ixabepilone (Ixempra)

Dosing and uses of Ixempra (ixabepilone)

• Adult
• Pediatric

 

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