Professional Drug Information > Idarubicin Hydrochloride

Idarubicin (Systemic)

VA CLASSIFICATION
Primary: AN200

Commonly used brand name(s): Idamycin.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antineoplastic—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.


Accepted

Leukemia, acute nonlymphocytic (treatment) or
[Leukemia, acute lymphocytic (treatment)]—Idarubicin is indicated for treatment of acute nonlymphocytic leukemia (including French-American-British [FAB] classifications M1 through M7) ^{{01} {05} {06} {07} {08} {09} {11} {12} {13}} and acute lymphocytic leukemia ^{02}.

Acceptance not established
Use of idarubicin for the treatment of high-risk myelodysplastic syndromes (e.g., RAEB, RAEB-t) has not been established. Insufficient efficacy data exists supporting its use as single-agent therapy or establishing its contribution in combination therapy^{{20}{21}{22}{23}{24}{25}{26}{27}{28}{29}{30}{31}{32}{33}}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Synthetic. Analog of daunorubicin. ^{{01} {05}}
Molecular weight—
    Idarubicin hydrochloride: 533.97 ^{03}


Other characteristics
    Lipophilic ^{{01} {05} {10}}.

Mechanism of action/Effect:

Idarubicin is an anthracycline glycoside ^{01}; it is classified as an antibiotic but is not used as an antimicrobial agent. Its exact mechanism of antineoplastic activity is unknown; however, it intercalates DNA strands ^{01}, inhibits DNA synthesis ^{01}, interacts with RNA polymerases ^{{05} {10}}, and inhibits topoisomerase II (an enzyme that promotes DNA strand supercoiling) ^{{01} {05}}.

Distribution:

High volume of distribution ^{{01} {05}} (approximately 2225 liters ^{{05} {10}}). Concentrations of both idarubicin and its primary metabolite idarubicinol are 400- and 200-fold higher, respectively, in nucleated blood and bone marrow cells than in plasma ^{05}. Data about whether idarubicin crosses the blood-brain barrier are conflicting ^{05}.

Protein binding:

Extensive tissue binding ^{{01} {05}}.


Plasma:

Idarubicin: Very high (97%) ^{{01} {05}}.

Idarubicinol: Very high (94%) ^{{01} {05}}.


Biotransformation:

Rapidly and extensively, both hepatically and extrahepatically, to produce the primary metabolite, idarubicinol, which is equipotent with idarubicin. ^{{01} {05}}

Half-life:


Idarubicin:

As a single agent: Average, 22 hours (range, 4 to 46 hours) ^{{01} {05}}.

In combination with cytarabine: Average, 20 hours (range, 7 to 38 hours) ^{01}.



Idarubicinol:

> 45 hours ^{01}.


Time to peak concentration:

Cellular (nucleated cells of blood and bone marrow)—Within a few minutes after injection ^{01}.

Elimination:
    Primarily biliary, as idarubicinol ^{{01} {05}}.
    Renal elimination occurs to a lesser extent, as idarubicinol ^{01}.
    In dialysis—Studies have not been done. However, because of the multicompartmental behavior, along with the extensive extravascular distribution and tissue binding, it is unlikely that significant amounts of idarubicin would be removable by dialysis ^{01}.


Precautions to Consider

Carcinogenicity/Mutagenicity

Secondary malignancies are potential delayed effects of many antineoplastic agents, although it is not clear whether the effect is related to their mutagenic or immunosuppressive action. The effect of dose and duration of therapy is also unknown, although the risk seems to increase with long-term use.

Long-term carcinogenicity studies have not been done. However, studies in experimental models (including bacterial systems, mammalian cells in culture, and female Sprague-Dawley rats) indicate that idarubicin has mutagenic and carcinogenic properties ^{01}.

Pregnancy/Reproduction
Fertility—
Idarubicin caused testicular atrophy (with inhibition of spermiogenesis and sperm maturation, resulting in few or no mature sperm) in male dogs given idarubicin in doses of 1.8 mg per square meter of body surface area per day three times a week for 13 weeks. Effects were not readily reversible after an 8-week recovery period ^{01}.

Pregnancy—
Adequate and well-controlled studies in humans have not been done.

