Idarubicin should be given slowly into a freely flowing intravenous infusion; it must never be given intramuscularly or subcutaneously. Severe local tissue necrosis can occur if there is extravasation during administration.
As is the case with other anthracyclines, the use of idarubicin can cause myocardial toxicity leading to congestive heart failure. Cardiac toxicity is more common in patients who have received prior anthracyclines or who have preexisting cardiac disease.
As is usual with antileukemic agents, severe myelosuppression occurs when idarubicin is used at effective therapeutic doses.
It is recommended that idarubicin be administered only under the supervision of a physician who is experienced in leukemia chemotherapy and in facilities with laboratory and supportive resources adequate to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity. The physician and institution must be capable of responding rapidly and completely to severe hemorrhagic conditions and/or overwhelming infection.
Dosage should be reduced in patients with impaired hepatic function.
Dosage should be reduced in patients with impaired renal function.
Idarubicin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).
Acute myeloid leukemia (AML): IV:
Manufacturer labeling: Induction: 12 mg/m2/day for 3 days (in combination with cytarabine); a second induction cycle may be administered if necessary.
Indication-specific dosing:
AML, relapsed/refractory: FLAG-IDA regimen: 10 mg/m2/day for 3 days (in combination with fludarabine, cytarabine, and filgrastim); a second course was given for consolidation upon hematologic recovery (Parker 1997)
Acute promyelocytic leukemia (APL):
LPA 2005 (high-risk patients):
Induction (all patients): 12 mg/m2/day on days 2, 4, 6, and 8 (day 8 dose was omitted in patients >70 years of age) in combination with ATRA (tretinoin) (Sanz 2010)
Consolidation (patients ≤60 years of age): 5 mg/m2/day for 4 days in consolidation cycle 1 and 12 mg/m2/day for 1 day in consolidation cycle 3 (in combination with ATRA [tretinoin] and cytarabine) (Sanz 2010)
APML4 protocol (Iland 2012): Induction (age-adjusted dosing):
Age <60 years of age: 12 mg/m2/day on days 2, 4, 6, and 8 (in combination with ATRA [tretinoin] and arsenic trioxide)
Age 61 to 70 years: 9 mg/m2/day on days 2, 4, 6, and 8 (in combination with ATRA [tretinoin] and arsenic trioxide)
Age >70 years of age: 6 mg/m2/day on days 2, 4, 6, and 8 (in combination with ATRA [tretinoin] and arsenic trioxide)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, it does recommend that dosage reductions be made. Patients with Scr ≥2 mg/dL did not receive treatment in many clinical trials. The following adjustments have been recommended (Aronoff 2007):
CrCl >50 mL/minute: No dosage adjustment is necessary.
CrCl 10 to 50 mL/minute: Administer 75% of dose.
CrCl <10 mL/minute: Administer 50% of dose.
Hemodialysis: Supplemental dose not needed.
Continuous ambulatory peritoneal dialysis (CAPD): Supplemental dose not needed.
Bilirubin 2.6 to 5 mg/dL: Administer 50% of dose (Perry 2012)
Bilirubin >5 mg/dL: Avoid use
(For additional information see "Idarubicin: Pediatric drug information")
Note: Dose, frequency, number of doses, and start date may vary by protocol and/or treatment phase; refer to specific protocol. In general, idarubicin use in pediatric patients is rare and has been replaced by newer agents and protocols. Idarubicin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (POGO [Dupuis 2011]).
Acute myeloid leukemia (AML): Limited data available: Infants, Children, and Adolescents:
New diagnosis (CCG-2961) (Lange 2008):
Induction: IV: IdaDCTER: Idarubicin 5 mg/m2/dose daily for 4 days on days 0 to 3 in combination with cytarabine, etoposide, thioguanine, and dexamethasone.
Consolidation: IV:
IdaDCTER: Idarubicin 5 mg/m2/dose daily for 4 days on days 0 to 3 in combination with cytarabine, etoposide, thioguanine, and dexamethasone.
OR
Idarubicin 12 mg/m2/dose daily for 3 days on days 0 to 2 in combination with fludarabine and cytarabine.
Relapsed/refractory: IV: Children and Adolescents: 12 mg/m2 once daily for 3 days in combination with fludarabine and cytarabine (Dinndorf 1997; Leahey 1997).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no specific dosage adjustments provided in the manufacturer's labeling; however, it does recommend that dosage reductions be made. Adult patients with Scr ≥2 mg/dL did not receive treatment in many clinical trials. The following adjustments have also been recommended (Aronoff 2007):
Infants, Children, and Adolescents:
GFR >50 mL/minute/1.73 m2: No adjustment necessary.
