roducts. (See section 4.8.)
In cases where coadministration of these medicinal products with ATOZET is necessary, the benefit and the risk of concurrent treatment should be carefully considered. When patients are receiving medicinal products that increase the plasma concentration of atorvastatin, a lower maximum dose of ATOZET is recommended. In addition, in the case of potent CYP3A4 inhibitors, a lower starting dose of ATOZET should be considered and appropriate clinical monitoring of these patients is recommended (see section 4.5).
Atorvastatin must not be co-administered with systemic formulations of fusidic acid or within 7 days of stopping fusidic acid treatment. In patients where the use of systemic fusidic acid is considered essential, statin treatment should be discontinued throughout the duration of fusidic acid treatment. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving fusidic acid and statins in combination (see section 4.5). The patient should be advised to seek medical advice immediately if they experience any symptoms of muscle weakness, pain or tenderness.
Statin therapy may be re-introduced seven days after the last dose of fusidic acid.
In exceptional circumstances, where prolonged systemic fusidic acid is needed, e.g., for the treatment of severe infections, the need for co-administration of ATOZET and fusidic acid should only be considered on a case by case basis and under close medical supervision.
Liver Enzymes
In controlled coadministration trials in patients receiving ezetimibe and atorvastatin, consecutive transaminase elevations (≥3 times the upper limit of normal [ULN]) have been observed (see section 4.8.).
Liver function tests should be performed before the initiation of treatment and periodically thereafter. Patients who develop any signs or symptoms suggestive of liver injury should have liver function tests performed. Patients who develop increased transaminase levels should be monitored until the abnormality(ies) resolve. Should an increase in transaminases of greater than 3 times the ULN persist, reduction of dose or withdrawal of ATOZET is recommended.
ATOZET should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease.
Hepatic Insufficiency
Due to the unknown effects of the increased exposure to ezetimibe in patients with moderate or severe hepatic insufficiency, ATOZET is not recommended (see section 5.2).
Fibrates
The safety and efficacy of ezetimibe administered with fibrates have not been established; therefore, coadministration of ATOZET and fibrates is not recommended (see section 4.5).
Ciclosporin
Caution should be exercised when initiating ATOZET in the setting of ciclosporin. Ciclosporin concentrations should be monitored in patients receiving ATOZET and ciclosporin (see section 4.5).
Anticoagulants
If ATOZET is added to warfarin, another coumarin anticoagulant, or fluindione, the International Normalised Ratio (INR) should be appropriately monitored (see section 4.5).
Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL)
In a post-hoc analysis of stroke subtypes in patients without coronary heart disease (CHD) who had a recent stroke or transient ischemic attack (TIA) there was a higher incidence of hemorrhagic stroke in patients initiated on atorvastatin 80 mg compared to placebo. The increased risk was par |
