Zocor Side Effects Center

Last updated on RxList: 6/10/2022
Zocor Side Effects Center

What Is Zocor?

Zocor (simvastatin) is a statin that lowers lipids and cholesterol levels used in conjunction with lifestyle changes such as a low-fat, low cholesterol diet, and exercise to reduce the chances of cardiovascular disease and ischemic strokes in patients with elevated lipids and cholesterol. Zocor is also used to treat heterozygous familial hypercholesterolemia (HeFH) in adolescents (males and females that are one-year post menarche, 10 to 17 years old). Zocor is available in generic form.

What Are Side Effects of Zocor?

Common side effects of Zocor include:

Contact your doctor if you have severe side effects of Zocor including:

Dosage for Zocor

Zocor tablets are supplied as 5, 10, 20, 40 or 80 mg tablets. Doses range from 5-80 mg per day depending on the patient's response to the drug as measured by repeated blood tests.

What Drugs, Substances, or Supplements Interact with Zocor?

Zocor may interact with colchicine, digoxin, digitalis, blood thinners, fenofibric acid or fenofibrate, antifungals, medicines that contain niacin, drugs that weaken your immune system (such as steroids, cancer medicine, or medicines used to prevent organ transplant rejection), or other "statin" medications. Tell your doctor all medications and supplements you use.

Zocor During Pregnancy and Breastfeeding

Do not take Zocor if you are pregnant. Stop taking Zocor and tell your doctor right away if you become pregnant. Zocor can harm a fetus or cause birth defects. Use effective birth control to avoid pregnancy while you are taking Zocor. Zocor may pass into breast milk and could harm a nursing baby. Breastfeeding while taking Zocor is not recommended.

Additional Information

Our Zocor (simvastatin) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

How to Lower Your Cholesterol & Save Your Heart See Slideshow
Zocor Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

In rare cases, simvastatin can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Call your doctor right away if you have unexplained muscle pain, tenderness, or weakness especially if you also have fever, unusual tiredness, and dark colored urine.

Also call your doctor at once if you have:

  • muscle weakness in your hips, shoulders, neck, and back;
  • trouble lifting your arms, trouble climbing or standing; or
  • liver problems--loss of appetite, stomach pain (upper right side), tiredness, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

  • headache;
  • nausea, stomach pain, constipation; or
  • cold symptoms such as stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

What is cholesterol? See Answer
Zocor Professional Information

SIDE EFFECTS

The following important adverse reactions are described below and elsewhere in the labeling:

  • Myopathy and Rhabdomyolysis [see WARNINGS AND PRECAUTIONS]
  • Immune-Mediated Necrotizing Myopathy [see WARNINGS AND PRECAUTIONS]
  • Hepatic Dysfunction [see WARNINGS AND PRECAUTIONS]
  • Increases in HbA1c and Fasting Serum Glucose Levels [see WARNINGS AND PRECAUTIONS]

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 clinical studies, 2,423 adult patients were exposed to ZOCOR with a median duration of follow-up of approximately 18 months. The most commonly reported adverse reactions (incidence ≥5%) in these ZOCOR clinical studies were: upper respiratory infections (9%), headache (7%), abdominal pain (7%), constipation (7%), and nausea (5%). Overall, 1.4% of patients discontinued ZOCOR due to adverse reactions. The most common adverse reactions that led to discontinuation were: gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia (0.1%).

In a Cardiovascular Outcomes Study (the Scandinavian Simvastatin Survival Study [Study 4S]), adult patients (age range 35-71 years, 19% women, 100% Caucasians) were treated with 20-40 mg per day of ZOCOR or placebo over a median of 5.4 years [see Clinical Studies]; adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 1.

Table 1: Adverse Reactions Reported ≥2% of Patients Treated with ZOCOR and Greater than Placebo in Study 4S

% Placebo
(N = 2,223)
% ZOCOR
(N = 2,221)
Bronchitis 6.3 6.6
Abdominal pain 5.8 5.9
Atrial fibrillation 5.1 5.7
Gastritis 3.9 4.9
Eczema 3.0 4.5
Vertigo 4.2 4.5
Diabetes mellitus 3.6 4.2
Insomnia 3.8 4.0
Myalgia 3.2 3.7
Urinary tract infection 3.1 3.2
Edema/swelling 2.3 2.7
Headache 2.1 2.5
Sinusitis 1.8 2.3
Constipation 1.6 2.2

Myopathy/Rhabdomyolysis

In clinical studies with a median follow-up of at least 4 years, in which 24,747 patients received ZOCOR, the incidence of myopathy (defined as unexplained muscle weakness, pain, or tenderness accompanied by CK increases greater than 10xULN) was approximately 0.03%, 0.08%, and 0.61% for the ZOCOR 20 mg, 40 mg, and 80 mg daily groups, respectively.

