Idamycin Drug Information

is indicated for the treatment of adult patients with acute myeloid leukemia (AML) as a component of a combination chemotherapy regimen. IDAMYCIN PFS is an anthracycline topoisomerase inhibitor indicated for the treatment of adult patients with acute myeloid leukemia (AML) as a component of a combination chemotherapy regimen.

• The following clinically significant adverse reactions are described elsewhere in the labeling:
• Cardiomyopathy [see Warnings and Precautions (5.1) ]
• Secondary Malignancies [see Warnings and Precautions (5.2) ]
• Severe Local Tissue Necrosis with Extravasation [see Warnings and Precautions (5.3) ]
• Severe Myelosuppression [see Warnings and Precautions (5.4) ]
• Tumor Lysis Syndrome [see Warnings and Precautions (5.5) ]
• Hypersensitivity [see Warnings and Precautions (5.6) ] Most common adverse reactions (≥30%) are infection, nausea/vomiting, alopecia, abdominal pain/diarrhea, hemorrhage, mucositis, dermatologic, mental status changes, and pulmonary disorders. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials and Postmarketing Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of IDAMYCIN PFS in combination with cytarabine has been evaluated in four controlled clinical studies with 823 patients with AML randomized to receive idarubicin hydrochloride (n=401) or daunorubicin (n=422) [see Clinical Studies (14) ] . Southeastern Cancer Study Group (SEG) Table 3 below lists the adverse reactions that occurred in patients with AML who received idarubicin hydrochloride in the Southeastern Cancer Study Group (SEG) study. Table 3: Adverse Reactions (≥5%) in Patients with AML Who Received Idarubicin Hydrochloride as Induction Therapy in the SEG Trial Adverse Reactions Idarubicin with Cytarabine (N=110) Daunorubicin with Cytarabine (N=118) All Grades % All Grades % Infection 95 97 Nausea/Vomiting 82 80 Alopecia 77 72 Abdominal Pain/Diarrhea 73 68 Hemorrhage 63 65 Mucositis 50 55 Dermatologic 46 40 Mental Status Changes 41 34 Pulmonary Disorders 39 39 Fever 26 28 Headache 20 24 Cardiac Disorder 16 24 Peripheral Neuropathy 7 9 Clinically relevant adverse reactions in <5% of patients who received idarubicin hydrochloride included pulmonary allergy, seizure, and cerebellar adverse reactions. Other Clinical Trials The following additional adverse reactions associated with the use of idarubicin hydrochloride were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac
• Asymptomatic declines in Left Ventricular Ejection Fraction (LVEF)
• Chest pain
• Congestive heart failure
• Myocardial infarction
• Serious arrhythmias including atrial fibrillation Dermatologic
• Bullous erythrodermatous rash (palms and soles)
• Generalized rash
• Radiation recall (skin reaction)
• Urticaria Gastrointestinal
• Severe enterocolitis with perforation Hepatic
• Increased ALT/AST Renal
• Renal impairment

Pregnancy Risk Summary Based on findings from animal reproduction studies and its mechanism of action, IDAMYCIN PFS can cause fetal harm when administered to a pregnant woman . There are no available data on the use of IDAMYCIN PFS in pregnant women to evaluate for a drug-associated risk. Idarubicin hydrochloride was embryotoxic and teratogenic in rats at doses of 1.2 mg/m 2 /day or 0.1 times the human dose. Idarubicin hydrochloride was embryotoxic but not teratogenic in rabbits at doses of 2.4 mg/m 2 /day or 0.2 times the human dose . Advise women of the potential risk to the fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Idarubicin hydrochloride was embryotoxic and teratogenic in the rat at a dose of 1.2 mg/m 2 /day or 0.1 times the human dose, which was not maternally toxic. Idarubicin hydrochloride was embryotoxic but not teratogenic in the rabbit even at a dose of 2.4 mg/m 2 /day or 0.2 times the human dose, which was maternally toxic.

Pediatric Use The safety and effectiveness of IDAMYCIN PFS in pediatric patients have not been established. Pediatric patients may be at greater risk for anthracycline-induced acute manifestations of cardiotoxicity or late cardiovascular dysfunction. The safety and effectiveness of idarubicin hydrochloride were assessed but not established in two open label clinical studies in pediatric patients aged 1 to <17 years with leukemia and solid tumors.

The pharmacokinetics of idarubicin hydrochloride in these pediatric patients were within range of that observed in adult patients given a similar dose based on body surface area. Idarubicin hydrochloride and idarubicinol were detected in CSF samples obtained in these patients; the clinical relevance of these findings is unknown.

There is no known antidote to idarubicin hydrochloride. Two cases of fatal overdosage in patients receiving therapy for AML have been reported. The doses were 135 mg/m 2 over 3 days and 45 mg/m 2 of idarubicin hydrochloride and 90 mg/m 2 of daunorubicin over a three-day period.

Based on multicompartment and extravascular distribution, tissue binding, and low unbound fraction available in plasma, hemodialysis or peritoneal dialysis are unlikely to significantly reduce exposure during an overdosage.