ADVERSE REACTIONS

In the pre-marketing controlled clinical studies and their open extensions (2, 423 patients with mean duration of follow-up of approximately 18 months), 1.4% of patients were discontinued due to adverse experiences attributable to ZOCOR. Adverse reactions have usually been mild and transient. ZOCOR has been evaluated for serious adverse reactions in more than 21,000 patients and is generally well tolerated.

Clinical Adverse Experiences

In Adults

Adverse experiences occurring in adults at an incidence of 1% or greater in patients treated with ZOCOR, regardless of causality, in controlled clinical studies are shown in Table 8.

In 4S (see CLINICAL PHARMACOLOGY, Clinical Studies) involving 4,444 patients treated with 20-40 mg/ day of ZOCOR (n= 2,221) or placebo (n= 2,223), the safety and tolerability profiles were comparable between groups over the median 5.4 years of the study. The clinical adverse experiences reported as possibly, probably, or definitely drug-related in 0.5% in either treatment group are shown in Table 9.

ZOCOR ® (simvastatin)

In HPS (see CLINICAL PHARMACOLOGY, Clinical Studies), involving 20,536 patients treated with ZOCOR 40 mg/ day (n= 10,269) or placebo (n= 10,267), the safety profiles were comparable between patients treated with ZOCOR and patients treated with placebo over the mean 5 years of the study. In this large trial, only serious adverse events and discontinuations due to any adverse events were recorded. Discontinuation rates due to adverse experiences were comparable (4. 8% in patients treated with ZOCOR compared with 5.1% in patients treated with placebo). The incidence of myopathy/ rhabdomyolysis was <0.1% in patients treated with ZOCOR.

The following effects have been reported with drugs in this class. Not all the effects listed below have necessarily been associated with simvastatin therapy.

Skeletal

muscle cramps, myalgia, myopathy, rhabdomyolysis, arthralgias.

Neurological

dysfunction of certain cranial nerves (including alteration of taste, impairment of extra-ocular movement, facial paresis), tremor, dizziness, vertigo, memory loss, paresthesia, peripheral neuropathy, peripheral nerve palsy, psychic disturbances, anxiety, insomnia, depression.