icks-a-BEP-i-lone

Therapeutic Classification: antineoplastics

Pharmacologic Classification: epothilone B analogues

• Metastatic or locally advanced breast cancer resistant to a taxane and anthracycline or resistant to a taxane and with contraindication to further anthracycline therapy (in combination with capecitabine).
• Metastatic or locally advanced breast cancer after failure of an anthracycline, a taxane, and capecitabine (as monotherapy).

• Binds to -tubulin subunits on microtubules; this action blocks cells in mitosis, leading to cell death.
• Also has antiangiogenic activity.

• Decreased spread of breast cancer.

Absorption: IV administration results in complete bioavailablity.

Distribution: Unknown.

Metabolism/Excretion: Extensively metabolized by the liver, primarily by the CYP3A4 isoenzyme. Metabolites are not active and are excreted mainly by the kidneys.

Half-life: 52 hr.

(plasma concentrations)

Contraindicated in:

• Previous hypersensitivity to any medications containing Cremophor EL or similar derivatives (polyoxyethylated castor oil)
• Neutrophils <1500 cells/m³ or platelets <100,000 cells/m³
• Severe hepatic impairment
• Use with capecitabine is contraindicated for hepatic impairment (AST or ALT >2.5× upper limit of normal [ULN] or bilirubin >1× ULN) due to ↑ risk of toxicity and death associated with neutropenia
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Diluent contains dehydrated alcohol; consider possible CNS effects
• Diabetes or history of neuropathy (↑ risk of severe neuropathy)
• History of cardiac disease (may ↑ risk of myocardial ischemia or ventricular dysfunction)
• Rep: Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CV: chest pain, edema, left ventricular dysfunction, myocardial ischemia.

Derm: alopecia, hyperpigmentation, nail disorder, palmar-plantar erythrodysesthesia (combination therapy with capecitabine), exfoliation, hot flushes, pruritus, rash.

EENT: ↑lacrimation.

GI: abdominal pain, anorexia, constipation, diarrhea, mucositis, nausea, stomatitis, vomiting, altered taste.

GU: ↓fertility.

Hemat: myelosuppression.

MS: arthralgia, musculoskeletal pain, myalgia.

Neuro: fatigue, peripheral neuropathy, weakness, dizziness, headache, insomnia.

Resp: dyspnea.

Misc: hypersensitivity reactions.

Drug-Drug:

• Strong CYP3A4 inhibitors, including ketoconazole, itraconazole, voriconazole, clarithromycin, atazanavir, ritonavir, and nefazodone, ↑ blood levels and the risk of serious toxicities; concurrent use should be avoided if possible. If concurrent use is required, dose reduction of ixabepilone is recommended.
• Inducers of the CYP3A4 enzyme system including dexamathasone, phenytoin, carbamazepine, phenobarbital, rifampin, rifampicin, or rifabutin may ↓ levels and effectiveness, avoid if possible.

Drug-Natural Products:

• St. John's wort may ↓ blood levels and should be avoided.

Drug-Food:

• Grapefruit juice may ↑ blood levels and toxicity; avoid concurrent use.

• IV (Adults): 40 mg/m² every 3 wk; not to exceed dose greater than that calculated for 2.2 m² (88 mg/dose).

• Powder for injection (requires specific diluent for initial reconstitution): 15-mg vial (contains 16 mg ixabepilone to allow for withdrawal losses) with 8 mL of diluent in a separate vial as a kit; 45-mg vial (contains 47 mg ixabepilone to allow for withdrawal losses) with 23.5 mL of diluent in a separate vial as a kit;

• Monitor for hypersensitivity reaction (flushing, rash, dyspnea, bronchospasm). If severe reactions occur stop infusion and provide aggressive supportive treatment with epinephrine and corticosteroids. In subsequent cycles, add corticosteroids to the premedication regimen.
• Monitor for myelosuppression frequently during therapy. Assess for signs of infection during neutropenia. Assess for bleeding (bleeding gums, bruising, petechiae, blood in stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min.
• Assess patient for signs of peripheral neuropathy (burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain); may occur early during treatment within the first 3 cycles. Patients experiencing new or worsening symptoms may require a reduction or delay in dose of ixabepilone. If neuropathy is Grade 2 (moderate) lasting for 7 days or Grade 3 (severe) lasting for <7 days, decrease dose by 20%. If neuropathy is Grade 3 lasting 7 days or is disabling, discontinue treatment.