First trimester: It is usually recommended that use of antineoplastics, especially combination chemotherapy, be avoided whenever possible, especially during the first trimester. Although information is limited because of the relatively few instances of antineoplastic administration during pregnancy, the mutagenic, teratogenic, and carcinogenic potential of these medications must be considered. There is one report of fetal death following maternal exposure to idarubicin during the second trimester ^{01}.

Other hazards to the fetus include adverse reactions seen in adults.

Studies in rats at a dose of 1.2 mg per square meter of body surface area per day (one tenth the human dose), which was nontoxic to dams, found idarubicin to be embryotoxic and teratogenic. Studies in rabbits at a dose of 2.4 mg per square meter of body surface area (two tenths the human dose), which was toxic to dams, found idarubicin to be embryotoxic but not teratogenic ^{01}.

FDA Pregnancy Category D ^{01}.

In general, use of contraception is recommended during cytotoxic drug therapy ^{04}.

Breast-feeding

It is not known whether idarubicin is distributed into breast milk ^{01}. Although very little information is available regarding distribution of antineoplastic agents into breast milk, breast-feeding is not recommended during chemotherapy because of the potential risks to the infant (adverse effects, mutagenicity, carcinogenicity).

Pediatrics

Appropriate studies on the relationship of age to the effects of idarubicin have not been performed in the pediatric population. In two small studies of the pharmacokinetics, conflicting results were obtained about a possible difference in clearance rate ^{05}. Safety and efficacy have not been established ^{01}.


Geriatrics


Although appropriate studies on the relationship of age to the effects of idarubicin have not been performed in the geriatric population, cardiotoxicity may be more frequent in older persons (over 60 years of age). Caution should also be used in patients who have inadequate bone marrow reserves due to old age. In addition, elderly patients are more likely to have age-related renal function impairment, which when severe may require reduction of dosage in patients receiving idarubicin.


Dental

The bone marrow depressant effects of idarubicin may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. Dental work, whenever possible, should be completed prior to initiation of therapy or deferred until blood counts have returned to normal. Patients should be instructed in proper oral hygiene during treatment, including caution in use of regular toothbrushes, dental floss, and toothpicks.

Idarubicin also commonly causes mucositis ^{01}, which may be associated with considerable discomfort.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Allopurinol or
Colchicine or
» Probenecid or
» Sulfinpyrazone    (idarubicin may raise the concentration of blood uric acid; dosage adjustment of antigout agents may be necessary to control hyperuricemia and gout; allopurinol may be preferred to prevent or reverse idarubicin-induced hyperuricemia because of risk of uric acid nephropathy with uricosuric antigout agents)


Blood dyscrasia–causing medications (see Appendix II )    (leukopenic and/or thrombocytopenic effects of idarubicin may be increased with concurrent or recent therapy if these medications cause the same effects; dosage adjustment of idarubicin, if necessary, should be based on blood counts)


» Bone marrow depressants, other (see Appendix II ) or
Radiation therapy    (additive bone marrow depression may occur; dosage reduction may be required when two or more bone marrow depressants, including radiation, are used concurrently or consecutively)


Daunorubicin or
Doxorubicin    (use of idarubicin in a patient who has previously received daunorubicin or doxorubicin increases the risk of cardiotoxicity ^{05}; in general, idarubicin should not be used in patients who have previously received complete cumulative doses of daunorubicin or doxorubicin ^{15})


Radiation therapy to mediastinal area    (concurrent use with idarubicin may result in increased cardiotoxicity ^{01})


Vaccines, killed virus    (because normal defense mechanisms may be suppressed by idarubicin therapy, the patient's antibody response to the vaccine may be decreased. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year)


» Vaccines, live virus    (because normal defense mechanisms may be suppressed by idarubicin therapy, concurrent use with a live virus vaccine may potentiate the replication of the vaccine virus, may increase the side/adverse effects of the vaccine virus, and/or may decrease the patient's antibody response to the vaccine; immunization of these patients should be undertaken only with extreme caution after careful review of the patient's hematologic status and only with the knowledge and consent of the physician managing the idarubicin therapy. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year. Patients with leukemia in remission should not receive live virus vaccine until at least 3 months after their last chemotherapy. In addition, immunization with oral poliovirus vaccine should be postponed in persons in close contact with the patient, especially family members)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]), serum and
Alkaline phosphatase, serum and
Aspartate aminotransferase (AST [SGOT]), serum    (values may be increased transiently ^{05})


