• Hodgkin’s disease (with other treatment modalities).

Unlabeled Uses:

• Other lymphomas.
• Brain and lung tumors.
• Multiple myeloma.
• Malignant melanoma.
• Polycythemia vera.

Contraindicated in:

• Hypersensitivity
• Alcoholism
• Severe renal or liver impairment
• Pheochromocytoma
• HF
• OB: Lactation: Pregnancy or lactation.

Use Cautiously in:

• Infection
• ↓bone marrow reserve
• Headache
• Psychiatric illness
• Liver impairment
• Cardiovascular disease
• OB: Women with childbearing potential should be advised to avoid pregnancy
• Pedi: Very close clinical monitoring required due to potential for toxicity.

CNS: SEIZURES, confusion, dizziness, drowsiness, hallucinations, headache, mania, mental depression, nightmares, psychosis, syncope, tremor.

EENT: nystagmus, photophobia, retinal hemorrhage.

Resp: cough, pleural effusions.

CV: edema, hypotension, tachycardia.

GI: nausea, vomiting, anorexia, diarrhea, dry mouth, dysphagia, hepatic dysfunction, stomatitis.

GU: gonadal suppression.

Derm: alopecia, photosensitivity, pruritus, rashes.

Endo: gynecomastia.

Hemat: anemia, leukopenia, thrombocytopenia.

Neuro: neuropathy, paresthesia.
Misc: ascites, secondary malignancy.

Drug-Drug:

• Concurrent use with sympathomimetics including methylphenidate may produce life-threatening hypertension (avoid concurrent use during and for 14 days following procarbazine).
• Deep coma and death may result from concurrent use of opioid analgesics; avoid meperidine. Use small incremental doses of other agents and titrate to effect.
• ↑bone marrow depression may occur with other antineoplastics or radiation therapy.
• Seizures and hyperpyrexia may occur with concurrent use of MAO inhibitors, tricyclic antidepressants, SSRI antidepressants (should not be used within 5 wk of fluoxetine), or carbamazepine.
• May ↓ serum digoxin levels.
• Concurrent use with levodopa may result in flushing and hypertension.
• ↑CNS depression with other CNS depressants, including alcohol, antidepressants, antihistamines, opioid analgesics, phenothiazines, and sedative/hypnotics.
• Disulfiram-like reaction may occur with alcohol.
• Cigarette smoking may ↑ the risk of secondary lung cancer.

Drug-Food:

• Ingestion of foods high in tyramine content (see Appendix M) may result in hypertension.
• Ingestion of foods high in caffeine content may result in arrhythmias.

• Capsules: 50 mg;

• PO (Adults): 2–4 mg/kg/day as a single dose or in divided doses for 1 wk, then 4–6 mg/kg/day until response is obtained; then maintenance dose of 1–2 mg/kg/day. Dosage should be rounded off to the nearest 50 mg.
• PO (Children): 50 mg/m²/day for 7 days, then 100 mg/m²/day, maintenance dose of 50 mg/m²/day.

Matulane

• Appears to inhibit DNA, RNA, and protein synthesis (cell-cycle S-phase–specific).

• Death of rapidly replicating cells, particularly malignant ones.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: alkylating agents

Absorption: Well absorbed following oral administration.

Distribution: Widely distributed; crosses the blood-brain barrier.

Metabolism/Excretion: Metabolized by the liver; <5% excreted unchanged by the kidneys; some respiratory elimination as methane and carbon dioxide.

Half-life: 1 hr.

Natulan

(effects on blood counts)

• Emphasize the need to take medication as directed. Take missed doses as soon as remembered within a few hours but not if several hours have passed or if almost time for next dose. Health care professional should be consulted if vomiting occurs shortly after a dose is taken.
• Instruct patient to notify health care professional promptly if signs of infection (fever, sore throat, chills, cough, thickened bronchial secretions, hoarseness, pain in lower back or side, difficult or painful urination); bleeding gums; bruising; petechiae; or blood in stool, urine, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Patient should not receive IM injections or rectal temperatures. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate gastric bleeding.
• Caution patient to avoid alcohol, caffeinated beverages, CNS depressants, OTC drugs, and foods or beverages containing tyramine (see Appendix M for foods included) during therapy and for at least 2 wk after therapy has been discontinued, because they may precipitate a hypertensive crisis.
• Advise patient that an additional interaction of alcohol with procarbazine is a disulfiram-like reaction (flushing, nausea, vomiting, headache, abdominal cramps).
• Instruct patient to inspect oral mucosa for erythema and ulceration. If ulceration occurs, advise patient to notify health care professional and to use sponge brush and rinse mouth with water after eating and drinking. Topical agents may be used if mouth pain interferes with eating. Stomatitis pain may require treatment with opioid analgesics.
• May cause drowsiness or dizziness. Caution patient to avoid driving or other activities that require alertness until response to medication is known.
• Advise patient that this medication may have teratogenic effects. Contraception should be practiced during therapy and for at least 4 mo after therapy is concluded.
• Discuss the possibility of hair loss with patient. Explore methods of coping.
• Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
• Instruct patient not to receive any vaccinations without advice of health care professional.
• Advise patient to notify health care professional of medication regimen prior to treatment or surgery. This therapy usually should be withdrawn at least 2 wk prior to surgery.
• Instruct patient to inform health care professional if muscle or joint pain, nausea, vomiting, sweating, tiredness, weakness, constipation, headache, difficulty swallowing, or loss of appetite becomes pronounced.
• Advise patient to carry identification describing medication regimen at all times.
• Emphasize the need for periodic lab tests to monitor for side effects.

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