• Verify negative pregnancy test before starting therapy.Monitor CBC and platelets frequently during therapy. If neutrophil count is <500 cells/mm³ for 7 days or patient has febrile neutropenia or if platelet count is <25,000/mm³ or platelets are <50,000/mm³ with bleeding, decrease the dose by 20%. Begin new treatment cycle only if neutrophil count is at least 1500 cells/mm³ and nonhematologic toxicities have improved to Grade 1 (mild) or resolved. May also cause leukopenia and anemia.
  • Monitor hepatic function prior to therapy. Patients with decreased hepatic function require a decreased dose. If AST and ALT 2.5 × ULN and bilirubin 1 × ULN, administer ixabepilone at 40 mg/m². If AST and ALT 10 × ULN and bilirubin 1 × ULN, administer ixabepilone at 32 mg/m². If AST and ALT 10 × ULN and bilirubin >1.5–3 × ULN, administer ixabepilone at 20–30 mg/m².

• Premedicate patient with an H₁ and an H₂ antagonist approximately 1 hr before ixabepilone infusion. Patients who experienced a hypersensitivity reaction in a previous ixabepilone cycle should also be premedicated with corticosteroids and extension of the infusion time should be considered.
  • To minimize risk of dermal exposure, wear impervious gloves when handling ixabepilone vials regardless of setting (unpacking and inspection, transport within a facility, dose preparation and administration).

IV Administration:

• Intermittent Infusion: Remove Ixempra kit (containing ixabepilone vial and diluent vial) from refrigerator and allow to stand at room temperature for 30 min prior to diluting. Ixempra kit must be stored in refrigerator. When vials are first removed from refrigerator, a white precipitate may be observed in the diluent vial; precipitate will dissolve to form a clear solution once diluent warms to room temperature. Use only diluent supplied in kit for reconstitution. Reconstitution: Reconstitute 15-mg vial with 8 mL and 45-mg vial with 23.5 mL of diluent. Gently swirl and invert vial until powder is completely dissolved.
  Diluent: Prior to administration, dilute constituted solution further with only LR supplied in DEHP-free bags. Dilute as soon as possible after constitution, but may be stored at room temperature and room light for up to 1 hr. For most doses use 250-mL bag of LR, 0.9% NaCl (pH adjusted 6.0–9.0 with sodium bicarbonate), or Plasma-lyte A injection (pH 7.4).Concentration: If final concentration is not between 0.2 mg/mL and 0.6 mg/mL, add to appropriate size bag of LR. Thoroughly mix infusion bag by manual rotation. Diluted solution is stable for up to 6 hr at room temperature and room light; must complete infusion during 6-hr period. DEHP-free infusion containers and administration sets must be used. Discard remaining solution.
• Rate: Infuse over 3 hr through an in-line filter with a microporous membrane of 0.2–1.2 microns.

• Explain purpose of ixabepilone to patient.
• Advise patient to avoid grapefruit juice during therapy; may lead to increased levels and side effects.
• Solution contains alcohol and may cause drowsiness or dizziness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
• Instruct patient to notify health care professional promptly if fever >100.5°F; chills; cough; hoarseness; sore throat; signs of infection; lower back or side pain; burning, painful or difficult urination; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; increased fatigue; dyspnea; or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections. Instruct patients to use a soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate bleeding.
• Instruct patient to notify health care professional promptly if signs and symptoms of hypersensitivity (hives, urticaria, pruritus, rash, flushing, swelling, dyspnea, chest tightness), peripheral neuropathy (numbness and tingling in hands and feet), or cardiac adverse reactions (chest pain, difficulty breathing, palpitations, unusual weight gain) occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products, especially St. John's wort.
• Instruct patient not to receive any vaccinations without advice of health care professional.
• Discuss the possibility of hair loss with patient. Explore methods of coping. Regrowth usually occurs 2–3 mo after discontinuation of therapy.
• Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 7 mo after last dose of therapy and to avoid breastfeeding during and for 2 wks after last dose of therapy. Advise males with female partners of reproductive potential to use effective contraception during and for four mo after last dose. May impair female and male fertility.

• Decreased progression of breast cancer.

Ixempra Kit

NDC Code^*

• 70020- R-Pharm US Operating, LLC
  • 70020-1910- IXEMPRA
    • 70020-1910-1- 1 KIT in 1 PACKAGE, COMBINATION (70020-1910-1) * 15 mg in 1 VIAL, SINGLE-USE * 8 mL in 1 VIAL, SINGLE-USE

• 70020- R-Pharm US Operating, LLC
  • 70020-1911- IXEMPRA
    • 70020-1911-1- 1 KIT in 1 PACKAGE, COMBINATION (70020-1911-1) * 45 mg in 1 VIAL, SINGLE-USE * 23.5 mL in 1 VIAL, SINGLE-USE