Oral Metastatic castration-sensitive prostate cancer
Adult: In combination with androgen deprivation therapy (ADT): 240 mg once daily. Continue medical castration with gonadotropin-releasing hormone analogue (GnRHa) during the treatment in patients who are not surgically castrated. If grade 3 or higher toxicity or an intolerable adverse reaction occurs, withhold dosing until symptoms improve to grade 1 or lower toxicity or original grade, then resume either at the same dose or a reduced dose (180 mg or 120 mg), if needed. Dosing discontinuation may be required according to individual safety and tolerability (refer to detailed product guidelines).
Oral Non-metastatic castration-resistant prostate cancer
Adult: In patients who are at high risk of developing metastatic disease: 240 mg once daily. Continue medical castration with GnRHa during the treatment in patients who are not surgically castrated. If grade 3 or higher toxicity or an intolerable adverse reaction occurs, withhold dosing until symptoms improve to grade 1 or lower toxicity or original grade, then resume either at the same dose or a reduced dose (180 mg or 120 mg), if needed. Dosing discontinuation may be required according to individual safety and tolerability (refer to detailed product guidelines).
May be taken with or without food.
Females who may become pregnant. Pregnancy and lactation.
Patient with history of seizure or predisposing factors for seizure (e.g. underlying brain injury, recent stroke [within 1 year], primary brain tumours, brain metastases); history or risk factors for QT prolongation; recent (within 6 months) CV disease, including recent MI, severe or unstable angina, symptomatic CHF, ventricular arrhythmias, arterial or venous thromboembolic events (e.g. pulmonary embolism, TIA). Severe renal and hepatic impairment. Elderly.
Significant: Seizures, falls and fractures, increased risk of CV disease, may prolong QT interval, hypothyroidism, elevated TSH; rash (usually macular or maculopapular). Blood and lymphatic system disorders: Anaemia, leucopenia, lymphopenia. Gastrointestinal disorders: Dysgeusia, diarrhoea, nausea. General disorders and administration site conditions: Fatigue, peripheral oedema. Investigations: Decreased weight. Metabolism and nutrition disorders: Decreased appetite, hypertriglyceridaemia, hypercholesterolaemia, hyperglycaemia, hyperkalaemia. Musculoskeletal and connective tissue disorders: Arthralgia, muscle spasm. Respiratory, thoracic and mediastinal disorders: Interstitial lung disease. Skin and subcutaneous tissue disorders: Alopecia, pruritus. Vascular disorders: Hypertension, hot flush. Potentially Fatal: Ischaemic heart disease, ischaemic cerebrovascular disorders, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Patient Counseling Information
Patients with female partners of childbearing potential must use effective birth control methods during therapy and for 3 months after stopping the treatment.
Evaluate patients for fall and fracture risk before starting therapy. Monitor thyroid function (e.g. TSH) as clinically needed; signs and symptoms of CV events (e.g. ischaemic heart disease), seizure, cerebrovascular events, and dermatologic toxicity.
Increased plasma concentration with strong CYP2C8 inhibitors (e.g. gemfibrozil) and strong CYP3A4 inhibitors (e.g. itraconazole). Decreased plasma concentration with rifampicin. May reduce the serum levels of warfarin; avoid co-administration or if necessary, conduct additional INR monitoring. May decrease the plasma concentrations of CYP3A4 substrates (e.g. darunavir, felodipine, simvastatin, midazolam), CYP2C19 substrates (e.g. diazepam, omeprazole), CYP2C9 substrates (e.g. phenytoin), UDP-glucuronosyltransferase (UGT) substrates (e.g. levothyroxine, valproic acid), P-glycoprotein (P-gp) substrates (e.g. colchicine, dabigatran etexilate, digoxin), breast cancer resistance protein (BCRP) or organic anion transporting polypeptide 1B1 (OATP1B1) substrates (e.g. rosuvastatin, lapatinib, methotrexate, repaglinide). May increase the risk of QT prolongation and may induce torsade de pointes with class IA (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic agents, methadone, moxifloxacin, and antipsychotics (e.g. haloperidol).
Description: Mechanism of Action: Apalutamide is a nonsteroidal androgen receptor inhibitor that binds directly to the androgen receptor ligand-binding domain to block androgen receptor nuclear translocation, DNA binding, and androgen receptor-mediated transcription leading to reduced tumour cell proliferation and increased apoptosis, thereby decreasing tumour volume. Pharmacokinetics: Absorption: Completely absorbed. Bioavailability: Approx 100%. Time to peak plasma concentration: 2 hours (range: 1-5 hours). Distribution: Volume of distribution: Approx 276 L. Plasma protein binding: 96% (apalutamide) and 95% (N-desmethyl apalutamide), mainly to albumin. Metabolism: Metabolised in the liver mainly by CYP2C8 and CYP3A4 isoenzymes into N-desmethyl apalutamide (active metabolite). Excretion: Mainly via urine (65%; 1.2% as apalutamide, 2.7% as N-desmethyl apalutamide); faeces (24%; 1.5% as apalutamide, 2% as N-desmethyl apalutamide). Elimination half-life: Approx 3 days.
Store between 15-30°C. Protect from light and moisture. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
L02BB05 - apalutamide ; Belongs to the class of anti-androgens. Used in treatment of neoplastic diseases.
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