Bilirubin, serum    (concentrations may be increased transiently ^{05})


Electrocardiogram (ECG) changes, transient, including:
Arrhythmias (atrial or ventricular premature beats, tachycardia)
ST-T wave changes
T-wave flattening
T-wave inversion    (may occur ^{05})


Left ventricular ejection fraction (LVEF)    (decrease from pretreatment baseline values usually occurs with idarubicin-induced cardiomyopathy ^{01})


Uric acid concentrations in blood and urine    (may be increased ^{01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Bone marrow depression^{01}
» Chickenpox, existing or recent (including recent exposure) or
» Herpes zoster    (risk of severe generalized disease)


Gout, history of or
Urate renal stones, history of    (risk of hyperuricemia)


» Heart disease    (increased risk of cardiotoxicity ^{{01} {05}})


» Hepatic function impairment    (reduction in dosage is recommended ^{01}; one half the normal dose is recommended in patients with serum bilirubin concentrations of 2.35 to 5 mg per 100 mL ^{05}; administration of idarubicin is not recommended in patients with serum bilirubin concentrations of greater than 5 mg per 100 mL ^{05})


» Infection    (should be controlled before initiation of idarubicin treatment ^{01})


Renal function impairment    (dosage reduction should be considered in patients with a serum creatinine of greater than 2.5 mg per 100 mL ^{05})


Sensitivity to idarubicin
» Caution should be used also in patients with inadequate bone marrow reserves due to previous cytotoxic drug or radiation therapy^{01}

Patient monitoring
Alanine aminotransferase (ALT [SGPT]) and
Alkaline phosphatase and
Aspartate aminotransferase (AST [SGOT]) and
Bilirubin, serum and
Lactate dehydrogenase (LDH), serum    (determinations recommended prior to initiation of therapy and at periodic intervals during therapy to monitor hepatic function; frequency varies according to clinical state, agent, dose, and other agents being used concurrently ^{01})


Chest x-ray and
» Echocardiography and
Electrocardiogram (ECG) studies and
» Radionuclide angiography determination of ejection fraction    (recommended prior to initiation of therapy and at periodic intervals during therapy ^{01})


Creatinine, serum    (recommended prior to treatment and at periodic intervals during treatment to monitor renal function ^{01})


» Examination of patient's mouth for ulceration    (recommended before administration of each dose ^{01})


» Hematocrit or hemoglobin and
» Platelet count and
» Leukocyte count, total and, if appropriate, differential    (determinations recommended prior to initiation of therapy and at periodic intervals during therapy; frequency varies according to clinical state, agent, dose, and other agents being used concurrently)


Uric acid, serum    (determinations recommended prior to initiation of therapy and at periodic intervals during therapy; frequency varies according to clinical state, agent, dose, and other agents being used concurrently)






Side/Adverse Effects

Note: Many “side effects” of antineoplastic therapy are unavoidable and represent the medication's pharmacologic action. Some of these (for example, leukopenia and thrombocytopenia) are actually used as parameters to aid in individual dosage titration.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Leukopenia^{01}{05} (fever or chills; cough or hoarseness; lower back or side pain; painful or difficult urination)
    
mucositis^{{01}{05}{06}{07}{09}{11}{12}} (sores in mouth and on lips)
    
thrombocytopenia^{05}{11} (unusual bleeding or bruising; black, tarry stools; blood in urine or stools; pinpoint red spots on skin)

Note: Severe leukopenia occurs in all patients ^{{01} {06}}; deaths due to infection have been reported ^{{01} {06}}. Nadir of leukocyte counts occurs 10 to 14 days after a dose; recovery usually occurs within 21 days after a dose ^{{16} {19}}.
Severe thrombocytopenia occurs in all patients ^{{01} {06}}; deaths due to bleeding have been reported ^{{01} {06}}. Nadir of platelet counts occurs 10 to 14 days after a dose; recovery usually occurs within 21 days after a dose ^{16}.


