Chlorambucil

Uses

Hodgkin's disease, certain forms of non-Hodgkin's lymphoma, chronic lymphocytic leukaemia, Waldenstrom's macroglobulinaemia.

Chlorambucil is also used to associated treatment for these conditions: Chronic Lymphocytic Leukaemia (CLL), Hodgkins Disease (HD), Nephrotic syndrome with lesion of minimal change glomerulonephritis, Non-Hodgkin's Lymphoma (NHL), Waldenström's Macroglobulinemia (WM), Giant follicular lymphoma

How Chlorambucil works

Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.

Dosage

Chlorambucil dosage

Hodgkin's disease: 200 mcg/kg/day for 4-8 wk.

Non-Hodgkin's lymphoma: 100-200 mcg/kg/day for 4-8 wk. Maintenance: Reduced daily dosage of intermittent courses of treatment.

Chronic lymphocytic leukaemia: Initially, 150 mcg/kg/day until the total leukocyte count falls to 10,000 microliter. Treatment may be resumed 4 wk after at a dose of 100 mcg/kg/day.

Waldenstrom's macroglobulinaemia: Starting dose of 6-12 mg daily until leucopenia occurs followed by 2-8 mg daily.

Should be taken on an empty stomach: Ensure adequate hydration. Swallow whole, do not chew/crush.

Side Effects

Bone marrow suppression, seizures in childn with nephrotic syndrome, nausea, vomiting, diarrhoea, oral ulceration. Rarely, irreversible bone marrow failure, allergic reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, seizures, movement disorders, interstitial pulmonary fibrosis, interstitial pneumonia, hepatotoxicity, jaundice, sterile cystitis, drug fever

Precaution

Monitor FBC closely. Bone marrow suppression reversible only if withdrawn early enough. Should not be given to patients who have recently undergone radio- or chemotherapy. In lymphocytic infiltration of bone marrow or hypoplastic bone marrow, max daily dose is 0.1 mg/kg. Childn with nephrotic syndrome, patients on high pulse dosing regimens, history of seizure disorders. Renal or hepatic impairment. Ensure adequate contraceptive precautions. Pregnancy.

Food Interaction

• Avoid echinacea. Echinacea should be used with caution, if at all, in patients receiving therapeutic immunosuppressants. Monitor for reduced efficacy of the immunosuppressant during concomitant use.
• Drink plenty of fluids.
• Take on an empty stomach. Co-administration with food decreases bioavailability.

Chlorambucil Drug Interaction

Unknown: aspirin, aspirin, celecoxib, celecoxib, sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, ubiquinone, ubiquinone, copper gluconate, copper gluconate, prednicarbate topical, prednicarbate topical, glycerin, glycerin, heparin, heparin, metoprolol, metoprolol, bioflavonoids, bioflavonoids

Chlorambucil Disease Interaction

Major: infections, myelosuppressionModerate: hepatic impairment, pneumonitis/fibrosis, seizures

Half Life

1.5 hours

Elimination Route

Chlorambucil is extensively metabolized in the liver primarily to phenylacetic acid mustard. The pharmacokinetic data suggests that oral chlorambucil undergoes rapid gastrointestinal absorption and plasma clearance and that it is almost completely metabolized, having extremely low urinary excretion.

Pregnancy & Breastfeeding use

Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindication

Pregnancy (1st trimester) & lactation.

Innovators Monograph

You find simplified version here Chlorambucil