ixabepilone

ixabepilone

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

Ixempra

(trade name) Pregnancy Category: D

Indications

Action

Pharmacokinetics

Time/action profile (blood levels)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	end of infusion	unknown

Contraindications/Precautions

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

Availability

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.