idarubicin (Rx)

>10%

Infection (95%)

Nausea (30-60%)

Vomiting (30-60%)

Alopecia (25-30%)

Hemorrhage (63%)

Stomatitis (11%)

Fever (26%)

Elevated bilirubin and transaminases (20-30%)

Myelosuppression: > 10%

1-10%

Seizure (4%)

CHF (2%)

Peripheral neuropathy (8%)

Frequency Not Defined

Fever

Chills

Headache

Flushing

Myocardial infarction

Cardiac dysrhythmia

Chest pain

Diarrhea

Inflammatory disease of mucous membrane

Hyperuricemia

Red discoloration of urine

Rash

Contraindications

Hypersensitivity

Serum bilirubin >5 mg/dL [>85.5 umol/L]

Cautions

Vesicant-avoid extravasation

Risk of myocardial toxicity leading to potentially fatal CHF; pre-existing heart disease and previous therapy with anthracyclines at high cumulative doses or other potentially cardiotoxic agents are co-factors for increased risk of cardiac toxicity; benefit to risk ratio of idarubicin therapy in such patients should be weighed before starting treatment

Monitor cardiac function during treatment in order to minimize risk of cardiac toxicity of the type described for other anthracycline compounds

Prior radiation treatment to mediastinal-pericardial area & prior anthracyclines increases cardiotoxic risk

Cumulative doses >150 mg/m² associated with decreased ejection fraction

Possibility of injection site reactions

Use caution in hepatic/renal impairment; dose reduction may be necessary

Not for administration to patients with pre-existing bone marrow suppression induced by previous drug therapy or radiotherapy unless the benefit warrants the risk

Due to the increased risk of cardiotoxicity, avoid concomitant use until cardiotoxic agent has been discontinued for at least 5 half-lives; specifically avoid therapy for up to 7 months after stopping trastuzumab

Avoid pregnancy

Pregnancy

There is no conclusive information about therapy adversely affecting human fertility or causing teratogenesis; there has been one report of a fetal fatality after maternal exposure to drug during second trimester

There are no adequate and well-controlled studies in pregnant women; drug should be used during pregnancy only if potential benefit justifies potential risk to fetus

If drug is to be used during pregnancy, or if patient becomes pregnant during therapy, patient should be apprised and informed of potential hazard to fetus

Women of childbearing potential should be advised to avoid pregnancy and advised to use effective contraception during treatment and for at least 6.5 months after the last dose

Men with female partners of childbearing potential should be advised to use effective contraception during treatment and for at least 3.5 months after last dose

Both men and women should seek advice for fertility preservation before treatment

Animal data

• Drug was embryotoxic and teratogenic in rat at dose of 1.2 mg/m2/day or one tenth the human dose, which was nontoxic to dams; Drug was embryotoxic but not teratogenic in rabbit even at a dose of 2.4 mg/m2/day or two tenths the human dose, which was toxic to dams

Lactation

Not known whether drug is excreted in human milk; because many drugs are excreted in human milk and because of potential for serious adverse reactions in nursing infants from drug, mothers should discontinue nursing prior to taking drug

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Anthracycline; intercalates between DNA base pairs, inhibits topoisomerase II, which in turn inhibits DNA and RNA synthesis

Pharmacokinetics

Half-Life: 14-35 hr (PO); 12-27 hr (IV)

Bioavailability: 30%

Protein Bound: 94-97%

Vd: 64 L/kg

Peak plasma time: 1-5 hr

Metabolism: Liver

Metabolites: Idarubicinol

Clearance: 122.8 L/hr

Excretion: Urine (5-13%)

IV Incompatibilities

Additive: heparin

Syringe: heparin

Y-site: acyclovir, allopurinol, ampicillin/sulbactam, cefazolin, cefepime, ceftazidime, clindamycin, dexamethasone Na-phosphate, etoposide, fluorouracil, furosemide, gentamicin, heparin, hydrocortisone Na-succinate, lorazepam, meperidine, methotrexate, piperacillin/tazobactam, Na-bicarb, teniposide, vancomycin, vincristine

IV Compatibilities

Solution: with most common diluents

Y-site (partial list): cimetidine, diphenhydramine, etoposide PO4, granisetron, MgSO4, metoclopramide, KCl

IV Preparation

Vials: reconstitute with NS to a concentration of 1 mg/mL

Standard dilution

• IV push: dose/syringe (concentration is 1 mg/mL); maximum syringe size for IVP is 30 mL syringe & syringe should be <75% full
• IVPB: dose/100 mL D5W or NS

IV Administration

Vesicant

Administer by intermittent infusion over 10-15 min

Administer into a free flowing IV solution of NS or D5W

Local erythematous streaking along the vein may indicate rapid administration

Extravasation Management

Topical cooling may be achieved using ice packs or cooling pad with circulating ice water

Cooling of site for 25 hr as tolerated by pt.

Elevate & rest extremity 24-48 hr, then resume normal activity as tolerated

Cold inhibits vesicant's cytotoxicity

Heat can be harmful & is contraindicated

If pain, erythema, &/or swelling persist beyond 48 hr, refer pt immediately to plastic surgeon for consultation & possible debridement

See also Totect

Storage

Store intact vials of lyophilized powder at room temp

Protect from light