Drug Information

Drug Interaction:

Antineuoplastic agents include-

Interferon ALFA 2a, Interferon ALFA -2b, Interferon ALFA -n3, Levamisole, Altretamine, Cladribine, Hydroxyurea, Aldesleukin, Paclitaxel, Docetaxel,Tretinion, Procarbazine,Dacarbazine, Gemcitabine, Mitotane, Asparaginase, Pegaspargase,Porfimer Sodium

Interacting drugs- summary

Procarbazine +

Digitalis glycosides

result in a decrease in digitoxin plasma levels, even

several days after stopping chemotherapy

Levodopa

flushing and significant increase in blood pressure result

in 1 hr of levodopa administration

Narcotics

concomittant use result in depresant effects on the CNS

leading to deep coma and death

Sympathomimetic

cause an abrupt increase in blood pressure, resulting in a

potentially fatal hypertensive crisis

Tricyclic antidepres

severe toxic and fatal reactions including excitability, fluctuations

in blood pressure, convulsions and coma may occur.Uneventual

concurrent use with MAOI inhibitors have been reported

Radiation or other chemotherapy

Radiation or other chemotherapy is known to have marrow

depressant activity.

Indication:

Hodgkins disease

Adverse Reaction:

GI- nausea, vomiting (frequent) anorexia, stomatitisis, dry mouth, dysphegia, abdominal pain, hematemesis, melena, diarrhea, constipation.

Hematologic- leukopenia, anemia, thrombocytopenia, (frequent) pancytopenia, eosinoiphillia,hemolytic anemia, bleeding tendencies such as petechiae, purpura , epistaxis, hemoptysis

Cardiovascular- hypotension, tachycardia, syncope

GU- hematuria, urinary frequency, noctura

Endocrine- gynaeconastia in perpubertal and early pubertal boys

Dermatologic- dermatitis, pruritus, rash, urticaria, herpes, hyperpigmentation, flushing, alopecia.

CNS- paresthesias and neuropathies, headache, diziness, depression, apprehension, nervousness, insomina, nightmares, hallucinations, falling, weakness, fatigue,lethargy, drowsiness, unsteadiness, ataxia, foot drop, decreased refluxes, tremors, coma, confusion, convulsions.

Ophthalmic- retinal hemorrhage, nystagmus, photophobia, diplopia, inability to focus,papilledema

Respiratory- pleural effusion, pneumonitis, cough

Miscellaneous- pain, including myalgia and arthalgia, pyrexia, diaphoresis, chills, intercurrent infections, edema, hoarseness, generalized allergic reactions, hearing loss. slurred speech.

Contra-Indications:

Hypersens to the drug

Special precautions:

Obtain base line laboratory data before initiating therapy. Monitor haemoglobin, hematocrit,

WBC differential, reticulocytes and platelets at every 3 or 4 days. Evaluate hepatic and renal function prior to therapy.

Evalutae hepatic an renal function prior to initiation of therapy

Repaet urinalysis ,transaminase ,alkaline phosphatase and BUN at least weekly.

Warnings-

Toxicity - common to hydrazine derivatives includes hemolysis, and the appearance of Heinz-Ehrlich

inclusion bodies in erythrocytes.

Discontinue- if any of these occurs- CNS signs orsymptoms , leukopenai, (WBC , 400mm3), thrombocytopenia (platelets < 100, 000mm3) hypersensitivity reactions, stomatitis (the first small ulceration or persistent spot soreness ) diarrhea, hemorrhage or bleeding tendencies

Resume therapy after side effects claer, adjust to a lower doseage schedule.

Renal.heaptic function impairment- undue toxicity may occur if usedc in aptients with known impairment of reanl or hepatic function. Consider hospitilization for the initial treatment course.

Carcinogenesis/ Mutagenesis/fertility impairment- there is sufficient evidence for human carconogenicity of procarbazine Hcl. when it is given in intenssive regimes which include other antineoplastic agents., but there is inadequate evidence of carcinogenicity in humans given procarbazine Hcl alone.

Pregnancy- advice woman of child bearinng potential to avoid pregnancy. If this drug is used during pregnancy,inform patient of the potential hazards to the fetus.

Lactation- becuase of the potential for tumorigenicity shown in animal studies womenshould not breast feed while receiving the drug

Children- close clinical monitoring is required. Toxicity ,evidenced by tremors, convulsions and coma, has occurred

Dosages/ Overdosage Etc:

Indication:

Hodgkins disease

Dosage:

Maintain daily dosage at 4 to 6mg/kg/day until the WBC falls below 4000/cu mm or these

platelets fall below 100,000/cu mm, until maximum response is obtained.

Overdose

Symptoms

Nausea, vomiting, enteritis, diarrhea, hypotension, tremors, convulsions, and coma.

Treatment

1. Administer of an emetic or gastric lavage

2. Use general supportive measures

3. Perform frequent complete blood counts and liver function tests throughout the recovery period and for 2 weeks thereafter.

4. Should abnormalities appear in any of these determinations, immediately undertake appropriate measures for correction and stabilization.

