PROCARBAZINE HYDROCHLORIDE
(proe-kar'ba-zeen)
Matulane, Natulan 
Classifications: antineoplastic; alkylating agent
Prototype: Cyclophosphamide
Pregnancy Category: D

Availability

50 mg capsules

Actions

Hydrazine derivative with antimetabolite properties; cell cycle-specific for the S phase of cell division. Precise mechanism of action unknown. Suppresses mitosis at interphase, and causes chromatin derangement.

Therapeutic Effects

Highly toxic to rapidly proliferating tissue. Has immunosuppressive properties and exhibits MAO inhibition activity. May delay myelosuppression. Reportedly does not affect survival time but may produce remissions of at least 1 mo duration.

Uses

Adjunct in palliative treatment of Hodgkin's disease.

Unlabeled Uses

Solid tumors.

Contraindications

Myelosuppression; alcohol ingestion; foods high in tyramine content; sympathomimetic drugs. MAO inhibitors should be discontinued 14 d prior to therapy; tricyclic antidepressants, 7 d before therapy. Safety during pregnancy (category D) or lactation is not established.

Cautious Use

Concomitant administration with CNS depressants; hepatic or renal impairment; following radiation or chemotherapy before at least 1 mo has elapsed; hepatic and renal impairment; infection; diabetes mellitus.

Route & Dosage

Adjunct for Hodgkin's Disease
Adult: PO 2–4 mg/kg/d in single or divided doses for 1 wk, then 4–6 mg/kg/d until WBC <4000/mm3 or platelets are <100,000/mm3 or maximum response obtained; drug is then discontinued until bone marrow recovery is satisfactory; treatment is started again at 1–2 mg/kg/d
Child: PO 50 mg/m2/d in single or divided doses for 1 wk, then 100 mg/m2/d until WBC is <4000/mm3 or platelets are <100,000/mm3 or maximum response obtained; drug is then discontinued until bone marrow recovery is satisfactory; treatment is started again at 50 mg/m2/d

Administration

Oral

Adverse Effects (1%)

CNS: Myalgia, arthralgia, paresthesias, weakness, fatigue, lethargy, drowsiness, neuropathies, mental depression, acute psychosis, hallucinations, dizziness, headache, ataxia, nervousness, insomnia, coma, confusion, seizures. GI: Severe nausea and vomiting, anorexia, stomatitis, dry mouth, dysphagia, diarrhea, constipation, jaundice, ascites. Hematologic: Bone marrow suppression (leukopenia, anemia, thrombocytopenia), hemolysis, bleeding tendencies. Skin: Dermatitis, pruritus, herpes, hyperpigmentation, flushing, alopecia. Respiratory: Pleural effusion, cough, hoarseness. CV: Hypotension, tachycardia. Body as a Whole: Chills, fever, sweating, photosensitivity; intercurrent infections. Urogenital: Gynecomastia, depressed spermatogenesis, atrophy of testes.

Diagnostic Test Interference

Procarbazine may enhance the effects of CNS depressants. A disulfiram-like reaction may occur following ingestion of alcohol.

Interactions

Drug: Alcohol, phenothiazines, and other cns depressants add to CNS depression; tricyclic antidepressants, mao inhibitors, sympathomimetics, ephedrine, phenylpropanolamine may precipitate hypertensive crisis, hyperpyrexia; seizures, or death. Food: Tyramine-containing foods may precipitate hypertensive crisis [see phenelzine sulfate (mao inhibitor)].

Pharmacokinetics

Absorption: Readily absorbed from GI tract. Peak: 1 h. Distribution: Widely distributed with high concentrations in liver, kidneys, intestinal wall, and skin. Metabolism: Metabolized in liver. Elimination: Excreted in urine. Half-Life: 1 h.

Nursing Implications

Assessment & Drug Effects

Patient & Family Education


Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug