ATOZET

Posology Hypercholesterolaemia and/or Coronary Heart Disease (with ACS History) The patient should be on an appropriate lipid-lowering diet and should continue on this diet during treatment with ATOZET. The dose range of ATOZET is 10/10 mg/day through 10/80 mg/day.

The typical dose is 10/10 mg once a day. The patient’s low-density lipoprotein cholesterol (LDL-C) level, coronary heart disease risk status, and response to current cholesterol-lowering therapy should be considered when starting therapy or adjusting the dose.

1, Table 4) and the response to the current cholesterol-lowering therapy. Adjustment of dose should be made at intervals of 4 weeks or more. Homozygous Familial Hypercholesterolaemia The dose of ATOZET in patients with homozygous FH is 10/10 to 10/80 mg daily.

, LDL apheresis) in these patients or if such treatments are unavailable. Co-administration with other medicines Dosing of ATOZET should occur either ≥2 hours before or ≥4 hours after administration of a bile acid sequestrant. 5). 2).

2). No data are available. 2). 3). 2). Method of administration ATOZET is for oral administration. ATOZET can be administered as a single dose at any time of the day, with or without food.

Summary of the safety profile ATOZET (or co-administration of ezetimibe and atorvastatin equivalent to ATOZET) has been evaluated for safety in more than 2400 patients in 7 clinical trials. Tabulated list of adverse reactions Adverse reactions observed in clinical studies of ATOZET (or co-administration of ezetimibe and atorvastatin equivalent to ATOZET) or ezetimibe or atorvastatin or reported from post- marketing use with ATOZET or ezetimibe or atorvastatin are listed in Table 3.

These reactions are presented by system organ class and by frequency. Frequencies are defined as: very common (≥1/10); common ≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000); and not known (cannot be estimated from the available data).

6% for patients treated with ATOZET. 4). 6 mmol/L, BMI> 30 kg/m2, raised triglycerides, history of hypertension) Muscle-related effects A Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis (2022) assessed 19 double blind trials of statin vs.

placebo trials (n=123,940) and four double blind trials of more intensive vs. less intensive statin regimen (n=30,724). The analysis concluded: • Statin therapy group reported a small relative increase (3%) in mild muscle pain or weakness, mainly in the first year of treatment.

• Intensive statin regimens increased first-episode muscle pain or weakness symptoms being more likely compared to moderate or less intense regimens. • Over 90% of reported muscle symptoms in participants on statin therapy were not related to the statin, which may be due to a nocebo effect.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Myopathy/Rhabdomyolysis In post-marketing experience with ezetimibe, cases of myopathy and rhabdomyolysis have been reported. Most patients who developed rhabdomyolysis were taking a statin concomitantly with ezetimibe. However, rhabdomyolysis has been reported very rarely with ezetimibe monotherapy and very rarely with the addition of ezetimibe to other agents known to be associated with increased risk of rhabdomyolysis.

ATOZET contains atorvastatin. Atorvastatin, like other HMG-CoA reductase inhibitors, may in rare occasions affect the skeletal muscle and cause myalgia, myositis, and myopathy that may progress to rhabdomyolysis, a potentially life-threatening condition characterised by markedly elevated creatine phosphokinase (CPK) levels (> 10 times ULN), myoglobinaemia and myoglobinuria, which may lead to renal failure.

Before the treatment ATOZET should be prescribed with caution in patients with pre-disposing factors for rhabdomyolysis. 2). In such situations, the risk of treatment should be considered in relation to possible benefit, and clinical monitoring is recommended.

If CPK levels are significantly elevated (> 5 times ULN) at baseline, treatment should not be started. Creatine phosphokinase measurement Creatine phosphokinase (CPK) should not be measured following strenuous exercise or in the presence of any plausible alternative cause of CPK increase as this makes value interpretation difficult.

If CPK levels are significantly elevated at baseline (> 5 times ULN), levels should be remeasured within 5 to 7 days later to confirm the results. Whilst on treatment • Patients must be asked to promptly report muscle pain, cramps, or weakness especially if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing ATOZET.

• If such symptoms occur whilst a patient is receiving treatment with ATOZET, their CPK levels should be measured. If these levels are found to be significantly elevated (> 5 times ULN), treatment should be stopped. • If muscular symptoms are severe and cause daily discomfort, even if the CPK levels are elevated to ≤ 5 times ULN, treatment discontinuation should be considered.

1. 6). ATOZET is contraindicated in patients with active liver disease or unexplained persistent elevations in serum transaminases exceeding 3 times the upper limit of normal (ULN). ATOZET is contraindicated in patients treated with the hepatitis C antivirals glecaprevir/pibrentasvir.