Adult Dosing
Metastatic or locally advanced breast cancer (Monotherapy or in combination with capecitabine)
- 40 mg/m2 IV over 3 hrs q3 wks
- Body surface area >2.2 m2, calculate the dose based on 2.2 m2
- If on strong CYP3A4 inhibitor, decrease the dose to 20 mg/m2, and if strong inhibitor is discontinued allow washout period of 1 wk before adjusting the dose upward
- If on strong CYP3A4 inducer, gradually increase to 60 mg/m2 administered over 4 hrs. and monitor patients for signs of toxicity
- To minimize the occurrence of a hypersensitivity reaction premedicate the patient with an H1, H2 antagonist and corticosteroid approximately 1 hr before the infusion
Note:
- See prescribing information for details about dose adjustments based on toxicity
Pediatric Dosing
- Safety and effectiveness in pediatric patients have not been established
[Outline]
- Peripheral neuropathy has been reported commonly with ixabepilone; monitor patients for the symptoms of neuropathy, such as burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, or neuropathic pain. Reduce or delay the dose if new or worsening of neuropathy occurs and use cautiously in patients with diabetes mellitus or preexisting peripheral neuropathy
- Dose-dependent myelosupression, primarily manifested as neutropenia, has been observed with ixabepilone therapy. Monitor peripheral blood count at baseline and then periodically and taper the dose if neutropenia or thrombocytopenia is noted. Do not use in patients with neutrophil count <1500 cells/mm3
- Hepatotoxicity occurs with ixabepilone therapy, do not use in combination with capecitabine in patients with AST or ALT >2.5 x ULN or bilirubin >1 x ULN due to increased risk of toxicity and neutropenia-related death [US Black Box Warning]
- When administered as monotherapy ixabepilone should be used in reduced dose depending on the degree of hepatic impairment. Do not use in patients with AST or ALT >10 x ULN or bilirubin >3 x ULN and use caution when treating patients with AST or ALT >5 x ULN
- Ixabepilone can cause hypersensitivity reactions especially in patients with a history of a severe hypersensitivity reaction to agents containing cremophor or its derivatives (e.g. polyoxyethylated castor oil). Do not use in these patients. Premedicate all patients with H1 and an H2 antagonist approximately 1 hour before infusion and in case of severe hypersensitivity discontinue the treatment and provide supportive treatment (epinephrine, corticosteroids)
- Ixabepilone can cause fetal harm when administered to pregnant women, advise patients not to become pregnant during therapy and if becomes pregnant while taking this drug, should be apprised of the potential hazard to the fetus
- Cardiac adverse reactions have been observed more frequently with ixabepilone in combination with capecitabine than in the capecitabine alone. Use cautiously in patients with history of cardiac disease and discontinue the drug if cardiac ischemia or impaired cardiac function develops
- As ixabepilone product contains dehydrated alcohol, consider the possibility of central nervous system and other effects of alcohol
Cautions: Use cautiously in
- AST or ALT >5 x ULN
- Diabetes mellitus
- Cardiac diseases
- History of cardiac diseases
- Preexisting peripheral neuropathy
Pregnancy Category:D
Breastfeeding: Safety unknown, as many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants a decision must be made whether to discontinue nursing or to discontinue ixabepilone taking into account the importance of the drug to the mother.
2.5 x ULN and bilirubin 
