Matulane Information
Matulane (Procarbazine hcl)
Matulane (Procarbazine hcl) Description
Matulane (Procarbazine hcl) (procarbazine hydrochloride), a hydrazine derivative antineoplastic agent, is available as capsules containing the equivalent of 50 mg procarbazine as the hydrochloride. Each capsule also contains cornstarch, mannitol and talc. Gelatin capsule shells contain parabens (methyl and propyl), potassium sorbate, titanium dioxide, FD&C Yellow No. 6 and D&C Yellow No. 10.
Chemically, procarbazine hydrochloride is -isopropyl-α-(2-methylhydrazino)--toluamide monohydrochloride. It is a white to pale yellow crystalline powder which is soluble but unstable in water or aqueous solutions. The molecular weight of procarbazine hydrochloride is 257.76 and the structural formula is:
Matulane (Procarbazine hcl) Clinical Pharmacology
The precise mode of cytotoxic action of procarbazine has not been clearly defined. There is evidence that the drug may act by inhibition of protein, RNA and DNA synthesis. Studies have suggested that procarbazine may inhibit transmethylation of methyl groups of methionine into t-RNA. The absence of functional t-RNA could cause the cessation of protein synthesis and consequently DNA and RNA synthesis. In addition, procarbazine may directly damage DNA. Hydrogen peroxide, formed during the auto-oxidation of the drug, may attack protein sulfhydryl groups contained in residual protein which is tightly bound to DNA.
Procarbazine is metabolized primarily in the liver and kidneys. The drug appears to be auto-oxidized to the azo derivative with the release of hydrogen peroxide. The azo derivative isomerizes to the hydrazone, and following hydrolysis splits into a benzylaldehyde derivative and methylhydrazine. The methylhydrazine is further degraded to CO and CH and possibly hydrazine, whereas the aldehyde is oxidized to -isopropylterephthalamic acid, which is excreted in the urine.
Procarbazine is rapidly and completely absorbed. Following oral administration of 30 mg of C-labeled procarbazine, maximum peak plasma radioactive concentrations were reached within 60 minutes.
After intravenous injection, the plasma half-life of procarbazine is approximately 10 minutes. Approximately 70% of the radioactivity is excreted in the urine as -isopropylterephthalamic acid within 24 hours following both oral and intravenous administration of C-labeled procarbazine.
Procarbazine crosses the blood-brain barrier and rapidly equilibrates between plasma and cerebrospinal fluid after oral administration.
Matulane (Procarbazine hcl) Indications And Usage
Matulane (Procarbazine hcl) is indicated for use in combination with other anticancer drugs for the treatment of Stage III and IV Hodgkin's disease. Matulane (Procarbazine hcl) is used as part of the MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) regimen.
Matulane (Procarbazine hcl) Contraindications
Matulane (Procarbazine hcl) 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.
Matulane (Procarbazine hcl) Warnings
To minimize CNS depression and possible potentiation, barbiturates, antihistamines, narcotics, hypotensive agents or phenothiazines should be used with caution. Ethyl alcohol should not be used since there may be an Antabuse (disulfiram)-like reaction. Because Matulane (Procarbazine hcl) exhibits some monoamine oxidase inhibitory activity, sympathomimetic drugs, tricyclic antidepressant drugs (eg, amitriptyline HCI, imipramine HCI) and other drugs and foods with known high tyramine content, such as wine, yogurt, ripe cheese and bananas, should be avoided. A further phenomenon of toxicity common to many hydrazine derivatives is hemolysis and the appearance of Heinz-Ehrlich inclusion bodies in erythrocytes.
Matulane (Procarbazine hcl) Precautions
Undue toxicity may occur if Matulane (Procarbazine hcl) is used in patients with impairment of renal and/or hepatic function. When appropriate, hospitalization for the initial course of treatment should be considered.
If radiation or a chemotherapeutic agent known to have marrow-depressant activity has been used, an interval of one month or longer without such therapy is recommended before starting treatment with Matulane (Procarbazine hcl) . The length of this interval may also be determined by evidence of bone marrow recovery based on successive bone marrow studies.
Prompt cessation of therapy is recommended if any one of the following occurs:
Bone marrow depression often occurs 2 to 8 weeks after the start of treatment. If leukopenia occurs, hospitalization of the patient may be needed for appropriate treatment to prevent systemic infection.
Baseline laboratory data should be obtained prior to initiation of therapy. The hematologic status as indicated by hemoglobin, hematocrit, white blood count (WBC), differential, reticulocytes and platelets should be monitored closely - at least every 3 or 4 days.
Hepatic and renal evaluation are indicated prior to beginning therapy. Urinalysis, transaminase, alkaline phosphatase and blood urea nitrogen tests should be repeated at least weekly.
See WARNINGS section.
No cross-resistance with other chemotherapeutic agents, radiotherapy or steroids has been demonstrated.
Matulane (Procarbazine hcl) Adverse Reactions
Leukopenia, anemia and thrombopenia occur frequently. Nausea and vomiting are the most commonly reported side effects.
Other adverse reactions are:
Pancytopenia; eosinophilia; hemolytic anemia; bleeding tendencies such as petechiae, purpura, epistaxis and hemoptysis.
Hepatic dysfunction, jaundice, stomatitis, hematemesis, melena, diarrhea, dysphagia, anorexia, abdominal pain, constipation, dry mouth.
Coma, convulsions, neuropathy, ataxia, paresthesia, nystagmus, diminished reflexes, falling, foot drop, headache, dizziness, unsteadiness.
Hypotension, tachycardia, syncope.
Retinal hemorrhage, papilledema, photophobia, diplopia, inability to focus.
Pneumonitis, pleural effusion, cough.
Herpes, dermatitis, pruritus, alopecia, hyperpigmentation, rash, urticaria, flushing.
Generalized allergic reactions.
Hematuria, urinary frequency, nocturia.
Pain, including myalgia and arthralgia; tremors.
Hallucinations, depression, apprehension, nervousness, confusion, nightmares.
Gynecomastia in prepubertal and early pubertal boys.
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.
Matulane (Procarbazine hcl) Overdosage
The major manifestations of overdosage with Matulane (Procarbazine hcl) 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.
Matulane (Procarbazine hcl) 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 (Procarbazine hcl) dose should be appropriately reduced, eg, in the MOPP regimen, the Matulane (Procarbazine hcl) dose is 100 mg/m 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.
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 (see PRECAUTIONS section), the drug should be discontinued until there has been satisfactory recovery, based on clinical evaluation and appropriate laboratory tests. After toxic side effects have subsided, therapy may then be resumed.
Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
Matulane (Procarbazine hcl) How Supplied
Capsules, ivory, containing the equivalent of 50 mg procarbazine as the hydrochloride; in bottles of 100 (NDC 54482-053-01). Imprint on capsules: Matulane (Procarbazine hcl) σ sigma-tau.
Matulane (Procarbazine hcl) References
Matulane (Procarbazine hcl) Principal Display Panel - Bottle Label
NDC 54482-053-01
Matulane (Procarbazine hcl)
(PROCARBAZINE HYDROCHLORIDE)
Each capsule contains 50 mg procarbazine
in the form of the hydrochloride salt.
Rx only
Disperse in tight, light-resistant containers as
defined in USP/NF.
LOT EXP.
M5-01/08AAl PC3986
package insert.
Mfd. for: ,
Gaithersburg, MD 20878 Mfd. by:
