abiraterone


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abiraterone

(a-bi-ra-te-rone) ,

Zytiga

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: enzyme inhibitors
Pregnancy Category: X

Indications

With prednisone in the treatment of metastatic castration-resistant prostate cancer.

Action

Inhibits the enzyme 17α-hydroxylase/C17,20–lyase, which is required for androgen production. May also result in increased mineralocortocoid production.

Therapeutic effects

Decreased androgen production with decreased spread of androgen-sensitive prostate cancer.

Pharmacokinetics

Absorption: Hydrolyzed to its active compound following oral administration.
Distribution: Unknown.
Protein Binding: >99%.
Metabolism and Excretion: Metabolized by esterases to inactive compounds; eliminated primarily in feces as unchanged drug and metabolites; 5% excreted in urine.
Half-life: 12 hr.

Time/action profile (blood level)

ROUTEONSETPEAKDURATION
POunknown2 hr 12 hr

Contraindications/Precautions

Contraindicated in: Severe hepatic impairment (Child-Pugh Class C); Obstetric: Pregnancy or potential to become pregnant (may cause fetal harm); Lactation: Lactation.
Use Cautiously in: Cardiovascular disease (safety not established if LVEF <50% or NYHA Class III or IV heart failure;Recent myocardial infarctionVentricular arrhythmiasElectrolyte abnormalities or hypertension (correct/treat prior to initiation);Pre-existing liver disease (dose modification required for Child-Pugh Class B);Stress, infection, trauma, acute disease process (may result in adrenocortical insufficiency requiring additional corticosteroids).

Adverse Reactions/Side Effects

Noted for combination treatment with prednisone

Respiratory

  • cough

Cardiovascular

  • arrhythmia
  • edema
  • hypertension

Gastrointestinal

  • hepatotoxicity (life-threatening)
  • diarrhea
  • dyspepsia

Dermatologic

  • hot flush

Endocrinologic

  • adrenocortical insufficiency (due to concurrent prednisone)

Fluid and Electrolyte

  • hypokalemia

Genitourinary

  • nocturia
  • urinary frequency

Musculoskeletal

  • fracture
  • joint pain/discomfort

Interactions

Drug-Drug interaction

Acts as an inhibitor of the CYP2D6 enzyme system; avoid concurrent use with agents that are substrates of CYP2D6, especially those with narrow therapeutic indices, including thioridazine and dextromethorphan; if concurrent use is necessary, dosage ↓ of substrate may be required. Abiraterone is a substrate of the CYP3A4 enzyme system. Concurrent use of strong CYP3A4 inducers including carbamazepine, phenobarbital, phenytoin, rifabutin, rifapentine, or rifampin should be avoided or undertaken with caution.

Route/Dosage

Oral (Adults) 1000 mg once daily used in combination with 5 mg prednisone twice daily; Concurrent use of strong CYP3A4 inducer—1000 mg twice daily.

Hepatic Impairment

Oral (Adults) Child-Pugh Class B—250 mg once daily with 5 mg prednisone twice daily.

Availability

Tablets: 250 mg

Nursing implications

Nursing assessment

  • Monitor BP and assess for fluid retention at least monthly. Control hypertension during therapy.
  • Monitor for signs and symptoms of adrenocortical insufficiency (hypotension, weight loss, weakness, nausea, vomiting, anorexia, lethargy, confusion, restlessness), especially in patients under stress or who are withdrawn from or have decreased prednisone dose. Symptoms may be masked by abiraterone.
  • Lab Test Considerations: Monitor AST, ALT, and bilirubin prior to, every 2 wks for 3 mo, and monthly thereafter. If AST and/or ALT ↑ >5 times upper limit of normal or bilirubin ↑ >3 times upper limit of normal in patients with baseline moderate hepatic impairment, interrupt abiraterone. Following return of liver function to baseline or AST and ALT ↑ >2.5 times upper limit of normal or bilirubin ↑ >1.5 times upper limit of normal may re-start at a reduced dose of 750 mg once daily. Monitor serum transaminases and bilirubin every 2 wks for 3 mo and monthly thereafter. If hepatotoxicity recurs, may restart at 500 mg once daily following return to baseline or AST and ALT ↑ >2.5 times upper limit of normal or bilirubin ↑ >1.5 times upper limit of normal. If hepatotoxicity recurs at 500 mg dose, discontinue therapy.
    • Monitor serum potassium and sodium at least monthly during therapy. May cause hypokalemia; control during therapy.
    • May cause ↑ triglycerides and ↓ phosphorous.

