:
Imi 30, NSC-256439
IDAMYCIN(r)
:
Antitumour antibiotic
Special pediatric considerations are noted when applicable, otherwise adult provisions apply.
:
[1]
Idarubicin is an anthracycline analogue of daunorubicin. It is 5 to 6 times more potent and less cardiotoxic than daunorubicin. The mechanism of action of anthracyclines is poorly understood. Cytotoxicity is generally attributed to intercalation of the drug into DNA and/or inhibition of DNA topoisomerase II activity resulting in double and single strand DNA breaks.
:
[2,3,4,5,6,7,8]
| Oral Absorption | rapid but erratic absorption, about 30% bioavailability | |
| Distribution | bone marrow, extensive tissue uptake and plasma protein binding | |
| cross blood brain barrier? | yes | |
| Vd | 64 L/kg | |
| PPB | 94-97% | |
| Metabolism | mainly in liver | |
| active metabolite(s) | idarubicinol | |
| inactive metabolite(s) | yes | |
| Excretion | 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 | |
| t1/2 a | 5-30 minutes | |
| t1/2 b | 1-22 hours | |
| t1/2 g | 15-35 hours | |
| Cl | 122.8 L/hour | |
:
[1,5]
Acute lymphocytic leukemia
Acute non-lymphocytic leukemia
Less frequent uses include: Acute myelogenous leukemia Breast cancer
1 May 2007
Chronic myelogenous leukemia Non-Hodgkin's lymphoma * Health Protection Branch approved indication.
:
[5,9]
Cardiac toxicity
is cumulative across members of the anthracycline (doxorubicin, epirubicin, daunorubicin, idarubicin) and anthracenedione (mitoxantrone) class 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.
Idarubicin has been shown to have mutagenic and carcinogenic properties in rats. Its safe use in pregnancy and its effects on fertility have not been established. Breast feeding is not recommended due to the potential secretion into breast milk.
:
[5,9,10]
| ORGAN SITE | SIDE EFFECT | ONSET | |||
| cardiovascular | arrhythmias (rare, transient) | I | |||
| congestive heart failure (serious 2%) | D | L | |||
| central nervous system | headache (rare) | E | |||
| seizures (rare) | E | ||||
| dermatologic | alopecia (75%, usually partial) | E | |||
| facial flushing with rapid injection | I | ||||
| radiation recall reaction (rare) | I | ||||
| extravasation hazard (refer to Appendix 2) | VESICANT | I | |||
| gastrointestinal | nausea and vomiting (80%) | I | |||
| stomatitis (appears day 3-10) (50%) | E | ||||
| diarrhea | E | ||||
| hematologic | myelosuppression , nadir 7-14 days, recovery 21-24 days | E | |||
| hepatic | transient elevation of liver function tests (20-30%) | E | |||
| hypersensitivity | rash, fever, chills | I | |||
| injection site | flare reaction (histamine release) | I | |||
| chemical phlebitis | I | ||||
| renal/metabolic | hyperuricemia (during periods of active cell lysis) | I | |||
1 May 2007
| ORGAN SITE | SIDE EFFECT | ONSET | |||
| red colouration of urine for 1-2 days | I | ||||
Dose-limiting side effects are underlined. I = immediate (onset in hours to days); E = early (days to weeks); D = delayed (weeks to months); L = late (months to years)
Hyperuricemia
during periods of active cell lysis, which is caused by cytotoxic chemotherapy of highly proliferative tumours of massive burden (eg, 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, if tumour lysis is expected.
Adverse effects are similar to those seen with other anthracyclines, although idarubicin may be associated with less cardiac toxicity than doxorubicin or daunorubicin. Cardiac toxicity as described for other anthracyclines, manifested by congestive heart failure or by a decrease in left ventricular ejection fraction may occur during or several weeks after therapy. There is no currently recommended maximum cumulative lifetime dose for idarubicin, but careful monitoring is advisable, particularly if there is significant exposure to other cardiotoxic drugs, a history of cardiac disease or a history of thoracic radiation. 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 the idarubicin. Recurrent injury to a previously irradiated site may occur weeks to months following radiation.
: No interactions reported 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.
:
[3,5,11,12,13]
For basic information on solution preparation and compatibility, see Chemotherapy Chart in Appendix.
