Nustendi

Posology The recommended dose of Nustendi is one film-coated tablet of 180 mg/10 mg taken once daily. Coadministration with bile acid sequestrants Dosing of Nustendi should occur either at least 2 hours before or at least 4 hours after administration of a bile acid sequestrant.

5). 2). Patients with renal impairment No dose adjustment is necessary in patients with mild or moderate renal impairment. 2). 4). Patients with hepatic impairment No dose adjustment is necessary in patients with mild hepatic impairment (Child-Pugh A).

4). Paediatric population The safety and efficacy of Nustendi in children aged less than 18 years have not been established. No data are available. Method of administration Each film-coated tablet should be taken orally with or without food.

Tablet should be swallowed whole.

7%). 2%) although differences between bempedoic acid and placebo were not significant. Serious adverse reactions reported for ezetimibe were myopathy, rhabdomyolysis, hepatitis, hypersensitivity, anaphylaxis, angioedema, erythema multiforme, cholelithiasis, cholecystitis, pancreatitis and thrombocytopenia.

Tabulated list of adverse reactions Adverse reactions reported with Nustendi are displayed by system organ class and frequency in table 1. Any additional adverse reactions that have been reported with bempedoic acid (based on incidence rates from phase 3 primary hyperlipidaemia studies and exposure adjusted incidence rates from CLEAR Outcomes study), or ezetimibe have also been presented to provide a more comprehensive adverse reaction profile for Nustendi.

Frequencies are defined as: 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); and not known (cannot be estimated from the available data). 9 Table 1: Adverse reactions (clinical studies and post-marketing experience) System organ class (SOC) Adverse reactions Frequency categories Adverse reactions with Nustendi Blood and lymphatic system disorders Anaemiaa Decreased haemoglobin Common Metabolism and nutrition disorders Hyperuricaemiaa,b Common Decreased appetite Common Nervous system disorders Dizziness Headache Common Vascular disorders Hypertension Common Respiratory, thoracic and mediastinal disorders Cough Common Gastrointestinal disorders Constipation Diarrhoea Abdominal pain Nausea Dry mouth Flatulence Gastritis Common Hepatobiliary disorders Liver function test increasedc Common Musculoskeletal and connective tissue disorders Back pain Muscle spasms Myalgia Pain in extremity Arthralgia Common Renal and urinary disorders Blood creatinine increased Common General disorders and administration site conditions Fatigue Asthenia Common Additional adverse reactions with bempedoic acid Metabolism and nutrition disorders Gout Common Weight decreasede Uncommon Hepatobiliary disorders Aspartate aminotransferase increased Common Alanine aminotransferase increased Uncommon Renal and urinary disorders Glomerular filtration rate decreased Common Blood urea increased Uncommon Additional adverse reactions with ezetimibe Blood and lymphatic system disorders Thrombocytopaenia Not known Immune system disorders Hypersensitivity, including rash, urticaria, anaphylaxis and angio-oedema Not known Psychiatric disorders Depression Not known Nervous system disorders Paraesthesiad Not known Vascular disorders Hot flush Uncommon Respiratory, thoracic and mediastinal disorders Dyspnoea Not known 10 System organ class (SOC) Adverse reactions Frequency categories Gastrointestinal disorders Dyspepsia Gastrooesophageal reflux disease Uncommon Pancreatitis Not known Hepatobiliary disorders Aspartate aminotransferase increased Alanine aminotransferase increased Gammaglutamyltransferase increased Uncommon Hepatitis Cholelithiasis Cholecystitis Not known Skin and subcutaneous tissue disorders Pruritusd Uncommon Erythema multiform Not known Musculoskeletal and connective tissue disorders Blood CPK increased Common Neck pain Muscular weaknessd Uncommon Myopathy/rhabdomyolysis Not known General disorders and administration site conditions Chest pain Pain Oedema peripherald Uncommon a.

5). 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 Nustendi 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 Nustendi 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 Nustendi and a statin, a lower maximum dose of the same statin or an alternative statin, or discontinuation of Nustendi 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 > 10× upper limit of normal (ULN), Nustendi and any statin that the patient is taking concomitantly should be immediately discontinued. Myositis with a CPK level > 10× ULN was rarely reported with bempedoic acid and background simvastatin 40 mg therapy.

3). 8). Treatment with Nustendi should be discontinued if hyperuricaemia accompanied with symptoms of gout appear. Elevated liver enzymes In clinical trials, elevations of > 3× 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 ≥ 2× 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 (≥ 3× ULN) have been observed.

1. 6). 5). • Nustendi coadministered with a statin is contraindicated in patients with active liver disease or unexplained persistent elevations in serum transaminases. • When Nustendi is coadministered with a statin, please refer to the summary of product characteristics (SmPC) for that particular statin therapy.

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