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

Patient Information:

1. May produce drowsiness and dizziness, patients should observe caution while driving or

performing tasks requiring alertness.

2. Consumption of alcoholic beverages while taking procarbazine may cause disulfram like

reaction.

3. Avoid ingestion of tyramine containing foods

4. Notify physician if cough, shortness of breath, thickened bronchial secretions, fever, chills,

sore throat , unusual bleeding or bruisng, black tarry stools or vomting of blood occurs

5. Allergies- tell your doctor if you have ever had any unusual or allergic reaction to procarbazine. Also tell your doctor if you are allergic to any other substances, such as foods, presevatives or dyes.

6. Pregnancy - although sterility has not been reported with this medicine procarbazine does affect production of sperm and the possiblity should be kept in mind.

7.Breast feeding- because procarbazine may cause serious side effects breast feeding is not generally recommended while you are taking it.

8. Children - shown expected to cause different side effects or problems than it does in adults.

9.Elderly- side effects are more likely to occur in the elderly.

9. Other medicines -

Amantadine or

Anticholinergics or

Antidiabetics or

Antidyskinetics or

Antihistamines or

Antipsychotics or

Buclizine or

Central nervous system or

Cyclizine or

Disopyramide or

Flavoxate or

Insulin or

Ipratropium or

Meclizine or

Orphenadrine or

Oxybutynin or

Procainamide or

Promethizine or

Quinidine or

Trimeprazine - efects of these medicines may be increased by procainamide

Amphetamines or

Appetite stimulants or

Dextromethorphan or

Levodopa or

Medicine for asthma or

Medicines for cold or

Methyldopa or

Methylphenidate or

Narcotic pain medicine - taking any of these medicines while you are taking or within 2 weels of taking procainamide may cause a severe high blod pressure reaction

Amphotericin B or

Antithyroid drugs or

Azathioprine or

Chloramphenicol or

Colchicine or

Flucytosine or

Interferon or

Plicamucin or

Zidovudine or

If you have treated with x-rays or radiation- procarbazine may increae the effects of these medicines.

Busiprone - risk of increased blood pressure

Carbamazepine or

Cyclobenzaprine or

Maprotiline or

MAOI - or

Tricyclic antidepressants - taking procarbazine while you are taking or within 2 weeks of taking any of these medicines may cause a severe high blood pressure reaction.

Cocaine - use of cocaine while taking or within 2 weeks of taking procarbazine may cause a severe high pressure reaction

Fluoxetine - taking this medicine whilr you are taking or within 2 weeks of taking procarbazine may cause a severe high blood pressure

Guanadrel or

Guanethidine or

Rauwolfia - taking these medicines while taking or within 2 weeks of taking procarbazine may cause a severe high blood pressure reaction.

10. Other medical problems -

Tell your doctor if you have any other medical problems especially -

Alcoholism

Angina or

Heart or blood vessel disease or

Heart atack or stroke - lowered blood pressure caused by procarbazine may make problems worse

Chickenpox or

Herpes zoster - risk of severe disease afecting othervparts of the body

Diabetes mellitus - procarbazine may change the amount of diabetic medicine needed

Epilepsy- procarbazine may changes the seizures

Headaches - you may realize when a severe headachhe is caused a dangerous reaction to procarbazine

Infection- procab may reduce immunity

Kidney disease - effects may be increased

Liver disease - procarb can cause severe liver disease

Mental illness - some case of mental illness worsened

Overactive thyroid- worsened

Pheochromocytoma - blood pressure affected

11. Missed dose -

If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

12. Storage -

Keep out of reach of children. Store away from heat or direct sunlight. Do not store

the capsule in bathroom, near the kitchen sink, or in other damp places.

13. Outdated medicines -

Do not keep outdated medicine or medicine no longer needed. Be sure that any

discarded medicine is out of reach of children.

Pharmacology/ Pharmacokinetics:

Pharmacology: Procarbazine may inhibit protein, ribonuleic acid (RNA) and deoxyribonucleic acid (DNA) synthesis

Pharmacokinetics: Procarbamazine is rapidly and completely absorbed from the GI tract and quickly equilbrates between plasma and cerbrospinal (CSF). Peak CSF levels occur in 30 to 90minutes.

Interaction with Food:

Drug/food interaction: Ingestion of foods with high tyramine content may cause an abrupt increase in blood pressure, resulting in a potentially fatal hypertensive crisis.

Pregnancy and lactation:

Pregnancy- Advice woman of child bearinng potential to avoid pregnancy. If this drug is used during pregnancy, inform patient of the potential hazards to the fetus.

Lactation- Becuase of the potential for tumorigenicity shown in animal studies women should not breast feed while receiving the drug

Children- Close clinical monitoring is required. Toxicity ,evidenced by tremors, convulsions and coma, has occured

Procarbazine hcl ( ** ) - @ Antineoplastics

Drug Interaction

Indication

Adverse Reaction

Contra-Indications

Dosages/ Overdosage Etc

Patient Information

Pharmacology/ Pharmacokinetics

Interaction with Food

Pregnancy and lactation