Simvastatin

Generic name: simvastatin · Brand names: Zocor, Flolipid (oral suspension, not covered by this record)

Quick facts

Drug class
Section
Highlights, Indications and Usage
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Medlineplus text
Simvastatin is in a class of medications called HMG-CoA reductase inhibitors (statins).
Medlineplus source
MedlinePlus Why is this medication prescribed?
Openfda pharm class epc
not queried
Source text (exact source wording)
Simvastatin tablets USP are an HMG-CoA reductase inhibitor indicated: (1)
Rx or otc
Value
Rx
Section
Patient Information
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
Simvastatin tablets are a prescription medicine that contains the cholesterol lowering medicine, simvastatin.
Controlled schedule
Not a controlled substance (no schedule appears anywhere in the captured label text)
Forms and strengths
Section
3 Dosage Forms and Strengths
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95); appearance is labeler-specific
Note
Section 16 of the Lupin label also says: '*The 5 mg strength of Simvastatin Tablets USP is no longer being marketed.' and 8.6 says: 'Simvastatin is not available in a 5 mg strength.' Appearance and imprints are labeler-specific.
Source text (exact source wording)
Simvastatin tablets 5 mg are tan colored, round, biconvex, film-coated tablets debossed with 'LL' on one side and 'C01' on the other side.
Simvastatin tablets 10 mg are peach colored, oval shaped, biconvex, film-coated tablets debossed with 'LL' on one side and 'C02' on the other side.
Simvastatin tablets 20 mg are tan colored, oval shaped, biconvex, film-coated tablets debossed with 'LL' on one side and 'C03' on the other side.
Simvastatin tablets 40 mg are brick red colored, round shaped, biconvex, film-coated tablets debossed with 'LL' on one side and 'C04' on the other side.
Simvastatin tablets 80 mg are brick red colored, capsule shaped, biconvex, film-coated tablets debossed with 'LL' on one side and 'C05' on the other side.
Generic available
Value
yes
Source
DailyMed SPL list (spls.json)
Source text (exact source wording)
DailyMed lists simvastatin tablets from Lupin, Accord, Biocon, Westminster and Aurobindo under the generic name (marketing category not captured from label text)
Common use one line
Used with diet to lower LDL cholesterol and to lower the risk of heart attack and stroke in people at high risk.

What it is used for

Simvastatin lowers the risk of death, heart attack, stroke and the need for heart and blood vessel procedures in adults with established heart or blood vessel disease and/or diabetes who are at high risk. With diet, it lowers LDL cholesterol in adults with primary hyperlipidemia and in adults and children aged 10 years and older with heterozygous familial hypercholesterolemia. With other therapies it lowers LDL-C in adults with homozygous familial hypercholesterolemia. It is also used with diet for adults with primary dysbetalipoproteinemia or hypertriglyceridemia.
Section
1 Indications and Usage
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
Simvastatin tablets USP are indicated:

To reduce the risk of total mortality by reducing risk of coronary heart disease death, non-fatal myocardial infarction and stroke, and the need for coronary and non-coronary revascularization procedures in adults with established coronary heart disease, cerebrovascular disease, peripheral vascular disease, and/or diabetes, who are at high risk of coronary heart disease events.
As an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C):
In adults with primary hyperlipidemia.
In adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH).
As an adjunct to other LDL-C-lowering therapies to reduce LDL-C in adults with homozygous familial hypercholesterolemia (HoFH).
As an adjunct to diet for the treatment of adults with:
Primary dysbetalipoproteinemia.
Hypertriglyceridemia.

How it works

Simvastatin is a prodrug that the body converts to its active form, simvastatin acid. The active form blocks HMG-CoA reductase, the enzyme that controls a key step in making cholesterol.
Section
12.1 Mechanism of Action
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin acid and its metabolites are inhibitors of HMG-CoA reductase, the rate-limiting enzyme that converts HMG-CoA to mevalonate, a precursor of cholesterol.

