MITOXANTRONE HYDROCHLORIDE

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

Mitoxantrone is a synthetic anthracenedione derivative that intercalates with DNA, inhibits topoisomerase II, and induces DNA strand breaks. It inhibits DNA and RNA synthesis, and has immunosuppressive activity by suppressing T-cell, B-cell, and macrophage functions.

What the body does with it

Metabolism	Mitoxantrone undergoes extensive hepatic metabolism, primarily by reduction to inactive mono- and dicarboxylic acid metabolites. It is also metabolized by cytochrome P450 enzymes (CYP2E1 and CYP3A4) to a lesser extent. Metabolites are excreted in bile and urine.
Excretion	Primarily hepatic (biliary/fecal) elimination (~73% of dose as unchanged drug and metabolites); renal excretion accounts for ~6-11% of unchanged drug.
Half-life	Terminal elimination half-life is approximately 23–60 hours (mean ~50 hours) in adults, with prolonged half-life in patients with hepatic impairment.
Protein binding	~78% bound to plasma proteins (primarily albumin).
Volume of Distribution	Large volume of distribution: approximately 1000–2000 L/m² (or ~14–28 L/kg) indicating extensive tissue binding.
Bioavailability	Not orally bioavailable; administered intravenously only.
Onset of Action	Intravenous: Clinical effect (e.g., tumor response) typically observed within 1–3 weeks after start of therapy.
Duration of Action	Duration of antineoplastic effect depends on regimen; myelosuppression nadir occurs at 10–14 days with recovery by day 21.

Classification & Brands

Dosing & administration

12 mg/m2 IV every 21 days as monotherapy; or 5-12 mg/m2 IV on days 1-3 in combination regimens for leukemia.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for mild to moderate impairment (GFR >10 mL/min). Severe impairment (GFR <10 mL/min): consider 50% dose reduction; not recommended if hemodialysis-dependent.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 25-50%. Child-Pugh C: contraindicated.
Pediatric use	For acute lymphoblastic leukemia (ALL): 6-10 mg/m2 IV daily for 3 days per cycle; for other solid tumors: 12 mg/m2 IV every 21 days.
Geriatric use	Increased risk of cardiotoxicity; consider starting at 75% of standard dose with close cardiac monitoring.

Use during pregnancy

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

Clinical note

Other cardiotoxic drugs increase risk Can cause severe myelosuppression and cardiotoxicity.

Breastfeeding	Not recommended due to potential serious adverse reactions in nursing infants. M/P ratio not determined; mitoxantrone has been measured in human milk at low concentrations.
Teratogenic Risk	Mitoxantrone is contraindicated in pregnancy. It is a potent teratogen. First trimester exposure is associated with major congenital malformations (e.g., skeletal, cardiac, CNS). Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and neonatal myelosuppression.

Warnings & precautions

■ FDA Black Box Warning

Mitoxantrone must not be used in patients with baseline left ventricular ejection fraction (LVEF) < 50% or with cumulative dose > 140 mg/m² due to risk of myocardial toxicity and congestive heart failure. It can cause secondary acute myeloid leukemia (AML) and should be used with caution in patients with prior cardiotoxic therapy.

Side Effect Profile

Common Effects	certain cancers
Serious Effects

Absolute Contraindications

["Hypersensitivity to mitoxantrone or components","Baseline LVEF < 50% or significant cardiac disease","Prior cumulative anthracycline or anthracenedione therapy (e.g., doxorubicin > 450 mg/m²)","Pregnancy and lactation","Severe hepatic impairment"]

Clinical Precautions

Precautions

["Cardiotoxicity: cumulative dose-dependent, monitor LVEF before each dose and after discontinuation; maximum cumulative lifetime dose is 140 mg/m²","Secondary acute myeloid leukemia (AML): reported in patients with MS and cancer; risk increases with cumulative dose","Myelosuppression: severe neutropenia, thrombocytopenia; monitor blood counts","Hepatotoxicity: monitor liver function tests","EMS-like syndrome (in MS patients): can occur years after therapy","Infusion reactions: urticaria, dyspnea, hypotension; premedicate with antihistamines and corticosteroids","Fetal harm: contraindicated in pregnancy; effective contraception required"]

Drug interactions

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MITOXANTRONE HYDROCHLORIDE

Clinical safety rating: avoid

Contraindicated (not allowed)

How it works

What the body does with it

Metabolism	Mitoxantrone undergoes extensive hepatic metabolism, primarily by reduction to inactive mono- and dicarboxylic acid metabolites. It is also metabolized by cytochrome P450 enzymes (CYP2E1 and CYP3A4) to a lesser extent. Metabolites are excreted in bile and urine.
Excretion	Primarily hepatic (biliary/fecal) elimination (~73% of dose as unchanged drug and metabolites); renal excretion accounts for ~6-11% of unchanged drug.
Half-life	Terminal elimination half-life is approximately 23–60 hours (mean ~50 hours) in adults, with prolonged half-life in patients with hepatic impairment.
Protein binding	~78% bound to plasma proteins (primarily albumin).
Volume of Distribution	Large volume of distribution: approximately 1000–2000 L/m² (or ~14–28 L/kg) indicating extensive tissue binding.
Bioavailability	Not orally bioavailable; administered intravenously only.
Onset of Action	Intravenous: Clinical effect (e.g., tumor response) typically observed within 1–3 weeks after start of therapy.
Duration of Action	Duration of antineoplastic effect depends on regimen; myelosuppression nadir occurs at 10–14 days with recovery by day 21.

Classification & Brands

Dosing & administration

12 mg/m2 IV every 21 days as monotherapy; or 5-12 mg/m2 IV on days 1-3 in combination regimens for leukemia.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment required for mild to moderate impairment (GFR >10 mL/min). Severe impairment (GFR <10 mL/min): consider 50% dose reduction; not recommended if hemodialysis-dependent.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 25-50%. Child-Pugh C: contraindicated.
Pediatric use	For acute lymphoblastic leukemia (ALL): 6-10 mg/m2 IV daily for 3 days per cycle; for other solid tumors: 12 mg/m2 IV every 21 days.
Geriatric use	Increased risk of cardiotoxicity; consider starting at 75% of standard dose with close cardiac monitoring.

Use during pregnancy

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

Clinical note

Other cardiotoxic drugs increase risk Can cause severe myelosuppression and cardiotoxicity.

Breastfeeding	Not recommended due to potential serious adverse reactions in nursing infants. M/P ratio not determined; mitoxantrone has been measured in human milk at low concentrations.
Teratogenic Risk	Mitoxantrone is contraindicated in pregnancy. It is a potent teratogen. First trimester exposure is associated with major congenital malformations (e.g., skeletal, cardiac, CNS). Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and neonatal myelosuppression.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Common Effects	certain cancers
Serious Effects

MITOXANTRONE HYDROCHLORIDE

How it works

What the body does with it

Classification & Brands

Dosing & administration

Use during pregnancy

Warnings & precautions

Side Effect Profile

Absolute Contraindications

Clinical Precautions

Drug interactions

MITOXANTRONE HYDROCHLORIDE

How it works

What the body does with it

Classification & Brands

Dosing & administration

Use during pregnancy

Warnings & precautions

Side Effect Profile

Absolute Contraindications

Clinical Precautions

Drug interactions

Clinical Tips & Counseling