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IDArubicin
Idarubicin is an analogue of daunorubicin. It is 5 to 6 times more potent than daunorubicin. The mechanism of action of anthracyclines is poorly understood. Cytotoxicity is generally attributed to intercalation of the drug into DNA and inhibition of DNA topoisomerase II activity resulting in double and single strand DNA breaks.
| Bioavailability |
Oral: Rapid but erratic absorption, about 35% bioavailability. |
Bone marrow, extensive tissue uptake and plasma protein binding
| Cross blood brain barrier? | yes |
| PPB | 97 % |
Mainly in liver
| Active metabolites | Idarubicinol |
| Inactive metabolites | yes |
Eliminated by biliary and renal excretion, mostly as idarubicinol.
| Feces | 17% (IV) 8% (oral) over 5 days |
| Urine | 16% (IV) 5% (oral) over 4 days |
| Half-life |
15 hours; 72 hrs for idarubicinol |
- Acute lymphocytic leukemia
- Acute non-lymphocytic leukemia
Refer to the product monograph for a full list and details of approved indications.
Emetogenic Potential:
Extravasation Potential: Vesicant
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Cardiovascular | Arrhythmia (rare, transient, or bundle branch block) | I | |||
| Heart failure (2%) (severe) | D L | ||||
| Myocarditis (rare) | E | ||||
| Pericarditis (rare) | E | ||||
| Venous thromboembolism | E | ||||
| Dermatological | Alopecia (75%) (usually partial) | E | |||
| Nail disorder | E | ||||
| Radiation recall reaction (rare) | I | ||||
| Rash | E | ||||
| Urticaria | E | ||||
| Gastrointestinal | Abdominal pain | E | |||
| Anorexia | E | ||||
| Dehydration | E | ||||
| Diarrhea | E | ||||
| Dyspepsia | E | ||||
| GI hemorrhage | E | ||||
| GI perforation (rare) | E | ||||
| Mucositis (50%) | E | ||||
| Nausea, vomiting (80%) | I | ||||
| Typhlitis (rare) | E | ||||
| Hematological | Hemorrhage | E | |||
| Myelosuppression (nadir 7-14 days, recovery 21-24 days) | E | ||||
| Hepatobiliary | ↑ LFTs (transient, 20-30%) | E | |||
| Hypersensitivity | Anaphylaxis (rare) | I | |||
| Infection | Infection | E | |||
| Sepsis | E | ||||
| Injection site | Injection site reaction (flare reaction - histamine release) | I | |||
| Phlebitis (chemical) | I | ||||
| Metabolic / Endocrine | Hyperuricemia | I | |||
| Neoplastic | Leukemia (secondary) | L | |||
| Reproductive and breast disorders | Infertility | E | |||
| Other (menopausal symptoms) | E | ||||
| Urinary | Urine discoloration (red, for 1-2 days) | I | |||
| Vascular | Flushing (facial; with rapid injection) | I | |||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare"
may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal
reports.
** I = immediate (onset in hours to days)
E = early (days to weeks)
D = delayed (weeks to months)
L = late (months to years)
Myelosuppression and cardiotoxicity are the major dose-limiting side effects.
Hyperuricemia during periods of active cell lysis, which is caused by cytotoxic chemotherapy of highly proliferative tumours of massive burden (e.g., some leukemias and lymphomas), can be minimized with allopurinol and hydration. In hospitalized patients the urine may be alkalinized, by addition of sodium bicarbonate to the IV fluids.
Acute life-threatening arrhythmias have been occasionally described during therapy. Cardiac toxicity is as described for other anthracyclines, manifested by congestive heart failure or by a decrease in left ventricular ejection fraction that may occur during or several weeks to years after therapy. There is no currently recommended maximum cumulative lifetime dose for idarubicin; however, cardiomyopathy was reported in 5% of patients who received cumulative idarubicin IV doses of 150 to 290 mg/m2. Cumulative oral doses of < 400mg/m2 have a low probability of cardiotoxicity. The risk of cardiotoxicity is increased with cardiac radiation, other cardiac abnormalities or prior exposure to anthracyclines, other cardiotoxic agents and trastuzumab; such patients should be carefully monitored.
The tissue necrosis that occurs with extravasation may happen days to weeks after the treatment. Patients must be observed for delayed reactions and prior injection sites carefully inspected. Local erythematous streaking along the vein and facial flushing may result from too rapid administration.
Idarubicin has the potential to enhance radiation injury to tissues. While often called radiation recall reactions, the timing of the radiation may be before, concurrent with or even after the administration of idarubicin. Recurrent injury to a previously irradiated site may occur weeks to months following radiation.
Refer to protocol by which patient is being treated.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline
Numerous dosing schedules exist and depend on disease, response and concomitant therapy. Consider prophylaxis with allopurinol and hydration for patients at risk of tumour lysis.
Guidelines for dosing also include consideration of white blood cell count. Dosage may be reduced and/or delayed in patients with bone marrow depression due to cytotoxic/radiation therapy.
