ALKERAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ALKERAN (ALKERAN).

How it works

Alkylating agent that crosslinks DNA, inhibiting DNA synthesis and transcription, leading to apoptosis.

What the body does with it

Metabolism	Primarily hydrolyzed spontaneously; minimal hepatic metabolism via CYP450 enzymes.
Excretion	Renal: 20–50% as unchanged drug and metabolites; fecal: minor (<10%); biliary: negligible.
Half-life	Terminal half-life: 1.5–2.5 hours (may extend to 4–5 hours in renal impairment); clinically relevant for dosing interval and myelotoxicity monitoring.
Protein binding	60–90% bound to albumin (alpha-1-acid glycoprotein involvement minor).
Volume of Distribution	0.4–0.8 L/kg; indicates distribution into total body water with some tissue binding.
Bioavailability	Oral: 56–85% (highly variable, dependent on food, first-pass metabolism).
Onset of Action	Oral: 7–10 days (with repeated doses); IV: 3–5 days.
Duration of Action	Oral: 3–4 weeks (nadir); IV: 4–5 weeks (nadir); suppression may persist until recovery of normal hematopoiesis.

Classification & Brands

Action Class	Alkylating agent
Brand Substitutes	Melfalax 2mg Tablet, Alkacel 2mg Tablet, Alphalan 2mg Tablet, Melphaz 2mg Tablet

Dosing & administration

Melphalan (Alkeran): 0.25 mg/kg/day orally for 4 consecutive days, repeated every 6 weeks; or 16 mg/m^2 IV over 15-20 minutes every 2 weeks for 4 doses, then every 4 weeks.

Dosage form	INJECTABLE
Renal impairment	For CrCl <60 mL/min: reduce oral dose by 50%; for CrCl <30 mL/min: avoid use or use extreme caution with dose reduction. For IV: CrCl ≥60 mL/min: full dose; CrCl 30-59 mL/min: reduce by 50%; CrCl <30 mL/min: not recommended.
Liver impairment	Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use or reduce dose by 75% with close monitoring.
Pediatric use	Children: 0.15 mg/kg/day orally for 4 consecutive days, repeated every 6 weeks; IV: 16 mg/m^2 every 2 weeks for 4 doses, then every 4 weeks. Adjust based on tolerance.
Geriatric use	Elderly patients (≥65 years): start at lower end of dosing range (e.g., 0.2 mg/kg/day orally for 4 days or 12 mg/m^2 IV) due to increased risk of myelosuppression, renal impairment, and comorbidities. Monitor blood counts closely.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ALKERAN (ALKERAN).

Breastfeeding	Melphalan is excreted into breast milk in low concentrations; M/P ratio unknown. Potential for severe adverse reactions (e.g., myelosuppression) in nursing infants. Breastfeeding is contraindicated during therapy and for at least 3 months after last dose.
Teratogenic Risk	Alkeran (melphalan) is embryotoxic and teratogenic in animals. In humans, first trimester exposure is associated with major congenital malformations (e.g., CNS, skeletal, cardiac). Second and third trimester exposure increases risk of fetal growth restriction, preterm birth, neonatal myelosuppression, and pancytopenia. Contraindicated in pregnancy unless critically necessary.

Warnings & precautions

■ FDA Black Box Warning

Melphalan is carcinogenic and mutagenic. It can cause severe bone marrow suppression and leukemogenic. Use with caution and monitor blood counts closely.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to melphalan, severe bone marrow suppression (unless for conditioning), concurrent radiotherapy (relative).

Clinical Precautions

Precautions	Bone marrow suppression (monitor CBC), hypersensitivity reactions, secondary malignancies, renal impairment (dose adjustment), pregnancy category D, fetal harm.
Food/Dietary	Grapefruit and grapefruit juice may alter melphalan metabolism and should be avoided. No other significant food interactions known. Alcohol may exacerbate hepatotoxicity and gastrointestinal adverse effects; limit or avoid consumption.