GFR ≤50 mL/minute/1.73 m2: Administer 75% of dose.
Intermittent hemodialysis: Administer 75% of dose.
Peritoneal dialysis (PD): Administer 75% of dose.
Continuous renal replacement therapy (CRRT): Administer 75% of dose.
There are no specific dosage adjustments provided in the manufacturer's labeling; however, it does recommend that dosage reductions be made. Based on experience in adult patients, avoid use if bilirubin is >5 mg/dL and dosage adjustment suggested if bilirubin is 2.6 to 5 mg/dL (Perry 2012).
Refer to adult dosing.
Manufacturer labeling: If patients experience severe mucositis during the first induction cycle, delay administration of the second cycle until mucositis has resolved; consider reducing the dose by 25%.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as hydrochloride [preservative free]:
Idamycin PFS: 5 mg/5 mL (5 mL); 10 mg/10 mL (10 mL); 20 mg/20 mL (20 mL)
Generic: 5 mg/5 mL (5 mL); 10 mg/10 mL (10 mL); 20 mg/20 mL (20 mL)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Idamycin PFS: 1 mg/mL (5 mL, 10 mL, 20 mL)
Generic: 1 mg/mL (5 mL, 10 mL, 20 mL)
Idarubicin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).
IV: For IV administration only. Do not administer IM or SubQ; administer as slow injection over 10 to 15 minutes into a free-flowing IV solution of NS or D5W.
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Initiate antidote (dexrazoxane or dimethyl sulfate [DMSO]). Apply dry cold compresses for 20 minutes 4 times daily for 1 to 2 days (ESMO/EONS [Pérez Fidalgo 2012]); withhold cooling beginning 15 minutes before dexrazoxane infusion; continue withholding cooling until 15 minutes after infusion is completed. Topical DMSO should not be administered in combination with dexrazoxane; may lessen dexrazoxane efficacy.
Dexrazoxane: 1,000 mg/m2 (maximum dose: 2,000 mg) IV (administer in a large vein remote from site of extravasation) over 1 to 2 hours days 1 and 2, then 500 mg/m2 (maximum dose: 1,000 mg) IV over 1 to 2 hours day 3; begin within 6 hours of extravasation. Day 2 and day 3 doses should be administered at approximately the same time (±3 hours) as the dose on day 1 (ESMO/EONS [Pérez Fidalgo 2012]; Mouridsen 2007). Note: Reduce dexrazoxane dose by 50% in patients with moderate to severe renal impairment (CrCl <40 mL/minute).
DMSO: Apply topically to a region covering twice the affected area every 8 hours for 7 days; begin within 10 minutes of extravasation; do not cover with a dressing (ESMO/EONS [Pérez Fidalgo 2012]).
Idarubicin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (POGO [Dupuis 2011]).
For IV administration only. Do not administer IM or SubQ; administer as slow push over 3 to 5 minutes, preferably into the side of a freely-running saline or dextrose infusion or as intermittent infusion over 10 to 15 minutes into a free-flowing IV solution of NS or D5W.
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Initiate antidote (dimethyl sulfate [DMSO] or dexrazoxane [adult]) (see Management of Drug Extravasations for more details). Apply dry cold compresses for 20 minutes 4 times daily for 1 to 2 days (ESMO/EONS [Pérez Fidalgo 2012]); withhold cooling beginning 15 minutes before dexrazoxane infusion; continue withholding cooling until 15 minutes after infusion is completed. Topical DMSO should not be administered in combination with dexrazoxane; may lessen dexrazoxane efficacy.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Acute myeloid leukemia: Treatment of acute myeloid leukemia (AML) in adults (in combination with other approved chemotherapy agents).
IDArubicin may be confused with DAUNOrubicin, DOXOrubicin, epiRUBicin, idaruCIZUmab, idelalisib
Idamycin PFS may be confused with Adriamycin
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. The relative cardiotoxicity of idarubicin compared to doxorubicin is unclear. Some investigators report no increase in cardiac toxicity for adults at cumulative oral idarubicin doses up to 540 mg/m2; other reports suggest a maximum cumulative intravenous dose of 150 mg/m2.
>10%:
Cardiovascular: Cardiac failure (dose-related), ECG abnormalities (transient; includes atrial premature contractions, S-T wave changes, supraventricular tachycardia, ventricular premature contractions; generally asymptomatic and self-limiting)
Central nervous system: Headache
Dermatologic: Alopecia (25% to 30%), skin rash (11%), urticaria
Gastrointestinal: Vomiting (30% to 60%), gastrointestinal hemorrhage (30%), diarrhea (9% to 22%), stomatitis (11%), nausea
Genitourinary: Urine discoloration (darker yellow)
Hematologic & oncologic: Anemia (effects are generally less severe with oral dosing), bone marrow suppression (nadir: 10 to 15 days; recovery: 21 to 28 days; primarily leukopenia; effects are generally less severe with oral dosing), thrombocytopenia (effects are generally less severe with oral dosing)
Hepatic: Increased serum bilirubin (≤44%), increased serum transaminases (≤44%)
Miscellaneous: Radiation recall phenomenon
1% to 10%:
Central nervous system: Peripheral neuropathy, seizure
<1%, postmarketing, and/or case reports: Cardiomyopathy, hyperuricemia, myocarditis, typhlitis (neutropenic)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to idarubicin, any component of the formulation, or to other anthracyclines or anthracenediones; uncontrolled infections; history of severe heart disease, recent myocardial infarction, severe myocardial insufficiency, severe arrhythmia; previous therapy with maximum cumulative doses of idarubicin, doxorubicin, daunorubicin, epirubicin, or other anthracycline and anthracenediones; severe persistent drug-induced myelosuppression; severe hepatic impairment; severe renal impairment
Documentation of allergenic cross-reactivity for drugs in this class is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Concerns related to adverse effects:
• Bone marrow suppression: Severe myelosuppression occurs when idarubicin is used at effective therapeutic doses. Patients are at risk of developing infection and bleeding due to neutropenia and thrombocytopenia, respectively (may be fatal). Do not use in patients with preexisting bone marrow suppression unless the benefit outweighs the risk.
• Cardiomyopathy: Idarubicin may cause myocardial toxicity leading to heart failure. Cardiotoxicity is more common in patients who have previously received anthracyclines or have preexisting cardiac disease. The risk of myocardial toxicity is also increased in patients with concomitant or prior mediastinal/pericardial irradiation, patients with anemia, bone marrow depression, infections, leukemic pericarditis, or myocarditis. Patients with active or dormant cardiovascular disease, concurrent administration of cardiotoxic drugs (eg, trastuzumab, cyclophosphamide, paclitaxel), prior therapy with other anthracyclines or anthracenediones are also at increased risk for cardiotoxicity. Potentially fatal heart failure, acute arrhythmias (may be life-threatening) or other cardiomyopathies may also occur. Regular monitoring of left ventricular ejection fraction (LVEF) is recommended, especially in patients with cardiac risk factors or impaired cardiac function. The half-life of other cardiotoxic agents must be considered. Avoid the use of anthracycline-based therapy for at least 5 half-lives after discontinuation of the cardiotoxic agent, and specifically avoid idarubicin for up to 7 months after discontinuation of trastuzumab. Monitor cardiac function during treatment.
ASCO has developed guidelines for prevention and monitoring of cardiac dysfunction in adult survivors of cancer (ASCO [Armenian 2017]). According to the guidelines, the risk of cardiac dysfunction is increased with the following:
• High-dose anthracycline therapy (eg, doxorubicin ≥250 mg/m2, epirubicin ≥600 mg/m2)
• High-dose radiotherapy (≥30 Gy) with the heart in the treatment field
• Lower-dose anthracycline (eg, doxorubicin <250 mg/m2, epirubicin <600 mg/m2) in combination with lower-dose radiotherapy (<30 Gy) with the heart in the treatment field
• Lower-dose anthracycline (eg, doxorubicin <250 mg/m2, epirubicin <600 mg/m2) or trastuzumab alone AND any of the following risk factors: Multiple cardiovascular risk factors (≥2 risk factors), including smoking, hypertension, diabetes, dyslipidemia, and obesity (during or after completion of therapy), or older age (≥60 years of age) at cancer treatment, or compromised cardiac function (eg, borderline low LVEF [50% to 55%], history of MI, moderate or higher valvular heart disease) before or during treatment
• Treatment with lower-dose anthracycline (eg, doxorubicin <250 mg/m2, epirubicin <600 mg/m2) followed by trastuzumab (sequential therapy)
• Other risk factors for anthracycline-induced cardiotoxicity include age ≥60 years of age at time of treatment and ≥2 cardiovascular risk factors (smoking, hypertension, diabetes, dyslipidemia, or obesity) during or after treatment.
