Abiraterone Formulations

A new presentation of abiraterone has been added to the Pharmaceutical Benefits Scheme (PBS). Abiraterone is available in several formulations that differ in strength, bioavailability, and administration instructions.

Abiraterone is an antiandrogen used in the treatment of prostate cancer. It selectively inhibits the CYP17 enzyme (17α hydroxylase/C17,20-lyase). This enzyme is involved in androgen biosynthesis in the testes, adrenal glands, and prostate tumour tissue. Blocking this enzyme significantly reduces the production of testosterone and other androgens, leading to suppression of tumour growth.

The CYP17 enzyme also plays a role in glucocorticoid production. When this enzyme is inhibited, there is a reduction in cortisol production which reduces negative feedback on adrenocorticotropic hormone (ACTH). As ACTH levels rise, there is an excess production of mineralocorticoids.

Some patients may experience symptoms of mineralocorticoid excess. This can include hypertension, hypokalaemia and fluid retention. Co-administration with a corticosteroid suppresses ACTH release. This reduces the incidence and severity of adverse effects associated with mineralocorticoid excess.

There are many brands of abiraterone available, as well as two products that also contain a corticosteroid, as shown in Table 1.

*Multiple generic brands available

**Dose may be reduced in response to toxicity

Andriga®

Andriga® is a composite pack containing 500mg abiraterone tablets and 5mg prednisolone tablets. It is marketed as Andriga-5® and Andriga-10® with both products containing the same strength and quantity of abiraterone. Andriga-5® is intended to provide 5mg per day of prednisolone while Andriga-10® provides 10mg per day of prednisolone.

The absorption of abiraterone is highly affected by food. Depending on the fat content of a meal, taking the tablet with food can increase systemic exposure up to 17 times compared to administration in a fasted state. As meals typically vary in composition, the manufacturer advises that the abiraterone tablets must be taken on an empty stomach, i.e. at least two hours after food and at least one hour before food.

The usual daily dose is abiraterone 1,000mg plus prednisolone 5mg (for hormone sensitive prostate cancer) or prednisolone 10mg (for metastatic castration-resistant prostate cancer).

Yonsa Mpred™

Yonsa Mpred™ is a composite pack containing 125mg abiraterone tablets and 4mg methylprednisolone tablets.

The abiraterone in this product is formulated as a fine particle which is intended to improve its bioavailability and reduce pharmacokinetic variability. Randomised studies found that 500mg fine particle abiraterone is bioequivalent to 1000mg in healthy subjects under fasted conditions. The effect of food on this formulation is not considered to be significant. Therefore, patients may take these tablets without regard to meals.

Therapeutic equivalence has also been demonstrated between 500mg fine particle abiraterone and 1000mg standard abiraterone in a study in men with progressive metastatic castration-resistant prostate cancer. Testosterone levels and prostate-specific antigen (PSA) were monitored after treatment with either 500mg fine particle abiraterone or 1000mg standard abiraterone. The study found comparable testosterone suppression, and a similar proportion of patients achieved at least 50% reduction in PSA from baseline.

The other key difference with Yonsa Mpred™ is the choice of glucocorticoid. Yonsa Mpred™ contains methylprednisolone instead of prednisolone. Methylprednisolone is a more potent corticosteroid, with 0.8mg methylprednisolone being approximately equivalent to 1mg of prednisolone.

The usual dose is abiraterone 500mg daily plus 4mg methylprednisolone (taken daily for metastatic hormone sensitive prostate cancer or twice daily for metastatic castration resistant prostate cancer).

Summary

Abiraterone is available in several presentations, and it is important to understand their differences. Standard abiraterone tablets must be taken on an empty stomach to reduce variations in drug exposure. Fine particle abiraterone (i.e. Yonsa Mpred™) has greater bioavailability and may be taken without regard to food. The two presentations are not interchangeable.

The current criteria for PBS subsidy is shown in Table 2.