Dosage: adults

Take it once a day in the evening. The recommended range for adults is 20 mg to 40 mg once daily, and 40 mg once daily is the maximum recommended dose. The 80 mg dose is limited to people who have taken 80 mg daily for a long time (for example 12 months or more) without muscle problems. LDL-C can be checked as early as 4 weeks after starting.
Section
2.1 Important Dosage and Administration Information
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Range section
2.2 Recommended Dosage in Adult Patients
Source text (exact source wording)
Take simvastatin tablets USP orally once daily in the evening.
The maximum recommended dosage is simvastatin tablets USP 40 mg once daily [see DOSAGE AND ADMINISTRATION(2.2, 2.3)]. An 80 mg daily dosage of simvastatin tablets USP is restricted to patients who have been taking simvastatin tablets USP 80 mg daily chronically (e.g., for 12 months or more) without evidence of muscle toxicity [see WARNINGS AND PRECAUTIONS(5.1)].
If as dose is missed, take the missed dose as soon as possible. Do not double the next dose.
For patients that require a high-intensity statin or are unable to achieve their LDL-C goal receiving simvastatin tablets USP 40 mg daily, prescribe alternative LDL-C-lowering treatment.
Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating simvastatin tablets USP, and adjust the dosage if necessary.
Range source text (exact source wording)
The recommended dosage range of simvastatin tablets USP is 20 mg to 40 mg once daily

Dosage: children

For children 10 years and older with heterozygous familial hypercholesterolemia, the recommended range is 10 mg to 40 mg daily. Safety and effectiveness are not established in children younger than 10 years or for other types of high cholesterol.
Section
2.3 Recommended Dosage in Pediatric Patients 10 Years of Age and Older with HeFH
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Section 8 4
8.4 Pediatric Use (last paragraph)
Source text (exact source wording)
The recommended dosage range of simvastatin tablets USP is 10 mg to 40 mg daily.
Source text 8 4 (exact source wording)
The safety and effectiveness of simvastatin have not been established in pediatric patients younger than 10 years of age with HeFH or in pediatric patients with other types of hyperlipidemia (other than HeFH).

Dosage adjustments

Drug interaction caps
With lomitapide, the dose is cut by 50% and capped at 20 mg once daily (40 mg for people who previously took 80 mg long-term). With verapamil, diltiazem or dronedarone, do not exceed 10 mg once daily. With amiodarone, amlodipine or ranolazine, do not exceed 20 mg once daily.
Section
2.5 Dosage Modifications Due to Drug Interactions
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
Concomitant use of simvastatin tablets USP with the following drugs requires dosage modification of simvastatin tablets USP [see WARNINGS AND PRECAUTIONS (5.1) AND DRUG INTERACTIONS (7.1)].

Patients taking Lomitapide

Reduce the dosage of simvastatin tablets USP by 50%. Do not exceed simvastatin tablets USP 20 mg once daily (or 40 mg once daily for patients who have previously taken an 80 mg daily dosage of simvastatin tablets USP chronically while taking lomitapide) [see DOSAGE AND ADMINISTRATION (2.1)].

Patients taking Verapamil, Diltiazem, or Dronedarone

Do not exceed simvastatin tablets USP 10 mg once daily.

Patients taking Amiodarone, Amlodipine, or Ranolazine

Do not exceed simvastatin tablets USP 20 mg once daily.
Kidney
For severe kidney impairment (creatinine clearance 15 – 29 mL/min), the recommended starting dose is 5 mg once daily, and the label says to use another simvastatin product to start dosing. No adjustment is recommended for mild or moderate impairment. The label also says simvastatin is not available in a 5 mg strength.
Section
2.4 Recommended Dosage in Patients with Renal Impairment; 8.6 Renal Impairment (source_text_8_6)
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
For patients with severe renal impairment [creatinine clearance (CLcr) 15 – 29 mL/min], the recommended starting dosage of simvastatin is 5 mg once daily [see WARNINGS AND PRECAUTIONS (5.1) AND USE IN SPECIFIC POPULATIONS (8.6)].

Use another simvastatin product to initiate dosing in such patients [see DOSAGE AND ADMINISTRATION (2.1)].

There are no dosage adjustment recommendations for patients with mild or moderate renal impairment.
Source text 8 6 (exact source wording)
Renal impairment is a risk factor for myopathy and rhabdomyolysis. Monitor all patients with renal impairment for development of myopathy. In patients with severe renal impairment (CLcr 15 – 29 mL/min), the recommended starting dosage is simvastatin 5 mg once daily [see DOSAGE AND ADMINISTRATION (2.4), WARNINGS AND PRECAUTIONS (5.1)]. Simvastatin is not available in a 5 mg strength. Use another simvastatin product to initiate dosing in such patients.
Liver
Section
8.7 Hepatic Impairment
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
Simvastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis [see CONTRAINDICATIONS (4), WARNINGS AND PRECAUTIONS (5.3)].
Elderly
The label gives no separate dose for older adults. In a study of patients on simvastatin 80 mg daily, patients 65 years of age or older had a higher risk of muscle problems (myopathy, including rhabdomyolysis) than patients younger than 65. In another study, the mean plasma level of total inhibitors was about 45% higher in patients 70-78 years of age than in patients 18-30 years of age.
Section
8.5 Geriatric Use
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
Of the total number of simvastatin-treated patients in clinical studies 1,021 (23%) patients, 5,366 (52%) patients, and 363 (15%) patients were ≥65 years old, respectively. In Study HPS, 615 (6%) patients were ≥75 years old [see CLINICAL STUDIES (14)]. In a clinical study of patients treated with simvastatin 80 mg daily, patients ≥65 years of age had an increased risk of myopathy, including rhabdomyolysis, compared to patients <65 years of age.

A pharmacokinetic study with simvastatin use showed the mean plasma level of total inhibitors to be approximately 45% higher in geriatric patients between 70-78 years of age compared with patients between 18-30 years of age [see CLINICAL PHARMACOLOGY (12.3)].

Missed dose

Take a missed dose as soon as possible and do not double the next dose. The Patient Information leaflet adds that if you do not remember until it is time for your next dose, skip the missed dose and go back to your regular schedule, and do not take 2 doses at the same time.
Section
2.1 Important Dosage and Administration Information (the typographical error 'as dose' is in the label text)
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Medlineplus text
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue the regular dosing schedule. Do not take a double dose to make up for a missed one.
Medlineplus source
MedlinePlus What should I do if I forget a dose?
Section 17 text
Instruct patients to take simvastatin tablets only as prescribed. If a dose is missed, it should be taken as soon as possible. Advise patients not to double their next dose.
Patient information text
If you miss a dose, take it as soon as you remember. If you do not remember until it is time for your next dose, skip the missed dose and go back to your regular schedule. Do not take 2 doses of simvastatin tablets at the same time. Talk with your healthcare provider if you have questions about a missed dose.
Source text (exact source wording)
If as dose is missed, take the missed dose as soon as possible. Do not double the next dose.

Overdose

No specific antidote is known. Call poison control at 1-800-222-1222, or 911 if the person has collapsed, had a seizure, has trouble breathing or cannot be woken.
Section
10 Overdosage
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Medlineplus text
In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.
Medlineplus source
MedlinePlus In case of emergency/overdose
Source text (exact source wording)
No specific antidotes for simvastatin are known. Contact Poison Control (1-800-222-1222) for latest recommendations.

Storage

The prescribing information says to store between 20° to 25°C (68° to 77°F) in a tight container. The Patient Information leaflet in the same label says to store between 41°F to 86°F (5°C to 30°C). Keep it out of the reach of children.
Section
16 HOW SUPPLIED/STORAGE AND HANDLING (Storage); Patient Information 'How should I store simvastatin tablets?'
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95); labeler-specific
Patient information text
Store simvastatin tablets between 41°F to 86°F (5°C to 30°C).

Keep simvastatin tablets and all medicines out of the reach of children.
Source text (exact source wording)
Store between 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Preserve in tight container as defined in USP.

Boxed warning

NONE (no boxed warning appears in the Lupin label highlights or full text)

Contraindications

Do not use simvastatin with strong CYP3A4 inhibitors (certain azole antifungals, macrolide antibiotics, antiviral medicines and nefazodone), or with cyclosporine, danazol or gemfibrozil. Do not use it with acute liver failure or decompensated cirrhosis, or if allergic to simvastatin or its ingredients. Allergic reactions have included anaphylaxis, angioedema and Stevens-Johnson syndrome.
Section
4 Contraindications
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
Simvastatin is contraindicated in the following conditions:

Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see DRUG INTERACTIONS (7.1)].
Concomitant use of cyclosporine, danazol or gemfibrozil [see DRUG INTERACTIONS (7.1)].
Acute liver failure or decompensated cirrhosis [see WARNINGS AND PRECAUTIONS (5.3)]
Hypersensitivity to simvastatin or any excipients in simvastatin tablets USP. Hypersensitivity reactions, including anaphylaxis, angioedema and Stevens-Johnson syndrome, have been reported [see ADVERSE REACTIONS (6.2)]

Warnings and precautions

Simvastatin may cause muscle problems (myopathy) and a serious muscle breakdown (rhabdomyolysis), which can lead to acute kidney injury and rare deaths. In studies of 24,747 patients, myopathy occurred in about 0.03% on 20 mg, 0.08% on 40 mg and 0.61% on 80 mg daily. In another study of 12,064 patients, myopathy occurred in about 0.02% on 20 mg and 0.9% on 80 mg daily.
Heading
5.1 Myopathy and Rhabdomyolysis
Section
5.1 Myopathy and Rhabdomyolysis (first two paragraphs)
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
Simvastatin may cause myopathy and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including simvastatin.

In clinical studies of 24,747 simvastatin -treated patients with a median follow-up of 4 years, the incidence of myopathy, defined as unexplained muscle weakness, pain, or tenderness accompanied by creatinine kinase (CK) increases greater than ten times the upper limit of normal (10xULN), were approximately 0.03%, 0.08%, and 0.61% in patients treated with simvastatin 20 mg, 40 mg, and 80 mg daily, respectively. In another clinical study of 12,064 simvastatin -treated patients (with a history of myocardial infarction) with a mean follow-up of 6.7 years, the incidences of myopathy in patients taking simvastatin 20 mg and 80 mg daily were approximately 0.02% and 0.9%, respectively. The incidences of rhabdomyolysis (defined as myopathy with a CK >40xULN) in patients taking simvastatin 20 mg and 80 mg daily were approximately 0% and 0.4%, respectively [see ADVERSE REACTIONS (6.1)].
Risk factors for muscle problems include age 65 years or greater, uncontrolled hypothyroidism, kidney impairment, certain other drugs and higher simvastatin dosage; Chinese patients may be at higher risk. Simvastatin should be stopped if CK levels are markedly raised or if muscle disease is diagnosed or suspected. Report unexplained muscle pain, tenderness or weakness, especially with malaise or fever.
Heading
5.1 Myopathy and Rhabdomyolysis (risk factors and steps to reduce risk)
Section
5.1 (Risk Factors for Myopathy first paragraph sentence; last three paragraphs; paragraphs between them omitted)
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs (including other lipid-lowering therapies), and higher simvastatin dosage; Chinese patients on simvastatin may be at higher risk for myopathy [see CONTRAINDICATIONS (4), DRUG INTERACTIONS (7.1), AND USE IN SPECIFIC POPULATIONS (8.8)].

Discontinue simvastatin if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Muscle symptoms and CK increases may resolve if simvastatin is discontinued. Temporarily discontinue simvastatin in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis, e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy.

Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the simvastatin dosage and advise patients receiving an 80 mg daily dosage of simvastatin tablet USP of the increased risk of myopathy and rhabdomyolysis. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.
Rare reports of an autoimmune muscle disease (IMNM) have been linked to statins. Simvastatin should be stopped if it is suspected.
Heading
5.2 Immune-Mediated Necrotizing Myopathy
Section
5.2 Immune-Mediated Necrotizing Myopathy
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use, including reports of recurrence when the same or a different statin was administered. IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy without significant inflammation; and improvement with immunosuppressive agents. Additional neuromuscular and serologic testing may be necessary. Treatment with immunosuppressive agents may be required. Discontinue simvastatin if IMNM is suspected
Liver enzyme increases have been reported, with persistent increases to more than 3 times the upper limit of normal in approximately 1% of patients. Rare fatal and non-fatal liver failure has been reported with statins. People who drink a lot of alcohol or have liver disease may be at higher risk. Liver enzyme testing should be considered before starting and when clinically indicated. If serious liver injury with symptoms or jaundice occurs, stop simvastatin.
Heading
5.3 Hepatic Dysfunction
Section
5.3 Hepatic Dysfunction
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
Increases in serum transaminases have been reported with use of simvastatin [see ADVERSE REACTIONS (6.1)]. In most cases, these changes appeared soon after initiation, were transient, were not accompanied by symptoms, and resolved or improved on continued therapy or after a brief interruption in therapy. Persistent increases to more than 3xULN in serum transaminases have occurred in approximately 1% of patients receiving simvastatin in clinical studies. Marked persistent increases of hepatic transaminases have also occurred with simvastatin. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including simvastatin.

Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury.

Consider liver enzyme testing before simvastatin initiation and when clinically indicated thereafter. Simvastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis [see CONTRAINDICATIONS (4)]. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue simvastatin.
Statins, including simvastatin, can raise HbA1c and fasting blood sugar. The label advises regular exercise, a healthy body weight and healthy food choices.
Heading
5.4 Increases in HbA1c and Fasting Serum Glucose Levels
Section
5.4
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
Increases in HbA1c and fasting serum glucose levels have been reported with statins, including simvastatin. Optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices.

Pregnancy and breastfeeding

Simvastatin should be stopped when pregnancy is recognized, or the ongoing needs of the patient should be considered, because it may cause fetal harm. Breastfeeding is not recommended during treatment.
Section
8.1 Pregnancy (Risk Summary, first two paragraphs); 8.2 Lactation (Risk Summary, two paragraphs); text between them omitted
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Medlineplus text
tell your doctor if you are pregnant or plan to become pregnant. If you become pregnant while taking simvastatin, call your doctor immediately. Simvastatin can harm the fetus. tell your doctor if you are breastfeeding. You should not breastfeed while you are taking simvastatin.
Medlineplus source
MedlinePlus What special precautions should I follow?
Source text (exact source wording)
Discontinue simvastatin when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient.

Simvastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, simvastatin may cause fetal harm when administered to pregnant patients based on the mechanism of action [see CLINICAL PHARMACOLOGY (12.1)]. In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients.

8.2 Lactation

Risk Summary

There is no information about the presence of simvastatin in human or animal milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production. However, it has been shown that another drug in this class passes into human milk. Statins, including simvastatin, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol and may cause harm to the breastfed infant.

Because of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with simvastatin [see USE IN SPECIFIC POPULATIONS (8.1), CLINICAL PHARMACOLOGY (12.1)].

Side effects

Common
In studies of 2,423 adults, the most common side effects (5% or more) were upper respiratory infections (9%), headache (7%), abdominal pain (7%), constipation (7%) and nausea (5%).
Threshold
Label: most commonly reported adverse reactions (incidence ≥5%)
Section
6.1 Clinical Trials Experience (2,423 adult patients, median follow-up approximately 18 months)
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
The most commonly reported adverse reactions (incidence ≥5%) in these simvastatin clinical studies were: upper respiratory infections (9%), headache (7%), abdominal pain (7%), constipation (7%), and nausea (5%).
Less common
In the long Study 4S, reactions reported in 2% or more of simvastatin patients and more than placebo included bronchitis (6.6% vs 6.3%), atrial fibrillation (5.7% vs 5.1%), gastritis (4.9% vs 3.9%), eczema (4.5% vs 3.0%), vertigo (4.5% vs 4.2%), diabetes mellitus (4.2% vs 3.6%) and muscle pain (3.7% vs 3.2%).
Section
6.1 Table 1: Adverse Reactions Reported ≥2% of Patients Treated with Simvastatin and Greater than Placebo in Study 4S
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
Table 1 (Study 4S), % Placebo (N = 2,223) vs % Simvastatin (N = 2,221): Bronchitis 6.3 vs 6.6; Abdominal pain 5.8 vs 5.9; Atrial fibrillation 5.1 vs 5.7; Gastritis 3.9 vs 4.9; Eczema 3.0 vs 4.5; Vertigo 4.2 vs 4.5; Diabetes mellitus 3.6 vs 4.2; Insomnia 3.8 vs 4.0; Myalgia 3.2 vs 3.7; Urinary tract infection 3.1 vs 3.2; Edema/swelling 2.3 vs 2.7; Headache 2.1 vs 2.5; Sinusitis 1.8 vs 2.3; Constipation 1.6 vs 2.2.
Serious
Serious problems include muscle breakdown, an autoimmune muscle disease, liver problems and raised blood sugar. Rare postmarketing reports include pancreatitis, hepatitis, liver failure, severe allergic reactions and interstitial lung disease. MedlinePlus says to call your doctor right away for muscle pain, tenderness or weakness, dark urine, yellow skin or eyes, upper right stomach pain, decreased urination, blisters, rash, swelling, trouble breathing or swallowing, joint pain or sensitivity to light.
Label section
6 Adverse Reactions (intro list); 6.2 Postmarketing Experience (selected categories)
Label source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Medlineplus source
MedlinePlus What side effects can this medication cause?
Label source text (exact source wording)
Myopathy and Rhabdomyolysis [see WARNINGS AND PRECAUTIONS (5.1)]; Immune-Mediated Necrotizing Myopathy [see WARNINGS AND PRECAUTIONS (5.2)]; Hepatic Dysfunction [see WARNINGS AND PRECAUTIONS (5.3)]; Increases in HbA1c and Fasting Serum Glucose Levels [see WARNINGS AND PRECAUTIONS (5.4)] (important adverse reactions). Postmarketing: 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. Respiratory and Thoracic: interstitial lung disease, dyspnea.
Medlineplus source text (exact source wording)
Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately or get emergency medical help. muscle pain, tenderness, or weakness with or without fever or lack of energy; tiredness, or weakness; fever or chills; dark-colored urine that may look red; yellowing of the skin or eyes; pain in the upper right part of the stomach; loss of appetite; decreased urination; flushing; blisters; rash, hives, itching; swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs; difficulty breathing or swallowing; hoarseness; joint pain; sensitivity to light
Led to discontinuation
Overall, 1.4% of patients stopped simvastatin because of side effects. The most common reasons were stomach and bowel problems (0.5%), muscle pain (0.1%) and joint pain (0.1%).
Section
6.1 Clinical Trials Experience
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Source text (exact source wording)
Overall, 1.4% of patients discontinued simvastatin 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%).

Interactions

Drugs
Strong CYP3A4 inhibitors such as itraconazole, ketoconazole, erythromycin, clarithromycin, certain HIV and hepatitis C protease inhibitors, cobicistat products and nefazodone must not be used with simvastatin. If one is unavoidable, simvastatin is suspended during that treatment.
Name
Strong CYP3A4 inhibitors
Section
7.1 Table 2
Source text (exact source wording)
Concomitant use of strong CYP3A4 inhibitors with Simvastatin is contraindicated [see CONTRAINDICATIONS (4)] . If treatment with a CYP3A4 inhibitor is unavoidable, suspend simvastatin 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 and gemfibrozil must not be used with simvastatin.
Name
Cyclosporine, danazol or gemfibrozil
Section
7.1 Table 2
Source text (exact source wording)
Concomitant use of cyclosporine, danazol, or gemfibrozil with simvastatin is contraindicated [see CONTRAINDICATIONS (4)] .
With verapamil, diltiazem or dronedarone, do not exceed 10 mg daily. With amiodarone, amlodipine or ranolazine, do not exceed 20 mg daily.
Name
Amiodarone, dronedarone, ranolazine, or calcium channel blockers
Section
7.1 Table 2
Source text (exact source wording)
For patients taking verapamil, diltiazem, or dronedarone, do not exceed simvastatin 10 mg daily. For patients taking amiodarone, amlodipine, or ranolazine, do not exceed simvastatin 20 mg daily [see DOSAGE AND ADMINISTRATION (2.5)] .
Cut the simvastatin dose by 50% when starting lomitapide, and do not exceed 20 mg daily (40 mg for people who previously took 80 mg long-term).
Name
Lomitapide
Section
7.1 Table 2
Source text (exact source wording)
Reduce the dose of simvastatin by 50% if initiating lomitapide. Do not exceed simvastatin 20 mg daily (or simvastatin 40 mg daily for patients who have previously taken an 80 mg daily dosage of simvastatin chronically) while taking lomitapide [see DOSAGE AND ADMINISTRATION (2.1, 2.5)] .
Consider temporarily suspending simvastatin during daptomycin treatment because of rhabdomyolysis reports.
Name
Daptomycin
Section
7.1 Table 2
Source text (exact source wording)
If treatment with daptomycin is required, consider temporarily suspending simvastatin during the course of daptomycin treatment.
Lipid-modifying doses of niacin with simvastatin are not recommended in Chinese patients. For others, the benefit must be weighed against the higher muscle risk.
Name
Niacin
Section
7.1 Table 2
Source text (exact source wording)
Concomitant use of simvastatin with lipid-modifying dosages of niacin is not recommended in Chinese patients [see USE IN SPECIFIC POPULATIONS (8.8)]. For non-Chinese patients, consider if the benefit of using lipid-modifying doses of niacin concomitantly with simvastatin 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 raise the risk of muscle problems. If used together, patients should be monitored for muscle symptoms.
Name
Fibrates (other than gemfibrozil)
Section
7.1 Table 2
Source text (exact source wording)
Consider if the benefit of using fibrates concomitantly with simvastatin 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.
Muscle problems and rhabdomyolysis have been reported when colchicine and simvastatin are used together.
Name
Colchicine
Section
7.1 Table 2
Source text (exact source wording)
Cases of myopathy and rhabdomyolysis have been reported with concomitant use of colchicine with simvastatin.
Simvastatin may strengthen warfarin-type blood thinners and raise the INR, so INR should be checked before starting and often after changes.
Name
Coumarin anticoagulants (warfarin)
Section
7.2 Table 3
Source text (exact source wording)
Clinical Impact:
Simvastatin may potentiate the effect of coumarin anticoagulants and increase the INR. The concomitant use of simvastatin (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 simvastatin 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.
Simvastatin may raise digoxin levels, so digoxin levels should be monitored when simvastatin is started.
Name
Digoxin
Section
7.2 Table 3
Source text (exact source wording)
Clinical Impact:
Concomitant use of digoxin with simvastatin may result in elevated plasma digoxin concentrations [see CLINICAL PHARMACOLOGY (12.3) ].

