Procarbazine Hydrochloride (1 brand name, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- MATULANE
Boxed Warning
WARNING It is recommended that MATULANE be given only by or under the supervision of a physician experienced in the use of potent antineoplastic drugs. Adequate clinical and laboratory facilities should be available to patients for proper monitoring of treatment.
Indications and Usage
Matulane is indicated for use in combination with other anticancer drugs for the treatment of Stage III and IV Hodgkin’s disease. Matulane is used as part of the MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) regimen.
Dosage and Administration
The following doses are for administration of the drug as a single agent. When used in combination with other anticancer drugs, the Matulane dose should be appropriately reduced, eg, in the MOPP regimen, the Matulane dose is 100 mg/m2 daily for 14 days. All dosages are based on the patient’s actual weight. However, the estimated lean body mass (dry weight) is used if the patient is obese or if there has been a spurious weight gain due to edema, ascites or other forms of abnormal fluid retention. Adults:To minimize the nausea and vomiting experienced by a high percentage of patients beginning Matulane therapy, single or divided doses of 2 to 4 mg/kg/day for the first week are recommended. Daily dosage should then be maintained at 4 to 6 mg/kg/day until maximum response is obtained or until the white blood count falls below 4000/cmm or the platelets fall below 100,000/ cmm. When maximum response is obtained, the dose may be maintained at 1 to 2 mg/kg/day. Upon evidence of hematologic or other toxicity (see PRECAUTIONS section), the drug should be discontinued until there has been satisfactory recovery. After toxic side effects have subsided, therapy may then be resumed at the discretion of the physician, based on clinical evaluation and appropriate laboratory studies, at a dosage of 1 to 2 mg/kg/day. Pediatric Patients:Very close clinical monitoring is mandatory. Undue toxicity, evidenced by tremors, coma and convulsions, has occurred in a few cases. Dosage, therefore, should be individualized. The following dosage schedule is provided as a guideline only. Fifty (50) mg per square meter of body surface per day is recommended for the first week. Dosage should then be maintained at 100 mg per square meter of body surface per day until maximum response is obtained or until leukopenia or thrombocytopenia occurs. When maximum response is attained, the dose may be maintained at 50 mg per square meter of body surface per day. Upon evidence of hematologic or other toxicity (s
Contraindications
Matulane is contraindicated in patients with known hypersensitivity to the drug or inadequate marrow reserve as demonstrated by bone marrow aspiration. Due consideration of this possible state should be given to each patient who has leukopenia, thrombocytopenia or anemia.
Adverse Reactions
Leukopenia, anemia and thrombopenia occur frequently. Nausea and vomiting are the most commonly reported side effects. Other adverse reactions are: Hematologic Pancytopenia; eosinophilia; hemolytic anemia; bleeding tendencies such as petechiae, purpura, epistaxis and hemoptysis. Gastrointestinal Hepatic dysfunction, jaundice, stomatitis, hematemesis, melena, diarrhea, dysphagia, anorexia, abdominal pain, constipation, dry mouth. Neurologic Coma, convulsions, neuropathy, ataxia, paresthesia, nystagmus, diminished reflexes, falling, foot drop, headache, dizziness, unsteadiness. Cardiovascular Hypotension, tachycardia, syncope. Ophthalmic Retinal hemorrhage, papilledema, photophobia, diplopia, inability to focus. Respiratory Pneumonitis, pleural effusion, cough. Dermatologic Herpes, dermatitis, pruritus, alopecia, hyperpigmentation, rash, urticaria, flushing. Allergic Generalized allergic reactions. Genitourinary Hematuria, urinary frequency, nocturia. Musculoskeletal Pain, including myalgia and arthralgia; tremors. Psychiatric Hallucinations, depression, apprehension, nervousness, confusion, nightmares. Endocrine Gynecomastia in prepubertal and early pubertal boys. Miscellaneous Intercurrent infections, hearing loss, pyrexia, diaphoresis, lethargy, weakness, fatigue, edema, chills, insomnia, slurred speech, hoarseness, drowsiness. Second nonlymphoid malignancies (including lung cancer, acute myelocytic leukemia and malignant myelosclerosis) and azoospermia have been reported in patients with Hodgkin’s disease treated with procarbazine in combination with other chemotherapy and/or radiation. The risks of secondary lung cancer from treatment appear to be multiplied by tobacco use.
Drug Interactions
See WARNINGS section. No cross-resistance with other chemotherapeutic agents, radiotherapy or steroids has been demonstrated.
Overdosage
The major manifestations of overdosage with Matulane would be anticipated to be nausea, vomiting, enteritis, diarrhea, hypotension, tremors, convulsions and coma. Treatment should consist of either the administration of an emetic or gastric lavage. General supportive measures such as intravenous fluids are advised. Since the major toxicity of procarbazine hydrochloride is hematologic and hepatic, patients should have frequent complete blood counts and liver function tests throughout their period of recovery and for a minimum of two weeks thereafter. Should abnormalities appear in any of these determinations, appropriate measures for correction and stabilization should be immediately undertaken. The estimated mean lethal dose of procarbazine hydrochloride in laboratory animals varied from approximately 150 mg/kg in rabbits to 1300 mg/kg in mice.