Table 3.
Dose Adjustments for Ixabepilone
| Adjustment | Suggested Dose or Dose Modification |
|---|---|
| Nonhematological toxicity* | |
| Grade 2 neuropathy (moderate) lasting ≥7 days | Decrease dose by 20% |
| Grade 3 neuropathy (severe) lasting <7 days | Decrease dose by 20% |
| Grade 3 neuropathy (severe) lasting ≥7 days or disabling neuropathy | Discontinue treatment |
| Any grade 3 toxicity (severe) | Decrease dose by 20% |
| Transient grade 3 arthralgia/myalgia or fatigue | No change in ixabepilone dose |
| Grade 3 hand–foot syndrome | No change in ixabepilone dose |
| Any grade 4 toxicity (disabling) | Discontinue treatment |
| Hematological toxicity* | |
| Neutrophils <500 cells/mm3 for ≥7 days | Decrease dose by 20% |
| Febrile neutropenia | Decrease dose by 20% |
| Platelets <25,000/mm3or platelets <50,000/mm3 with bleeding | Decrease dose by 20% |
| Hepatic Impairment | |
| Ixabepilone monotherapy | |
| AST and ALT ≤2.5 × ULN and bilirubin ≤1 × ULN | Recommended dose: 40 mg/m2 |
| AST and ALT ≤10 × ULN and bilirubin ≤1.5 × ULN | Recommended dose: 32 mg/m2 |
| AST and ALT ≤10 × ULN and bilirubin >1.5 × ULN ≤3 × ULN | Recommended dose: 20–30 mg/m2 |
| Ixabepilone + capecitabine combination therapy | |
| AST or ALT >2.5 × ULN or bilirubin >1 × ULN | Contraindicated |
| Coadministration with other drugs | |
| Strong inhibitors of CYP 3A4†‡ | Starting dose: 20 mg/m2 |
ALT = alanine aminotransferase;AST = aspartate aminotransferase; CYP 3A4 = cytochrome P450 isoenzyme 3A4; ULN = upper limit of normal.
*
Toxicities graded in accordance with the National Cancer Institute Common Toxicity Criteria (CTC) for adverse events.
†
Inhibiting oxidative metabolism of ixabepilone may significantly increase its plasma concentrations.
‡
Examples of strong cytochrome CYP 3A4 inhibitors: ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine, and voriconazole.