ENZALUTAMIDE SANDOZ

Treatment with enzalutamide should be initiated and supervised by specialist physicians experienced in the medical treatment of prostate cancer. Posology The recommended dose is 160 mg enzalutamide (four 40 mg film-coated tablets or two 80 mg film-coated tablets) as a single oral daily dose.

Medical castration with a luteinising hormone-releasing hormone (LHRH) analogue should be continued during treatment of patients with CRPC or mHSPC who are not surgically castrated. Patients with high-risk BCR nmHSPC may be treated with enzalutamide with or without a LHRH analogue.

2 ng/mL) after 36 weeks of therapy. 0 ng/mL for patients who had prior primary radiation therapy. 1). If a patient misses taking Enzalutamide at the usual time, the prescribed dose should be taken as close as possible to the usual time.

If a patient misses a dose for a whole day, treatment should be resumed the following day with the usual daily dose. If a patient experiences a ≥ Grade 3 toxicity or an intolerable adverse reaction, dosing should be withheld for one week or until symptoms improve to ≤ Grade 2, then resumed at the same or a reduced dose (120 mg or 80 mg) if warranted.

Concomitant use with strong CYP2C8 inhibitors The concomitant use of strong CYP2C8 inhibitors should be avoided if possible. If patients must be co-administered a strong CYP2C8 inhibitor, the dose of enzalutamide should be reduced to 80 mg once daily.

5). 2). Hepatic impairment No dose adjustment is necessary for patients with mild, moderate or severe hepatic impairment (Child- Pugh Class A, B or C, respectively). 2). 2). 4). Paediatric population There is no relevant use of enzalutamide in the paediatric population in the indication of treatment of adult men with CRPC, mHSPC, or high-risk BCR nmHSPC.

Method of administration Enzalutamide is for oral use. The film-coated tablets should not be cut, crushed or chewed but should be swallowed whole with water, and can be taken with or without food.

Summary of the safety profile The most common adverse reactions are asthenia/fatigue, hot flush, hypertension, fractures, and fall. Other important adverse reactions include ischemic heart disease and seizure. 3% in bicalutamide-treated patients.

4). 4). Tabulated list of adverse reactions Adverse reactions observed during clinical studies are listed below by frequency category. Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 5) Vascular disorders Very common: hot flush, hypertension Gastrointestinal disorders Not known*: nausea, vomiting, diarrhoea Hepatobiliary disorders Uncommon: hepatic enzymes increased Skin and subcutaneous tissue disorders Common: dry skin, pruritus Not known*: erythema multiforme rash Musculoskeletal and connective tissue disorders Very common: fractures‡ Not known*: myalgia, muscle spasms, muscular weakness, back pain Reproductive system and breast disorder Common: gynaecomastia, nipple pain#, breast tenderness# General disorders and administration site conditions Very common: asthenia, fatigue Injury, poisoning and procedural Very common: fall * Spontaneous reports from post-marketing experience ¥ As evaluated by narrow SMQs of ‘Convulsions’ including convulsion, grand mal convulsion, complex partial seizures, partial seizures, and status epilepticus.

This includes rare cases of seizure with complications leading to death. † As evaluated by narrow SMQs of ‘Myocardial Infarction’ and ‘Other Ischemic Heart Disease’ including the following preferred terms observed in at least two patients in randomized placebo-controlled phase 3 studies: angina pectoris, coronary artery disease, myocardial infarctions, acute myocardial infarction, acute coronary syndrome, angina unstable, myocardial ischaemia, and arteriosclerosis coronary artery.

‡ Includes all preferred terms with the word ‘fracture’ in bones. # Adverse reactions for enzalutamide as monotherapy. 3%) receiving bicalutamide, experienced a seizure. Dose appears to be an important predictor of the risk of seizure, as reflected by preclinical data, and data from a dose-escalation study.

In the controlled clinical studies, patients with prior seizure or risk factors for seizure were excluded. 2%) patients treated with enzalutamide experienced a seizure. 3 months. The mechanism by which enzalutamide may lower the seizure threshold is not known but could be related to data from in vitro studies showing that enzalutamide and its active metabolite bind to and can inhibit the activity of the GABA-gated chloride channel.

5% of patients treated with enzalutamide plus ADT compared to 2% of patients treated with placebo plus ADT. 1%) patients treated with placebo plus ADT had an ischemic heart disease event that led to death. 4% of patients treated with enzalutamide plus leuprolide and 9% of patients treated with enzalutamide as monotherapy.

3%) patient treated with enzalutamide as monotherapy had an ischemic heart disease event that led to death. 9%) who were treated with enzalutamide as monotherapy. 8%) who were treated with enzalutamide as monotherapy. 3%) who were treated with enzalutamide as monotherapy.

Grade 3 or higher nipple pain was not observed in any patients who were treated with enzalutamide plus leuprolide or with enzalutamide as monotherapy. Breast tenderness In the EMBARK study, breast tenderness (all grades) was observed in 5 […]

8). The decision to continue treatment in patients who develop seizures should be taken case by case. 8). PRES is a rare, reversible, neurological disorder which can present with rapidly evolving symptoms including seizure, headache, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension.

A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). Discontinuation of Enzalutamide in patients who develop PRES is recommended. Second Primary Malignancies Cases of second primary malignancies have been reported in patients treated with enzalutamide in clinical studies.

2%). Patients should be advised to promptly seek the attention of their physician if they notice signs of gastrointestinal bleeding, macroscopic haematuria, or other symptoms such as dysuria or urinary urgency develop during treatment with enzalutamide.

5). A review of concomitant medicinal products should therefore be conducted when initiating enzalutamide treatment. 5) 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. 5). Renal impairment Caution is required in patients with severe renal impairment as enzalutamide has not been studied in this patient population. Severe hepatic impairment An increased half-life of enzalutamide has been observed in patients with severe hepatic impairment, possibly related to increased tissue distribution.

The clinical relevance of this observation remains unknown. 5) may be increased. Recent cardiovascular disease The phase 3 studies excluded patients with recent myocardial infarction (in the past 6 months) or unstable angina (in the past 3 months), New York Heart Association Class (NYHA) III or IV heart failure except if Left Ventricular Ejection Fraction (LVEF) ≥ 45%, bradycardia or uncontrolled hypertension.

This should be taken into account if Enzalutamide is prescribed in these patients. 5) physicians should assess the benefit risk ratio including the potential for Torsade de pointes prior to initiating Enzalutamide. Use with chemotherapy The safety and efficacy of concomitant use of Enzalutamide with cytotoxic chemotherapy has not been established.

5); however, an increase in the occurrence of docetaxel-induced neutropenia cannot be excluded. Severe skin reactions Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, which can be life threatening or fatal, has been reported with enzalutamide treatment.

At the time of prescription, patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of this reaction appear, enzalutamide should be withdrawn immediately and an alternative treatment considered (as appropriate).

8). 1). Enzalutamide in combination with androgen deprivation therapy is considered the preferred treatment option except for cases in which the addition of androgen deprivation therapy may result in unacceptable toxicity or risk. Enzalutamide contains lactose Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Enzalutamide contains sodium This medicine contains less than 1 mmol sodium (less than 23 mg) per film-coated tablet, that is to say essentially ‘sodium-free’.

1. 6).