Merck Sharp & Dohme Limited

SPC changes as follows

Section 4.2- Posology and method of administration: Under the sub heading of Homozygous familial hypercholesterolaemia, treatment with 80 mg is no longer recommended. Changes to the sub heading concomitant therapy have been made. These are detailed fully in section 4.5.

Section 4.3- Contraindications: concomitant administration of gemfibrozil, ciclosporin, and danazol have been added.

Section 4.4- Warnings and Precautions: additional information stating that risk of myopathy is increased in patients on simvastatin 80 mg compared to other statin based therapies. The following sentence has also been added, 'Patients taking other medicines labelled as having a moderate inhibitory effect on CYP3A4 at therapeutic doses concomitantly with simvastatin, particularly higher simvastatin doses, may have an increased risk of myopathy'.

Section

based on the Study of the Effectiveness of Additonal Reductions in Cholesterol and Homocysteine (SEARCH). Sections 4.2, 4.4, 4.5 and 5.1 of the SmPC have been updated as follows: 

Section 4.2 - It has been clarified that the 80mg dose should only be used in patients who have not achieved their treatment goals on lower doses and when the benefits are expected to outweigh the potential risks

Under the sub heading 'Concomitant therapy' the following sentence has been added, 'In patients taking diltiazem or amlopidine concomitantly with Zocor, the dose of Zocor should not exceed 40 mg/day.' Section 4.4 - Under the sub-heading of 'Myopathy/rhabdomyolysis' the following paragraph has been added, 'In a clinical trial in which patients with a history of myocardial infarction were treated with Zocor 80 mg/day (mean follow-up 6.7 years), the incidence of myopathy was approximately 1.0% compared with 0.02% for patients on 20 mg/day. Approximately half of these myopathy cases occurred during the first year of treatment. The incidence of myopathy during each subsequent year of treatment was approximately 0.1%. (See sections 4.8 and 5.1).

Under the sub-heading 'Before the treatment' some changes have been made to the group of patients where particular caution should be exercised, the age has been changed to > 65 years instead of >70 years. Also females have been added to this group.

Under the sub-heading 'Whilst on treatment' the following paragraphs have been added,

'A higher rate of myopathy has been observed in patients titrated to the 80mg dose (see section 5.1). Periodic CK measurements are recommended as they may be useful to identify subclinical cases of myopathy. However, there is no assurance that such monitoring will prevent myopathy.

'The combined use of simvastatin at doses higher then 40 mg daily with diltiazem or amlopidine should be avoided unless the clinical benefit is likely to outweigh the increased risk of myopathy (see sections 4.2 and 4.5).'Section 4.5-Under the sub-heading 'Amiodarone' the following sentence has been added, ' Therefore the dose of simvastatin should not exceed 20 mg daily in patients receiving concomitant medication with amiodarone, unless the clinical benefit is likely to outweigh the increased risk of myopathy and rhabdomyolysis

Under the sub heading 'Verapamil' the following sentence has been added, 'The risk of myopathy and rhabdomyolysis is increased by concomitant administration of verapamil with simvastatin 40mg or 80mg (see section 4.4).'

Under the sub-heading 'Diltiazem' the following sentence has been added, 'The risk of myopathy and rhabdomyolysis is increased by concomitant administration of diltiazem with simvastatin 80 mg (see section 4.4).'

An additional section on amlopidine has been added reading as follows:' Patients on amlodipine treated concomitantly with simvastatin 80 mg have a slightly increased risk of myopathy. The risk of myopathy in patients taking simvastatin 40 mg was not increased by concomitant amlodipine. In a pharmacokinetic study, concomitant administration of amlodipine caused a 1.6-fold increase in exposure of simvastatin acid. Therefore, the dose of simvastatin should not exceed 40mg daily in patients receiving concomitant medication with amlopidine, unless the clinical benefit is likely to outweigh the increased risk of myopathy and rhabdomyolysis'

Section 5.1 - A paragraph summarising the results of SEARCH has been added.

Section 4.2 - Dosing instructions for children and adolescents aged 10-17 years have been added.

Section 4.4 - Details of a controlled clinical trial in adolescent boys and girls have been added.

Section 4.8 - A paragraph on safety and tolerability of Zocor during the clinical trial in adolescents has been added.

Section 5.1 - Details of the clinical study in children and adolescents has been added.

Section 5.2 - Sentence stating that pharmacokinetic data in children and adolescents is not available

- A section has been added to state that rare cases of myopathy/rhabdomyolysis have been associated with concomitant administration of CoA reductase inhibitors and lipid modifying doses of niacin.

A section has been added detailing that a higher than expected incidence of myopathy has been seen in Chinese patients taking lipid- modifying doses of niacin and simvastatin (particularly doses of 40 mg and higher).

- Information has been added to state that

Section 4.4 - This paragraph has been added-

Section 2 - the quantities of lactose have been added.

Section 4.6- minor editorial revisions

Section 6.1 - Changes to the layout of the excipients.

4.2 - Reference to niacin has been removed from the section on concomitant therapy.

4.4 - Under the sub -heading "Measures to reduce the risk of myopathy caused by medicinal product interactions" Niacin has been removed from the 4th paragraph.

4.5 - Niacin has been removed from the table of drug interactions associated with increased risk of myopathy/rhabdomyolysis.