Ixempra

ixabepilone

(icks-a-bep-i-lone) ,

Ixempra

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: epothilone b analogues
Pregnancy Category: D

Indications

Combination use with capecitabine for the treatment of metastatic or locally advanced breast cancer currently resistant to a taxane and anthracycline or resistant to a taxane and cannot tolerate further anthracycline. May also be used as monotherapy for breast cancers that are not responding to anthracyclines, taxane, or capecitabine.

Action

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

Therapeutic effects

Decreased spread of breast cancer.

Pharmacokinetics

Absorption: IV administration results in complete bioavailablity.
Distribution: Unknown.
Metabolism and Excretion: Extensively metabolized by the liver, primarily by the CYP3A4 enzyme system. Metabolites are not active and are excreted mainly by the kidneys.
Half-life: 52 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
IVunknownend of infusionunknown

Contraindications/Precautions

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 limits of normal or bilirubin >1 × upper limit of normal) due to ↑ risk of toxicity and death associated with neutropenia; Obstetric / Lactation: Pregnancy or lactation.
Use Cautiously in: Toxicity; dose adjustments may be required for neuropathy/arthralgia/myalgia/fatigue, neutropenia, thrombocytopenia, moderate hepatic impairment or palmar-plantar erythrodysesthesia;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; Obstetric: Patients with childbearing potential; Pediatric: Effectiveness not established.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue (most frequent)
  • weakness (most frequent)
  • dizziness
  • headache
  • insomnia

Ear, Eye, Nose, Throat

  • ↑ lacrimation

Cardiovascular

  • chest pain
  • edema
  • left ventricular dysfunction
  • myocardial ischemia

Respiratory

  • dyspnea

Gastrointestinal

  • abdominal pain (most frequent)
  • anorexia (most frequent)
  • constipation (most frequent)
  • diarrhea (most frequent)
  • mucositis (most frequent)
  • nausea (most frequent)
  • stomatitis (most frequent)
  • vomiting (most frequent)
  • altered taste

Dermatologic

  • alopecia (most frequent)
  • hyperpigmentation (most frequent)
  • nail disorder (most frequent)
  • palmar-plantar erythrodysesthesia (combination therapy with capecitabine) (most frequent)
  • exfoliation
  • pruritus
  • rash
  • hot flushes

Hematologic

  • myelosuppression

Musculoskeletal

  • arthralgia (most frequent)
  • musculoskeletal pain (most frequent)
  • myalgia (most frequent)

Neurologic

  • peripheral neuropathy (most frequent)

Miscellaneous

  • hypersensitivity reactions

Interactions

Drug-Drug interaction

Strong CYP3A4 inhibitors including ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, atazanavir, delavirdine, ritonavir, saquinavir, 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.St. John's wort may ↓ blood levels and should be avoided.Grapefruit juice may ↑ blood levels and toxicity; avoid concurrent use.

Route/Dosage

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

Hepatic Impairment

Intravenous (Adults) Moderate Impairment—20 mg/m2 every 3 wk; not to exceed 30 mg/m2.

Availability

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

Nursing implications

Nursing assessment

  • 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.
  • Lab Test Considerations: 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 × the upper limits of normal (ULN) and bilirubin ≤1 × ULN administer ixabepilone at 40 mg/m2. If AST and ALT ≤10 × the upper limits of normal (ULN) and bilirubin ≤1 X ULN administer ixabepilone at 32mg/m2. If AST and ALT ≤10 × the upper limits of normal (ULN) and bilirubin >1.5 × ULN—≤3 × ULN administer ixabepilone at 20–30 mg/m2.

Potential Nursing Diagnoses

Risk for injury (Adverse Reactions)

Implementation

  • 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).
  • Intravenous Administration
  • pH: 6.0–7.5.
  • 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. 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. Administer through an in-line filter with a microporous membrane of 0.2–1.2 microns. DEHP-free infusion containers and administration sets must be used. Discard remaining solution.
  • Rate: Infuse over 3 hr.

Patient/Family Teaching

  • 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 difficulty 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.
  • Advise women of childbearing potential to use effective contraception during therapy and to avoid breast feeding during therapy.

Evaluation/Desired Outcomes

  • Decreased progression of breast cancer.

Ixempra

a trademark for ixabepilone.
Mentioned in ?
References in periodicals archive ?
The global breast cancer therapeutics market report estimates the market size (Revenue USD million - 2013 to 2020) for key market segments based on the drug classes - brand name (chemical name) such as antimetabolites - Gemzar (gemcitabine), aromatase inhibitors - Afinitor (everolimus), Arimidex (anastrozole), Aromasin (exemestane), Femara (leterozole), Ibrance (palbociclib); Her2 Inhibitors - Herceptin (trastuzumab), Kadcyla (ado-trastuzumab emtansine), Perjeta (pertuzumab), Tykerb (lapatinib); Hormone receptors - Fareston, Faslodex, Zoladex; and Mitotic inhibitors - Halaven (eribulin), Ixempra (ixabepilone), Taxotere (docetaxel), and forecasts growth trends (CAGR% - 2016 to 2020).
M2 EQUITYBITES-August 19, 2015-Bristol-Myers Squibb sells IXEMPRA to R-PHARM US
M2 PHARMA-August 19, 2015-Bristol-Myers Squibb sells IXEMPRA to R-PHARM US
Perhaps emboldened by the Nexavar license, the government department in charge of intellectual property rights policy making, the Department of Industrial Policy and Promotion, is reportedly considering the issuance of more compulsory licenses to enable local Indian manufacturers to produce generic varieties of three specific anti-cancer drugs: (110) Sprycel (dasatinib), Ixempra (ixabepilone), and Herceptin (trastuzumab), each of which is currently patented by large foreign pharmaceutical companies.
M2 EQUITYBITES-August 18, 2015-R-PHARM reports purchase of IXEMPRA and announces launch of US commercial operations
M2 PHARMA-August 18, 2015-R-PHARM reports purchase of IXEMPRA and announces launch of US commercial operations
BMS paid $400 million upfront, will take a reduced share of revenues (with Otsuka contributing 30% of commercialization costs, up from nothing), and the two companies will now collaborate on a pair of oncology drugs, Sprycel and Ixempra.
Marketed as Ixempra by Bristol-Myers Squibb, it is in the vanguard of a new class of anticancer agents called epothilones.
GlobalData's pharmaceuticals report, Ixempra (Breast Cancer) - Analysis and Forecasts to 2020 provides Ixempra sales estimates for the US.
The companies have also established an oncology collaboration for two BMS products, Sprycel and Ixempra.
Sprycel sales were up 54% to $86 million and Ixempra sales were $25 million (+67%).
oncologists use Ixempra, which is neither approved in Europe nor in Japan, primarily from the third-line setting onward for both HER2-negative and HER2-positive metastatic disease with the highest patient share seen in fourth line (20 percent).