MITOXANTRONE HYDROCHLORIDE
Clinical safety rating: avoid
Contraindicated (not allowed)
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.
| 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. |
| Molecular Weight | 517.4 |
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. |
| 1st trimester | Contraindicated due to teratogenicity; avoid pregnancy. |
| 2nd trimester | Contraindicated due to fetal toxicity; avoid pregnancy. |
| 3rd trimester | Contraindicated due to fetal toxicity; avoid pregnancy. |
Clinical note
Other cardiotoxic drugs increase risk Can cause severe myelosuppression and cardiotoxicity.
| Placental transfer | Crosses the placenta; documented in animal and human studies. |
| Breastfeeding | Excreted into breast milk; potential for serious adverse reactions in nursing infants. Women should not breastfeed during therapy and for at least 1 month after last dose. |
| Lactation Rating |
■ 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.
| Common Effects | certain cancers |
| Serious Effects |
Hypersensitivity to mitoxantrone or any componentIntrathecal administrationSevere hepatic impairmentMyelosuppression with baseline absolute neutrophil count less than 1500 cells/mm³ (except for acute nonlymphocytic leukemia)
| 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 |
Loading safety data…
| L5 - Contraindicated |
| 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. |
| Fetal Monitoring | Monitor complete blood count, hepatic function, and cardiac function (LVEF) before and during therapy. Fetal monitoring includes ultrasound for growth and amniotic fluid volume in second/third trimester. If inadvertent use, refer to maternal-fetal medicine specialist. |
| Fertility Effects | Mitoxantrone can cause irreversible amenorrhea in premenopausal women due to ovarian toxicity. May reduce fertility. Men may experience oligospermia or azoospermia; effects may be transient or permanent. |
| Food/Dietary | Avoid grapefruit juice as it may increase mitoxantrone levels. No other significant food interactions. |
| Clinical Pearls | Monitor left ventricular ejection fraction (LVEF) prior to each dose; cumulative doses >140 mg/m2 increase cardiotoxicity risk. Pre-medicate with antiemetics due to high emetogenic potential. Avoid extravasation; if occurs, apply ice and elevate limb. Dose adjust for hepatic impairment (bilirubin >3 mg/dL). |
| Patient Advice | This medication may cause blue-green discoloration of urine and sclera for 24-48 hours; this is harmless. · Report any signs of infection (fever, sore throat) or bleeding (easy bruising, black stool) immediately. · Avoid grapefruit and grapefruit juice during treatment. · Do not receive live vaccines while on this drug. |