The ASCO guidelines recommend a comprehensive assessment in patients with cancer that includes a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking. An echocardiogram should be obtained prior to initiating potentially cardiotoxic therapies. Modifiable risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) should be actively managed before initiating potentially cardiotoxic therapies. Consider cardioprotectants (eg, dexrazoxane) or continuous infusions in patients who are likely to receive high-dose anthracycline therapy. In patients who develop signs/symptoms of cardiac dysfunction during therapy, an echocardiogram is recommended for diagnostic workup; if echocardiogram is not available or feasible, a cardiac MRI (preferred) or MUGA scan may be utilized. Serum cardiac biomarkers are recommended, along with referral to a cardiologist if indicated.
• Extravasation: Vesicant; may cause severe local tissue necrosis if extravasation occurs. For IV administration only; not for IM or SubQ administration. Administer through a freely flowing IV infusion line. Ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.
• GI toxicity: Nausea/vomiting, mucositis, abdominal pain, and diarrhea commonly occur, although are severe in a small percentage of patients. Severe enterocolitis with perforation has been reported rarely (risk of perforation may be increased by instrumental intervention); consider the possibility of perforation in patients who develop severe abdominal pain and evaluate/manage appropriately.
• Hyperuricemia: Rapid lysis of leukemic cells may lead to hyperuricemia. Ensure adequate hydration and consider use of antihyperuricemic prophylaxis.
Disease-related concerns:
• Hepatic impairment: Dosage reductions are recommended in patients with hepatic impairment. Idarubicin use is not recommended if bilirubin >5 mg/dL.
• Infections: Systemic infections should be controlled prior to initiation of treatment.
• Renal impairment: Dosage reductions are recommended in patients with renal impairment.
Special populations:
• Elderly: Patients >60 years of age who were undergoing induction therapy experienced heart failure, serious arrhythmias, chest pain, MI, and asymptomatic declines in LVEF more frequently than younger patients.
• Pediatrics: A panel from the American Society of Pediatric Hematology/Oncology (ASPHO) and International Society of Pediatric Oncology (SIOP) recommends in favor of an anthracycline infusion duration of at least 1 hour in pediatric patients to reduce the potential for cardiotoxicity (ASPHO/SIOP [Loeffen 2017]). However, extravasation risks should also be minimized and the protocol infusion duration specified in a protocol should be followed, particularly if the patient is receiving dexrazoxane as a cardioprotectant.
Substrate of P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Ado-Trastuzumab Emtansine: May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with ado-trastuzumab emtansine should avoid anthracycline-based therapy for up to 7 months after stopping ado-trastuzumab emtansine. Monitor closely for cardiac dysfunction in patients receiving this combination. Risk D: Consider therapy modification
Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Bevacizumab: May enhance the cardiotoxic effect of Anthracyclines. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Cardiac Glycosides: May diminish the cardiotoxic effect of Anthracyclines. Anthracyclines may decrease the serum concentration of Cardiac Glycosides. The effects of liposomal formulations may be unique from those of the free drug, as liposomal formulation have unique drug disposition and toxicity profiles, and liposomes themselves may alter digoxin absorption/distribution. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Risk C: Monitor therapy
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Consider administration of a 3rd dose of COVID-19 vaccine, at least 28 days after completion of the primary 2-dose series, in patients 5 years of age and older taking immunosuppressive therapies. Risk D: Consider therapy modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
Cyclophosphamide: May enhance the cardiotoxic effect of Anthracyclines. Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider avoiding echinacea in patients receiving therapeutic immunosuppressants, such cytotoxic chemotherapy. If combined, monitor for reduced efficacy of cytotoxic chemotherapy. Risk D: Consider therapy modification
Fam-Trastuzumab Deruxtecan: May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with fam-trastuzumab deruxtecan should avoid anthracycline-based therapy for up to 7 months after stopping fam-trastuzumab deruxtecan. Monitor closely for cardiac dysfunction in patients receiving this combination. Risk D: Consider therapy modification
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification
Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Risk D: Consider therapy modification
Margetuximab: Anthracyclines may enhance the adverse/toxic effect of Margetuximab. Specifically, the risk of cardiac dysfunction may be increased. Management: Avoid anthracycline-based therapy for up to 4 months after discontinuing margetuximab due to an increased risk of cardiac dysfunction. If anthracyclines must be used with margetuximab monitor cardiac function closely. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Risk D: Consider therapy modification
Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Taxane Derivatives: May enhance the adverse/toxic effect of Anthracyclines. Taxane Derivatives may increase the serum concentration of Anthracyclines. Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. Management: Consider separating doxorubicin and paclitaxel administration by as much time as possible, using liposomal doxorubicin or epirubicin instead of doxorubicin, or using docetaxel instead of paclitaxel. Monitor closely for cardiovascular and other toxicities. Risk D: Consider therapy modification
Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Trastuzumab: May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with trastuzumab should avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab. Monitor closely for cardiac dysfunction in patients receiving anthracyclines with trastuzumab. Risk D: Consider therapy modification
Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Evaluate pregnancy status prior to use in patients who may become pregnant; pregnancy should be avoided during treatment with idarubicin.
