procarbazine hydrochloride

procarbazine hydrochloride

[prōkär′bəzēn]

an antineoplastic.

indications It is prescribed in the treatment of a variety of neoplasms, including Hodgkin's disease, lymphomas, brain tumors, and lung cancer.

contraindications Bone marrow depression or known hypersensitivity to this drug prohibits its use.

adverse effects Among the most serious adverse effects are bone marrow depression and GI disturbances, particularly nausea and vomiting.

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procarbazine hydrochloride Warning - Hazardous drug!

Matulane, Natulan (CA)

Pharmacologic class: Alkylating agent

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Boxed 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.

Route	Onset	Peak	Duration
P.O.	Rapid	1 hr	Unknown

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.
☞ Monitor neurologic status for seizures, paresthesia, neuropathy, and confusion. Discontinue drug and notify prescriber if these occur.
☞ 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.
☞ Evaluate patient's concurrent drug use to ensure that he isn't receiving other drugs that could cause potentially fatal interactions.
☞ 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.
☞ Discontinue drug at first sign of hypersensitivity, stomatitis, diarrhea, or bleeding.

Patient teaching

• Instruct patient to avoid caffeine-containing foods and beverages.
☞ 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.