s with pre-disposing factors for rhabdomyolysis. A CPK level should be measured before starting treatment in the following situations:
• renal impairment
• hypothyroidism
• personal or familial history of hereditary muscular disorders
• previous history of muscular toxicity with a statin or fibrate
• previous history of liver disease and/or where substantial quantities of alcohol are consumed
• in elderly (age >70 years), the necessity of such measurement should be considered, according to the presence of other predisposing factors for rhabdomyolysis
• situations where an increase in plasma levels may occur, such as interactions (see section 4.5) and special populations including genetic subpopulations (see section 5.2)
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.
• 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.
• If symptoms resolve and CPK levels return to normal, then re-introduction of ATOZET or introduction of another statin-containing product may be considered at the lowest dose and with close monitoring.
• ATOZET must be discontinued if clinically significant elevation of CPK levels (>10 times ULN) occur, or if rhabdomyolysis is diagnosed or suspected.
• There have been very rare reports of an immune-mediated necrotising myopathy (IMNM) during or after treatment with some statins. IMNM is clinically characterised by persistent proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment.
Due to the atorvastatin component of ATOZET, the risk of rhabdomyolysis is increased when ATOZET is administered concomitantly with certain medicinal products that may increase the plasma concentration of atorvastatin such as potent inhibitors of CYP3A4 or transport proteins (e.g. ciclosporin, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole, and HIV protease inhibitors including ritonavir, lopinavir, atazanavir, indinavir, darunavir, etc). The risk of myopathy may also be increased with the concomitant use of gemfibrozil and other fibric acid derivatives, boceprevir, erythromycin, niacin, telaprevir, or the combination of tipranavir/ritonavir. If possible, alternative (non-interacting) therapies should be considered instead of these medicinal p |