Incidence less frequent
    
Cardiotoxicity, in the form of arrhythmias^{{01}{05}{07}{11}} , congestive heart failure^{01}{05} , or other cardiomyopathies^{01} (shortness of breath; swelling of feet and lower legs; fast or irregular heartbeat)
    
hyperuricemia^{01} or uric acid nephropathy (joint pain, lower back or side pain)
    
tissue necrosis caused by extravasation^{01}{05} (pain at injection site)

Note: Incidence of cardiotoxicity is more frequent in patients who have received previous chest irradiation or medications increasing cardiotoxicity and in patients with a history of cardiac disease or mediastinal radiation ^{01}, and may be more frequent in the elderly ^{01}. Cumulative cardiotoxicity has not been studied ^{01}.
Extravasation may occur with or without accompanying stinging or burning and even if blood returns well on aspiration of the infusion needle ^{01}.
Hyperuricemia or uric acid nephropathy occurs most commonly during initial treatment of patients with leukemias a result of rapid cell breakdown, which leads to elevated serum uric acid concentrations ^{01}.


Incidence rare
    
Enterocolitis, with perforation^{01} (severe stomach pain)
    
skin rash or hives^{05}{09}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Diarrhea or stomach cramps^{{01}{05}{07}{09}{12}}
    
headache^{01}{05}
    
nausea and vomiting^{{01}{05}{06}{07}{11}{12}{13}}

Note: Nausea and vomiting are usually mild ^{{01} {13}}.


Incidence less frequent
    
Peripheral neuropathy^{01} (numbness or tingling of fingers, toes, or face)
    
recall postirradiation erythema^{01} (darkening or redness of skin)

Note: Recall postirradiation erythema occurs if patient has received previous radiation therapy.




Those not indicating need for medical attention
Incidence more frequent
    
Alopecia^{{01}{05}{11}{13}} (loss of hair)
    
reddish urine^{17}

Note: Alopecia occurs in most patients. Hair growth should return after treatment has ended.




Those indicating the need for medical attention if they occur after medication is discontinued
    
Cardiotoxicity (fast or irregular heartbeat; shortness of breath; swelling of feet and lower legs)




Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Treatment of overdose
Treatment of overdose involves supportive care, including:

• Platelet transfusions and antibiotics for severe and prolonged myelosuppression ^{01}.


• Symptomatic treatment of mucositis ^{01}.


It is unlikely that dialysis would remove significant amounts of idarubicin or its metabolites ^{01}.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Idarubicin (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to idarubicin

Pregnancy—Use not recommended because of mutagenic, teratogenic, and carcinogenic potential; advisability of using contraception; telling physician immediately if pregnancy is suspected





Breast-feeding—Not recommended because of risk of serious side effects





Use in the elderly—Cardiotoxicity may be more frequent in patients over 60 years of age
Other medications, especially probenecid, sulfinpyrazone, other bone marrow depressants, or previous cytotoxic drug or radiation therapy
Other medical problems, especially chickenpox, herpes zoster, heart disease, hepatic function impairment, or other infections

Proper use of this medication
Caution in taking combination therapy; taking each medication at the right time

Importance of ample fluid intake and subsequent increase in urine output to aid in excretion of uric acid

Frequency of nausea and vomiting; importance of continuing medication despite stomach upset

» Proper dosing

Precautions while using this medication
» Importance of close monitoring by the physician

» Avoiding immunizations unless approved by physician; other persons in patient's household should avoid immunizations with oral poliovirus vaccine; avoiding persons who have taken oral poliovirus vaccine or wearing a protective mask that covers nose and mouth

Caution if bone marrow depression occurs
» Avoiding exposure to persons with infections, especially during periods of low blood counts; checking with physician immediately if fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination occurs

» Checking with physician immediately if unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on skin occur

Caution in use of regular toothbrush, dental floss, or toothpick; physician, dentist, or nurse may suggest alternatives; checking with physician before having dental work done

Not touching eyes or inside of nose unless hands washed immediately before

Using caution to avoid accidental cuts with use of sharp objects such as safety razor or fingernail or toenail cutters

Avoiding contact sports or other situations where bruising or injury could occur
» Possibility of local tissue injury and scarring if infiltration of intravenous solution occurs; telling doctor or nurse right away about redness, pain, or swelling at injection site


Side/adverse effects
Importance of discussing possible effects, including cancer, with physician

Signs of potential side effects, especially leukopenia, mucositis, thrombocytopenia, cardiotoxicity, tissue necrosis caused by extravasation, hyperuricemia, uric acid nephropathy, enterocolitis, and skin rash or hives

Possibility of hair loss; growth should return after treatment has ended


General Dosing Information
Patients receiving idarubicin should be under supervision of a physician experienced in cancer chemotherapy ^{01}.

