MATULANE- procarbazine hydrochloride capsule

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

PROCARBAZINE HYDROCHLORIDE (UNII: XH0NPH5ZX8) (PROCARBAZINE - UNII:35S93Y190K)

Available from:

Sigma-Tau Pharmaceuticals, Inc.

INN (International Name):

PROCARBAZINE HYDROCHLORIDE

Composition:

PROCARBAZINE 50 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

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. 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.

Product summary:

Capsules, ivory, containing the equivalent of 50 mg procarbazine as the hydrochloride; in bottles of 100 (NDC 54482-053-01). Imprint on capsules: MATULANE σ sigma-tau.

Authorization status:

New Drug Application

Summary of Product characteristics

MATULANE- PROCARBAZINE HYDROCHLORIDE CAPSULE
SIGMA-TAU PHARMACEUTICALS, INC.
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MATULANE (PROCARBAZINE HYDROCHLORIDE) CAPSULES
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.
DESCRIPTION
Matulane (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
_N_-isopropyl-α-(2-methylhydrazino)- _p_-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:
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
methylh