Enzalutamide Case Study

Bridge Hospital
35 Cromwell Crescent
Glasgow
G456ST
Radio Page 8957

Dear Mr Green,
I am writing in response to Enquiry 1, received 18/12/15, concerning Mr P McLachlan (CHI: 1709669921), and a request for advice on interactions between enzalutamide and statins.
Enzalutamide is a non-steroidal anti-androgen drug. It is a strong inducer of the CYP3A4 enzyzme1 which means that it may reduce the plasma concentration and hence the patient’s exposure to drugs metabolised by this route.
Simvastatin is metabolised by CYP3A4, as are lovastatin, cerivastatin and atorvastatin2. Due to a pharmacokinetic interaction, their concentrations may be reduced to sub-therapeutic levels with concomitant use of enzalutamide. There is no evidence in the literature
to support this theory however the UK manufacturer advises avoidance of statins metabolised by CYP3A4 where possible or use with caution if they are necessary3.
There is also no literature available on the use of simvastatin with enzalutamide, therefore I would recommend using an alternative to avoid the interaction.
Rosuvastatin, pravastatin and pitavistatin are not extensively metabolised by cytochrome enzymes2 and would therefore be safe and efficacious if a statin is required. I would advise using rosuvastatin 20mg daily as no significant interactions were found between rosuvastatin and Mr McLachlan’s other medications in the BNF4 or Stockley’s Drug Interactions5.
I have checked Mr McLachlan’s other medication and there may also be an interaction between enzalutamide and bisoprolol. The manufacturer specifically mentions that bisoprolol may be affected by enzalutamide3. This may be due to the fact that bisoprolol is partially metabolised by CYP3A46. However, it is also metabolised by CYP2D66 so the potential for reduced exposure is not as significant as with
simvastatin.
The full induction effects of enzalutamide may not be seen until concentrations reach steady-state at one month3.
The manufacturer advises monitoring for change in pharmacological response and adjusting the dose as required for drugs like bisoprolol3. This is the approach I would advise for Mr McLachlan as there is no evidence in the literature to support changing to another beta blocker to resolve the issue. Close monitoring of blood pressure and side effects should be undertaken as Mr McLachlan has only used enzalutamide for two weeks and any induction effects may not have been observed yet. If required, I advise increasing to 5mg bisoprolol daily.
It is also worth noting that the enzalutamide manufacturer excluded patients who had suffered from myocardial infarction (MI) in the last six months, and patients who had other cardiovascular conditions such as uncontrolled hypertension and unstable angina from phase 3 studies3. As Mr McLachlan’s past medical history shows that he has had an MI, depending on how recently it occurred, the safety data available may not be applicable to him. If this is the case, enzalutamide use should be very carefully
monitored.
In summary, due to the interaction with simvastatin and enzalutamide, I would advise changing to rosuvastatin whilst using enzalutamide. I would also suggest careful monitoring of bisoprolol and dose adjustment if required.

Laurie Swan (Pharmacist)
Pharmacy Department
Strathclyde Hospital
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