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Indications and Dosage
Oral
Non-metastatic castration-resistant prostate cancer Adult: For the treatment of men who are at high risk of developing metastatic disease: 600 mg bid. Continue medical castration with gonadotrophin-releasing hormone analogue during darolutamide treatment in patients not surgically castrated. If ≥Grade 3 toxicity or intolerable adverse reaction occurs, withhold treatment or reduce to 300 mg bid until symptoms improve, then may resume at the usual dose.
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Renal Impairment
In patients with severe cases (eGFR 15-29 mL/min/1.73 m2) who are not receiving haemodialysis: 300 mg bid.
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Hepatic Impairment
Moderate and severe (Child-Pugh class B and C): 300 mg bid.
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Administration
Should be taken with food.
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Special Precautions
Patient with significant CV disease in the past 6 months (e.g. stroke, MI, severe or unstable angina pectoris, CABG or peripheral artery bypass graft, symptomatic CHF); history or risk factors for QT-interval prolongation. Not indicated for use in females. Severe renal impairment (eGFR 15-29 mL/min/1.73 m2); moderate and severe hepatic impairment (Child-Pugh class B and C).
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Adverse Reactions
Significant: Neutropenia.
Cardiac disorders: Heart failure, ischaemic heart disease. General disorders and administration site conditions: Fatigue, asthenic conditions. Investigations: Increased AST or bilirubin. Musculoskeletal and connective tissue disorders: Fractures, pain in extremity, musculoskeletal pain. Skin and subcutaneous tissue disorders: Rash. |
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Patient Counseling Information
Males with female partners of childbearing potential must use highly effective contraception (or condoms if their partner is pregnant) during therapy and for 1 week following the last darolutamide dose.
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Monitoring Parameters
Monitor renal and hepatic function as clinically indicated. Evaluate for signs and symptoms of infection or toxicity.
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Drug Interactions
Concurrent use with moderate and strong CYP3A4 and P-glycoprotein (P-gp) inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifampicin) may decrease the serum concentration of darolutamide. May increase the serum concentration of breast cancer resistance protein (BCRP), organic anion transporting polypeptides (OATP) 1B1 or 1B3 substrates (e.g. rosuvastatin, atorvastatin, pitavastatin, fluvastatin, methotrexate, sulfasalazine). May increase the risk of adverse reactions with combined P-gp and strong CYP3A4 inhibitor (e.g. itraconazole). May increase the risk of QT prolongation with QT-prolonging drugs such as antiarrhythmic agents (e.g. disopyramide, quinidine, sotalol, amiodarone, ibutilide, dofetilide), moxifloxacin, methadone, antipsychotics (e.g. haloperidol).
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Food Interaction
May decrease serum concentration with St. John's wort. Increased bioavailability with food.
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Action
Description:
Mechanism of Action: Darolutamide is a non-steroidal competitive androgen receptor inhibitor that binds with high affinity directly to the receptor ligand-binding domain. It also inhibits androgen receptor nuclear translocation and androgen receptor-mediated transcription. The inhibition of androgen receptor causes reduced prostate tumour cell proliferation and increased apoptosis, resulting in a decrease in tumour volume. Pharmacokinetics: Absorption: Increased bioavailability by 2- to 2.5-fold when given with food. Bioavailability: Approx 30% (after 300 mg dose under fasted conditions). Time to peak plasma concentration: Approx 4 hours. Distribution: Widely distributed throughout the body. Plasma protein binding: 92% (darolutamide); 99.8% (keto-darolutamide); mainly to albumin. Metabolism: Mainly metabolised via oxidative metabolism by CYP3A4, also via direct glucuronidation by UGT1A9 and UGT1A1; keto-darolutamide is the active major metabolite. Excretion: Via urine (63.4%; approx 7% as unchanged drug); faeces (32.4%; approx 30% as unchanged drug). Elimination half-life: Approx 20 hours (darolutamide; keto-darolutamide). |
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Chemical Structure
 Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 67171867, Darolutamide. https://pubchem.ncbi.nlm.nih.gov/compound/Darolutamide. Accessed Nov. 25, 2021. |
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Storage
Store between 15-30°C. Follow applicable procedures for receiving, handling, administration, and disposal.
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MIMS Class
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ATC Classification
L02BB06 - darolutamide ; Belongs to the class of anti-androgens. Used in treatment of neoplastic diseases.
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References
Anon. Darolutamide. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 08/10/2021. Anon. Darolutamide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/11/2021. Buckingham R (ed). Darolutamide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/10/2021. Joint Formulary Committee. Darolutamide. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/10/2021. Nubeqa 300 mg Film-Coated Tablets (Bayer Healthcare Limited). MIMS Hong Kong. http://www.mims.com/hongkong. Accessed 08/10/2021. Nubeqa 300 mg Film-Coated Tablets (Bayer plc). MHRA. https://products.mhra.gov.uk. Accessed 08/10/2021. Nubeqa Tablet, Film-Coated (Bayer Healthcare Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 08/10/2021.
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