A variety of dosage schedules of idarubicin, alone or in combination with other antitumor agents, are used. The prescriber may consult the medical literature as well as the manufacturer's literature in choosing a specific dosage.

Dosage must be adjusted to meet the individual requirements of each patient, on the basis of clinical response and appearance or severity of toxicity.

The desired dose of idarubicin is withdrawn from the vial of reconstituted solution and then injected over 10 to 15 minutes into the tubing of a freely running intravenous infusion of 5% dextrose injection or 0.9% sodium chloride injection ^{01}. The tubing should be attached to a butterfly needle or other suitable device and inserted preferably into a large vein ^{01}.

Care must be taken to avoid extravasation during intravenous administration because of the risk of severe ulceration and necrosis.

If extravasation of idarubicin occurs during intravenous administration, possibly indicated by local burning or stinging (may also be painless ^{01}), the injection and infusion should be stopped immediately and resumed, completing the dose, in another vein ^{01}. Treatment of known or suspected subcutaneous extravasation may include intermittent ice packs (one-half hour immediately, then one-half hour four times a day for 3 days) over the area of extravasation and elevation of the affected extremity ^{01}. Frequent examinations of the area, as well as an early plastic surgery consultation, are recommended if there is any sign of a local reaction such as pain, erythema, edema, or vesication. Early excision of the involved area should be considered if ulceration begins or there is severe persistent pain at the site ^{01}.

Because it will cause local tissue necrosis, idarubicin must not be administered intramuscularly or subcutaneously ^{01}.

Development of uric acid nephropathy in patients with leukemia may be prevented by adequate oral hydration and, in some cases, administration of allopurinol. Alkalinization of urine may be necessary if serum uric acid concentrations are elevated.

In patients who experience severe mucositis, a second course of idarubicin should be delayed until recovery has occurred and a dose reduction of 25% is recommended ^{{01} {05}}.

In acute leukemia, idarubicin may be administered despite the presence of thrombocytopenia and bleeding; stoppage of bleeding and increase in platelet count can occur during or after treatment. Platelet transfusions may be necessary ^{18}.

Special precautions are recommended in patients who develop thrombocytopenia as a result of administration of idarubicin. The precautions may include extreme care in performing invasive procedures; regular inspection of intravenous sites, skin (including perirectal area), and mucous membrane surfaces for signs of bleeding or bruising; limiting frequency of venipuncture and avoiding intramuscular injections; testing urine, emesis, stool, and secretions for occult blood; care in use of regular toothbrushes, dental floss, toothpicks, safety razors, and fingernail and toenail cutters; avoiding constipation; and using measures to prevent falls and other injuries. Such patients should avoid alcohol and aspirin intake because of the risk of gastrointestinal bleeding. Platelet transfusions may be required.

Patients who develop leukopenia should be observed carefully for signs of infection. Antibiotic support may be required. In neutropenic patients who develop fever, broad-spectrum antibiotic coverage should be initiated empirically, pending bacterial cultures and appropriate diagnostic tests.

Safety considerations for handling this medication
There is concern and limited evidence that personnel involved in preparation and administration of parenteral antineoplastics may be at some risk because of the potential mutagenicity, teratogenicity, and/or carcinogenicity of these agents, although the actual risk is unknown. USP advisory panels recommend cautious handling both in preparation and disposal of antineoplastic agents. Precautions that have been suggested include:    • Use of a biological containment cabinet during reconstitution and dilution of parenteral medications and wearing of disposable surgical gloves and masks.
   • Use of proper technique to prevent contamination of the medication, work area, and operator during transfer between containers (including proper training of personnel in this technique).
   • Cautious and proper disposal of needles, syringes, vials, ampuls, and unused medication.
A number of medical centers have developed detailed guidelines for handling of antineoplastic agents.


