Xtandi Special Precautions

Risk of seizure: Use of enzalutamide has been associated with seizure (see Adverse Reactions). The decision to continue treatment in patients who develop seizures should be taken case by case.
Posterior reversible encephalopathy syndrome: There have been rare reports of posterior reversible encephalopathy syndrome (PRES) in patients receiving Xtandi (see Adverse Reactions). 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 Xtandi 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. In phase 3 clinical studies, the most frequently reported events in enzalutamide treated patients, and greater than placebo, were bladder cancer (0.3%), adenocarcinoma of the colon (0.2%), transitional cell carcinoma (0.2%) and bladder transitional cell carcinoma (0.1%).
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.
Concomitant use with other medicinal products: Enzalutamide is a potent enzyme inducer and may lead to loss of efficacy of many commonly used medicinal products (see examples in Interactions). A review of concomitant medicinal products should therefore be conducted when initiating enzalutamide treatment. Concomitant use of enzalutamide 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 Xtandi 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).
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. A prolonged time to reach steady-state concentrations is however anticipated, and the time to maximum pharmacological effect as well as time for onset and decline of enzyme induction (see Interactions) 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 Xtandi is prescribed in these patients.
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 Xtandi.
Use with chemotherapy: The safety and efficacy of concomitant use of Xtandi with cytotoxic chemotherapy has not been established. Co-administration of enzalutamide has no clinically relevant effect on the pharmacokinetics of intravenous docetaxel (see Interactions); however, an increase in the occurrence of docetaxel-induced neutropenia cannot be excluded.
Hypersensitivity reactions: Hypersensitivity reactions manifested by symptoms including, but not limited to, rash, or face, tongue, lip, or pharyngeal oedema, have been observed with enzalutamide (see Adverse Reactions). Severe cutaneous adverse reactions (SCARs) have been reported with enzalutamide. At the time of prescription, patients should be advised of the signs and symptoms and monitored closely for skin reactions.
Excipients: Xtandi contains 57.8 mg sorbitol (E420) per soft capsule.
Effects on ability to drive and use machines: Xtandi may have moderate influence on the ability to drive and use machines as psychiatric and neurologic events including seizure have been reported (see Adverse Reactions). Patients should be advised of the potential risk of experiencing a psychiatric or neurological event while driving or operating machines. No studies to evaluate the effects of enzalutamide on the ability to drive and use machines have been conducted.