PROCARBAZINE HYDROCHLORIDE (proe-kar'ba-zeen) Matulane, Natulan Classifications: antineoplastic; alkylating agent Prototype: Cyclophosphamide Pregnancy Category: D
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50 mg capsules
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.
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.
Adjunct in palliative treatment of Hodgkin's disease.
Solid tumors.
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.
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.
Adjunct for Hodgkin's Disease Adult: PO 24 mg/kg/d in single or divided doses for 1 wk, then 46 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 12 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
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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.
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.
Procarbazine may enhance the effects of CNS depressants. A disulfiram-like reaction may occur following ingestion of alcohol.
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)].
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.
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 q34d. 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 28 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.
- Do not breast feed while taking this drug without consulting physician.