Intravenous:
- q3w: 8 mg/m2 IV daily x 5 days (ANLL)
- q3w: 12 mg/m2 IV daily x 3 days (ANLL or ALL)
Dosage with changes in cardiac function:
- Discontinue at first sign of impaired cardiac function; investigate and treat appropriately.
Dosage with myelosuppression:
-
Modify according to protocol by which patient is being treated; if no guidelines available, refer to Appendix 6 "Dosage Modification for Hematologic and Non-Hematologic Toxicities."
Management of Infusion-related reactions with Anthracyclines:
| Grade | Management | Re-challenge |
| 1 or 2 |
|
|
| 3 or 4 |
|
|
Do not treat with severe hepatic impairment.
|
Bilirubin (µmol/L) |
% usual dose |
|
> 40-85 |
50% |
|
>85 |
OMIT |
|
Creatinine (µmol/L) |
% usual dose |
|
> 200 |
50% |
|
Severe impairment |
Discontinue |
There is an increased rate of adverse events in patients ≥ 60 years (cardiac).
- 8-10 mg/m2/day IV x 3 days. Children may be more at risk of developing cardiac toxicity.
Intravenous
- Slow push through sidearm of free flowing IV (5% Dextrose, Normal Saline, or 2/3-1/3); Give over 5-10 minutes.
- Direct IV push not recommended due to risk of extravasation
- Slow down injection rate if erythematous streaking or facial flushing occurs.
- Diluents containing bacteriostatic agents are not recommended.
- When admixed with heparin, precipitation may occur.
The oral dosage form has been discontinued by the manufacturer.
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
Other Drug Properties:
-
Carcinogenicity:
Yes
-
Mutagenicity:
Yes
-
Genotoxicity:
Yes
-
Embryotoxicity:
Yes
-
Fetotoxicity:
Yes
-
Teratogenicity:
Documented in animals
Idarubicin is not recommended for use in pregnancy.
- Adequate contraception should be used by patients who can become pregnant and their partners during treatment, and for at least 6.5 months after the last dose.
- Adequate contraception should be used by patients who produce sperm and their partners during treatment, and for at least 3.5 months after the last dose.
-
Excretion into breast milk:
Likely
Breastfeeding is not recommended during treatment and for 14 days after the last dose.
-
Fertility effects:
Probable
Idarubicin is contraindicated in patients with a history of allergic reactions to the drug, its excipients or other anthracyclines or anthracenediones, pre-existing myelosuppression, severe renal and liver impairment, uncontrolled infections, recent myocardial infarction, severe cardiac disease, severe arrhythmias, or prior maximal cumulative lifetime doses of anthracyclines or anthracenediones. Do not use live vaccines.
Cardiac toxicity is cumulative across members of the anthracycline (doxorubicin, epirubicin, daunorubicin, idarubicin) and anthracenedione (mitoxantrone) classes of drugs. Patients who have received these agents are at increased risk of toxicity, and should be carefully monitored. The cumulative doses are lower in patients who have received radiation to the mediastinal area or concomitant therapy with other cardiotoxic agents such as cyclophosphamide.
No formal interaction studies have been performed to date. Since idarubicin is an anthracycline it may interact with radiation and drugs in a manner similar to doxorubicin. Please refer to the Doxorubicin monograph for details.
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| Other cardiotoxic drugs (ie. trastuzumab cyclophosphamide, paclitaxel) | ↑ risk of cardiotoxicity | Additive cardiotoxic effects | Avoid. Monitor cardiac function if must use. Avoid use for ≥ 24 weeks after stopping trastuzumab. |
| Drugs that suppress cardiac contractility (ie. Verapamil) | May exacerbate cardiotoxicity | Caution; monitor cardiac function closely | |
| Medications that may cause GI complications (ie. NSAIDS) | ↑ risk of gastrointestinal perforation or bleeding (associated with oral idarubicin) | Caution |
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
| Monitor Type | Monitor Frequency |
|---|---|
| Renal function tests | Baseline and regular |
| Liver function tests | Baseline and regular |
| CBC | Baseline and regular |
Cardiac tests for all patients with cardiac risk factors, or patients at or above 150mg/m2 IV cumulative dose |
periodic |
Clinical toxicity assessment for cardiac failure, infection, GI toxicity |
At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
| Monitor Type | Monitor Frequency |
|---|---|
| Cardiac function tests (Echo, RNA and/or MUGA scans), especially in patients with risk factors for cardiotoxicity | Baseline |
Cancer Drug Manual (the Manual), 1994, British Columbia Cancer Agency (BCCA)
Idarubicin: Micromedex® Healthcare Series. Accessed March 5, 2009.
Prescribing information: idarubicin. Pfizer Labs (US), April 2022.
Product Monograph: idarubicin. Pfizer Canada, February 2009 and September 2022.
Summary of product characteristics: Idarubicin. Pfizer Ltd (UK), Sep 2022.
October 2023 Modified Indications and Pregnancy/lactation sections
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
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