LEUKERAN- chlorambucil tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

CHLORAMBUCIL (UNII: 18D0SL7309) (CHLORAMBUCIL - UNII:18D0SL7309)

Available from:

Woodward Pharma Services LLC

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

LEUKERAN (chlorambucil) is indicated in the treatment of chronic lymphatic (lymphocytic) leukemia, malignant lymphomas including lymphosarcoma, giant follicular lymphoma, and Hodgkin’s disease. It is not curative in any of these disorders but may produce clinically useful palliation. Chlorambucil should not be used in patients whose disease has demonstrated a prior resistance to the agent. Patients who have demonstrated hypersensitivity to chlorambucil should not be given the drug. There may be cross-hypersensitivity (skin rash) between chlorambucil and other alkylating agents.

Product summary:

LEUKERAN is supplied as brown, film-coated, round, biconvex tablets containing 2 mg chlorambucil in amber glass bottles with child-resistant closures. One side is engraved with “GX EG3” and the other side is engraved with an “L.” Bottle of 25 (NDC 69784-610-25) Store in a refrigerator, 2° to 8°C (36° to 46°F).

Authorization status:

New Drug Application

Summary of Product characteristics

LEUKERAN- CHLORAMBUCIL TABLET, FILM COATED
WOODWARD PHARMA SERVICES LLC
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LEUKERAN
(CHLORAMBUCIL) TABLETS
WARNING
LEUKERAN (chlorambucil) can severely suppress bone marrow function.
Chlorambucil is a carcinogen in humans. Chlorambucil is probably
mutagenic and
teratogenic in humans. Chlorambucil produces human infertility (see
WARNINGS
and PRECAUTIONS).
DESCRIPTION
LEUKERAN (chlorambucil) was first synthesized by Everett et al. It is
a bifunctional
alkylating agent of the nitrogen mustard type that has been found
active against
selected human neoplastic diseases.
Chlorambucil is known chemically as
4-[bis(2-chlorethyl)amino]benzenebutanoic acid and
has the following structural formula:
Chlorambucil hydrolyzes in water and has a pKa of 5.8.
LEUKERAN (chlorambucil) is available in tablet form for oral
administration. Each film-
coated tablet contains 2 mg chlorambucil and the inactive ingredients
colloidal silicon
dioxide, hypromellose, lactose (anhydrous), macrogol/PEG 400,
microcrystalline
cellulose, red iron oxide, stearic acid, titanium dioxide, and yellow
iron oxide.
CLINICAL PHARMACOLOGY
MECHANISM OF ACTION
Chlorambucil, an aromatic nitrogen mustard derivative, is an
alkylating agent.
Chlorambucil interferes with DNA replication and induces cellular
apoptosis via the
accumulation of cytosolic p53 and subsequent activation of Bax, an
apoptosis
promoter.
PHARMACOKINETICS
In a study of 12 patients given single oral doses of 0.2 mg/kg of
LEUKERAN, the mean
®
dose-adjusted (±SD) plasma chlorambucil C
was 492 ± 160 ng/mL, the AUC was
883 ± 329 ng.h/mL, the mean elimination half-life (t½) was 1.3 ±
0.5 hours, and the
T
was 0.83 ± 0.53 hours. For the major metabolite, phenylacetic acid
mustard
(PAAM), the mean dose-adjusted (± SD) plasma C
was 306 ± 73 ng/mL, the AUC
was 1204 ± 285 ng.h/mL, mean t½ was 1.8 ± 0.4 hours, and the T
was 1.9 ± 0.7
hours.
After single oral doses of 0.6 to 1.2 mg/kg, peak plasma chlorambucil
levels (C
) are
reached within 1 hour and the terminal elimination half-life (