ENZALUNIX (ENZALUTAMIDE) 40MG 120`S

ENZALUNIX contains enzalutamide, a next-generation androgen receptor (AR) signalling inhibitor that targets multiple steps in the androgen signalling pathway.

Enzalutamide inhibits androgen binding to the androgen receptor; inhibits nuclear translocation of the activated receptor; and inhibits binding of the activated receptor to DNA. This results in near-complete androgen blockade with no agonist activity.

ENZALUNIX is used for:

·       Metastatic castration-resistant prostate cancer (mCRPC) — in men whose disease has progressed on or after docetaxel chemotherapy, or before chemotherapy;

·       Non-metastatic castration-resistant prostate cancer (nmCRPC) with high risk of metastasis (PSA doubling time of 10 months or less);

·       Metastatic castration-sensitive prostate cancer (mCSPC) in combination with GnRH agonist/antagonist.

Enzalutamide is taken in combination with ongoing androgen deprivation therapy (GnRH agonist or bilateral orchiectomy). In clinical trials (PREVAIL, ARCHES, TERRAIN), enzalutamide significantly prolonged overall survival and radiographic progression-free survival compared to bicalutamide or placebo.

The standard dose is 160 mg (four 40 mg capsules) taken orally once daily, with or without food. Capsules should be swallowed whole — do not open, dissolve, or chew.

Dose Modifications

•       Grade 3 or greater toxicity (including seizure): withhold until toxicity resolves to Grade 1 or less, then resume at the same or reduced dose (120 mg, then 80 mg).

•       Co-administration with strong CYP2C8 inhibitors (e.g., gemfibrozil): reduce enzalutamide dose to 80 mg once daily.

•       Mild-to-moderate hepatic or renal impairment: no dose adjustment required. Severe impairment: use with caution.

Missed Doses

If a dose is missed, take it as soon as remembered on the same day. If the missed dose is not remembered until the next day, skip that dose. Do not take two doses on the same day.

Very Common Side Effects (greater than 1 in 10)

•       Fatigue and asthenia — the most common side effect.

•       Hot flushes — due to androgen deprivation.

•       Headache.

•       Hypertension.

•       Musculoskeletal pain (arthralgia, back pain, myalgia).

•       Peripheral oedema.

Common Side Effects

•       Dizziness and cognitive changes (attention, memory).

•       Falls, fractures — partly related to fatigue and cognitive effects.

•       Weight gain, gynaecomastia.

•       Dry skin, pruritus.

Serious Side Effects

•       Seizures — reported in approximately 0.5% of patients. Risk increased by prior history of seizures, CNS pathology, or use of drugs that lower seizure threshold.

•       Posterior Reversible Encephalopathy Syndrome (PRES) — rare; symptoms: seizures, headache, confusion, visual disturbances.

•       Ischaemic heart disease — myocardial infarction, angina.

Seizure Risk

Enzalutamide lowers the seizure threshold. Before prescribing, review for history of seizures, prior brain surgery, stroke, or medications that lower seizure threshold (e.g., bupropion, tramadol, antipsychotics). Permanently discontinue if a seizure occurs during treatment. Patients must not drive or operate machinery after any seizure episode.

Cardiovascular Monitoring

Ischaemic heart disease events have been reported. Assess cardiovascular risk factors before treatment. Monitor blood pressure during therapy. Androgen deprivation therapy (ongoing in these patients) independently increases cardiovascular risk.

Falls and Fractures

Enzalutamide increases fall and fracture risk. Patients should be assessed for fall risk and advised on bone health measures (calcium, Vitamin D, bisphosphonate if indicated). DEXA scanning at baseline is recommended.

Drug Interactions — CYP Enzyme Induction

Enzalutamide is a strong inducer of CYP3A4 and CYP2C9, and a moderate inducer of CYP2C19 and P-glycoprotein. This can substantially reduce the plasma levels of many co-administered drugs. Review all medications for CYP3A4-sensitive substrates before starting enzalutamide.

•       Strong CYP2C8 inhibitors (gemfibrozil) — increase enzalutamide exposure significantly; reduce dose to 80 mg/day.

•       Strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, St John's Wort) — decrease enzalutamide plasma levels; avoid co-administration.

•       CYP3A4 substrates (simvastatin, tacrolimus, ciclosporin, warfarin, midazolam, many others) — enzalutamide induces CYP3A4 and reduces their levels significantly; dose adjustment or alternative agents required.

•       Warfarin — enzalutamide induces CYP2C9 (warfarin metabolism); INR may fall significantly; increase monitoring frequency when starting, stopping, or changing enzalutamide dose.

•       Drugs lowering seizure threshold (bupropion, tramadol, antipsychotics) — increased seizure risk; avoid if possible.

•       Store below 30 degrees Celsius.

•       Keep in original packaging, away from moisture.

•       Keep out of reach of children — enzalutamide is a reproductive toxin and must be kept away from women of childbearing potential.

•       Do not use after the expiry date.

ENZALUNIX is a prescription-only medicine (POM) in Kenya, regulated by the Pharmacy and Poisons Board. It must be prescribed by a consultant oncologist or urologist with expertise in prostate cancer management.

It is a specialist oncology treatment and should not be initiated in primary care settings.

Medication Review at Initiation

Perform a comprehensive medication review before prescribing ENZALUNIX. Enzalutamide is a strong CYP3A4 inducer — drugs with narrow therapeutic windows (warfarin, tacrolimus, statins, antiepileptics, DOACs) will require dose adjustments or switching. Consult a clinical pharmacist if multiple interactions are identified.

Monitoring Parameters

•       PSA: every 3 months — primary efficacy marker.

•       Testosterone: confirm castrate levels less than 50 ng/dL maintained.

•       Blood pressure: monthly for the first 3 months, then every 3 months.

•       Bone density (DEXA): at baseline and annually.

•       INR: 1–2 weeks after starting enzalutamide in patients on warfarin, then monthly.

Sequencing in mCRPC

ENZALUNIX can be used before or after docetaxel in mCRPC. Cross-resistance between enzalutamide and abiraterone exists; switching between the two AR-targeting agents after progression is generally not recommended. Cabazitaxel or lutetium-177 PSMA therapy are preferred next-line option post-enzalutamide.

Why do I take four capsules at once?

Each ENZALUNIX capsule contains 40 mg of enzalutamide. The daily therapeutic dose is 160 mg, which means you take four capsules together once a day. This is the standard regimen established in clinical trials. Do not split the dose across the day — once-daily dosing is important for maintaining consistent drug levels.

Can enzalutamide cause fits or seizures?

Seizures have been reported in approximately 0.5% of patients on enzalutamide. The risk is higher if you have a history of seizures, brain injury, or are taking medicines that lower the seizure threshold. If you have a seizure while on this medicine, stop immediately and seek emergency medical care. You should also avoid driving during treatment.

Why do I still need injections or tablets for hormone control while taking ENZALUNIX?

ENZALUNIX blocks the androgen receptor (the protein that testosterone binds to), but it does not stop testosterone production. GnRH agonist injections (such as triptorelin or leuprolide) or having the testes removed (orchiectomy) are needed to suppress testosterone levels, while ENZALUNIX ensures that any residual androgen cannot stimulate tumour growth. Both treatments work together for maximum effect.