IXEMPRA KIT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IXEMPRA KIT (IXEMPRA KIT).
Ixabepilone is a semi-synthetic analog of epothilone B that binds to tubulin and promotes microtubule assembly, stabilizing microtubule dynamics and leading to mitotic arrest and cell death.
| Metabolism | Primarily metabolized by CYP3A4; also metabolized by CYP2C8 and CYP2C19 to a minor extent. |
| Excretion | Primarily hepatic/biliary (approx. 75% of dose in feces), with renal excretion of unchanged drug accounting for approximately 6% in urine. |
| Half-life | Terminal elimination half-life is approximately 52 hours; supports every-3-week dosing regimen. |
| Protein binding | Approximately 94% bound to human serum proteins, predominantly albumin and alpha1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution at steady state (Vss) is approximately 1000 L/m² (or ~20 L/kg for a 50 kg patient), indicating extensive tissue distribution. |
| Bioavailability | Administered only intravenously; bioavailability is 100% by IV route. |
| Onset of Action | Intravenous: onset not well-defined; clinical effects observed within first cycle of treatment (3 weeks). |
| Duration of Action | Prolonged due to long half-life; effects persist over the 3-week dosing interval. |
40 mg/m2 intravenously over 3 hours every 3 weeks
| Dosage form | INJECTABLE |
| Renal impairment | For creatinine clearance less than 15 mL/min or on hemodialysis, reduce dose to 20 mg/m2; no adjustment for mild to moderate renal impairment |
| Liver impairment | Child-Pugh A: 32 mg/m2; Child-Pugh B: 20 mg/m2; Child-Pugh C: not recommended |
| Pediatric use | Safety and efficacy not established in pediatric patients |
| Geriatric use | No specific dose adjustment recommended, but monitor for increased toxicity |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for IXEMPRA KIT (IXEMPRA KIT).
| Breastfeeding | No data on ixabepilone excretion in human milk, effects on breastfed infant, or milk production. Due to potential for serious adverse reactions, advise patients not to breastfeed during treatment and for 2 weeks after the last dose. M/P ratio is unknown. |
| Teratogenic Risk | Ixabepilone (IXEMPRA KIT) is embryotoxic and fetotoxic in animal studies, causing increased resorption, reduced fetal weight, and skeletal abnormalities. No adequate human studies exist. Pregnancy Category D: Positive evidence of human fetal risk, but potential benefits may outweigh risks in life-threatening situations. Avoid in pregnancy unless absolutely necessary. |
■ FDA Black Box Warning
Ixabepilone in combination with capecitabine is contraindicated in patients with AST or ALT >2.5 x ULN or bilirubin >1 x ULN due to increased risk of neutropenia-related death.
| Serious Effects |
["Known hypersensitivity to ixabepilone or any component of the formulation","Neutrophil count <1500/mm^3","Platelet count <100,000/mm^3","Severe hepatic impairment (AST or ALT >5 x ULN or bilirubin >3 x ULN)"]
| Precautions | ["Peripheral neuropathy: monitor for symptoms; dose reduction or discontinuation may be required","Myelosuppression: monitor blood counts; severe neutropenia may occur","Hypersensitivity reactions: premedicate with antihistamines and corticosteroids","Cardiac toxicity: caution in patients with history of cardiac disease","Hepatic impairment: dose adjustment required; contraindicated with severe hepatic impairment"] |
| Food/Dietary | Avoid grapefruit and grapefruit juice during treatment with ixabepilone as they may increase drug concentrations. No other significant food interactions reported. |
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| Fetal Monitoring | Monitor complete blood counts (absolute neutrophil count, platelet count) prior to each dose. Assess for peripheral neuropathy, hypersensitivity reactions, and cardiac toxicity (ECG if history of cardiac disease). In pregnant patients, perform fetal ultrasound and monitoring for growth restriction. |
| Fertility Effects | Ixabepilone may impair fertility in males and females based on animal studies showing testicular degeneration, reduced sperm motility, and altered estrous cycles. Human data insufficient. |
| Clinical Pearls | IXEMPRA KIT (ixabepilone) is an epothilone B analog that stabilizes microtubules, similar to taxanes. It is indicated for metastatic or locally advanced breast cancer after failure of an anthracycline, a taxane, and capecitabine, or in combination with capecitabine after failure of an anthracycline and a taxane. Administer as a 3-hour IV infusion every 3 weeks. Premedicate with an H1 and H2 antagonist to prevent hypersensitivity reactions. Monitor for peripheral neuropathy, myelosuppression, and cardiac effects. Dose reduction required for hepatic impairment (Child-Pugh A or B). Contraindicated in Child-Pugh C. Use with caution in patients with diabetes or pre-existing neuropathy. |
| Patient Advice | This medication is given intravenously every 3 weeks for breast cancer. · You will receive premedication to reduce the risk of allergic reactions. · Report any numbness, tingling, or pain in hands/feet (peripheral neuropathy) immediately. · Common side effects include fatigue, nausea, diarrhea, and low blood counts (infection risk). · Avoid grapefruit or grapefruit juice during treatment as it may affect drug levels. · Tell your doctor all medications, including over-the-counter and herbal supplements. · Do not become pregnant; use effective contraception during and for 4 weeks after treatment. |