procarbazine hydrochloride
procarbazine hydrochloride
Pharmacologic class: Alkylating agent
Therapeutic class: Antineoplastic
Pregnancy risk category D
FDA Box Warning
• Give under supervision of physician experienced in use of potent antineoplastics, in setting with adequate clinical and laboratory facilities to monitor patient.
Action
Thought to inhibit DNA, RNA, and protein synthesis, resulting in death of rapidly dividing cells. Also inhibits MAO.
Availability
Capsules: 50 mg
Indications and dosages
➣ Hodgkin's disease
Adults: 2 to 4 mg/kg P.O. daily as a single dose or in divided doses for 1 week, then 4 to 6 mg/kg P.O. daily until white blood cell (WBC) count is less than 4,000/mm3 or platelet count is less than 100,000/mm3, or until desired response occurs. With desired response, give maintenance dosage of 1 to 2 mg/kg P.O. daily (rounded off to nearest 50 mg). As component of MOPP (mechlorethamine, vincristine, procarbazine, prednisone) regimen for advanced Hodgkin's disease, usual dosage is 100 mg/m2 P.O. daily on days 1 to 14 of 28-day cycle.
Children: Dosage highly individualized. Usual dosage is 50 mg/m2 P.O. daily for first week, then 100 mg/m2 P.O. daily until leukopenia, thrombocytopenia, or desired response occurs. With desired response, maintenance dosage is 50 mg/m2 P.O. daily.
Off-label uses
• Brain tumor
• Lymphoma
Contraindications
• Hypersensitivity to drug
• Inadequate bone marrow reserve
Precautions
Use cautiously in:
• infection, chronic debilitating illness, headache, hepatic or renal impairment, cardiovascular disease, heart failure, diarrhea, stomatitis, pheochromocytoma, psychiatric illness, alcoholism
• patients who have undergone radiation therapy or received other chemotherapy drugs within previous month
• elderly patients
• pregnant or breastfeeding patients
• females of childbearing age.
Administration
• Weigh patient; know that dosages are based on weight. However, use caution in patients with edema or ascites.
Adverse reactions
CNS: confusion, dizziness, drowsiness, hallucinations, headache, mania, depression, nightmares, psychosis, syncope, tremor, neuropathy, paresthesia, seizures
CV: edema, hypotension, tachycardia
EENT: nystagmus, photophobia, retinal hemorrhage
GI: nausea, vomiting, diarrhea, dysphagia, ascites, stomatitis, dry mouth, anorexia
GU: gonadal suppression, gynecomastia
Hematologic: anemia, leukopenia, thrombocytopenia
Hepatic: hepatic dysfunction
Respiratory: cough, pleural effusion
Skin: alopecia, photosensitivity, pruritus, rash
Interactions
Drug-drug. Digoxin: decreased digoxin blood level
Levodopa: flushing, hypertension
Opioids: deep coma, death Sympathomimetics (indirect-acting): abrupt, life-threatening hypertension
Tricyclic antidepressants: severe toxicity and fatal reactions (including blood pressure fluctuations, seizures, and coma)
Drug-diagnostic tests. Hematocrit, hemoglobin, platelets, reticulocytes, WBCs: decreased levels
Drug-food. Caffeine-containing foods and beverages: hypertension, arrhythmias
Tyramine-containing foods and beverages: life-threatening hypertension
Drug-behaviors. Alcohol use: disulfiram-like reaction
Patient monitoring
• Monitor vital signs and nutritional status.
• Assess fluid intake and output. Watch for evidence of fluid overload.
See Monitor neurologic status for seizures, paresthesia, neuropathy, and confusion. Discontinue drug and notify prescriber if these occur.
See Monitor CBC and platelet count. Discontinue drug and contact prescriber if WBC count falls below 4,000/mm3 or platelet count falls below 100,000/mm3.
See Evaluate patient's concurrent drug use to ensure that he isn't receiving other drugs that could cause potentially fatal interactions.
See Check for diarrhea. Discontinue drug and contact prescriber if patient has frequent bowel movements or watery stools.
• Monitor blood urea nitrogen level, liver and kidney function tests, and urinalysis.
See Discontinue drug at first sign of hypersensitivity, stomatitis, diarrhea, or bleeding.
Patient teaching
• Instruct patient to avoid caffeine-containing foods and beverages.
See Tell patient to avoid foods and beverages containing tyramine (such as cheese, Chianti wine, tea, coffee, cola, and bananas).
• Advise patient to avoid alcohol.
• Tell female of childbearing age to discuss contraception with prescriber.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and behaviors mentioned above.