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:

Leadiant Biosciences, 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 54482-054-01). Imprint on capsules: MATULANE LB213.

Authorization status:

New Drug Application

Summary of Product characteristics

MATULANE- PROCARBAZINE HYDROCHLORIDE CAPSULE
LEADIANT BIOSCIENCES, 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 titanium dioxide, FD&C Yellow No. 6 and D&C Yellow No.
10.
Chemically, procarbazine hydrochloride is
_N_‑isopropyl-∝-(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 methylhydrazine is
further
degraded to CO
and