Intervention:
Monitor digoxin levels in patients taking digoxin when simvastatin is initiated.
Food and alcohol
Grapefruit juice can raise simvastatin levels and the risk of muscle problems, so the label says to avoid it.
Name
Grapefruit juice
Section
7.1 Table 2
Source text (exact source wording)
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 simvastatin.
People who drink substantial amounts of alcohol may be at increased risk of liver injury.
Name
Alcohol
Section
5.3 Hepatic Dysfunction
Source text (exact source wording)
Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury.
Other
Niacin may interact with simvastatin; do not start it without talking to your healthcare provider.
Name
Niacin (nonprescription)
Section
MedlinePlus What special precautions should I follow?
Source text (exact source wording)
the following nonprescription product may interact with simvastatin: niacin.
Liverpool checkers
Label contraindicates strong CYP3A4 inhibitors including HIV and hepatitis C protease inhibitors and cobicistat products, so antiviral interactions apply. Liverpool HIV/HEP checkers: not checked.

Patient tips

Take it exactly as prescribed, once a day in the evening, and do not change your dose or stop without talking to your healthcare provider. Keep following your cholesterol-lowering diet and exercise. Tell your healthcare provider right away about unexplained muscle pain, tenderness or weakness, especially with fever. Call your provider right away for signs of liver problems: feeling tired or weak, loss of appetite, right-sided upper belly pain, dark urine, or yellowing of your skin or the whites of your eyes. Talk with your healthcare provider about all medicines you take, including grapefruit juice. MedlinePlus adds: continue to take simvastatin even if you feel well, and talk to your doctor about grapefruit.
Label source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95) Section 17 Patient Counseling Information (full section, verbatim)
Medlineplus source
MedlinePlus (https://medlineplus.gov/druginfo/meds/a692030.html)
Patient information how to take text
How should I take simvastatin tablets?

Take simvastatin tablets exactly as your healthcare provider tells you to take it.
Do not change your dose or stop taking simvastatin tablets without talking to your healthcare provider.
Take simvastatin tablets 1 time each day in the evening.
If you miss a dose, take it as soon as you remember. If you do not remember until it is time for your next dose, skip the missed dose and go back to your regular schedule. Do not take 2 doses of simvastatin tablets at the same time. Talk with your healthcare provider if you have questions about a missed dose.
While taking simvastatin tablets, continue to follow your cholesterol-lowering diet and to exercise as your healthcare provider told you to.
Your healthcare provider may do blood tests to check your cholesterol while you take simvastatin tablets. Your healthcare provider may change your dose of simvastatin tablets if needed.
In case of overdose, get medical help or contact a live Poison Center expert right away at 1-800-222-1222. Advice is also available online at poisonhelp.org
Patient information liver text
Liver problems.Your healthcare provider should do blood tests to check your liver before you start taking simvastatin tablets and if you have any symptoms of liver problems while you take simvastatin tablets. Call your healthcare provider right away if you have the following symptoms of liver problems:
feeling tired or weak
loss of appetite
right-sided upper belly pain
dark urine
yellowing of your skin or the whites of your eyes
Patient information source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95) Patient Information leaflet (SPL patient package insert), verbatim excerpts
Label source text (exact source wording)
Advise the patient to read the FDA-approved patient labeling (Patient Information).

