Oral Castration-resistant metastatic prostate cancer
Adult: In patient with disease progression after docetaxel therapy: 160 mg once daily. If ≥ grade 3 toxicity or intolerable side effects occurs, withhold treatment for 1 week or until symptoms improve, then resume to normal dosing or reduce to 80-120 mg once daily if needed. Dose reduction or discontinuation of treatment may be required according to individual safety or tolerability (refer to detailed product guideline).
Special Patient Group
Patient taking strong CYP2C8 inhibitors: 80 mg once daily.
Patient taking strong CYP3A4 inducers: 240 mg once daily.
May be taken with or without food. Swallow whole, do not chew/dissolve/open cap.
Females. Pregnancy and lactation. Concomitant use of warfarin and coumarin-like anticoagulants.
Patient with history or risk factors for seizures or other pre-disposing factors (e.g. underlying brain injury, stroke, brain tumours or brain metastases, or alcoholism), cardiovascular disease, QT prolongation. Severe renal and hepatic impairment.
Significant: Posterior reversible encephalopathy syndrome, seizures, hypospermatogenesis, risk of CV disease, QT prolongation. Blood and lymphatic system disorders: Neutropenia, thrombocytopenia, leucopenia. Gastrointestinal disorders: Constipation, diarrhoea, nausea, dysgeusia. General disorders and administration site conditions: Fatigue, asthenia, weakness. Immune system disorders: Myasthenia gravis. Infections and infestations: Infection. Injury, poisoning and procedural complications: Falls. Investigations: Weight loss. Metabolism and nutrition disorders: Peripheral oedema, decreased appetite. Musculoskeletal and connective tissue disorders: Back pain, arthralgia, musculoskeletal pain, bone fracture. Nervous system disorders: Headache, dizziness, paraesthesia, cauda equina syndrome, spinal cord compression, hypoaesthesia, restless leg syndrome, cognitive disorder, memory impairment, amnesia. Psychiatric disorders: Insomnia, anxiety, altered mental status, hallucination. Renal and urinary disorders: Haematuria, pollakiuria. Reproductive system and breast disorders: Gynaecomastia. Respiratory, thoracic and mediastinal disorders: Respiratory tract infection, dyspnoea. Skin and subcutaneous tissue disorders: Dry skin, pruritus. Vascular disorders: Hypertension, hot flash.
This drug may cause dizziness or vertigo, if affected, do not drive or operate machinery.
Monitor CBC with differential, LFT, blood pressure at baseline and periodically thereafter. Monitor for signs and symptoms of seizure or predisposing factors, infections, weight loss, posterior reversible encephalopathy syndrome, and risk of cardiovascular disease or peripheral oedema.
Decreased serum concentration with strong CYP2C8 and CYP3A4 inducers (e.g. carbamazepine, phenytoin, ritonavir). Increased risk of QT prolongation with antiarrhythmics (e.g. quinidine, amiodarone). Increased serum concentration and systemic exposure with strong CYP2C8 inhibitors (e.g. gemfibrozil), strong CYP3A4 inhibitors (e.g. itraconazole). Potentially Fatal: May decrease serum concentration of warfarin.
Decreased serum concentration with St John’s wort.
Description: Enzalutamide is a nonsteroidal antiandrogen which competitively inhibits binding of androgen to its receptor sites, nuclear translocation of the activated androgen receptors, and binding of the androgen receptor complex to DNA. This leads to cellular apoptosis and decreased tumour volume. Pharmacokinetics: Absorption: Rapidly absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 1 hour. Distribution: Volume of distribution: 110 L. Plasma protein binding: Approx 97% mainly to albumin; 95% (N-desmethyl enzalutamide), to plasma protein. Metabolism: Metabolised in the liver by CYP2C8 to active metabolite, N-desmethyl enzalutamide and by CYP3A4 enzyme; further metabolised to inactive carboxylic acid metabolite. Excretion: Mainly via urine (71% as inactive metabolites); faeces (14% as inactive metabolites). Elimination half-life: Approx 6 days (enzalutamide); approx 8 days (N-desmethyl enzalutamide).
Store between 20-25°C. Protect from moisture.
This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal. Wear gloves during receiving, unpacking, and placing in storage.
L02BB04 - enzalutamide ; Belongs to the class of anti-androgens. Used in treatment of neoplastic diseases.
Anon. Enzalutamide. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 27/03/2018.Anon. Enzalutamide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 27/03/2018.Buckingham R (ed). Enzalutamide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 27/03/2018.Joint Formulary Committee. Enzalutamide. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 27/03/2018.Xtandi Capsules (Astellas Pharma US, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 27/03/2018.