Abiraterone

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

17-(3-Pyridyl)androsta-5,16-dien-3β-ol; Abiaterone; Abiraterone acetate

Definition
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Abiraterone is a substance with antiandrogenic effect. It acts as an androgen biosynthesis inhibitor. The effective form of the prodrug abiraterone acetate and is well orally bioavailable. The preparation is used together with prednisone or prednisolone for the treatment of advanced prostate cancer (Ryan CJ et al. 2015).

Half-life
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The plasma half-life of abiraterone is about 15 hours in healthy volunteers. Abiraterone is mainly excreted in the stool and to a lesser extent in urine.

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Pharmacodynamics (Effect)
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Abiraterone acetate is metabolised in vivo to abiraterone. Abiraterone selectively inhibits the enzyme steroid-17α hydroxylase (CYP17A1), which catalyses a biochemical step in androgen (testosterone) and estrogen biosynthesis. This also inhibits extratesticular androgen production (adrenal gland and prostate). Here, abiraterone blocks the conversion of pregnenolone or progesterone into the testosterone precursors DHEA or androstenedione (see figure). This complex inhibition leads to mineralocorticoid overproduction in the adrenal glands. To reduce the mineralocorticoid toxicity, abiraterone acetate must always be administered together with prednisone or prednisolone (Ang, JE et al. 2009).

Indication
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Treatment of metastatic castration-resistant prostate cancer in adult men whose disease progresses during or after docetaxel-containing chemotherapy.

Treatment of metastatic castration-resistant prostate cancer (mCRPC) in adults with no or mild symptoms after failure of hormone withdrawal therapy if chemotherapy is not yet indicated.

Treatment of a newly diagnosed metastatic hormone sensitive high-risk prostate cancer (mHSPC) in adults in combination with androgen deprivation therapy (de Bono JS et al. 2011)

Undesirable effects
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Hypertension, hypokalemia, peripheral edema, diarrhea, urinary tract infections, joint swelling or pain, heart failure, angina pectoris, cardiac arrhythmia.

Interactions
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CYP2D6: Abiraterone acetate interacts with drugs that are metabolized by CYP2D6 For drugs with a narrow therapeutic range that are metabolised by CYP2D6, dose reduction should be considered. Medicinal products metabolised by CYP2D6 include dextromethorphan, metoprolol, propranolol, desipramine, venlafaxine, haloperidol, risperidone, propafenone, flecainide, codeine, oxycodone and tramadol.

CYP2C8: Abiraterone acetate is an inhibitor of the drug-metabolizing liver enzyme CYP2C8. Drugs which are metabolized by CYP2C8 include paclitaxel and repaglinide.

CYP3A4: Abiraterone acetate is a substrate of CYP3A4. Thus, an influence of strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) or CYP3A4 inducers (e.g. ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) is possible. e.g. phenytoin, carbamazepine, rifampicin, rifabutin, rifapentin, phenobarbital) on the pharmacokinetics of abiraterone acetate. Strong CYP3A4 inhibitors or inducers should be avoided during treatment if possible or used with caution.

Contraindication
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Hypersensitivity to the active substance abiraterone acetate or any of the other ingredients.

Pregnant women or women who might be pregnant. Severe liver dysfunction (Child-Pugh Class C).

Preparations
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Abiraterone acetate has been approved in Germany under the trade name Zytiga® since October 2011.

Note(s)
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During treatment with GnRH analogues the production of androgens in the testicles is reduced. This medication has no effect on androgen production in the adrenal glands or tumour.

Literature
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  1. Ang, JE et al (2009) CYP17 blockade by abiraterone: further evidence for frequent continued hormone-dependence in castration-resistant prostate cancer. IBritish Journal of Cancer 100: 671-675
  2. Argawal,N et al (2010) Abiraterone acetate: a promising drug for the treatment of castration-resistant prostate cancer. Future Oncology 6: 665-679
  3. de Bono JS et al (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364:1995-2005.
  4. Ryan CJ et al (2015) Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 16:152-160.

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Last updated on: 29.10.2020