In a clinical outcomes study in which 12,064 adult 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 CK >10x [1200 U/L] ULN) in patients taking ZOCOR 20 mg and 80 mg daily was approximately 0.02% and 0.9%, respectively. The incidence of rhabdomyolysis (defined as myopathy with a CK >40xULN) in patients on ZOCOR 20 mg and 80 mg daily was approximately 0% and 0.4%, respectively. The incidence of myopathy and rhabdomyolysis were highest during the first year and then decreased during the subsequent years of treatment.

In another clinical outcomes study in which 10,269 adult patients were treated with ZOCOR 40 mg per day (mean follow-up of 5 years), the incidence of myopathy/rhabdomyolysis was <0.1% in patients treated with ZOCOR.

Elevations In Liver Enzyme Tests

Moderate (less than 3xULN) elevations of serum transaminases have been reported with use of ZOCOR.

Persistent increases to more than 3xULN in serum transaminases have occurred in approximately 1% of patients receiving ZOCOR in clinical studies. Marked persistent increases of hepatic transaminases have occurred with ZOCOR. Elevated alkaline phosphatase and γ-glutamyl transpeptidase have also been reported.

In Study 4S, with a median follow-up of 5.4 years, 1,986 adult patients were treated with ZOCOR 20 mg once daily, of whom 37% titrated to 40 mg once daily. The percentage of patients with one or more occurrences of transaminase elevations to >3xULN was 0.7% in patients taking ZOCOR compared with 0.6% in patients taking placebo. Elevated transaminases leading to discontinuation of study treatment occurred in 0.4% of patients taking ZOCOR and 0.2% of patients taking placebo. The majority of elevated transaminases leading to treatment discontinuation occurred within in the first year.

Adverse Reactions In Pediatric Patients With Heterozygous Familial Hypercholesterolemia

In a 48-week clinical study in pediatric patients 10 years of age and older (43% female, 97.7% Caucasians, 1.7% Hispanics, 0.6% Multiracial) with HeFH (n=175), treated with placebo or ZOCOR (10- 40 mg daily), the most common adverse reactions were upper respiratory infection, headache, abdominal pain, and nausea [see Use In Specific Populations and Clinical Studies].

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ZOCOR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as whole: fever, chills, malaise, asthenia

Blood and Lymphatic System Disorders: anemia, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia

Gastrointestinal Disorders: pancreatitis, vomiting

Hepatic and Pancreatic Disorders: hepatitis/jaundice, fatal and non-fatal hepatic failure

Immune System Disorders: hypersensitivity syndrome including: anaphylaxis, angioedema, lupus erythematous-like syndrome, dermatomyositis, vasculitis

Musculoskeletal and Connective Tissue Disorders: muscle cramps, immune-mediated necrotizing myopathy, polymyalgia rheumatica, arthritis

Nervous System Disorders: dizziness, depression, paresthesia, peripheral neuropathy. Rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. Cognitive impairment was generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).

Skin and Subcutaneous Tissue Disorders: pruritus, alopecia, a variety of skin changes (e.g., nodules, discoloration, dryness of skin/mucous membranes, changes to hair/nails), purpura, lichen planus, urticaria, photosensitivity, flushing, toxic epidermal necrolysis, erythema multiforme, including Stevens- Johnson syndrome

Respiratory and Thoracic: interstitial lung disease, dyspnea

Reproductive System Disorders: erectile dysfunction

DRUG INTERACTIONS

Drug Interactions That Increase The Risk Of Myopathy And Rhabdomyolysis With ZOCOR

ZOCOR is a substrate of CYP3A4 and of the transport protein OATP1B1. ZOCOR exposure can be significantly increased with concomitant administration of inhibitors of CYP3A4 and OATP1B1. Table 2 includes a list of drugs that increase the risk of myopathy and rhabdomyolysis when used concomitantly with ZOCOR and instructions for preventing or managing them [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Table 2: Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with ZOCOR