Clinical Tips & Counseling

Drug interactions

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ALKERAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ALKERAN (ALKERAN).

How it works

Alkylating agent that crosslinks DNA, inhibiting DNA synthesis and transcription, leading to apoptosis.

What the body does with it

Metabolism	Primarily hydrolyzed spontaneously; minimal hepatic metabolism via CYP450 enzymes.
Excretion	Renal: 20–50% as unchanged drug and metabolites; fecal: minor (<10%); biliary: negligible.
Half-life	Terminal half-life: 1.5–2.5 hours (may extend to 4–5 hours in renal impairment); clinically relevant for dosing interval and myelotoxicity monitoring.
Protein binding	60–90% bound to albumin (alpha-1-acid glycoprotein involvement minor).
Volume of Distribution	0.4–0.8 L/kg; indicates distribution into total body water with some tissue binding.
Bioavailability	Oral: 56–85% (highly variable, dependent on food, first-pass metabolism).
Onset of Action	Oral: 7–10 days (with repeated doses); IV: 3–5 days.
Duration of Action	Oral: 3–4 weeks (nadir); IV: 4–5 weeks (nadir); suppression may persist until recovery of normal hematopoiesis.

Classification & Brands

Action Class	Alkylating agent
Brand Substitutes	Melfalax 2mg Tablet, Alkacel 2mg Tablet, Alphalan 2mg Tablet, Melphaz 2mg Tablet

Dosing & administration

Melphalan (Alkeran): 0.25 mg/kg/day orally for 4 consecutive days, repeated every 6 weeks; or 16 mg/m^2 IV over 15-20 minutes every 2 weeks for 4 doses, then every 4 weeks.

Dosage form	INJECTABLE
Renal impairment	For CrCl <60 mL/min: reduce oral dose by 50%; for CrCl <30 mL/min: avoid use or use extreme caution with dose reduction. For IV: CrCl ≥60 mL/min: full dose; CrCl 30-59 mL/min: reduce by 50%; CrCl <30 mL/min: not recommended.
Liver impairment	Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use or reduce dose by 75% with close monitoring.
Pediatric use	Children: 0.15 mg/kg/day orally for 4 consecutive days, repeated every 6 weeks; IV: 16 mg/m^2 every 2 weeks for 4 doses, then every 4 weeks. Adjust based on tolerance.
Geriatric use	Elderly patients (≥65 years): start at lower end of dosing range (e.g., 0.2 mg/kg/day orally for 4 days or 12 mg/m^2 IV) due to increased risk of myelosuppression, renal impairment, and comorbidities. Monitor blood counts closely.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ALKERAN (ALKERAN).

Breastfeeding	Melphalan is excreted into breast milk in low concentrations; M/P ratio unknown. Potential for severe adverse reactions (e.g., myelosuppression) in nursing infants. Breastfeeding is contraindicated during therapy and for at least 3 months after last dose.
Teratogenic Risk	Alkeran (melphalan) is embryotoxic and teratogenic in animals. In humans, first trimester exposure is associated with major congenital malformations (e.g., CNS, skeletal, cardiac). Second and third trimester exposure increases risk of fetal growth restriction, preterm birth, neonatal myelosuppression, and pancytopenia. Contraindicated in pregnancy unless critically necessary.

Warnings & precautions

■ FDA Black Box Warning

Melphalan is carcinogenic and mutagenic. It can cause severe bone marrow suppression and leukemogenic. Use with caution and monitor blood counts closely.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to melphalan, severe bone marrow suppression (unless for conditioning), concurrent radiotherapy (relative).

Clinical Precautions

Precautions	Bone marrow suppression (monitor CBC), hypersensitivity reactions, secondary malignancies, renal impairment (dose adjustment), pregnancy category D, fetal harm.
Food/Dietary	Grapefruit and grapefruit juice may alter melphalan metabolism and should be avoided. No other significant food interactions known. Alcohol may exacerbate hepatotoxicity and gastrointestinal adverse effects; limit or avoid consumption.

Clinical Tips & Counseling

Drug interactions

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