IDArubicin (Monograph)

Brand name: Idamycin PFS
Drug class: Antineoplastic Agents
VA class: AN200
Chemical name: (7S-cis)-9-Acetyl-7-[(3-amino-2,3,6-trideoxy-α-l-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,9,11-trihydroxyhydrochloride-5,12-naphthacenedione
Molecular formula: C₂₆H₂₇NO₉HCl
CAS number: 57852-57-0

Introduction

Antineoplastic agent;¹ semisynthetic anthracycline; structurally and pharmacologically related to daunorubicin.¹

Uses for IDArubicin

Acute Myeloid Leukemia

Used in combination with other antineoplastic agents for the treatment of acute myeloid (myelogenous, nonlymphocytic) leukemia (AML), including French-American-British classifications M1 through M7.^{1 7 10 16 21}

Regimen consisting of cytarabine with either daunorubicin or idarubicin is a regimen of choice for remission induction in AML.^{7 10}

Used in combination with cytarabine for the treatment of recurrent or refractory AML.^{7 13 14}

IDArubicin Dosage and Administration

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastic drugs.

• Monitor serum creatinine and bilirubin concentrations prior to initiating and during idarubicin therapy.¹

Administration

IV Administration

Administer by slow IV injection into the tubing of a freely flowing IV infusion of 0.9% sodium chloride or 5% dextrose injection.¹ Attach tubing to a butterfly needle or other suitable device and preferably insert into a large vein.¹

Must not administer IM or sub-Q.¹

Avoid extravasation.¹ Extremely irritating to tissues.¹ Stinging or burning sensation during IV administration may be a symptom, but extravasation may occur without these symptoms and even when blood returns well during initial aspiration of the infusion needle.¹ If signs or symptoms of extravasation occur (i.e., pain, erythema, edema, vesication), immediately discontinue administration and restart in another vein;¹ apply intermittent ice packs (immediately for 30 minutes, then 30 minutes 4 times daily for 3 days) over the affected area and elevate the involved extremity.¹ Examine affected area frequently and promptly consult specialist in plastic surgery.¹ In case of ulceration or severe persistent pain at the site of extravasation, consider early wide excision of the affected area.¹ (See Local Effects under Cautions.)

Prepare and handle cautiously to avoid skin reactions.¹ Use of goggles, gloves, and protective gowns recommended during preparation and administration.¹ If skin contact occurs, thoroughly wash affected areas with soap and water; if eye contact occurs, standard irrigation techniques should be used immediately.¹

Rate of Administration

Administer slowly (i.e., over 10–15 minutes) into a freely flowing IV infusion of 0.9% sodium chloride or 5% dextrose injection.¹

Dosage

Available as idarubicin hydrochloride; dosage expressed in terms of the salt.¹

Adults

Acute Myeloid Leukemia

Induction Therapy

IV

12 mg/m² daily for 3 days in combination with cytarabine 100 mg/m² daily by continuous IV infusion for 7 days.¹

Alternatively, 12 mg/m² daily for 3 days in combination with cytarabine (25-mg/m² IV loading dose followed by 200 mg/m² daily) by continuous IV infusion for 5 days.^{1 3}

A second induction course may be administered in the event of an incomplete antileukemic response after the first course.¹

Consolidation Therapy

IV

Patients who have complete remission of disease following 1 or 2 courses of induction therapy generally receive consolidation chemotherapy.^{7 21} The optimal regimen has not been established, but in clinical studies, consolidation chemotherapy typically consists of a cytarabine-based regimen similar to that used in induction therapy administered over a short-term period.^{1 7}

Dosage Modification for Toxicity

IV

In patients who experience severe mucositis with the first course of induction therapy, delay administration of a second course until the mucositis resolves and reduce dosage by 25%.^{1 22}

Special Populations

Hepatic Impairment

Consider dosage reduction; monitor hepatic function.¹ Administration not recommended in patients with serum bilirubin concentration >5 mg/dL.¹ (See Hepatic Impairment under Cautions.)

In one clinical study, patients with serum bilirubin concentration of 2.6–5 mg/dL received 50% of the recommended dosage.¹

Renal Impairment

Consider dosage reduction; monitor renal function.¹ (See Renal Impairment under Cautions.)

Cautions for IDArubicin

Contraindications

Serum bilirubin concentration >5 mg/dL.¹

Warnings/Precautions

Warnings

Adequate Patient Evaluation and Monitoring

Administer only under the supervision of qualified clinicians experienced in the use of cytotoxic agents for leukemia therapy.¹ Close observation of the patient and careful laboratory monitoring are required; appropriate diagnostic and treatment facilities must be readily available in case the patient develops severe hemorrhagic conditions, infection, or other drug toxicity.¹

Prior to and during therapy, assess hepatic and renal function; carefully assess hematopoietic and cardiac function during therapy.¹

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenic and embryotoxic in animals.¹ Avoid pregnancy during therapy.¹ If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.¹

Major Toxicities

Hematologic Effects

Severe and potentially fatal myelosuppression occurs following adminstration of therapeutic dosages.¹ Careful hematologic monitoring required; perform CBCs at frequent intervals during therapy.¹

Use generally not recommended in patients with preexisting bone marrow suppression caused by previous drug or radiation therapy unless the potential benefit outweighs the risk.¹

