In the pre-marketing controlled clinical studies and their open extensions (2,423 patients with median duration of follow-up of approximately 18 months), 1.4% of patients were discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were: gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia (0.1%). The most commonly reported adverse reactions (incidence ≥5%) in simvastatin controlled clinical trials were: upper respiratory infections (9.0%), headache (7.4%), abdominal pain (7.3%), constipation (6.6%), and nausea (5.4%).

Scandinavian Simvastatin Survival Study

In 4S involving 4,444 (age range 35-71 years, 19% women, 100% Caucasians) treated with 20-40 mg/day of ZOCOR (n=2,221) or placebo (n=2,223) over a median of 5.4 years, adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 2.

Table 2: Adverse Reactions Reported Regardless of Causality by ≥2% of Patients Treated with ZOCOR and Greater than Placebo in 4S   ZOCOR
(N = 2,221)
% Placebo
(N = 2,223)
%
Body as a Whole
    Edema/swelling
    Abdominal pain
2.7
5.9
2.3
5.8
Cardiovascular System Disorders
    Atrial fibrillation
5.7
5.1
Digestive System Disorders
    Constipation
    Gastritis
 
2.2
4.9
1.6
3.9
Endocrine Disorders
    Diabetes mellitus
 
4.2
3.6
Musculoskeletal Disorders
    Myalgia
3.7
3.2
Nervous System / Psychiatric Disorders
    Headache
    Insomnia
    Vertigo
2.5
4.0
4.5
2.1
3.8
4.2
Respiratory System Disorders
    Bronchitis
    Sinusitis
 
6.6
2.3
6.3
1.8
Skin / Skin Appendage Disorders
    Eczema
4.5
3.0
Urogenital System Disorders
    Infection, urinary tract
 
3.2
3.1
Heart Protection Study

In the Heart Protection Study (HPS), involving 20,536 patients (age range 40-80 years, 25% women, 97% Caucasians, 3% other races) treated with ZOCOR 40 mg/day (n=10,269) or placebo (n=10,267) over a mean of 5 years, only serious adverse reactions and discontinuations due to any adverse reactions were recorded. Discontinuation rates due to adverse reactions were 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.

Other Clinical Studies

In a clinical trial in which 12,064 patients with a history of myocardial infarction were treated with ZOCOR (mean follow-up 6.7 years), the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum creatine kinase [CK] >10 times upper limit of normal [ULN]) in patients on 80 mg/day was approximately 0.9% compared with 0.02% for patients on 20 mg/day. The incidence of rhabdomyolysis (defined as myopathy