Mitoxantrone

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals

-3.1

0.07

Warning

H351 (100%): Suspected of causing cancer [Warning Carcinogenicity]

P203, P273, P280, P318, P391, P405, and P501 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Chemotherapy with mitoxantrone alone is associated with serum enzyme elevations in up to 40% of patients, but these elevations are generally mild-to-moderate in severity, transient and not accompanied by symptoms or jaundice. Higher rates of liver enzyme elevations have been reported with combination chemotherapeutic regimens that include mitoxantrone. In high doses, mitoxantrone has been associated with a high rate of jaundice, but the degree of hyperbilirubinemia has been mild, transient and not associated with significant serum enzyme elevations or evidence of hepatitis. Rare instances of acute liver injury have been reported in patients taking mitoxantrone, including a single case of drug-rash with eosinophilia and systemic symptoms (DRESS). The latency to onset was 8 weeks and the pattern of serum enzyme elevations was cholestatic and later mixed. Immunoallergic features were prominent and appeared to respond to corticosteroid therapy. Other drugs were being taken and the association with mitoxantrone was not definite (Case 1). Thus, idiosyncratic and clinically apparent liver injury from mitoxantrone may occur but is quite rare.

Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity.

Mitoxantrone

Group 2B: Possibly carcinogenic to humans

Volume 76: (2000) Some Antiviral and Antineoplastic Drugs, and Other Pharmaceutical Agents

2000

1999

2B, possibly carcinogenic to humans. (L135)

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

mitoxantrone

DILI Positive

Intravenous

DOI:10.1016/j.drudis.2019.09.022

L01DB07

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity.

Hepatic

Hepatic Half Life: 75 hours

BZ114NVM5P

MITOXANTRONE

Established Pharmacologic Class [EPC] - Topoisomerase Inhibitor

Mechanisms of Action [MoA] - Topoisomerase Inhibitors

Mitoxantrone is a Topoisomerase Inhibitor. The mechanism of action of mitoxantrone is as a Topoisomerase Inhibitor.

MITOXANTRONE

Compounds capable of relieving pain without the loss of CONSCIOUSNESS.

Substances that inhibit or prevent the proliferation of NEOPLASMS.

Compounds that inhibit the activity of DNA TOPOISOMERASE II. Included in this category are a variety of ANTINEOPLASTIC AGENTS which target the eukaryotic form of topoisomerase II and ANTIBACTERIAL AGENTS which target the prokaryotic form of topoisomerase II.

Poorly absorbed following oral administration

1000 L/m2

21.3 L/hr/m2 [Elderly patients with breast cancer receiving IV administration of 15-90 mg/m2]

Use (kg) in USA (2002): 1

For the treatment of secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis. Mitoxantrone is an Anthracenedione (not an anthracycline) antineoplastic agent.