Nexlizet Special Precautions

Potential risk of myopathy with concomitant use of statins: Bempedoic acid increases plasma concentrations of statins (see Interactions). Statins occasionally cause myopathy. In rare cases, myopathy may take the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and can lead to fatality. In postmarketing experience with ezetimibe, very rare cases of myopathy and rhabdomyolysis have been reported. Most patients who developed rhabdomyolysis were taking a statin concomitantly with ezetimibe.
Patients receiving Nexlizet as adjunctive therapy to a statin should be monitored for adverse reactions that are associated with the use of high doses of statins. All patients receiving Nexlizet in addition to a statin should be advised of the potential increased risk of myopathy and told to report promptly any unexplained muscle pain, tenderness, or weakness. If such symptoms occur while a patient is receiving treatment with Nexlizet and a statin, a lower maximum dose of the same statin or an alternative statin, or discontinuation of Nexlizet and initiation of an alternative lipid-lowering therapy should be considered under close monitoring of lipid levels and adverse reactions. If myopathy is confirmed by a creatine phosphokinase (CPK) level >10x upper limit of normal (ULN), Nexlizet and any statin that the patient is taking concomitantly should be immediately discontinued.
Myositis with a CPK level >10x ULN was rarely reported with bempedoic acid and background simvastatin 40 mg therapy. Doses of simvastatin >40 mg should not be used with Nexlizet (see Dosage & Administration and Contraindications).
Increased serum uric acid: Bempedoic acid may raise the serum uric acid level due to inhibition of renal tubular OAT2 and may cause or exacerbate hyperuricaemia and precipitate gout in patients with a medical history of gout or predisposed to gout (see Adverse Reactions). Treatment with Nexlizet should be discontinued if hyperuricaemia accompanied with symptoms of gout appear.
Elevated liver enzymes: In clinical trials, elevations of >3x ULN in the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been reported with bempedoic acid. These elevations have been asymptomatic and not associated with elevations ≥2x ULN in bilirubin or with cholestasis and have returned to baseline with continued treatment or after discontinuation of therapy. In controlled coadministration trials in patients receiving ezetimibe with a statin, consecutive transaminase elevations (≥3x ULN) have been observed. Liver function tests should be performed at initiation of therapy. Treatment with Nexlizet should be discontinued if an increase in transaminases of >3x ULN persists (see Contraindications and Adverse Reactions).
Renal impairment: There is limited experience with bempedoic acid in patients with severe renal impairment (defined as eGFR <30 mL/min/1.73 m²), and patients with ESRD on dialysis have not been studied with bempedoic acid (see Pharmacology: Pharmacokinetics under Actions). Additional monitoring for adverse reactions may be warranted in these patients when Nexlizet is administered.
Hepatic impairment: Due to the unknown effects of the increased exposure to ezetimibe in patients with moderate to severe hepatic impairment (Child-Pugh B and C), Nexlizet is not recommended in these patients (see Pharmacology: Pharmacokinetics under Actions).
Fibrates: The safety and efficacy of ezetimibe administered with fibrates have not been established. If cholelithiasis is suspected in a patient receiving Nexlizet and fenofibrate, gallbladder investigations are indicated and this therapy should be discontinued (see Interactions and Adverse Reactions).
Ciclosporin: Caution should be exercised when initiating Nexlizet in the setting of ciclosporin. Ciclosporin concentrations should be monitored in patients receiving Nexlizet and ciclosporin (see Interactions).
Anticoagulants: If Nexlizet is added to warfarin, other coumarin anticoagulants, or fluindione, the International Normalised Ratio (INR) should be appropriately monitored (see Interactions).
Excipients: Nexlizet contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.
This medicine contains less than 1 mmol sodium (23 mg) per 180 mg/10 mg film-coated tablet (daily dose), that is to say essentially 'sodium free'.
Patients at high risk of cardiovascular disease: Evidence for the use of the fixed combination medicinal product of bempedoic acid with ezetimibe in patients at high risk of cardiovascular disease is only available for the lipid-lowering effect in absence of any cardiovascular risk reduction estimation for ezetimibe in primary prevention patients (see Pharmacology: Pharmacodynamics under Actions).
Effects on ability to drive and use machines: Nexlizet has minor influence on the ability to drive and use machines. When driving vehicles or using machines, it should be taken into account that dizziness has been reported with bempedoic acid and ezetimibe (see Adverse Reactions).
Use in Pregnancy: See Use in Pregnancy & Lactation section for further information.