- It is recommended to administer idarubicin gradually as a freely flowing intravenous infusion. It should never be administered subcutaneously or intramuscularly. If there is extravasation during administration, severe local tissue necrosis may develop.
- Administering Idarubicin can result in cardiac toxicity and congestive heart failure, similar to other anthracyclines. Patients with any pre-existing cardiac disease or those who have previously received anthracyclines are more likely to experience cardiac toxicity.
- Idarubicin causes severe myelosuppression when used at therapeutically effective doses, as is typical with antileukemic drugs.
- Suppose a patient is compromised by drug toxicity. In that case, it is advised that Idarubicin be administered only under the supervision of a physician with experience in leukemia chemotherapy and in facilities equipped with sufficient laboratory and supportive resources to monitor drug tolerance. In cases of severe hemorrhagic conditions and/or overwhelming infection, the physician and the institution must be able to respond promptly and thoroughly.
- The dosage should be lowered in patients with impaired renal or hepatic function.
Allopathy
Prescription Required
DCGI (Drugs Controller General of India)
Schedule H
Idarubicin is an antineoplastic agent belonging to the pharmacological class of anthracycline antibiotics.
The FDA approves Idarubicin for Acute Myeloid Leukemia(AML) in adults.
After administration, idarubicin absorbs quickly (18–39% bioavailability). It spreads widely and binds firmly to plasma proteins. It is changed into the active metabolite idarubicinol by hepatic metabolism. Excretion is primarily in urine (30%) and faeces (61%).
The most common side effects of Idarubicin include vomiting, nausea, infection, hair loss, and fever.
Idarubicin is available as an injectable solution.
The molecule is available in India, the United States, Canada, countries within the European Union, Australia, Japan and South Korea.
Idarubicin is an antineoplastic agent belonging to the pharmacological class of anthracycline antibiotics.
Several possible mechanisms of action for idarubicin's cytotoxic and antimitotic effects have been proposed. By stabilizing the DNA-topoisomerase II complex and preventing the religation step of the ligation-religation reaction that topoisomerase II catalyzes, idarubicin forms complexes with DNA through base pair intercalation. This inhibits topoisomerase II activity.
Several possible mechanisms of action for idarubicin's cytotoxic and antimitotic effects have been proposed. By stabilizing the DNA-topoisomerase II complex and preventing the religation step of the ligation-religation reaction that topoisomerase II catalyzes, idarubicin forms complexes with DNA through base pair intercalation. This inhibits topoisomerase II activity.
Injectable solutions: To be administered parenterally as applicable.
The physician recommends taking this medication once daily, with or without food.
Blood cancer (Acute lymphocytic leukaemia)
Parenterally: Administer idarubicin as an intermittent infusion into a freely flowing IV solution of either 5% dextrose in water (D5W) or normal saline (NS) for 10 to 15 minutes. If the vein exhibits localized erythematous streaking, prompt administration may be necessary. Use topical cooling with ice packs or cooling pads with ice water circulating in case of extravasation. As long as the patient tolerates it, apply cooling for 25 hours. Return to regular activities after elevating and resting the affected limb for 24 to 48 hours. Heat is not advised and may even be harmful, but cold reduces the cytotoxicity of the vesicant. Referred the patient promptly to a plastic surgeon for consultation and potential debridement if the patient's pain, erythema, and/or swelling persist after 48 hours.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
Idarubicin is available as an injectable solution.
Dose Adjustment in Adult Patients:
Acute Myeloid Leukemia
Induction: 12 mg/m² IV every Day over 10 to15 min for 3 days with concomitant cytarabine
Consolidation: 10 to 12 mg/m²/day IV for 2 days
While using Idarubicin, adhere to dietary recommendations. Consume a balanced diet featuring nutrient-rich fruits, vegetables, and low-fat proteins (e.g., lean meats, fish, poultry). Stay adequately hydrated with a daily water intake, as specific cancer treatments may lead to dehydration.