Myopathy and Rhabdomyolysis

Advise patients that simvastatin may cause myopathy and rhabdomyolysis. Inform patients taking an 80 mg daily dose of simvastatin that they are at an increased risk. Inform patients that the risk is also increased when taking certain types of medication or consuming grapefruit juice and they should discuss all medication, both prescription and over the counter, with their healthcare provider. Instruct patients to inform other healthcare providers prescribing a new medication or increasing the dose of an existing medication that they are taking simvastatin. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever [see CONTRAINDICATIONS (4), WARNINGS AND PRECAUTIONS (5.1), AND DRUG INTERACTIONS (7.1)].

Hepatic Dysfunction

Inform patients that simvastatin may cause liver enzyme elevations and possibly liver failure. Advise patients to promptly report fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice [see WARNINGS AND PRECAUTIONS (5.3)].

Increases in HbA1c and Fasting Serum Glucose Levels

Inform patients that increases in HbA1c and fasting serum glucose levels may occur with simvastatin. Encourage patients to optimize lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices [see WARNINGS AND PRECAUTIONS (5.4)].

Pregnancy

Advise pregnant patients and patients who can become pregnant of the potential risk to a fetus. Advise patients to inform their healthcare provider of a known or suspected pregnancy to discuss if simvastatin should be discontinued [see USE IN SPECIFIC POPULATIONS (8.1)].

Lactation

Advise patients that breastfeeding is not recommended during treatment with simvastatin [see USE IN SPECIFIC POPULATIONS (8.2)].

Missed Dose

Instruct patients to take simvastatin tablets only as prescribed. If a dose is missed, it should be taken as soon as possible. Advise patients not to double their next dose.
Medlineplus source text (exact source wording)
Continue to take simvastatin even if you feel well. Do not stop taking simvastatin without talking to your doctor. Eat a low-fat, low-cholesterol diet. Talk to your doctor about eating grapefruit or drinking grapefruit juice while taking this medicine.

Alternatives

Class per label
HMG-CoA reductase inhibitor (statin)
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95) Highlights; MedlinePlus

Frequently asked questions

Question
What is simvastatin used for?
Answer
It lowers the risk of death, heart attack and stroke in adults at high risk, and with diet lowers LDL cholesterol. It is also used for several inherited or severe forms of high cholesterol and for hypertriglyceridemia in adults.
Source section
1 Indications and Usage
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Question
When should I take simvastatin?
Answer
Take it once daily in the evening.
Source section
2.1
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Question
What if I miss a dose?
Answer
Take it as soon as possible. Do not double the next dose. MedlinePlus adds that if it is almost time for the next dose, skip the missed one.
Source section
2.1; MedlinePlus What should I do if I forget a dose?
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95); MedlinePlus
Question
Can I have grapefruit juice with simvastatin?
Answer
The label says to avoid grapefruit juice because it can raise simvastatin levels and the risk of muscle problems.
Source section
7.1 Table 2 (Grapefruit Juice)
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Question
What are the common side effects?
Answer
The label's most common side effects (5% or more) were upper respiratory infections (9%), headache (7%), abdominal pain (7%), constipation (7%) and nausea (5%).
Source section
6.1 Clinical Trials Experience
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Question
Is simvastatin safe in pregnancy or while breastfeeding?
Answer
It should be stopped when pregnancy is recognized, or the ongoing needs of the patient should be considered, because it may cause fetal harm. Breastfeeding is not recommended during treatment.
Source section
8.1 Pregnancy; 8.2 Lactation
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Question
What medicines can I not take with simvastatin?
Answer
Strong CYP3A4 inhibitors (certain azole antifungals, macrolide antibiotics, antiviral medicines and nefazodone), cyclosporine, danazol and gemfibrozil are contraindicated. Other medicines such as amiodarone, amlodipine, verapamil, diltiazem and lomitapide require dose limits.
Source section
4 Contraindications; 2.5
Source
DailyMed label (Lupin Pharmaceuticals, Inc., set ID 3e48217f-8175-4e9b-9fd0-909be4bbba95)
Question
Should I stop simvastatin when my cholesterol is normal?
Answer
MedlinePlus says to keep taking simvastatin even if you feel well and not to stop without talking to your doctor.
Source section
How should this medicine be used?
Source
MedlinePlus

Sources

Information is taken from the cited sources and is for general reference only. It is not medical advice. Report side effects to FDA MedWatch at 1-800-FDA-1088. For a poison emergency call 1-800-222-1222. See prices for this drug