Simvastatin (Zocor) is a lipid-lowering medicine or a statin that is used to treat patients with abnormal blood lipid levels. It is used for the primary and secondary prevention of atherosclerotic cardiovascular disease.

Simvastatin Uses:

Hyperlipidemias:

• Dysbetalipoproteinemia:
  • Reduce triglyceride levels and very-low-density lipoprotein cholesterol levels.
  • Used in therapy of primary dysbetalipoproteinemia (Fredrickson type III)
• Heterozygous familial and nonfamilial hypercholesterolemia and mixed dyslipidemia:
  • Decrease triglycerides, overall cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B.
  • surge high-density lipoprotein cholesterol.
  • Used in therapy of primary hyperlipidemia (Fredrickson type IIa and Fredrickson type IIb)
• Heterozygous familial hypercholesterolemia (HeFH) in adolescents:
  • Decrease overall cholesterol, low-density lipoprotein cholesterol & apo B levels in preteens and youngsters with heterozygous familial hypercholesterolemia with:
  • A. LDL cholesterol more than 190 mg/dL
  • B. Or LDL cholesterol more than 160 mg/dL with a family history of premature cardiovascular disease.
  • C. Or LDL cholesterol more than 160 mg/dL with two or more other cardiovascular disease risk issues.
• Homozygous familial hypercholesterolemia:
  • Reduce total cholesterol and LDL cholesterol in patients with homozygous familial hypercholesterolemia along with other lipid-decreasing treatments (e.g., LDL apheresis) or if such treatments are not accessible.
• Hypertriglyceridemia:
  • Decreases serum triglyceride levels in patients with hypertriglyceridemia (Fredrickson type IV)
  • Limitations of use:
  • Not researched for treatment Fredrickson Types I and V as no data available regarding the effect on chylomicrons.
• Prevention of cardiovascular events:
  • Decreases risk of MI, stroke & total fatalities.
  • & to decrease the necessity for coronary/non-coronary revascularization procedures in patients at elevated risk of coronary events (e.g., patients with coronary heart disease, diabetes, PVD, history of stroke or other cerebrovascular diseases)
• Off Label Use of Simvastatin in Adults:
  • For noncardiac surgery, decrease in Cardiac risk (perioperative therapy).
  • Non cardioembolic stroke/Transient ischemic attack (secondary prevention)

Simvastatin (Zocor) Dose in Adults:

Note:

• According to the standard LDL-cholesterol levels, doses should be personalized, the proposed goal of treatment, and the patient's response.
• Modifications should be made with gaps of one month or more.
• Based on parallel medications, doses may need to be adjusted.

Note:

• Dosing limitation:

  • Simvastatin 80 mg is restricted to patients that have been taking this dose for more than12 consecutive months without indication of myopathy and are not presently taking or starting to take a simvastatin dose-limiting or contraindicated interacting medication.
  • Increasing to 80 mg dose is not advised if the patient is unable to attain low-density lipoprotein-cholesterol (LDL-C) goal using the 40 mg dose of simvastatin.
  • Switch patient to an alternative LDL-C-lowering treatment instead, delivering greater LDL-C reduction.

Dose in the treatment of Homozygous familial hypercholesterolemia:

• P/O:
  • In the evening, 40 mg one time a day.

Simvastatin (Zocor) Dose in the Prevention of cardiovascular events (also see ACC/AHA Blood Cholesterol Guideline recommendations), hyperlipidemias:

• P/O:
• Initial:
  • 10-20 mg one time a day in the evening.
• Range:
  • 5-40 mg per day

• Patients requiring only moderate reduction of LDL-C:

  • In the evening, maybe initiated at 5-10 mg one time a day.
  • Adjust to achieve suggested LDL-C goal.

• Patients requiring reduction of >40% of LDL-C:

  • In the evening, maybe initiated at 40 mg one time a day.
  • Adjust to achieve the proposed LDL-C goal.

• Patients with CHD or at high risk for cardiovascular events (patients with diabetes, PVD, history of stroke, or other cerebrovascular diseases):

  • In the evening, dosing should be started at 40 mg one time a day.
  • Start together with diet treatment.

Simvastatin (Zocor) Dose in the Prevention of cardiovascular disease/ reduce the risk of atherosclerotic cardiovascular disease:

P/O:

ACC/AHA Blood Cholesterol Guideline recommendations:

Note:

• Consider atherosclerotic cardiovascular disease (ASCVD) risk, risk-enhancing factors, the possibility for side effects, and drug interactions when choosing to initiate therapy and selecting dose-intensity.

• Primary prevention:

  • LDL-C ≥190 mg/dL and age 20-75 years:

    • High-grade treatment required.
    • Use alternate statin treatment(e.g., atorvastatin or rosuvastatin)

  • Diabetes, age 40 to 75 years, and an estimated 10-year ASCVD risk <7.5%:

    • Moderate-intensity therapy:
    • 20-40 mg one time a day

  • Diabetes, age 40-75 years, and an estimated 10-year ASCVD risk ≥7.5%:

    • High dose treatment required.
    • Use alternate statin treatment (eg, atorvastatin or rosuvastatin)
  • LDL-C 70-189 mg/dL, age 40-75 years, and an estimated 10-year ASCVD risk ≥7.5%:
    • Moderate- to high-intensity therapy:
    • Daily 20-40 mg once or ponder using high-intensity statin treatment (eg, atorvastatin or rosuvastatin)

• Secondary prevention:

  • If the patient has clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) or is post-CABG and:

    • Age ≤75 years:
      • High-grade treatment required.
      • Use alternate statin therapy (eg, atorvastatin or rosuvastatin)
    • Age >75 years:
    • Moderate- to high-intensity therapy:
      • Daily 20-40 mg once or consider using high-intensity statin therapy (eg, atorvastatin or rosuvastatin).
      • Increase to a high-intensity statin therapy within 3 months if moderate-level treatment has begun and is well endured(Rosenson 2019).