Cardiac Effects

Risk of anthracycline-associated cardiotoxicity manifested by potentially fatal CHF, acute life-threatening arrhythmias (e.g., atrial fibrillation), MI, chest pain, asymptomatic decreases in left ventricular ejection fraction, or other cardiomyopathies.¹

Cardiac insufficiency and arrhythmias generally reversible; usually occur in setting of sepsis, anemia, and aggressive IV fluid administration.¹

Increased risk of cardiotoxicity in patients >60 years of age, patients with preexisting cardiac disease, or those who have received prior therapy with anthracyclines or other cardiotoxic agents.¹ Possible increased risk in patients with concomitant or previous radiation therapy to the mediastinal-pericardial area or in patients with anemia, bone marrow suppression, infections, or leukemic pericarditis and/or myocarditis.¹

Risk of anthracycline-induced cardiotoxicity increases with increasing dose; a cumulative dose of idarubicin beyond which the incidence of cardiotoxicity rapidly increases has not been determined.²

Monitor cardiac function carefully, particularly in those patients at increased risk for cardiotoxicity.¹ Anthracyline-induced cardiomyopathy usually is associated with a decrease in left ventricular ejection fraction from pretreatment baseline values.¹ Institute appropriate therapeutic measures for the management of CHF and/or arrhythmias as clinically indicated.¹

General Precautions

Hyperuricemia

Hyperuricemia may result from the rapid lysis of leukemic cells.¹ Appropriate measures should be taken to prevent the occurrence of hyperuricemia.¹

GI Effects

Nausea and/or vomiting, abdominal pain and/or diarrhea, and mucositis reported frequently, but were severe in <5% of patients.¹ Delay subsequent administration and reduce dosage if severe mucositis occurs.¹ (See Dosage Modification for Toxicity under Dosage and Administration.)

Hepatic Effects

Changes in liver function test results reported; usually transient and tended to occur in patients with sepsis who were receiving potentially hepatotoxic anti-infective agents.¹

Renal Effects

Changes in renal function test results reported; usually transient and tended to occur in patients with sepsis who were receiving potentially nephrotoxic anti-infective agents.¹

Local Effects

Extravasation produces severe tissue necrosis.¹ If signs or symptoms of extravasation occur (i.e., pain, erythema, edema, vesication), immediately discontinue administration and restart in another vein.¹ (See Administration under Dosage and Administration.)

Urticaria, hives, and erythematous streaking reported.¹

Specific Populations

Pregnancy

Category D.¹

Lactation

Not known whether idarubicin is distributed into milk.¹ Discontinue nursing because of potential risk to nursing infants.¹

Pediatric Use

Safety and efficacy not established.¹

Geriatric Use

Increased risk of cardiovascular toxicity including CHF, serious arrhythmias, chest pain, MI, and asymptomatic declines in left ventricular ejection fraction in patients >60 years of age.¹

Hepatic Impairment

Pharmacokinetics have not been fully evaluated.¹ However, possible decreased metabolism and increased systemic exposure in patients with moderate or severe hepatic dysfunction.¹ Consider dosage adjustment.¹ Use not recommended in patients with serum bilirubin concentration >5 mg/dL.¹ (See Contraindications under Cautions.)

Renal Impairment

Pharmacokinetics have not been fully evaluated.¹ However, disposition of idarubicin may be altered; consider dosage adjustment.¹

Common Adverse Effects

Infection, nausea, vomiting, hair loss, abdominal cramps/diarrhea, hemorrhage, mucositis, mental status changes, fever, headache.¹

No formal drug interaction studies to date.¹

Specific Drugs

IDArubicin Pharmacokinetics

Distribution

Extent

Rapidly and widely distributed into tissues following IV administration.¹ Concentrations in nucleated blood and bone marrow cells exceed plasma concentrations by more than 100 times.¹

Following IV administration in pediatric patients, idarubicin and idarubicinol were detected in CSF.^{1 20}

Not known whether idarubicin is distributed into milk.¹

Plasma Protein Binding

Idarubicin: Approximately 97%.¹

Idarubicinol: Approximately 94%.¹

Elimination

Metabolism

Metabolized principally to an active metabolite, idarubicinol, via aldoketoreductase.¹ Undergoes extensive extrahepatic metabolism.¹

Elimination Route

Excreted principally in feces via biliary excretion and to a lesser extent in urine.¹

Half-life

Idarubicin: Terminal half-life is approximately 15 hours.¹

Idarubicinol: Terminal half-life is approximately 72 hours.¹

Stability

Storage

Parenteral

Injection

2–8°C; protect from light.¹

Compatibility

Parenteral

Solution CompatibilityHID

Do not mix with other drugs (unless specific compatibility data are available).¹ Precipitation occurs when mixed with heparin; prolonged contact with any alkaline solution will cause degradation of idrarubicin.¹

Drug Compatibility

Actions

• A DNA-reactive agent, although the exact mechanism(s) of action has not been fully elucidated.¹

• Intercalates into DNA and/or inhibits topoisomerase II, resulting in disruption of nucleic acid synthesis.^{1 2}

• Compared with other anthracyclines, is more lipophilic, and consequently undergoes more rapid cellular uptake.¹

Advice to Patients

• Importance of recognizing and reporting adverse effects, including GI, and myelosuppresive (and related precautions), infectious complications, CHF symptoms, and injection site pain.¹

• Risk of myocardial toxicity.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy and advise pregnant women of risk to the fetus.¹

• Importance of advising patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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