Patients who may become pregnant should use effective contraception during therapy and for at least 6.5 months after the last idarubicin dose. Patients with partners who may become pregnant should also use effective contraception during therapy and for at least 3.5 months after the last dose of idarubicin.
Idarubicin is associated with an intermediate risk of azoospermia and infertility in males (ESMO [Lambertini 2020]). Fertility preservation should be considered for both females and males prior to treatment with idarubicin. Recommendations are available for fertility preservation of male and female adult patients treated with anticancer agents (ASCO [Oktay 2018]).
Idarubicin is more lipophilic than other anthracycline antineoplastic agents, therefore placental transfer is more likely (BSH [Ali 2015]; ELN [Döhner 2010]). Neonatal neutropenia, cardiac cardiomyopathy, and an increased risk of other fetal complications may be associated with in utero exposure to idarubicin (BSH [Ali 2015]; Chang 2015; Lishner 2016; Thomas 2015). Fetal fatality has been reported following maternal use during the second trimester.
Available guidelines recommend use of an anthracycline agent other than idarubicin (in combination with cytarabine) for induction treatment in acute myeloid leukemia (AML) in pregnant patients, and treatment should only be in the second and third trimester (BSH [Ali 2015]; ESMO [Peccatori 2013]; Lishner 2016). The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy; the guidelines recommend referral to a facility with expertise in cancer during pregnancy and a multidisciplinary team (obstetrician, neonatologist, oncology team) is encouraged (ESMO [Peccatori 2013]).
A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (1-877-635-4499).
It is not known if idarubicin is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding should be discontinued prior to idarubicin therapy.
CBC with differential and platelet count (frequently), cardiac function (LVEF; prior and during treatment), serum electrolytes, renal function (serum creatinine; prior to and during treatment), uric acid, liver function (ALT, AST, bilirubin; prior to and during treatment). Evaluate pregnancy status prior to use in patients who may become pregnant. Monitor infusion site for signs of extravasation; monitor for GI toxicity and infection.
Cardiovascular monitoring (ASCO [Armenian 2017]): Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking. Echocardiogram (prior to treatment). In patients who develop signs/symptoms of cardiac dysfunction during therapy, an echocardiogram is recommended for diagnostic workup; if echocardiogram is not available or feasible, a cardiac MRI (preferred) or MUGA scan may be utilized; obtain serum cardiac biomarkers.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Idarubicin inhibits DNA and RNA synthesis by intercalation between DNA base pairs and by steric obstruction. Although the exact mechanism is unclear, it appears that direct binding to DNA (intercalation) and inhibition of DNA repair (topoisomerase II inhibition) result in blockade of DNA and RNA synthesis and fragmentation of DNA.
Distribution: Vdss: 1,500 L/m2 (Robert 1993); extensive tissue binding; CSF
Protein binding: 94% (idarubicinol) to 97% (idarubicin)
Metabolism: Hepatic to idarubicinol (active metabolite)
Half-life elimination:
Children: Children ≥1 year of age and adolescents: 17.6 ± 6.8 hours (range: 8.3 to 29.6 hours) (Reid 1990)
Adults: Adults: 22 hours (range: 4 to 48 hours); >45 hours (idarubicinol)
Excretion: Primarily biliary; urine (8 to 10% as idarubicinol, ~2% to 5% as unchanged drug [Robert 1993])
Renal function impairment: The disposition may be affected in patients with renal impairment.
Hepatic function impairment: Possible impaired metabolism leading to higher systemic concentrations in patients with moderate and severe impairment; disposition may also be affected.
Solution (Idamycin PFS Intravenous)
5 mg/5 mL (per mL): $12.94
10 mg/10 mL (per mL): $12.93
20 mg/20 mL (per mL): $12.42
Solution (IDArubicin HCl Intravenous)
5 mg/5 mL (per mL): $7.20 - $19.76
10 mg/10 mL (per mL): $7.20 - $19.76
20 mg/20 mL (per mL): $7.20 - $19.76
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