MYLERAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MYLERAN (MYLERAN).

How it works

Busulfan is a bifunctional alkylating agent that crosslinks DNA, primarily at guanine N-7 positions, leading to DNA fragmentation and cell cycle arrest. It is cell cycle phase-nonspecific.

What the body does with it

Metabolism	Primarily hepatic metabolism via conjugation with glutathione (glutathione S-transferase, especially GSTA1) to form inactive metabolites. A minor pathway involves cytochrome P450 (not major).
Excretion	Primarily renal (30-60% unchanged drug), biliary/fecal (minor, <10%)
Half-life	Terminal half-life ~2.5 hours (range 2-3 hours); prolonged in hepatic impairment
Protein binding	~32% (albumin); minimal binding to other proteins
Volume of Distribution	0.6-0.8 L/kg; indicates distribution in total body water
Bioavailability	Oral: ~80% (extensive absorption, first-pass metabolism minimal)
Onset of Action	Oral: 1-2 hours for myelosuppression; busulfan level monitoring used for conditioning
Duration of Action	Myelosuppression persists 2-4 weeks; clinical effect on bone marrow lasts 3-6 weeks after oral dose

Classification & Brands

Dosing & administration

60 mg/m2 orally as a single dose, or 4-12 mg/day orally for 2-7 days depending on regimen (e.g., for chronic myeloid leukemia: 4-8 mg/day for 2-3 weeks then 2-4 mg/day as maintenance; for conditioning in stem cell transplant: 1 mg/kg every 6 hours for 4 days).

Dosage form	TABLET
Renal impairment	No specific GFR-based guidelines; monitor for myelosuppression. Avoid in severe renal impairment (CrCl <10 mL/min) due to potential accumulation. For CrCl 10-50 mL/min, consider dose reduction by 50% based on toxicity.
Liver impairment	Child-Pugh A: no adjustment required. Child-Pugh B: reduce dose by 50% and monitor toxicity. Child-Pugh C: avoid use or use with extreme caution, reduce dose by 75% and monitor closely.
Pediatric use	For conditioning: 1 mg/kg/dose (max 50 mg/dose) every 6 hours for 16 doses (total 16 mg/kg). For CML: 0.06-0.1 mg/kg/day initially, adjusted based on WBC response. Monitor blood counts closely.
Geriatric use	Start at lower end of dosing range (e.g., 50% of standard dose) due to increased risk of myelosuppression and renal/hepatic decline. Monitor CBCs weekly during dose titration.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MYLERAN (MYLERAN).

Breastfeeding	No data available on M/P ratio. Contraindicated in breastfeeding due to potential severe adverse effects in nursing infants including myelosuppression and carcinogenesis.
Teratogenic Risk	Pregnancy category D. First trimester exposure associated with major congenital malformations including craniofacial, skeletal, and visceral anomalies. Second and third trimester exposure may cause intrauterine growth restriction, myelosuppression, and pancytopenia in the fetus. All trimesters carry risk of fetal loss.

Warnings & precautions

■ FDA Black Box Warning

MYLERAN can cause severe bone marrow suppression, including irreversible aplastic anemia. It is also associated with the development of secondary malignancies. Use caution when administering to patients with compromised bone marrow reserve.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to busulfan or any component of the formulation; patients with a history of bone marrow suppression not related to their underlying disease (absolute); caution in patients with low baseline neutrophil/platelet counts (relative).

Clinical Precautions

Precautions

Bone marrow suppression (monitor blood counts); pulmonary toxicity (interstitial pneumonitis, pulmonary fibrosis); hepatotoxicity (veno-occlusive disease, especially with high doses); secondary malignancies; ovarian failure, azoospermia; fetal harm; seizures at high doses; cardiac tamponade; sinusoidal obstruction syndrome.

Clinical Tips & Counseling

Drug interactions

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MYLERAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for MYLERAN (MYLERAN).

How it works

Busulfan is a bifunctional alkylating agent that crosslinks DNA, primarily at guanine N-7 positions, leading to DNA fragmentation and cell cycle arrest. It is cell cycle phase-nonspecific.

What the body does with it

Metabolism	Primarily hepatic metabolism via conjugation with glutathione (glutathione S-transferase, especially GSTA1) to form inactive metabolites. A minor pathway involves cytochrome P450 (not major).
Excretion	Primarily renal (30-60% unchanged drug), biliary/fecal (minor, <10%)
Half-life	Terminal half-life ~2.5 hours (range 2-3 hours); prolonged in hepatic impairment
Protein binding	~32% (albumin); minimal binding to other proteins
Volume of Distribution	0.6-0.8 L/kg; indicates distribution in total body water
Bioavailability	Oral: ~80% (extensive absorption, first-pass metabolism minimal)
Onset of Action	Oral: 1-2 hours for myelosuppression; busulfan level monitoring used for conditioning
Duration of Action	Myelosuppression persists 2-4 weeks; clinical effect on bone marrow lasts 3-6 weeks after oral dose

Classification & Brands

Dosing & administration

Dosage form	TABLET
Renal impairment	No specific GFR-based guidelines; monitor for myelosuppression. Avoid in severe renal impairment (CrCl <10 mL/min) due to potential accumulation. For CrCl 10-50 mL/min, consider dose reduction by 50% based on toxicity.
Liver impairment	Child-Pugh A: no adjustment required. Child-Pugh B: reduce dose by 50% and monitor toxicity. Child-Pugh C: avoid use or use with extreme caution, reduce dose by 75% and monitor closely.
Pediatric use	For conditioning: 1 mg/kg/dose (max 50 mg/dose) every 6 hours for 16 doses (total 16 mg/kg). For CML: 0.06-0.1 mg/kg/day initially, adjusted based on WBC response. Monitor blood counts closely.
Geriatric use	Start at lower end of dosing range (e.g., 50% of standard dose) due to increased risk of myelosuppression and renal/hepatic decline. Monitor CBCs weekly during dose titration.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for MYLERAN (MYLERAN).

Breastfeeding	No data available on M/P ratio. Contraindicated in breastfeeding due to potential severe adverse effects in nursing infants including myelosuppression and carcinogenesis.
Teratogenic Risk	Pregnancy category D. First trimester exposure associated with major congenital malformations including craniofacial, skeletal, and visceral anomalies. Second and third trimester exposure may cause intrauterine growth restriction, myelosuppression, and pancytopenia in the fetus. All trimesters carry risk of fetal loss.