PROCARBAZINE HYDROCHLORIDE

PROCARBAZINE HYDROCHLORIDE
(proe-kar'ba-zeen)
Matulane, Natulan 
Classifications: antineoplastic; alkylating agent;
Therapeutic: antineoplastic

Prototype: Cyclophosphamide
Pregnancy Category: D

Availability

50 mg capsules

Action

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

Therapeutic Effect

Highly toxic to rapidly proliferating tissue. May delay myelosuppression.

Uses

Adjunct in palliative treatment of Hodgkin's disease.

Unlabeled Uses

Solid tumors.

Contraindications

Severe myelosuppression; pheochromocytoma; 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; pregnancy (category D), lactation.

Cautious Use

Concomitant administration with CNS depressants; hepatic or renal impairment; cardiac disease; bipolar disorder, mania, paranoid schizophrenia; G6PD deficiency; parkinsonism; following radiation or chemotherapy before at least 1 mo has elapsed; alcoholism; 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
  • Do not give if WBC count <4000/mm3 or platelet count <100,000/mm3. Consult physician.
  • Store at 15°–30° C (59°–86° F). Protect from freezing, moisture, and light.

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

Nursing Implications

Assessment & Drug Effects

  • Start flow sheet and record baseline BP, weight, temperature, pulse, and I&O ratio and pattern.
  • Lab tests: Determine hematologic status (Hgb, Hct, WBC, differential, reticulocyte, and platelet counts) initially and at least q3–4d. Hepatic and renal studies (transaminase, alkaline phosphatase, BUN, urinalysis) are also indicated initially and at least weekly during therapy.
  • Protect patient from exposure to infection and trauma when nadir of leukopenia (<4000/mm3) is approached. Note and report changes in voiding pattern, hematuria, and dysuria (possible signs of urinary tract infection). Monitor I&O ratio and temperature closely.
  • Withhold drug and notify physician of any of the following: CNS S&S (e.g., paresthesias, neuropathies, confusion); leukopenia [WBC count <4000/mm3; thrombocytopenia (platelet count <100,000/mm3)]; hypersensitivity reaction, the first small ulceration or persistent spot of soreness in oral cavity, diarrhea, and bleeding.
  • Monitor for and report any of the following: chills, fever, weakness, shortness of breath, productive cough. Drug will be discontinued.
  • Assess for signs of liver dysfunction: Jaundice (yellow skin, sclerae, and soft palate), frothy or dark urine, clay-colored stools.
  • Tolerance to nausea and vomiting (most common adverse effects) usually develops by end of first week of treatment. Doses are kept at a minimum during this time. If vomiting persists, therapy will be interrupted.

Patient & Family Education

  • Avoid OTC nose drops, cough medicines, and antiobesity preparations containing sympathomimetic drugs (e.g., ephedrine, amphetamine, epinephrine) and tricyclic antidepressants because they may cause hypertensive crises since procarbazine has MAO inhibitory activity. Do not to use OTC preparations without physician's approval.
  • Report to physician any sign of impending infection.
  • Do not eat foods high in tyramine content (e.g., aged cheese, beer, wine).
  • Avoid alcohol; ingestion of any form of alcohol may precipitate a disulfiram-type reaction (see Appendix F).
  • Report to physician immediately signs of hemorrhagic tendencies: Bleeding into skin and mucosa, epistaxis, hemoptysis, hematemesis, hematuria, melena, ecchymoses, petechiae. Bone marrow depression often occurs 2–8 wk after start of therapy.
  • Avoid excessive exposure to the sun because of potential photosensitivity reaction: Cover as much skin area as possible with clothing, and use sunscreen lotion (SPF >12) on all exposed skin surfaces.
  • Use caution while driving or performing hazardous tasks until response to drug is known since drowsiness, dizziness, and blurred vision are possible adverse effects.
  • Use contraceptive measures during procarbazine therapy.

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

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