60 mg film-coated tabletsPRESCRIBING INFORMATION
Please refer to Summary of Product Characteristics (SmPC) before prescribing.
Treatment of adult men with non-metastatic castration-resistant prostate cancer (nm-CRPC), at high risk of developing metastatic disease; metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT).
Dosage & Administration:
Adults: 240 mg (four 60 mg tablets) single daily dose, swallowed whole with or without food. Continue medical castration with gonadotropin releasing hormone analogue (GnRHa) during treatment in patients not surgically castrated. In the event of ≥ grade 3 toxicity or intolerable side effects, hold dose until symptoms improve to ≤ grade 1 or original grade; resume at same or reduced dose if warranted.
Children: No relevant use.
Elderly: No dose adjustment.
Renal impairment: Mild to moderate - no dose adjustment. Severe - not studied; caution advised. If treating, monitor patients for side effects, reduce dose if required.
Hepatic impairment: Baseline mild or moderate (Child Pugh Class A and B) - no dose adjustment. Severe - not recommended.
Hypersensitivity to active substance or any excipient. Women who are or may become pregnant.
Special warnings & Precautions:
Seizure: History of seizures or other predisposing factors - Erleada not recommended. Discontinue permanently if seizure develops during treatment. Risk of seizure may be increased in patients receiving concomitant medicinal products that lower the seizure threshold.
Ischaemic heart disease and ischaemic cerebrovascular disorders: Reported, including events leading to death; monitor for signs and symptoms of ischaemic heart disease and ischaemic cerebrovascular disorders, optimise management of risk factors, including hypertension, diabetes, dyslipidaemia.
Falls and fractures: Reported; evaluate patients for risk before starting Erleada; continue monitoring and manage according to established guidelines, consider use of bone-targeted agents.
Concomitant use with other medicinal products: Apalutamide is a potent enzyme inducer; may lead to loss of efficacy of concomitant medication. Review concomitant medication and refer to SmPC for further guidance. Avoid co-administration with warfarin and coumarin-like anticoagulants. If co-administered with an anticoagulant metabolised by CYP2C9 (e.g. warfarin or acenocoumarol), conduct additional International Normalised Ratio (INR) monitoring.
Recent cardiovascular disease: Monitor patients with clinically significant cardiovascular disease for risk factors (e.g. hypercholesterolaemia, hypertriglyceridaemia, other cardio-metabolic disorders) as safety in patients with clinically significant cardiovascular disease in the past 6 months has not been established. Refer to SmPC for further guidance.
Androgen deprivation therapy may prolong QT interval: Assess benefit-risk, including potential for Torsade de pointes, prior to initiating Erleada in patients with a history or risk factors for QT prolongation and those receiving concomitant medicinal products that might prolong QT interval.
Effects on ability to drive and use machines: Seizures reported; advise patients of risk for driving or operating machines.
Refer to SmPC for other side effects.
Very common: Hot flush, hypertension, diarrhoea, skin rash, fracture, arthralgia, fatigue, weight decreased, fall, decreased appetite.
Common: Hypothyroidism, hypercholesterolaemia,
hypertriglyceridaemia, dysgeusia, ischaemic heart disease, ischaemic cerebrovascular disorders, pruritus, alopecia, muscle spasm.
Other side effects: Seizure, QT prolongation, toxic epidermal necrolysis.
FERTILITY, PREGNANCY and LACTATION:
For patients having sex with female partners of reproductive potential, use a condom along with another highly effective contraception method, during treatment and for 3 months after last dose of Erleada. May cause harm to foetus (contraindicated in pregnancy). Do not use during breast-feeding.
Refer to SmPC for full details of interactions.
CYP2C8 and CYP3A4 inhibitors: CYP2C8 and CYP3A4 mediate the elimination of apalutamide and formation of active metabolite. No initial dose adjustment necessary with strong inhibitors of CYP2C8 (e.g., gemfibrozil, clopidogrel) or strong inhibitors of CYP3A4 (e.g., ketoconazole, ritonavir, clarithromycin), but consider reduction of Erleada dose based on tolerability.
Drug metabolising enzymes: Apalutamide is a strong inducer of CYP3A4 and CYP2Cl9, and weak inducer of CYP2C9. Concomitant use with medicinal products primarily metabolised by CYP3A4 (e.g., darunavir, felodipine, midazolam, simvastatin), CYP2Cl9 (e.g., diazepam, omeprazole), or CYP2C9 (e.g., warfarin, phenytoin) can result in lower exposure to these medicinal products. Substitution for these medicinal products is recommended or evaluation for loss of efficacy if no substitution. If given with warfarin, monitor INR. Concomitant administration with medicinal products that are substrates of UDP glucuronosyl transferase (UGT) (e.g., levothyroxine, valproic acid) can result in lower exposure to these medicinal products; evaluate for loss of efficacy and adjust dose of substrate if required. Concomitant use of substrates of CYP286 (e.g., efavirenz) has not been evaluated in vivo; monitor for side effects and loss of efficacy, perform dose adjustment if required.
Drug transporters: Apalutamide is a weak inducer of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide 181 (OATPlBl). Concomitant use with medicinal products that are substrates of P-gp (e.g., colchicine, dabigatran etexilate, digoxin), BCRP or OATPlBl (e.g., lapatinib, methotrexate, rosuvastatin, repaglinide) can result in lower exposure of these medicinal products; evaluate for loss of efficacy and adjust dose of substrate if required.
Medicinal products which prolong QT interval: Carefully evaluate use of Erleada, along and also with medicinal products able to induce Torsade de pointes such as class IA (e.g. quinidine, disopyramide) or class Ill (e.g., amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmics, methadone, moxifloxacin, antipsychotics (e.g. haloperidol), etc.
LEGAL CATEGORY: POM
PRESENTATIONS, PACK SIZES, MARKETING AUTHORISATION NUMBER(S) & BASIC NHS COSTS
|PRESENTATIONS||PACK SIZES||MARKETING AUTHORISATION NUMBER(S)||BASIC NHS COSTS|
MARKETING AUTHORISATION HOLDER: JANSSEN-CILAG INTERNATIONAL NV, Turnhoutseweg 30, B-2340 Beerse, Belgium.
FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK.
Prescribing information last revised: March 2021