Potential Nursing Diagnoses

Activity intolerance

Implementation

  • Control hypertension and correct hypokalemia prior to starting therapy.
  • Oral: Administer twice daily with prednisone on an empty stomach at least 2 hrs before or 1 hr after meals; food increases absorption. Swallow tablets whole with water; do not crush, break, or chew.

Patient/Family Teaching

  • Instruct patient to take medication as directed and not to stop abiraterone or prednisone without consulting health care professional. If a dose is missed, take the following day. If more than 1 dose is missed, consult health care professional. Do not share medication with others, even if they have the same symptoms; may be dangerous.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Advise patient to notify health care professional of side effects that are bothersome or persistent.
  • Advise female patient to use effective contraception during therapy and for 1 wk after therapy and to notify health care professional immediately of pregnancy is suspected or if breast feeding. Male patients should use a condom and another form of contraception during sex with a women of child-bearing potential during and for 1 wk after therapy. Pregnant women should not touch the tablets without wearing gloves.
  • Explain need for continued follow-up exams and lab tests to assess possible side effects.

Evaluation/Desired Outcomes

  • Decreased spread of androgen-sensitive prostate cancer.
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References in periodicals archive ?
Release date- 22072011 - Beerse, Belgium, Janssen-Cilag International NV announced today that the Committee for Medical Products for Human Use (CHMP) of the European Medicines Agency (EMA) has granted a positive opinion recommending approval of ZYTIGA (abiraterone acetate) under an accelerated regulatory review procedure.
"In this trial, abiraterone shrank or stabilised men's cancers for an average of almost six months, which is a very impressive result." About three-quarters of men experienced a drop in PSA levels, including a fall of at least 50% for around half of the patients in the trial.
The once-a-day pill abiraterone hasbeen found to cut PSA (prostate specific antigen) levels by more than 90% in about half the patients given the drug.
Early PSA response was observed with the addition of onvansertib to daily abiraterone in 2 of 6 patients, with 1 patient achieving the efficacy endpoint of disease control and a 30% decrease in tumor size by RECIST criteria.
M2 PHARMA-June 5, 2018-AstraZeneca and MSD present data on Lynparza in combination with abiraterone
Janssen, a Johnson and Johnson (NYSE: JNJ) company, stated that the licence for Zytiga (abiraterone acetate) plus prednisone/prednisolone will be widened to include an earlier stage of metastatic prostate cancer than its current indications.
Abiraterone acetate (AA) is the prodrug of abiraterone, an irreversible, highly selective CYP17 inhibitor that targets its 17[alpha]-hydroxylase and [C.sub.17,20]-lyase activities (Fig.
Both health boards said the men " had previously taken another drug, abiraterone, and there were concerns about cross-resistance.
The All-Wales Medicines Strategy Group (AWMSG) has approved the use of the drug abiraterone acetate for men with cancer, which has spread beyond the prostate and is resistant to conventional hormone treatment (metastatic castration-resistant prostate cancer).
ICR scientist Dr Gert Attard has been at the forefront of developing the prostate cancer drug abiraterone and is one of the scientists doing the skydive.
The ProSTAR study is evaluating CPI-1205, Constellation's potent and highly selective small-molecule EZH2 inhibitor, in combination with either enzalutamide or abiraterone / prednisone, in mCRPC patients who experienced disease progression while receiving the other ARS inhibitor.