Seizure: ERLEADA is not recommended in patients with a history of seizures or other predisposing factors including, but not limited to, underlying brain injury, recent stroke (within one year), primary brain tumours or brain metastases. If a seizure develops during treatment with ERLEADA, treatment should be discontinued permanently. The risk of seizure may be increased in patients receiving concomitant medicinal products that lower the seizure threshold.
Seizure occurred in 0.2% of patients receiving ERLEADA in clinical studies. These studies excluded patients with a history of seizure or predisposing factors for seizure.
There is no clinical experience in re-administering ERLEADA to patients who experienced a seizure.
Falls and fractures: Falls and fractures occurred in patients receiving ERLEADA (see Adverse Reactions). Patients should be evaluated for fractures and fall risk before starting ERLEADA and should continue to be monitored and managed for fractures according to established treatment guidelines and use of bone-targeted agents should be considered.
Concomitant use with other medicinal products: Apalutamide is a potent enzyme inducer and may lead to loss of efficacy of many commonly used medicinal products (see Interactions). A review of concomitant medicinal products should therefore be conducted when apalutamide treatment is initiated. Concomitant use of apalutamide with medicinal products that are sensitive substrates of many metabolising enzymes or transporters (see Interactions) should generally be avoided if their therapeutic effect is of large importance to the patient, and if dose adjustments cannot easily be performed based on monitoring of efficacy or plasma concentrations.
Co-administration with warfarin and coumarin-like anticoagulants should be avoided. If ERLEADA is co-administered with an anticoagulant metabolised by CYP2C9 (such as warfarin or acenocoumarol), additional International Normalised Ratio (INR) monitoring should be conducted (see Interactions).
Recent cardiovascular disease: Patients with clinically significant cardiovascular disease in the past 6 months including severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias were excluded from the clinical studies. Therefore, the safety of apalutamide in these patients has not been established. If ERLEADA is prescribed, patients with clinically significant cardiovascular disease should be monitored for risk factors such as hypercholesterolaemia, hypertriglyceridaemia, or other cardio-metabolic disorders (see Adverse Reactions). Patients should be treated, if appropriate, after initiating ERLEADA for these conditions according to established treatment guidelines.
Androgen deprivation therapy may prolong the QT interval: In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval (see Interactions), physicians should assess the benefit-risk ratio including the potential for Torsade de pointes prior to initiating ERLEADA.
Effects on ability to drive and use machines: ERLEADA has no or negligible influence on the ability to drive and use machines. However, seizures have been reported in patients taking ERLEADA. Patients should be advised of the risk in regards to driving or operating machines.