ixabepilone (Ixempra)
Classes: Antineoplastics, Antimicrotubular; Antineoplastics, Epothilone B Analog
Dosing and uses of Ixempra (ixabepilone)
Adult dosage forms and strengths
powder for injection
- 15mg/vial
- 45mg/vial
Breast Cancer
Metastatic or locally advanced
After failure to anthracyclines
40 mg/m² IV infusion over 3 hr q3week; not to exceed 88 mg/dose
Monitor: CBC, LFTs
Premedication
Give H1-blocker and H2-blocker 1 hour prior to infusion
If patient had hypersensitivity to drug in prior infusion, also premedicate with corticosteroid
Concomitant CYP3A4
Consider dose reduction to 20 mg/m²
Increase dose 1 week after inhibitor discontinuation
Hepatic Impairment
AST/ALT <2.5 times upper limit of normal and Bilirubin < 1 time upper limit of normal: 40 mg/m²
AST/ALT <10 times upper limit of normal and Bilirubin < 1.5 times upper limit of normal: 32 mg/m²
AST/ALT <10 times upper limit of normal and Bilirubin 1.5-3 times upper limit of normal: 20-30 mg/m²
Do NOT use with capecitabine if AST/ALT >2.5 times upper limit of normal or bilirubin >1 time upper limit of normaL
Monotherapy not recommended if AST/ALT >10 times upper limit of normal or bili >3 times upper limit of normaL
Pediatric dosage forms and strengths
Safety and efficacy not established
Ixempra (ixabepilone) adverse (side) effects
>10%
Fatigue (63%)
Asthenia (63%)
Neuropathy (63%)
Leukopenia (49%)
Alopecia (48%)
Nausea (42%)
Stomatitis (29%)
Vomiting (29%)
Diarrhea (22%)
Myalgia (20%)
Arthralgia (20%)
Inflammatory disease of mucous membrane (19%)
Anorexia (19%)
Constipation (16%)
Abdominal pain (13%)
Dysgeusia
Mucositis
1-10%
Nail changes (9%)
Hand-foot syndrome (8%)
Neutropenia (3%)
Anemia
Dizziness
Dyspnea
Edema
Gastroesophageal reflux disease
Thrombocytopenia
Frequency not defined
Left ventricular cardiac dysfunction
Myocardial ischemia
Supraventricular arrhythmia
Hypersensitivity reaction (severe)
Warnings
Black box warnings
This drug in combination with capecitabine is contraindicated in patients with AST or ALT > 2.5 times the upper limit of normal (ULN) or bilirubin >1 times ULN due to increased risk of toxicity and neutropenia-related death
Contraindications
History of hypersensitivity to Cremophor EL or its derivatives
ANC <1.5 K/m³ or Platelets <100 K/m³
Ixabepilone/capecitabine combo contraindicated if AST/ALT >2.5 times ULN or bilirubin >1 time ULn
Cautions
Risk of usual chemotherapy ADRs (esp peripheral neuropathy and myelosuppression)
Avoid grapefruit juice
Strong CYP3A4 inducers (eg, rifampin) decrease ixabepilone AUC by 43% compared to ixabepilone treatment alone
Avoid pregnancy
History of cardiac disease
May cause neuropathy, primarily sensory; neuropathy is cumulative, generally reversible, and should be managed by dose adjustment and delays
Pregnancy and 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 of Ixempra (ixabepilone)
Mechanism of action
Microtubule inhibitor of epothilone group; promotes tubulin polymerization and stabilizes microtubular function, causing cell cycle (G2/M) arrest and subsequently apoptosis
Pharmacokinetics
Half-life elimination: 52 hr
Peak plasma time: 3 hr
Protein bound: 67-77%
Vd: >1000 L
Metabolism: Liver CYP3A4
Excretion: Feces (65%); urine (21%)
Administration
IV Preparation
If kit refrigerated, warm kit at room temp for 30 min (dissolves precipitate in diluent if any and produces clear diluent)
Reconstitute vials with supplied diluent: 15 mg with the 8 mL diluent; 45 mg with the 23.5 mL diluent (final conc 2 mg/mL)
Aseptically withdraw diluent and add to drug vial; swirl and invert to completely dissolve
Reconstituted solution stable for 1 hr at room temp and light
Dilute further in LR ~250 mL in DEHP-free bag
Stable for up to 6 hr at room temp and light (including 3 hr infusion time, ie upto 3 hr idle storage+3 hr infusion)
IV Administration
Use 0.2-1.2 micron inline filter
Use DEHP-free infusion apparatus
Infuse over 3 hr
Storage
Store original kit refrigerated and unopened