Combination chemotherapy
Idarubicin may be used in combination with other agents in various regimens. As a result, incidence and/or severity of side effects may be altered and different dosages (usually reduced) may be used.

For specific dosages and schedules, consult the literature. For information regarding each agent, consult the individual monographs.


Parenteral Dosage Forms

IDARUBICIN HYDROCHLORIDE FOR INJECTION USP

Usual adult dose
Leukemia, acute nonlymphocytic
Intravenous, slow (over ten to fifteen minutes), 12 mg per square meter of body surface area per day for three days. This is given in combination with cytarabine in a dose of either 100 mg per square meter of body surface area per day by continuous intravenous infusion for seven days or 25 mg per square meter of body surface area intravenously, followed by 200 mg per square meter of body surface area per day by continuous intravenous infusion for five days. ^{01}

Note: A second course may be given to patients with unequivocal evidence of leukemia after the first course ^{01}.



Usual pediatric dose
Safety and efficacy have not been established ^{01}.

Size(s) usually available:
U.S.—


5 mg (Rx) [Idamycin (lactose 50 mg)]


10 mg (Rx) [Idamycin (lactose 100 mg)]

Canada—


5 mg (Rx) [Idamycin (lactose 50 mg)]


10 mg (Rx) [Idamycin (lactose 100 mg)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by the manufacturer. Protect from light.

Preparation of dosage form:
Idarubicin Hydrochloride for Injection USP is reconstituted for intravenous administration by adding 5 or 10 mL, respectively, of 0.9% sodium chloride injection to the 5- or 10-mg vial, producing a solution containing 1 mg of idarubicin hydrochloride per mL. Use of bacteriostatic diluents is not recommended. Care should be taken when the needle is inserted in the vial, whose contents are under negative pressure to minimize aerosol formation during reconstitution ^{01}.

Stability:
Reconstituted solutions of idarubicin are physically and chemically stable for 72 hours at room temperature or at least 168 hours (7 days) between 2 and 8 °C (36 and 46 °F) when protected from light ^{01}.

Incompatibilities:
Idarubicin should not be mixed with heparin, since a precipitate may form ^{01}.

Note: Great care should be taken to prevent exposure of the skin to idarubicin. Any idarubicin powder or solution that comes into contact with the skin or mucosa should be washed off thoroughly with soap and water ^{01}.

Revised: 03/09/2001

References

Note: References used in the development and subsequent revisions of this monograph have not been incorporated into the database and therefore are not listed below.

1. Idamycin package insert (Pharmacia & Upjohn—US), Rev 5/96.
   

2. Idamycin product monograph (Pharmacia—Canada), Rev 4/95.
   

3. Canada J, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention Inc; 1997.
   

4. General precaution per Hematology-Oncology Advisory Panel, 6/91.
   

5. Fields SM, Koeller JM. Idarubicin: a second generation anthracycline. DICP, Ann Pharmacother 1991 May; 25: 505-17.
   

6. Carella AM, Pungolino E, Piatti G, et al. Idarubicin in combination with intermediate-dose cytarabine in the treatment of refractory or relapsed acute leukemias. Eur J Haematol 1989 Oct; 43(4): 309-13.
   

7. Leone G, Pagano L, Marra R, et al. Idarubicin combined with intermediate-dose cytosine arabinoside in the treatment of refractory acute leukemia. Haematologica (Pavia) 1989 Jan-Feb; 74(1): 57-61.
   

8. Malik ST, Tucker J, Rohatiner AZ, et al. Oral idarubicin in the treatment of acute myelogenous leukaemia and the blast phase of chronic myeloid leukaemia. Hematol Oncol 1989 Nov-Dec; 7(6): 423-7.
   

9. Harousseau JL, Reiffers J, Hurteloup P, et al. Treatment of relapsed acute myeloid leukemia with idarubicin and intermediate-dose cytarabine. J Clin Oncol 1989 Jan; 7(1): 45-9.
   

10. Speth PAJ, Minderman H, Haanen C. Idarubicin v. Daunorubicin: preclinical and clinical pharmacokinetic studies. Semin Oncol 1989 Feb; 16 (1 Suppl 2): 2-9.
    

