Indications

Apalutamide is an androgen receptor inhibitor indicated for the treatment of patients with- metastatic castration-sensitive prostate cancer non-metastatic castration-resistant prostate cancer.

Composition

Pharmacology

Apalutamide is an orally administered, selective Androgen Receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR. Apalutamide prevents AR nuclear translocation, inhibits DNA binding, impedes AR-mediated transcription, and lacks androgen receptor agonist activity. Apalutamide treatment decreases tumor cell proliferation and increases apoptosis leading to potent antitumor activity.

Dosage & Administration

The recommended dose of Apalutamide is 240 mg (four 60 mg tablets) administered orally once daily. Swallow the tablets whole. Apalutamide can be taken with or without food. Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had a bilateral orchiectomy.

Contraindications

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

Side Effects

The following clinically significant adverse reactions are observed in clinical trial: Endocrine disorders: Hypothyroidism Metabolism and nutrition disorders: hypercholesterolaemia, hypertriglyceridaemia Nervous system disorders: Dysgeusia, seizure Cardiac disorders: ischaemic heart disease Vascular disorders: hot flush, hypertension Gastrointestinal disorders: diarrhea Skin and subcutaneous tissue disorders: skin rash, pruritus Musculoskeletal and connective tissue disorders: fracture, arthralgia, muscle spasm General disorders and administration site conditions: fatigue Investigations: weight decreased Injury, poisoning and procedural complications: fall, fracture

Pregnancy & Lactation

Pregnancy : Apalutamide is contraindicated in women who are or may become pregnant. Based on its mechanism of action, Apalutamide may cause foetal harm when administered during pregnancy. There are no data available from the use of Apalutamide in pregnant women. Animal reproductive studies have not been conducted with Apalutamide. Breast-feeding : It is unknown whether apalutamide/metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. Apalutamide should not be used during breast-feeding. Females and Males of Reproductive Potential : Contraception in males and females: It is not known whether apalutamide or its metabolites are present in semen. Apalutamide may be harmful to a developing foetus. For patients having sex with female partners of reproductive potential, a condom should be used along with another highly effective contraceptive method during treatment and for 3 months after the last dose of Apalutamide. Fertility : Based on animal studies, Apalutamide may decrease fertility in males of reproductive potential.

Precautions & Warnings

Seizure : Apalutamide 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 Apalutamide, treatment should be discontinued permanently. In two randomised studies (SPARTAN and TITAN), seizure occurred in 0.4% of patients receiving apalutamide 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 apalutamide. Patients should be evaluated for fracture and fall risk before starting Apalutamide 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 Apalutamide. 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 : Apalutamide is a potent enzyme inducer and may lead to loss of efficacy of many commonly used medicinal products. Concomitant use of apalutamide 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 apalutamide with warfarin and coumarin-Iike anticoagulants should be avoided. If Apalutamide 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 apalutamide in these patients has not been established. If Apalutamide 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 Apalutamide 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 Apalutamide.

Therapeutic Class

Cytotoxic Chemotherapy

Storage Conditions

Store below 30°C. Keep Apalutamide out of the sight and reach of children. Protect from moisture and light.