Apalutamide

Hypersensitivity to the active substance
Women who are or may become pregnant

Seizure
: Apaluda 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 Apaluda, treatment should be discontinued permanently. In two randomised studies (SPARTAN and TITAN), seizure occurred in 0.4% of patients receiving Apaluda and in 0.2% of patients treated with placebo. These studies excluded patients with a history of seizure or predisposing factors for seizure.
Falls and fractures
: Falls and fractures occurred in patients receiving Apaluda. Patients should be evaluated for fracture and fall risk before starting Apaluda and should continue to be monitored and managed according to established treatment guidelines and use of bone-targeted agents should be considered.
Ischaemic heart disease
: Ischaemic heart disease, including events leading to death, occurred in patients treated with Apaluda. The majority of patients had cardiac risk factors. Patients should be monitored for signs and symptoms of ischaemic heart disease and management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidaemia should be optimised as per standard of care.
Concomitant use with other medicinal products
: Apaluda is a potent enzyme inducer and may lead to loss of efficacy of many commonly used medicinal products. Concomitant use of Apaluda with medicinal products that are sensitive substrates of many metabolising enzymes or transporters 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 of Apaluda with warfarin and coumarin-Iike anticoagulants should be avoided. If Apaluda is co-administered with an anticoagulant metabolised by CYP2C9 (such as warfarin or acenocoumarol), additional International Normalised Ratio (INR) monitoring should be conducted.
Recent cardiovascular disease
: Patients with clinically significant cardiovascular disease in the past 6 months including severe/unstabie angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischaemic attacks), or clinically significant ventricular arrhythmias were excluded from the clinical studies. Therefore, the safety of Apaluda in these patients has not been established. If Apaluda is prescribed, patients with clinically significant cardiovascular disease should be monitored for risk factors such as hypercholesterolaemia, hypertriglyceridaemia, or other cardio-metabolic disorders. Patients should be treated after initiating Apaluda 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, physicians should assess the benefit-risk ratio including the potential for Torsade de pointes prior to initiating Apaluda.