Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 1mg/mL
Acute Myeloid Leukemia
Induction: 12 mg/m² IV qDay over 10-15 min for 3 day with concomitant cytarabine
Consolidation: 10-12 mg/m²/day IV for 2 days
Renal Impairment
Children
- CrCl < 50 mL/min: 75% of dose
- Peritoneal dialysis: 75% of dose
- Hemodialysis: 75% of dose
- Renal replacement therapy: 75% of dose
Adults
- CrCl 10-50 mL/min: 75% of dose
- CrCl <10 mL/min: 50% of dose
- Hemodialysis: Supplemental dose not necessary
- Peritoneal dialysis: Supplemental dose not necessary
Hepatic Impairment
Bilirubin 2.6-5 mg/dL: 50% of dose
Bilirubin >5 mg/dL: Avoid use
Monitor
CBC, LFTs, cardiac & renal function
Administration
Mucositis Development: Discontinue if severe mucositis after 1st course, after resolution continue w/ 25% dose reduction
Dosage Forms & Strengths
injectable solution
- 1mg/mL
Acute Myeloid Leukemia
10-12 mg/m² IV qDay for 3 days q3weeks
Acute Lymphoblastic Leukemia (Orphan)
Treatment of acute lymphoblastic leukemia in pediatric patients.
Orphan indication sponsor
- Pharmacia & Upjohn; 7000 Portage Road, Unit 0633-298-113; Kalamazoo, MI 49001-0199
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Infection (95%)
Nausea (30-60%)
Vomiting (30-60%)
Alopecia (25-30%)
Hemorrhage (63%)
Stomatitis (11%)
Fever (26%)
Elevated bilirubin and transaminases (20-30%)
Myelosuppression: > 10%
1-10%
Seizure (4%)
CHF (2%)
Peripheral neuropathy (8%)
Frequency Not Defined
Fever
Chills
Headache
Flushing
Myocardial infarction
Cardiac dysrhythmia
Chest pain
Diarrhea
Inflammatory disease of mucous membrane
Hyperuricemia
Red discoloration of urine
Rash
Warnings
Black Box Warnings
The drug should be administered under the supervision of a cancer chemotherapy physician experienced in acute leukemia treatment in a facility with appropriate equipment to monitor patients compromised by drug toxicity. Severe hemorrhagic conditions or overwhelming infection resulting from the therapy should also be able to be treated at the facility.
Only administer intravenously into a freely flowing IV infusion. Do not administer intramuscularly or subcutaneously. Severe local tissue damage can occur with extravasation.
Myocardial toxicity leading to CHF may occur. Toxicity is more common with prior anthracycline use or preexisting cardiac disease.
Myelosuppression can be severe at therapeutic doses
Reduce dose in renal or hepatic impairment
Contraindications
Hypersensitivity
Serum bilirubin >5 mg/dL [>85.5 umol/L]
Cautions
Vesicant-avoid extravasation
Risk of myocardial toxicity leading to potentially fatal CHF
Prior radiation treatment to mediastinal-pericardial area & prior anthracyclines increases cardiotoxic risk
Cumulative doses >150 mg/m² associated with decreased ejection fraction
Possibility of injection site reactions
Hepatic/renal impairment
Avoid pregnancy
Pregnancy & Lactation
Pregnancy Category: D
Lactation: not known if excreted in breast milk; do not nurse
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
Anthracycline; intercalates between DNA base pairs, inhibits topoisomerase II, which in turn inhibits DNA and RNA synthesis
Pharmacokinetics
Half-Life: 14-35 hr (PO); 12-27 hr (IV)
Bioavailability: 30%
Protein Bound: 94-97%
Vd: 64 L/kg
Peak plasma time: 1-5 hr
Metabolism: Liver
Metabolites: Idarubicinol
Clearance: 122.8 L/hr
Excretion: Urine (5-13%)
Administration
IV Incompatibilities
Additive: heparin
Syringe: heparin
Y-site: acyclovir, allopurinol, ampicillin/sulbactam, cefazolin, cefepime, ceftazidime, clindamycin, dexamethasone Na-phosphate, etoposide, fluorouracil, furosemide, gentamicin, heparin, hydrocortisone Na-succinate, lorazepam, meperidine, methotrexate, piperacillin/tazobactam, Na-bicarb, teniposide, vancomycin, vincristine
IV Compatibilities
Solution: with most common diluents
Y-site (partial list): cimetidine, diphenhydramine, etoposide PO4, granisetron, MgSO4, metoclopramide, KCl
IV Preparation
Vials: reconstitute with NS to a concentration of 1 mg/mL
Standard dilution
- IV push: dose/syringe (concentration is 1 mg/mL); maximum syringe size for IVP is 30 mL syringe & syringe should be <75% full
- IVPB: dose/100 mL D5W or NS
IV Administration
Vesicant
Administer by intermittent infusion over 10-15 min
Administer into a free flowing IV solution of NS or D5W
Local erythematous streaking along the vein may indicate rapid administration
Extravasation Management
Topical cooling may be achieved using ice packs or cooling pad with circulating ice water
Cooling of site for 25 hr as tolerated by pt.
Elevate & rest extremity 24-48 hr, then resume normal activity as tolerated
Cold inhibits vesicant's cytotoxicity
Heat can be harmful & is contraindicated
If pain, erythema, &/or swelling persist beyond 48 hr, refer pt immediately to plastic surgeon for consultation & possible debridement
See also Totect
Storage
Store intact vials of lyophilized powder at room temp
Protect from light
Images
Patient Handout
Formulary
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Adding plans allows you to:
- View the formulary and any restrictions for each plan.
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- Compare formulary status to other drugs in the same class.
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