DRUG STUDY AND INFORMATION FORM Generic Name: Idarubicin Trade Name: Idamycin PFS Drug Class: Anthracyclines

and Anthracenediones (Antibiotics) Structure/Chemistry: Possess a tetracycline ring structure attached to a sugar, daunosamine, with quinone and hydroquinone moieties on adjacent rings that permit the gain and loss of electrons.

Pharmacodynamics

Mechanism of Action: Intercalates with DNA, directly affecting transcription and translation. Forms a tripartite complex with topoisomerase II and DNA and prevents re-ligation of doublestranded breaks made by topoisomerase II which leads to apoptosis. Also generates free radicals by formation of semiquinone radical intermediates from quinone groups that react with O2 to produce superoxide anion radicals (increased radical production in combination with iron).

Pharmacologic Effects: DNA damage through inhibition of re-ligation by topoisomerase II. Apoptosis due to p53 and caspases.

Drug Resistance or Tolerance: Overexpression of transcription-linked DNA repair, multidrug resistance, MRP (Multidrug Resistance-associated Proteins) transporter family, breast cancer resistance protein, increased glutathione peroxidase activity, decreased activity or mutation of topoisomerase II, and enhanced ability to repair DNA strand breaks.

Pharmacokinetics

Absorption: IV administration of 12 mg/m2/day for 3 days in combination with cytarabine.

Distribution: Rapidly enters heart, kidneys, lungs, liver, and spleen. Does not cross bloodbrain barrier.

Elimination: Idarubicin has a t1/2 of 15 hours. Idarubicinol has a t1/2 of 40 hours. Eliminated by metabolic conversion to a variety of aglycones and other inactive products. Biliary excretion. Delayed in presence of hepatic dysfunction.

Metabolism: Metabolized to idarubicinol, which accumulates in plasma and likely contributes signficantly to its activity.

Adverse Side Effects/Toxicity: Less cardiac toxicity in comparison to other anthracyclines subsequent to free radical generation (protection against via iron chelators [Dexrazoxane]), bone marrow suppression, stomatitis, alopecia, GI disturbances, and rash. Avoid extravasation.

Drug Interactions:

Therapeutic uses: Acute leukemias. Also used for AML (Acute myelogenous leukemia) in combination with Ara-C.

Miscellaneous: Derived from Streptomyces peucetius var. caesius. May impart red color to urine.