Strong CYP3A4 inhibitors
Clinical Impact: Simvastatin is a substrate of CYP3A4. Concomitant use of strong CYP3A4 inhibitors with ZOCOR increases simvastatin exposure and increases the risk of myopathy and rhabdomyolysis, particularly with higher ZOCOR dosages.
Intervention: Concomitant use of strong CYP3A4 inhibitors with ZOCOR is contraindicated [see CONTRAINDICATIONS]. If treatment with a CYP3A4 inhibitor is unavoidable, suspend ZOCOR during the course of strong CYP3A4 inhibitor treatment.
Examples: Select azole anti-fungals (e.g., itraconazole, ketoconazole, posaconazole, and voriconazole), select macrolide antibiotics (e.g., erythromycin and clarithromycin), select HIV protease inhibitors (e.g., nelfinavir, ritonavir, and darunavir/ritonavir), select HCV protease inhibitors (e.g., boceprevir and telaprevir), cobicistat-containing products, and nefazodone.
Cyclosporine, Danazol, or Gemfibrozil
Clinical Impact: The risk of myopathy and rhabdomyolysis is increased with concomitant use of cyclosporine, danazol, or gemfibrozil with ZOCOR. Gemfibrozil may cause myopathy when given alone.
Intervention: Concomitant use of cyclosporine, danazol, or gemfibrozil with ZOCOR is contraindicated [see CONTRAINDICATIONS].
Amiodarone, Dronedarone, Ranolazine, or Calcium Channel Blockers
Clinical Impact: The risk of myopathy and rhabdomyolysis is increased by concomitant use of amiodarone, dronedarone, ranolazine, or calcium channel blockers
Intervention: For patients taking verapamil, diltiazem, or dronedarone, do not exceed ZOCOR 10 mg daily. For patients taking amiodarone, amlodipine, or ranolazine, do not exceed ZOCOR 20 mg daily [see DOSAGE AND ADMINISTRATION].
Lomitapide
Clinical Impact: Simvastatin exposure is approximately doubled with concomitant use of lomitapide and the risk of myopathy and rhabdomyolysis is increased.
Intervention: Reduce the dose of ZOCOR by 50% if initiating lomitapide. Do not exceed ZOCOR 20 mg daily (or ZOCOR 40 mg daily for patients who have previously taken ZOCOR 80 mg daily chronically) while taking lomitapide [see DOSAGE AND ADMINISTRATION].
Daptomycin
Clinical Impact: Cases of rhabdomyolysis have been reported with simvastatin administered with daptomycin. Both ZOCOR and daptomycin can cause myopathy and rhabdomyolysis when given alone and the risk of myopathy and rhabdomyolysis may be increased by coadministration.
Intervention: If treatment with daptomycin is required, consider temporarily suspending ZOCOR during the course of daptomycin treatment.
Niacin
Clinical Impact: Cases of myopathy and rhabdomyolysis have been observed with concomitant use of lipid modifying dosages of niacin-containing products (≥1 gram/day niacin) with ZOCOR. The risk of myopathy is greater in Chinese patients. In a clinical study (median follow-up 3.9 years) of patients at high risk of CVD and with well-controlled LDL-C levels on simvastatin 40 mg/day with or without ezetimibe 10 mg/day, there was no incremental benefit on cardiovascular outcomes with the addition of lipid-modifying doses of niacin.
Intervention: Concomitant use of ZOCOR with lipid-modifying dosages of niacin is not recommended in Chinese patients [see Use In Specific Populations]. For non-Chinese patients, consider if the benefit of using lipid-modifying doses of niacin concomitantly with ZOCOR outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug.
Fibrates (other than Gemfibrozil)
Clinical Impact: Fibrates may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of fibrates with ZOCOR.
Intervention: Consider if the benefit of using fibrates concomitantly with ZOCOR outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug.
Colchicine
Clinical Impact: Cases of myopathy and rhabdomyolysis have been reported with concomitant use of colchicine with ZOCOR.
Intervention: Consider if the benefit of using colchicine concomitantly with ZOCOR outweighs the increased risk of myopathy and rhabdomyolysis. If concomitant use is decided, monitor patients for signs and symptoms of myopathy, particularly during initiation of therapy and during upward dose titration of either drug.
Grapefruit Juice
Clinical Impact: Grapefruit juice can raise the plasma levels of simvastatin and may increase the risk of myopathy and rhabdomyolysis.
Intervention: Avoid grapefruit juice when taking ZOCOR.

ZOCOR Effects On Other Drugs

Table 3 presents ZOCOR’s effect on other drugs and instructions for preventing or managing them.

Table 3: ZOCOR Effects on Other Drugs

Coumarin Anticoagulants
Clinical Impact: ZOCOR may potentiate the effect of coumarin anticoagulants and increase the INR. The concomitant use of ZOCOR (20 to 40 mg) and coumarin anticoagulants increased the INR from a baseline of 1.7 to 1.8 in healthy subjects and from 2.6 to 3.4 in patients with hyperlipidemia. There are postmarketing reports of clinically evident bleeding and/or increased INR in patients taking concomitant statins and warfarin.
Intervention: In patients taking coumarin anticoagulants, obtain an INR before starting ZOCOR and frequently enough after initiation, dose titration, or discontinuation to ensure that no significant alteration in INR occurs. Once the INR is stable, monitor INR at regularly recommended intervals.
Digoxin
Clinical Impact: Concomitant use of digoxin with ZOCOR may result in elevated plasma digoxin concentrations [see CLINICAL PHARMACOLOGY].
Intervention: Monitor digoxin levels in patients taking digoxin when ZOCOR is initiated

Read the entire FDA prescribing information for Zocor (Simvastatin)

© Zocor Patient Information is supplied by Cerner Multum, Inc. and Zocor Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Health Solutions From Our Sponsors