enzalutamide

enzalutamide

(en-za-loo-ta-mide) ,

Xtandi

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: androgen receptor inhibitors
Pregnancy Category: X

Indications

Management of metastatic castration-resistant prostate cancer in patients previously treated with docetaxel.

Action

Acts as an androgen receptor inhibitor, preventing the binding of androgen; also inhibits androgen nuclear translocation and DNA interaction.
Decreases proliferation and induces cell death of prostate cancer cells.

Therapeutic effects

Decreased growth and spread of prostate cancer.

Pharmacokinetics

Absorption: Well absorbed following oral administration.
Distribution: Unknown.
Protein Binding: Enalutamide—97–98%; N-desmethylenzalutamide—95%.
Metabolism and Excretion: Extensively metabolized by the liver (CYP2C8 and CYP3A4 enzyme systems); one metabolite (N-desmethylenzalutamide) has antineoplastic activity. Metabolites are primarily renally excreted, only minimal amounts as unchanged drug.
Half-life: Enalutamide—5.8 days; N-desmethylenzalutamide—7.8–8.6 days.

Time/action profile (improved survival)

ROUTEONSETPEAKDURATION
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Contraindications/Precautions

Contraindicated in: Pregnancy (may cause fetal harm) or women with child-bearing potential.
Use Cautiously in: History of seizures, underlying brain pathology, cerebrovascular accident, transient ischemic attack (within 12 mo), brain metastases or brain arteriovenous malformation (may increase risk of seizures); Geriatric: elderly may be more sensitive to drug effects; Pediatric: Safe and effective in children has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • seizures (life-threatening)
  • spinal cord compression/cauda equina syndrome (life-threatening)
  • headache (most frequent)
  • weakness (most frequent)
  • anxiety
  • dizziness
  • hallucinations
  • insomnia
  • mental impairment disorders

Ear, Eye, Nose, Throat

  • epistaxis

Cardiovascular

  • peripheral edema (most frequent)
  • hypertension

Gastrointestinal

  • diarrhea (most frequent)

Genitourinary

  • hematuria
  • urinary frequency

Dermatologic

  • hot flush (most frequent)
  • dry skin
  • pruritus

Musculoskeletal

  • arthralgia (most frequent)
  • musculoskeletal pain (most frequent)
  • muscular stiffness
  • musular weakness

Neurologic

  • hypoesthesia
  • paresthesia

Interactions

Drug-Drug interaction

Strong inhibitors of the CYP2C8 enzyme system (including gemfibrozil ) may ↑ blood levels and the risk of adverse reactions/toxicity and should be avoided; if concurrent administration is necessary, dose of enzalutamide should be ↓.Strong/moderate inducers of the CYP3A4 or CYP2C8 enzyme systems (including rifampin ) may alter levels and response and should be avoided.Substrates of the CYP3A4, CYP2C9 (including warfarin) and CYP2C19 systems that have narrow therapeutic indexes should be avoided as their levels and activity may be decreased; careful monitoring is recommended.Concurrent use of drugs that ↓ seizure threshold may ↑ risk of seizures.

Route/Dosage

Oral (Adults) 160 mg (four 40-mg capsules) once daily; if ≥Grade 3 toxicity or intolerable adverse reactions occur, discontinue for 1 wk and resume at the same or lower dose (80 or 120 mg). Concurrent use of strong CYP2C8 inhibitors—80 mg once daily.

Availability

Capsules: 40 mg

Nursing implications

Nursing assessment

  • Monitor for seizures. Implement seizure precautions.
  • Lab Test Considerations: May cause hematuria.

Potential Nursing Diagnoses

Activity intolerance

Implementation

  • Oral: Administer 4 capsules once daily without regard to food. Swallow capsules whole; do not open, dissolve, or chew.
    • If ≥Grade 3 toxicity or intolerable side effects occur, withhold dose for 1 wk or until symptoms improve to <Grade 2, then resume at same or reduced dose (120 mg or 80 mg).

Patient/Family Teaching

  • Instruct patient to take enzalutamide as directed at the same time each day. Take missed doses as soon as remembered within the same day. If a whole day is missed, omit dose and take next day's scheduled dose; do not double doses. Advise patient not to interrupt, modify dose, or stop taking enzalutamide without consulting health care professional.
  • May cause seizures, dizziness, mental impairment, paresthesia, hypoesthesia, falls, and hallucinations. Caution patient to avoid driving and other activities requiring alertness until response to medication is known. Notify health care professional immediately if loss of consciousness or seizure occurs.
  • Inform patient of common side effects associated with enzalutamide: asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper and lower respiratory infection, muscular weakness, dizziness, insomnia, spinal cord compression, cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension. Notify health care professional if falls or problems thinking clearly, or if side effects are bothersome.
  • Caution patients that enzalutamide is teratogenic. Advise patient to avoid pregnancy and breast feeding during and for 3 mo following completion of therapy. Male patients should use a condom if having sex with a pregnant woman, and a condom and another effective method of birth control should be used if having sex with a woman of child-bearing potential.

Evaluation/Desired Outcomes

  • Decreased growth and spread of prostate cancer.
Drug Guide, © 2015 Farlex and Partners
References in periodicals archive ?
(3.) Antonarakis ES, Lu CX, Wang H, et al.: AR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer.
The National Institute for Health and Care Excellence said enzalutamide, also known as xtandi, should be offered to men in whom the disease has spread to other parts of the body.
He was promoted from his position as executive director of oncology marketing, where he oversaw the launch of prostate cancer drug, Xtandi (enzalutamide), and promotion of lung cancer therapy, Tarceva (erlotinib).
Several studies investigating such possibilities are ongoing; these include docetaxel + ADT; enzalutamide/abiraterone; enzalutamide/degarelix ± trametinib or dasatinib; and enzalutamide ± LHRH analogue.
Enzalutamide blocks hormone signals and works on cancers that fail to respond to other treatment.
Oral VERU-111 was evaluated in the 22Rv1 prostate cancer model, which represents a highly resistant and aggressive form of the disease possessing androgen receptor splice variants that are commonly found in prostate cancer resistant to hormonal approaches like abiraterone and enzalutamide. In the same model, docetaxel administered by injection did not have significant effect on tumor growth.
M2 EQUITYBITES-March 25, 2016-Medivation & Astellas Pharma initiates Pivotal Phase III trial of enzalutamide with ADT in metastatic hormone sensitive prostate cancer
Effect of prior abiraterone on enzalutamide activity in metastatic castrate-resistant prostate cancer
M2 PHARMA-March 20, 2018-Astellas announces US FDA priority review for XTANDI (enzalutamide) sNDA for non-metastatic castration-resistant prostate cancer
Clinical activity of enzalutamide against metastatic castration-resistant prostate cancer (mCRPC) in patients who have progressed on abiraterone acetate: The Princess Margaret experience.