:
[3,10,14,15]
| BCCA administration guideline noted in bold, italics | |
| Subcutaneous | not used due to corrosive nature |
| Intramuscular | not used due to corrosive nature |
| Direct intravenous | Preferred method due to need for frequent monitoring for signs of extravasation. Via small (21 or 23) gauge needle into tubing of running IV. Push slowly, so that drip of IV solution does not stop or reverse. Check for blood return before administration and after every 2-3 mL of drug. If no |
1 May 2007
| blood return, stop the injection and assess the IV site. Flush with 20 mL NS or D5W after administration to clear any remaining drug from tubing. | |
| Intermittent infusion | not recommended in children: dilute in 15-20 mL and infuse over 15-30 minutes |
| Continuous infusion | not recommended |
| Intraperitoneal | no information available on this route |
| Intrapleural | no information available on this route |
| Intrathecal | no information available on this route |
| Intra-arterial | no information available on this route |
| Intravesical | has been used as 1 hour instillation |
:
[3,13,14,16]
Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease, response and concomitant therapy. 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. Adults: q3w: 8 mg/m2 IV daily x 5 days q3w: 12 mg/m2 IV daily x 3 days
Dosage in myelosuppression:
Modify according to protocol by which patient is being treated; if no guidelines
available, refer to Appendix 6 "Dosage Modification for Myelosuppression"
Dosage in renal failure: Creatinine (umol/L) % usual dose
>200 50
Dosage in hepatic failure: Bilirubin (umol/L) % usual dose
>40<85 50 >85 Omit Children: 8-10 mg/m2/day IV x 3 days
:
Hollingshead LM, Faulds D. Idarubicin: a review of its pharmacodynamic and pharcokinetic properties and therapeutic potential in the chemotherapy of cancer. Drugs 1991; 42:690-719.
Gillies HC, Herriott D, Liang R, et al. Pharmacokinetics of idarubicin (4-demthoxydaunorubicin; IMI-30; NSC 256439) following intravenous and oral administration in patients with advanced cancer. Br J Clin Pharmacol 1987; 23:303-10.
Adria Laboratories of Canada. Idamycin product monograph. Mississauga; November 1992.
Smith DB, Margison JM, Lucas SB, et al. Clinical pharmacology of oral and intranvenous 4-demethoxydaunorubicin. Cancer Chemother Pharmacol 1987; 19:138-42.
Krogh CME, ed. Compendium of pharmaceuticals and specialties, 28th ed. Ottawa: Canadian Pharmaceutical Association, 1993:561-2.
Speth PAJ, Minderman H, Hannen C. Idarubicin vs daunorubicin: preclinical and clinical pharmacokinetic studies. Semin Oncol 1989; 16(Suppl 2):2-9.
Tamasia V, Pacciarini MA, Moro E, et al. Pharmacokinetic study of intravenous and oral idarubicin in cancer patients. Int J Clin Pharm Res 1987; 7:419-26.
Camaggi CM, Strocchi E, Carisi P, et al. Idarubicin metabolism and pharmacokinetics after intravenous and oral administration in cancer patients: A cross-over study. Cancer Chemother Pharmacol 1992; 30:307-16.
1 May 2007
Fields SM, Koeller JM. Idarubicin: a second generation anthracycline. DICP 1991; 25:505-17.
Cersosimo RJ. Idarubicin: an anthracycline antineoplastic agent. Clin Pharm 1992; 11:152-67.
Trissel LA. Handbook on injectable drugs, 7th ed. Bethesda: American Society of Hospital Pharmacists, 1992.
Williamson MJ, et al. Doxorubicin hydrochloride-aluminum interaction (Letter). Am J Hosp Pharm 1983; 40:214.
Turowski RC, Durthaler JM. Visual compatibility of idarubicin hydrochloride with selected drugs during simulated Y-site injection. Am J Hosp Pharm 1991; 48:2181-4.
Feig SA, Krailo MD, Harris RE, et al. Determination of the maximum tolerated dose of idarubicin when used in a combination chemotherapy program of reinduction of childhood ALL at first marrow relapse and a preliminary assessment of toxicity compared to that of daunorubicin: A report from the Childens' Cancer Study Group. Med Pediatr Oncol 1992; 20:124-9.
Mross K, Hamm K, Schultze-Seeman W, et al. Tissue disposition and plasma concentrations of idarubicin after intravesical therapy in patients with bladder tumours. Cancer Chemother Pharmacol 1992; 29:490-4.
Madon E, Grazia G, DeBernardi B, et al. Phase II study of idarubicin administered IVto pediatric patients with acute lymphoblastic leukemia. Cancer Treat Rep 1987; 71:855-6.
USP DI Volume I: Drug information for the health care professional, 13th ed. Rockville: United States Pharmacopeial Convention Inc, 1993:1561-4.
USP DI Volume II: Advice for the patient: drug information in lay language, 13th ed. Rockville: United States Pharmacopeial Convention Inc, 1993:723-5.