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Busulfan information from DrugsUpdate  

See Available Brands of Busulfan in India

P - Contraindicated in pregnancy
L - Contraindicated in lactation

Busulfan is a chemotherapy drug that is a cell cycle non-specific alkylating antineoplastic agent (slows the growth of cancer cells). More specifically it belongs to a subclass of alkylating agents known as alkyl sulfonates. It is marketed in the U.S. by GlaxoSmithKline under the brand name Myleran, and has been in clinical use since 1959. Busulfan is also available in an IV formulation marketed as Busulfex by PDL BioPharma, Inc. Its chemical designation is 1,4-butanediol dimethanesulfonate.

 

Pharmacodynamics

Pharmacokinetics

Busulfan reacts with N-7 position of guanosine and interferes with DNA replication and RNA transcription by alkylating and cross-linking the DNA strands.
Absorption: Readily absorbed from the GIT (oral).
Distribution: Crosses the blood-brain barrier.
Metabolism: Extensively hepatic.
Excretion: Urine (as sulfur-containing metabolites); 2-3 hrs (elimination half-life).


 

Busulfan Indications / Busulfan Uses

In palliative treatment of chronic myeloid leukemia, in polycythemia vera, essential thrombocythaemia, conditionong regimens for bonemarrow transplantation.

Busulfan Adverse Reactions / Busulfan Side Effects

GI symptoms, anorexia, wt loss, weakness, hyperpigmentation, amenorrhoea, cataracts, cough or hoarseness, impaired fertility and gonadal function, dry skin, liver damage, gynaecomastia.
Potentially Fatal: Bone marrow depression manifesting as thrombocytopaenia, leucopaenia, anaemia. Interstitial pulmonary fibrosis (known as "busulfan lung" on prolonged treatment).

Precautions

Warnings
Use with extreme caution in patients with prior radiation or chemotherapy.
Perform hematological testing weekly during therapy.
Hematopoietic toxicity
Most frequent and serious side effect is bone marrow failure, resulting in severe pancytopenia. Recovery from busulfan-induced pancytopenia may take from 1 mo to 2 yr of age. The most consistent dose-related toxicity is bone marrow suppression. This may be manifested by anemia, leukopenia, neutropenia, thrombocytopenia, or any combination of these. Busulfan-induced bone marrow suppression may be prolonged. The WBC may continue to drop for 2 to 3 wk after therapy is discontinued and may take up to 2 mo to recover.
Monitor
Monitor patients for signs of local or systemic infection or bleeding. Frequently evaluate hematologic status.
Hepatic Function
High doses may be associated with an increased risk of developing hepatic VOD.
Carcinogenesis
Malignant tumors have occurred in patients on busulfan therapy; this drug may be a human carcinogen.
Adrenal insufficiency
A clinical syndrome closely resembling adrenal insufficiency and characterized by anorexia, melanoderma, nausea, severe fatigue, vomiting, weakness, and weight loss has developed after prolonged therapy.
Cellular dysplasia
Busulfan may cause cellular dysplasia in many organs, in addition to the lung. Giant hyperchromatic nuclei have been reported in the adrenal glands, bone marrow, liver, lymph nodes, pancreas, and thyroid.
CV
Cardiac tamponade, which was often fatal, has been reported in a small number of children with thalassemia (2% in 1 series) who received high doses of busulfan and cyclophosphamide as the preparatory regimen for bone marrow transplantation and hematopoietic progenitor cell transplantation. Abdominal pain and vomiting preceded the tamponade in most patients.
Hyperuricemia and hyperuricosuria
May occur in patients with CML. Minimize adverse effects by increased hydration, urine alkalization, and the prophylactic administration of allopurinol.
Ovarian suppression and amenorrhea with menopausal symptoms
Commonly occurs during busulfan therapy in premenopausal patients. Busulfan has been associated with ovarian failure, including failure to achieve puberty in females.
Pulmonary effects
A rare but important complication of busulfan therapy is the development of bronchopulmonary dysplasia with pulmonary fibrosis. Symptoms have occurred within 4 mo to 10 yr after initiation of therapy. Clinically, patients report the insidious onset of cough, dyspnea, and low-grade fever. Pulmonary function studies reveal diminished diffusion capacity and decreased pulmonary compliance.
Seizures
Seizures have been reported in patients receiving high oral doses of busulfan. Risk of seizures may be reduced by prophylactic administration of phenytoin.

Special Precautions

Prior treatment with other myelosuppressive drugs, patients predisposed to seizures. May cause secondary malignancies (tumors, acute leukaemias, ovarian failure). Previous irradiation/therapy. Monitor blood counts carefully during therapy. Discontinue if lung toxicity develops.

Other Drug Interactions

Decreased clearance when used with cyclophosphamide and itraconazole. Increased clearance by phenytoin. May reduce response to vaccines, possibility of generalized infections with live vaccines. Combination with thioguanine results in oesophageal varices and abdominal liver function tests.
Potentially Fatal: Cytotoxic agents may increase risk of pulmonary toxicity.

Other Interactions

Information Not Available

Dosage

Oral
Palliative treatment of chronic myeloid leukemia
Adult: 60 mcg/kg daily. Maintenance: 0.5-2 mg daily. Max: 4 mg daily.
Oral
Polycythemia vera
Adult: 4-6 mg daily continued for 4-6 wk with blood counts monitoring.
Oral
Essential thrombocythaemia
Adult: 2-4 mg daily.
Oral
Conditioning regimens for bone marrow transplantation
Adult: 3.5-4 mg/kg daily in divided doses for 4 days up to a total dose of 14-16 mg/kg. Usually used with cyclophosphamide for ablation of recipient's bone marrow.
Intravenous
Conditioning regimens for bone marrow transplantation
Adult: When used with phenytoin, recommended dose: 3.2 mg/kg ideal body-weight/day for 4 days (total dose 12.8 mg/kg); actual body-weight is used for dose calculation if it is <the ideal weight. Daily dose is given as 4 infusions of 800 mcg/kg at 6-hrly intervals; each dose is diluted in sodium chloride 0.9% or glucose 5% to a final concentration of about 500 mcg/mL, given over 2 hr through a central venous catheter using an infusion pump. Start cyclophosphamide only at least 24 hr after last dose of busulfan.

Food(before/after)

May be taken with or without food. (Take w/ chilled liqd, ensure adequate fluid intake.)

List of Contraindications

Busulfan and Pregnancy

Contraindicated in 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).

Busulfan and Lactation

Contraindicated in lactation

Busulfan and Children

Safety and efficacy not established

Busulfan and Geriatic

Use with caution, usually starting at the low end of the dosage range because of the greater frequency of decreased cardiac, hepatic, or renal function, and concomitant diseases or other drug therapy.

Busulfan and Other Contraindications

Pregnancy and lactation. Hypersensitivity

Storage

Oral: Store below 25°C

Lab interference

Oral: Store below 25°C

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