Xtandi Special Precautions

Risk of seizure: Use of enzalutamide has been associated with events of seizure (see Adverse Reactions). Permanently discontinue Xtandi in patients who develop a seizure during treatment.
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.
Hypersensitivity: Hypersensitivity reactions manifested by symptoms including, but not limited to, face edema, tongue edema, lip edema, pharyngeal edema, and rash have been observed with enzalutamide (see Adverse Reactions). Advise patients who experience any symptoms of hypersensitivity to discontinue enzalutamide and promptly seek medical care.
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.
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.
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.
Excipients: Xtandi contains 57.8 mg sorbitol (E420) per soft capsule.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed. However, there are some adverse events (such as seizure, amnesia, fatigue, memory impairment, cognitive disorder, and disturbance in attention) associated with this product that may affect some patients' ability to drive or operate machinery (see as previously mentioned and Adverse Reactions).