IXABEPILONE

IXABEPILONE
(ix-a-be-pi'lone)
Ixempra
Classifications: antineoplastic agent; epothilone; Therapeutic: ; antineoplastic agent; antimitotic agent
Pregnancy Category: D

Availability

15 mg and 45 mg lyophilized powder, single-use vials

Action

Binds directly to microtubules needed to form the spindles required in mitosis of dividing cells.

Therapeutic Effect

Blocks new cell formation during the mitotic phase of their cell division cycle, thus leading to cancer cell death.

Uses

Treatment of metastatic or locally advanced breast cancer either alone or in combination with capecitabine in patients who have failed therapy with an anthracycline and a taxane. Monotherapy is indicated only if a patient has also failed with capecitabine therapy.

Contraindications

Hepatic impairment in patients with AST or ALT >10 x ULN, and/or bilirubin >3 x ULN; concomitant use of capecitabine and bilirubin >1 x ULN, or AST or ALT >2.5 x ULN; concomitant use of strong CYP3A4 inhibitors (e.g., itraconazole, saquinavir, etc.) or requires decreased dosage adjustment; grade 4 neuropathy or any other grade 4 toxicity; pregnancy (category D); lactation.

Cautious Use

Hypersensitivity to ixabepilone; monotherapy of patients with hepatic impairment baseline values of AST or ALT >5 x ULN.

Route & Dosage

Breast Cancer
Adult: IV 40 mg/m² over 3 h q3wk

Obesity
BSA >2.2 m²: dosage should be calculated based on 2.2 m² instead of m²

Dosage Adjustments
Grade 2 neuropathy ≥7 d, or grade 3 neuropathy <7 d, or grade 3 toxicity other than neuropathy: 32 mg/m²
Neutrophil <500 cells/mm³ ≥7 d, or febrile neutropenia, or platelets <25,000/mm³ or platelets <50,000/mm³ with bleeding: decrease dose by 20%
Grade 3 neuropathy ≥7 d or disabling neuropathy, or any grade 4 toxicity: do not administer
Regimen with a strong CYP3A4 inhibitor: 20 mg/m²

Hepatic Impairment in Monotherapy
AST and ALT ≤10 x ULN and bilirubin ≤1.5 x ULN: 32 mg/m²
AST and ALT ≤10 x ULN and bilirubin >1.5 x ULN but ≤3 x ULN: 20–30 mg/m²
AST and ALT >10 x ULN or bilirubin >3 x ULN: do not administer

Administration

Intravenous

Use gloves when handling vials containing ixabepilone.

PREPARE: IV Infusion: ??Supplied in kit containing a powder vial and diluent vial. Allow kit to come to room temperature for 30 min before reconstitution. ??Slowly inject diluent into the powder vial to yield 2 mg/mL. Swirl gently and invert vial to dissolve. ??Further dilute in RL solution in DEHP-free bags. Select a volume of RL to produce a final concentration of 0.2–0.6 mg/mL. Mix thoroughly.

ADMINISTER: IV Infusion: ??Use DEHP-free infusion line with a 0.2–1.2 micron in-line filter.??Infuse at a rate appropriate to the total volume of solution. Complete infusion within 6 h of preparation.

INCOMPATIBILITIES Solution/additive: Diluents other than lactated Ringer's injection should not be combined with ixabepilone. Y-site: Do not use a Y-site connection with this drug.

Store drug kit refrigerated at 2°–8° C (36°–46° F) in original packaging.
Reconstituted solution may be stored in the vial for a maximum of only 1 h at room temperature/light.
Once further diluted with lactated Ringer's injection, solution is stable at room temperature/light for 6 h.

Adverse Effects (≥1%)

Body as a Whole: Chest pain, dehydration, edema, fatigue, hypersensitivity reactions, pain, peripheral neuropathy, pyrexia. CNS: Dizziness, headache, insomnia. CV: Flushing. GI: Abdominal pain, anorexia, constipation, diarrhea, gastroesophageal reflux disease (GERD), mucositis, nausea, stomatitis, vomiting, taste disorder. Hematologic: Anemia, leukopenia, neutropenia, thrombocytopenia. Metabolic: Weight loss. Musculoskeletal: Arthralgia, myalgia, musculoskeletal pain. Respiratory: Cough, dyspnea, upper respiratory tract infection. Skin: Alopecia, exfoliation, hyperpigmentation, nail disorder, palmar-plantar erythrodysesthesia syndrome, pruritus, rash. Special Senses: Lacrimation.

Interactions

Drug: Inhibitors of CYP3A4 (e.g., hiv protease inhibitors, macrolide antibiotics, azole antifungal agents) increase the plasma level of ixabepilone. Strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital) decrease the plasma level of ixabepilone. Food: Grapefruit and grapefruit juice increase the plasma level of ixabepilone. Herbal: St. John's wort decreases the plasma level of ixabepilone.

Pharmacokinetics

Distribution: 67–77% protein bound. Metabolism: In liver. Elimination: Stool (major) and urine (minor). Half-Life: 52 h.

Nursing Implications

Actions & Drug Effects

Monitor for signs of an infusion-related hypersensitivity reaction.
Monitor for and promptly report signs of neuropathy.
Lab tests: Baseline and periodic WBC count with differential, platelet count, LFTs; periodic serum electrolytes.

Patient & Family Education

Report promptly any of the following: numbness and tingling of the hands or feet, S&S of infection (e.g., fever of 100.5° F or greater, chills, cough, burning or pain on urination), hives, itching, rash, flushing, swelling, shortness of breath, difficulty breathing, chest tightness or pain, palpitations or unusual weight gain.
Use effective contraceptive measures to prevent pregnancy.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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