetic stimulation in central nervous system result in loss of control on blood pressure, hyperexcitability and hallucination.MajorCoadministration is considered contraindicated. Start treatment with methyldopa after stopping (atleast 14 days) of procarbazine.MoracizineMoracizine increase severity of side effects of Procarbazine.ParegoricThe coadministration of narcotic analgesics and monoamine oxidase inhibitors (MAOIs) may rarely result in hypotension, respiratory depression, or coma. The mechanism is unknown but may be related to additive CNS and respiratory depressant effects. Rare case reports of severe hypotensive reactions have included propoxyphene (with multiple medications), morphine, and methadone, although others have reported the safe use of MAOIs with narcotic analgesics including methadone and morphine.MajorSome manufacturers consider the administration of narcotics and MAOIs within 2 weeks of each other to be contraindicated. However, morphine has been safely used in MAOI patients who previously had an adverse reaction with meperidine and is generally suggested as an alternative to meperidine in anesthesia, as long as vital signs are closely monitored. Other recommendations include giving patients small initial test doses of narcotics and monitoring vital signs for adverse reactions.ParoxetinePotassium GuaiacolsulphonatePotassium Guaiacolsulphonate should not be used with or within 14 days of taking Procarbazine.Thioguanine These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.

Interfrence

Urinanalysis Hematocrit Value Complete blood cell count

Risks

Drug should not be given to Pregnant Mothers, Geriatrics, and Neonates.If prescribing authority justifies the benefits of the drug against the possible damages he/she should reevaluate them and consult the reference material and previous studies.

Storage

Caps Store in a well closed container. Protect from Sunlight.

Warnings

Procarbazine should be used with caution in patients with angina (chest pain), heart or blood vessel problems, recent case of chickenpox, diabetes, seizures, kidney or liver disease, severe or frequent headaches, infection, mental or emotional conditions, thyroid problems, Parkinson`s disease, history of alcohol use, radiation therapy, blood diseases and any allergy, especially drug allergies. Before having surgery of any kind or emergency treatment, inform the doctor or dentist about the use of the drug. Caution is advised when performing tasks requiring alertness (e.g., driving). Get up slowly, to avoid dizziness and lightheadedness when rising from a seated or lying position. Since this drug may cause sun sensitivity, so use sunscreens. It should be used with caution while using sharp objects like safety razors or nail cutters and avoid activities such as contact sports in order to lower the chance of getting cut, bruised or injured. Avoid touching eyes or inside nose without first washing hands. Do not have immunizations or vaccinations without consent of doctor and avoid contact with people who have recently received oral polio vaccine. Effective birth control measures are recommended for use in men and women while taking this. It is not recommended for use during pregnancy or lactation. All precautions related to food, drinks and other drugs apply for at least 2 weeks after treatment with this drug is stopped.

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