The dietary restriction should be individualized as per patient requirements.
- Hypersensitivity to Idarubicin, its excipients, or other anthracyclines or anthracenediones (i.e., epirubicin, daunorubicin, mitoxantrone, mitomycin C)
- Total bilirubin >86 mcmol/L2
- Pregnancy
- Potentially fatal CHF risk: It is advised to assess prior anthracycline therapy, heart disease history, and the benefit-to-risk ratio before treatment.
- When taking an anthracycline, keep a close watch on the cardiovascular system to reduce potential toxicity.
- Anthracycline therapy or prior radiation therapy increases the risk of cardiotoxicity; cumulative doses exceeding 150 mg/m² are linked to a reduced ejection fraction.
- Risk of adverse reactions at the injection site; exercise caution in case of any liver or renal impairment, as this could require lowering your dosage.
- Unless the benefits outweigh the risks, administration should be avoided in patients with bone marrow suppression.
- Take caution when using medications concurrently, especially after stopping cardiotoxic medications like trastuzumab; therapy should be avoided for up to seven months after stopping trastuzumab.
Alcohol Warning
Breast Feeding Warning
Pregnancy Warning
Food Warning
The adverse reactions related to Idarubicin can be categorized as:
- Common Adverse Effects: Myelosuppression, infection, nausea, vomiting, alopecia, bleeding, stomatitis, fever, and elevated bilirubin and transaminases.
- Less Common Adverse Effects: Seizure, CHF, Peripheral neuropathy
- Rare Adverse Effects: Severe cardiac toxicity, leading to congestive heart failure and secondary malignancies.
The clinically relevant drug interactions of Idarubicin are briefly summarized here.
Additive myelosuppressive effects in combination with other agents (e.g., anti-cancer drugs) that function similarly. Increased risk of cardiotoxicity when combined with other cardioactive substances (like Ca channel blockers) or cardiotoxic other medicines (like trastuzumab, cyclophosphamide, and paclitaxel).
Potentially fatal: Serious infections could arise from administering live or live-attenuated vaccines simultaneously.
The common side effects of Idarubicin include:
Gastrointestinal effects: Vomiting, nausea, and loss of appetite. Systemic responses: Fever, weakness, pale skin, and headache.
Injection-related issues: Pain at the injection site.
Hepatic alterations: Increased liver enzymes.
Neurological symptoms: Peripheral neuropathy (tingling and numbness), stomatitis (mouth inflammation), bleeding, and myelosuppression (decreased blood cell counts)
- Pregnancy
Pregnancy Category D (FDA): Use in cases where no safer medication is available and life is in danger. Positive evidence of prenatal risk in humans.
There is one report of a fetal death following mother drug exposure during the second trimester, but there is insufficient proof that therapy adversely affects human fertility or causes teratogenesis.
Pregnant women should not use drugs unless the possible benefit outweighs the potential risk to the fetus due to the lack of sufficient and well-controlled studies in this regard.
Patients should be made aware of any possible risks to the developing fetus if drugs are to be taken during pregnancy or if they become pregnant while receiving therapy.
During treatment and for at least 6.5 months following the last dose, women who are or may become pregnant should be advised to avoid getting pregnant and to use effective contraception.
It is recommended that men who have female partners who are capable of having children use effective contraception both during their treatment and for a minimum of 3.5 months after their last dose.
Before beginning treatment, men and women should consult a fertility preservation expert. Afterwards, they should seek out genetic counselling.
Animal data
In rats, the drug was teratogenic and embryotoxic at 1.2 mg/m2/day, or one-tenth the human dose, but it was not toxic to dams. In rabbits, the drug was toxic to dams even at a dose of 2.4 mg/m2/day or two-tenths the human dose.
- Nursing Mothers
Although it is unknown if the medication is excreted in human milk, mothers should stop nursing before taking the medication and refrain from breastfeeding for 14 days following the last dose because many drugs are excreted in human milk and can have serious adverse effects on nursing infants.