11. Wiernik PH, Case DC, Periman PO, et al. A multicenter trial of cytarabine plus idarubicin or daunorubicin as induction therapy for adult nonlymphocytic leukemia. Semin Oncol 1989 Feb; 16 (1 Suppl 2): 25-9.
    

12. Berman E, Raymond V, Gee T, et al. Idarubicin in acute leukemia: results of studies at Memorial Sloan-Kettering Cancer Center. Semin Oncol 1989 Feb; 16 (1 Suppl 2): 30-4.
    

13. Carella AM, Berman E, Maraone MP, et al. Idarubicin in the treatment of acute leukemias. An overview of preclinical and clinical studies. Haematologica 1990 Mar-Apr; 75(2): 159-69.
    

14. No reference
    

15. Per responses to panel question #5, panel review, 9/91.
    

16. Per responses to panel question #6, panel review, 9/91.
    

17. Per responses to panel question #8, panel review, 9/91.
    

18. Per responses to panel question #9, panel review, 9/91.
    

19. Gianni L, Vigano L, Surbone A, et al. Pharmacology and clinical toxicity of 4´-iodo-4´-deoxydoxorubicin: an example of successful application of pharmacokinetics to dose escalation in phase I trials. JNCI 1990 Mar 21; 82(6): 469-77.
    

20. Reviewers' consensus on the use of idarubicin for the treatment of high-risk myelodysplastic syndromes (MDS), 1/17/01.
    

21. de Witte T, Suciu S, van Dijk J, et al. The impact of cytogenetic features and clonality on the prognosis of patients with poor-risk MDS and secondary AML treated with intensive chemotherapy and stem cell transplantation: a joint study of the EORTC, EBMT, SAKK, HOVON, and GIMENA Leukemia Groups. www.abstracts-on-line.com/abstracts/hem/: [Abst 2346].
    

22. Koller CA, Cortes JE, Freireich EJ, et al. Interferon Alfa-2B + low-dose cytarabine for the maintenance of remission in AML and advanced MDS. www.abstracts-on-line.com/abstracts/hem/: [Abst 4639].
    

23. Beran M, Shen Y, Kantarjian H, et al. High-dose chemotherapy in high-risk MDS: covariate adjusted comparison of five regimens. www.abstracts-on-line.com/abstracts/hem/: [Abst 633].
    

24. Gardin C, Chaibi P, Boiron JM, et al. Intensive chemotherapy followed by stem cell transplantation in high-risk myeloid malignancies: results of the CRH01 G-CSF Trail. www.abstracts-on-line.com/abstracts/hem/: [Abst 1260].
    

25. Ganser A, Heil G, Seipelt G, et al. Intensive chemotherapy with idarubicin, ara-C, etoposide, and m-AMSA followed by immunotherapy with IL-2 for MDS and high-risk AML. Ann Hematol 2000; 79(1): 30-5.
    

26. Estey EH, Thall P, Wang X. Routine use of fludarabine- or topotecan-containing chemotherapy is not indicated in AML, RAEB-t, or RAEB. www.abstracts-on-line.com/abstracts/hem/: [Abst 2170].
    

27. Pedemonte BM, Butler SL, Moore S, et al. Molecular abnormalities in MDS: an immunohistochemical study. Proc Am Soc Clin Oncol 1999; 18: 637a [Abst 2461].
    

28. Estey EH, Thall PF, Pierce S, et al. Randomized phase II study of fludarabine + cytosine arabinoside + idarubicin +/- all-trans retinoic acid +/- G-CSF in poor prognosis newly diagnosed acute myeloid leukemia and MDS. Blood 1999; 93(8): 2478-84.
    

29. Bernasconi C, Alessandrino EP, Bernasconi P, et al. Randomized clinical study comparing aggressive chemotherapy with or without G-CSF support for high-risk MDS or secondary acute myeloid leukemia evolving from MDS. Br J Haematol 1998; 102(3): 678-83.
    

30. Parker JE, Pagliuca A, Mijovic A, et al. Fludarabine, cytarabine, G-CSF, and idarubicin (FLAG-IDA) for the treatment of poor-risk MDS and acute myeloid leukemia. Br J Haematol 1997; 99(4): 939-44.
    

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