Enzalutamide


Concise Prescribing Info
Indications/Uses
Castration-resistant metastatic prostate cancer.
Dosage/Direction for Use
Adult : PO 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. May reduce dose or discontinue based on individual safety and tolerability.
Dosage Details
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.
Administration
May be taken with or without food. Swallow whole, do not chew/dissolve/open cap.
Contraindications
Females. Pregnancy and lactation. Concomitant use of warfarin and coumarin-like anticoagulants.
Special Precautions
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.
Adverse Reactions
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.
Patient Counseling Information
This drug may cause dizziness or vertigo, if affected, do not drive or operate machinery.
MonitoringParameters
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.
Overdosage
Symptoms: Seizures. Management: Supportive treatment.
Drug Interactions
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.
Food Interaction
Decreased serum concentration with St John’s wort.
Action
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).
Chemical Structure

Chemical Structure Image
Enzalutamide

Source: National Center for Biotechnology Information. PubChem Database. Enzalutamide, CID=15951529, https://pubchem.ncbi.nlm.nih.gov/compound/Enzalutamide (accessed on Jan. 22, 2020)

Storage
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.
ATC Classification
L02BB04 - enzalutamide ; Belongs to the class of anti-androgens. Used in treatment of neoplastic diseases.
References
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.

Disclaimer: This information is independently developed by MIMS based on Enzalutamide from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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