- Pediatric Use
The safety and effectiveness of Idarubicin in pediatric patients have not been established.
Dose Adjustments
Acute Myeloid Leukemia
10-12 mg/m² IV every Day for 3 days q3weeks
- Geriatric Use
Compared with younger patients, patients over 60 receiving induction therapy were more likely to experience asymptomatic decreases in LVEF, congestive heart failure, severe arrhythmias, chest pain, and myocardial infarction.
Dose Adjustment in Kidney Impairment Patients:
Children
75% of the dose if CrCl < 50 mL/min
Dialysis peritoneal: 75% of dosage
75% of the dose in hemodialysis
75% of the dose of renal replacement therapy
Adults
10–50 mL/min CrCl: 75% of the dose
50% of the dose if CrCl < 10 mL/min
Hemodialysis: No need for an additional dosage
Supplemental dosage is not required for peritoneal dialysis
Dose Adjustment in Hepatic Impairment Patients:
Bilirubin: 50% of the dose, 2.6–5 mg/dL
Use with caution if bilirubin >5 mg/dL.
Signs and Symptoms
Overconsumption of Idarubicin could lead to Acute myocardial toxicity (e.g. cardiac failure, severe arrhythmias), severe myelosuppression, and increased severity of gastrointestinal toxicity.
Management
In the event of an Idarubicin overdose, supportive and symptomatic care must be started as soon as possible, and administration must stop immediately. Reverse-barrier nursing, blood transfusions, and antibiotic administration are examples of supportive measures. It's also essential to treat symptomatic mucositis. It is unlikely that traditional peritoneal or hemodialysis will significantly alter therapeutic efficacy or toxicity due to the characteristics of idarubicin, which include extensive extravascular distribution, tissue binding, and a low unbound fraction in the plasma pool. The management of Idarubicin overdose requires frequent monitoring and the use of suitable supportive interventions.
Pharmacodynamics
Idarubicin interacts with DNA by inhibiting topoisomerase II, breaking DNA strands, and intercalating. These medications, derived from natural sources and antibiotics, are notably toxic because they lack the specificity of antimicrobial antibiotics. Idarubicin and other anthracyclines are essential antitumor medications; doxorubicin is primarily used to treat solid tumours, while daunorubicin and idarubicin are only used to treat leukaemia. Idarubicin may disrupt the regulation of gene expression, inhibit polymerase activity, and damage DNA with free radicals. Phenotypic anthracenes have antitumor effects on various tumours and are not cycle-specific.
Pharmacokinetics
- Absorption: Oral administration of idarubicin results in fast absorption with an absolute bioavailability of 18% to 39%. The peak plasma concentration is reached 2-4 hours after oral administration.
- Distribution: Intravenous administration of idarubicin distributes quickly throughout the body tissues. It has high plasma protein binding, with 97% of the drug and 94% of its active metabolite, idarubicinol.
- Metabolism: There is extensive hepatic metabolism, which mainly breaks down idarubicin into its active metabolite.
- Excretion: When taken orally, the drug is mainly eliminated through the urine (30%) and faeces (61%), with only 1-2% remaining as unchanged drugs. Idarubicin has a half-life in the terminal plasma that varies from 10 to 35 hours. Biliary and, to a lesser extent, urinary excretion are the main processes involved in intravenous administration. Idarubicin's terminal half-life is fifteen hours, while idarubicinol's is seventy-two hours. Idarubicin has a plasma half-life of roughly 20–22 hours, while idarubicin has a half-life of 45 hours.
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- US Food and Drug Administration (FDA) [Internet]. Maryland. USA; Package leaflet information for the user; Idamycin PFS® (idarubicin hydrochloride)
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/050734s027lbl.pdf
- http://www.bccancer.bc.ca/drug-database-site/Drug Index/Idarubicin_monograph.pdf
