Zocor (Simvastatin) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

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

Other adverse reactions reported in clinical trials were: diarrhea, rash, dyspepsia, flatulence, and asthenia.

Laboratory Tests

Marked persistent increases of hepatic transaminases have been noted [see Warnings and Precautions]. Elevated alkaline phosphatase and γ-glutamyl transpeptidase have also been reported. About 5% of patients had elevations of CK levels of 3 or more times the normal value on one or more occasions. This was attributable to the noncardiac fraction of CK. [See Warnings and Precautions.]

Adolescent Patients (ages 10-17 years)

In a 48-week, controlled study in adolescent boys and girls who were at least 1 year post-menarche, 10-17 years of age (43.4% female, 97.7% Caucasians, 1.7% Hispanics, 0.6% Multiracial) with heterozygous familial hypercholesterolemia (n=175), treated with placebo or ZOCOR (10-40 mg daily), the most common adverse reactions observed in both were being upper respiratory infection, headache, abdominal pain, and nausea [see Use in Specific Populations and Clinical Studies].

Post-Marketing Experience

Because the below reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following additional adverse reactions have been identified during postapproval use of simvastatin: pruritus, alopecia, a variety of skin changes (e.g., nodules, discoloration, dryness of skin/mucous membranes, changes to hair/nails), dizziness, muscle cramps, myalgia, pancreatitis, memory impairment, paresthesia, peripheral neuropathy, vomiting and anemia, rhabdomyolysis, hepatitis/jaundice, hepatic failure, depression.

An apparent hypersensitivity syndrome has been reported rarely which has included some of the following features: anaphylaxis, angioedema, lupus erythematous-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, chills, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme, including Stevens-Johnson syndrome.

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO ZOCOR

Possible Zocor side effects / adverse reactions in 64 year old female

Reported by a consumer/non-health professional from United States on 2007-01-03

Patient: 64 year old female weighing 83.0 kg (182.6 pounds)

Reactions: Impaired Driving Ability, Nephrolithiasis, Polymyositis, Loss of Employment, Walking AID User

Suspect drug(s):
Zocor
    Dosage: see above daily po
    Administration route: Oral
    Indication: Blood Cholesterol Increased
    Start date: 2004-03-04
    End date: 2005-10-14

Vytorin
    Dosage: see above po
    Administration route: Oral
    Start date: 2005-10-14
    End date: 2006-06-15

Possible Zocor side effects / adverse reactions in 54 year old female

Reported by a health professional (non-physician/pharmacist) from United States on 2007-01-04

Patient: 54 year old female weighing 95.3 kg (209.6 pounds)

Reactions: Muscular Weakness, Myopathy

Suspect drug(s):
Zocor

Possible Zocor side effects / adverse reactions in 91 year old male

Reported by a health professional (non-physician/pharmacist) from United Kingdom on 2007-01-08

Patient: 91 year old male

Reactions: Rhabdomyolysis, Renal Failure, Myopathy

Adverse event resulted in: hospitalization

Suspect drug(s):
Zocor

Other drugs received by patient: Allopurinol; Amlodipine Besylate; Bisoprolol; Clopidogrel Bisulfate; Esomeprazole; Furosemide; Nicorandil; Tamsulosin Hydrochloride; Levothyroxine Sodium

Possible Zocor side effects / adverse reactions in 60 year old female

Reported by a health professional (non-physician/pharmacist) from Norway on 2007-01-08

Patient: 60 year old female

Reactions: Myalgia, Alanine Aminotransferase Increased, Aspartate Aminotransferase Increased, Muscle Contracture, Drug Interaction

Adverse event resulted in: hospitalization

Suspect drug(s):
Zocor
    Administration route: Oral
    Indication: Hypercholesterolaemia
    End date: 2006-12-17

Erythromycin Stearate
    Administration route: Oral
    Indication: Upper Respiratory Tract Infection
    Start date: 2006-12-14
    End date: 2006-12-17

Possible Zocor side effects / adverse reactions in 48 year old female

Reported by a health professional (non-physician/pharmacist) from France on 2007-01-11

Patient: 48 year old female weighing 55.0 kg (121.0 pounds)

Reactions: Blood Creatine Phosphokinase Increased, Rhabdomyolysis, Drug Interaction

Adverse event resulted in: hospitalization

Suspect drug(s):
Zocor
    Administration route: Oral
    Indication: Hypercholesterolaemia
    Start date: 2003-02-12
    End date: 2006-07-20

Lopinavir and Ritonavir
    Administration route: Oral
    Indication: HIV Infection
    Start date: 2006-06-22

Other drugs received by patient: Emtricitabine and Tenofovir Disoproxil Fumarate; Nicardipine Hydrochloride; Perindopril; Atenolol; Insulin