What is Zocor (simvastatin)?

Zocor (simvastatin) is a cholesterol-lowering drug called an HMG-CoA reductase inhibitor (a “statin”) used to reduce total cholesterol, LDL cholesterol, and triglycerides, and to increase HDL cholesterol.

In patients with coronary heart disease, diabetes, peripheral vascular disease, or history of stroke or other cerebrovascular disease, simvastatin is prescribed for reducing the risk of mortality by reducing death from coronary heart disease, reducing nonfatal myocardial infarction (heart attack) and stroke, and reducing the need for coronary and noncoronary revascularization procedures.

Common side effects of Zocor include:

Serious side effects of Zocor include:

  • liver damage,
  • muscle inflammation or breakdown (rhabdomyolysis), and
  • increases in HbA1c and fasting serum glucose levels as are seen in diabetes.

Drug interactions of Zocor include:

Zocor should not be taken with:

Zocor increases the effect of warfarin and the blood concentration of digoxin. Zocor should be taken 2 hours before or at least 4 hours after cholestyramine.

Pregnant women should not use Zocor because the developing fetus requires cholesterol for development, and Zocor reduces the production of cholesterol. Because of the risk of adverse effects to the developing infant, Zocor should not be administered to breastfeeding mothers.

What are the important side effects of Zocor (simvastatin)?

The most common side effects of simvastatin are:

Other side effects include:

  • memory loss,
  • forgetfulness,
  • amnesia,
  • confusion, and
  • memory impairment.
What are the more serious side effects of Zocor?
  • The most serious potential side effects are liver damage and muscle inflammation or breakdown. Simvastatin shares side effects, such as liver and muscle damage associated with all statins. Serious liver damage caused by statins is rare. More often, statins cause abnormalities of liver tests. Abnormal tests usually return to normal even if a statin is continued, but if the abnormal test value is greater than three times the upper limit of normal, the statin usually is stopped. Liver tests should be measured before simvastatin is started and if there is a medical concern about liver damage thereafter.
  • Inflammation of the muscles caused by statins can lead to a serious breakdown of muscle cells called rhabdomyolysis. Rhabdomyolysis causes the release of muscle protein (myoglobin) into the blood. Myoglobin can cause kidney failure and even death. When used alone, statins cause rhabdomyolysis in less than one percent of patients. To prevent the development of rhabdomyolysis, patients taking simvastatin should contact their health care professional immediately if they develop unexplained muscle pain, weakness, or muscle tenderness.
  • Statins have been associated with increases in HbA1c and fasting serum glucose levels as are seen in diabetes.

Zocor (simvastatin) side effects list for healthcare professionals

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:

The most commonly reported adverse reactions (incidence ≥5%) in simvastatin controlled clinical trials were:

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/swelling2.72.3
Abdominal pain5.95.8
Cardiovascular System Disorders
Atrial fibrillation5.75.1
Digestive System Disorders
Constipation2.21.6
Gastritis4.93.9
Endocrine Disorders
Diabetes mellitus4.23.6
Musculoskeletal Disorders
Myalgia3.73.2
Nervous System/ Psychiatric Disorders
Headache2.52.1
Insomnia4.03.8
Vertigo4.54.2
Respiratory System Disorders
Bronchitis6.66.3
Sinusitis2.31.8
Skin / Skin Appendage Disorders
Eczema4.53.0
Urogenital System Disorders
Infection, urinary tract3.23.1

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 with a CK >40 times ULN) in patients on 80 mg/day was approximately 0.4% compared with 0% for patients on 20 mg/day. The incidence of myopathy, including rhabdomyolysis, was highest during the first year and then notably decreased during the subsequent years of treatment. In this trial, patients were carefully monitored and some interacting medicinal products were excluded.

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. 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.

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 groups were upper respiratory infection, headache, abdominal pain, and nausea.

Postmarketing 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:

There have been rare reports of immune-mediated necrotizing myopathy associated with statin use.

An apparent hypersensitivity syndrome has been reported rarely which has included some of the following features:

There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).

What drugs interact with Zocor (simvastatin)?

Strong CYP3A4 Inhibitors, Cyclosporine, Or Danazol

Strong CYP3A4 Inhibitors

Simvastatin, like several other inhibitors of HMG-CoA reductase, is a substrate of CYP3A4. Simvastatin is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4.

Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.

Cyclosporine Or Danazol

The risk of myopathy, including rhabdomyolysis is increased by concomitant administration of cyclosporine or danazol. Therefore, concomitant use of these drugs is contraindicated.

Lipid-Lowering Drugs That Can Cause Myopathy When Given Alone

Gemfibrozil: Contraindicated with simvastatin.

Other fibrates: Caution should be used when prescribing with simvastatin.

Amiodarone, Dronedarone, Ranolazine, Or Calcium Channel Blockers

The risk of myopathy, including rhabdomyolysis, is increased by concomitant administration of amiodarone, dronedarone, ranolazine, or calcium channel blockers such as verapamil, diltiazem, or amlodipine.

Niacin

Cases of myopathy/rhabdomyolysis have been observed with simvastatin coadministered with lipid-modifying doses (=1 g/day niacin) of niacin-containing products. In particular, caution should be used when treating Chinese patients with simvastatin doses exceeding 20 mg/day coadministered with lipid-modifying doses of niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of niacin-containing products.

Digoxin

In one study, concomitant administration of digoxin with simvastatin resulted in a slight elevation in digoxin concentrations in plasma. Patients taking digoxin should be monitored appropriately when simvastatin is initiated.

Coumarin Anticoagulants

In two clinical studies, one in normal volunteers and the other in hypercholesterolemic patients, simvastatin 20-40 mg/day modestly potentiated the effect of coumarin anticoagulants: the prothrombin time, reported as International Normalized Ratio (INR), increased from a baseline of 1.7 to 1.8 and from 2.6 to 3.4 in the volunteer and patient studies, respectively. With other statins, clinically evident bleeding and/or increased prothrombin time has been reported in a few patients taking coumarin anticoagulants concomitantly.

In such patients, prothrombin time should be determined before starting simvastatin and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs. Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on coumarin anticoagulants. If the dose of simvastatin is changed or discontinued, the same procedure should be repeated. Simvastatin therapy has not been associated with bleeding or with changes in prothrombin time in patients not taking anticoagulants.

Colchicine

Cases of myopathy, including rhabdomyolysis, have been reported with simvastatin coadministered with colchicine, and caution should be exercised when prescribing simvastatin with colchicine.

Summary

Zocor (simvastatin) is a cholesterol-lowering drug called an HMG-CoA reductase inhibitor (a “statin”) used to reduce total cholesterol, LDL cholesterol, and triglycerides, and to increase HDL cholesterol. Common side effects of Zocor include headache, nausea, vomiting, diarrhea, abdominal pain, muscle pain, abnormal liver tests, hypersensitivity reactions, memory loss, forgetfulness, amnesia, confusion, and memory impairment. Pregnant women should not use Zocor because the developing fetus requires cholesterol for development, and Zocor reduces the production of cholesterol. Because of the risk of adverse effects to the developing infant, Zocor should not be administered to breastfeeding mothers.

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Medically Reviewed on 5/4/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.
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