US Preventive Services Task Force recommendations:

• Age 40 to 75 years, no history of CVD, with ≥1 CVD risk factor (dyslipidemia, diabetes, hypertension, or smoking), and calculated 10-year CVD event risk of ≥10%:

  • Primary prevention:

    • Low-intensity therapy:
      • Daily 10 mg once
    • Moderate-intensity therapy:
      • Daily 20-40 mg once

Note:

• to patients with very high CVD risk factors (eg, LDL >190 mg/dL, familial hypercholesterolemia) (were excluded from primary prevention trials), these recommendations do not pertain.
• in the treatment of these patients, use clinical judgment.
• May consider the use of a statin based on patient characteristics in patients with a calculated 10-years CVD event risk of 7.5%-10%.

• Dosage adjustment for simvastatin with concomitant medications:

Note:

• Patients currently enduring and needing a dose of simvastatin 80 mg who require initiation of an interacting drug with a dose cap for simvastatin should be switched to another statin with less potential for drug-drug interaction.

  • Amiodarone, amlodipine, or ranolazine:

    • Simvastatin dose should not cross 20 mg/day

  • Diltiazem, dronedarone, or verapamil:

    • Simvastatin dose should not cross 10 mg/day

  • Lomitapide:

    • When starting lomitapide, decrease simvastatin dose by half
    • Simvastatin dose should not exceed 20 mg/day (or 40 mg daily for those who previously tolerated simvastatin 80 mg daily for ≥1 year without indications of muscle toxicity).

Simvastatin (Zocor) Dose in Childrens

Note:

• A lower, conventional dosing schedule may be required in-patient residents susceptible to myopathy including patients of Chinese descent or those simultaneously getting other lipid-lowering agents (eg, niacin, fibric acid derivatives), amiodarone, amlodipine, diltiazem, dronedarone, ranolazine, verapamil (see the following conservative, max adult doses).
• According to the criterion LDL-C level, dosage should be personalized, the recommended target of treatment, and patient reaction.
• Adjustments should be made with monthly gaps.
• For at least 6-12 months prior to commencing pharmacotherapy, lifestyle alterations are advised to be implemented.

Simvastatin (Zocor) Dose in the treatment of Hyperlipidemia or heterozygous familial hypercholesterolemia (HeFH) and nonfamilial hypercholesterolemia:

Note:

• For nonfamilial hypercholesterolemia or other forms of non-HeFH hyperlipidemia, constrained information.

• Begin treatment if, after adequate trial (6-12 months) of intensive lifestyle modification emphasizing body weight normalization and diet, the following are present:

  • LDL-C ≥190 mg/dL or
  • LDL-C remains ≥160 mg/dL and two or more cardiovascular risk factors:
    • Family background of premature atherosclerotic cardiovascular disease (<55 years of age), overweight, obesity, or other factors of insulin resistance syndrome or
    • LDL-C ≥130 mg/dL and diabetes mellitus.
    • For children, 8-9 years of age who meet the above criteria or for children with diabetes mellitus and LDL-C ≥130 mg/dL, treatment may also be considered.

• Children ≥4 years and <10 years:

  • P/O:
  • Initial:
    • In the evening, 5 mg one time a day increasing to 10 mg once daily after a month & to 20 mg one time a month after another 4 weeks as endured.
  • Max daily dose: 20 mg/day.
    • Maximum experience is with children at least 8 years of age.
    • The youngest reported patient was 4 years of age in trials.

• Children ≥10 years and Adolescents:

  • P/O:
  • Initial:
    • In the evening, 10 mg one time a day increasing to 20 mg one time a day after 6 weeks & to 40 mg one time a day after another 6 weeks as endured.
  • Max daily dose:
    • 40 mg/day

• Dosing adjustment for simvastatin with concomitant medications:

  • In the manufacturer's labeling for patients less than18 years, there are no suggestions.
  • In adolescents ≥18 years, the following have been recommended:
    • Diltiazem, dronedarone, or verapamil:
      • Max simvastatin daily dose: 10 mg/day
    • Amiodarone or amlodipine:
      • Max daily dose: 20 mg/day

Dosing adjustment for toxicity:

• Muscle symptoms (potential myopathy):

  • Children ≥4 years and Adolescents:

    • Till symptoms can be assessed, terminate use.
    • Check CPK level.
    • Also, assess the patient for conditions that may increase the risk for muscle symptoms (e.g., hypothyroidism, decreased kidney or hepatic function, rheumatologic conditions such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases) built on experience in adult patients.
    • Continue the initial or a lower dose of simvastatin and re-titrate upon resolution (symptoms and any associated CPK abnormalities).
    • Suspend the utilization of simvastatin if muscle symptoms happen again.
    • May then restart a different statin at an initial low dose after muscle symptom resolution.
    • If tolerated well then increase steadily.
    • Based on experience in adult patients, contemplate other reasons for muscle symptoms or elevated CPK stays for 2 months in the absence of continuous statin use.
    • May continue statin treatment at the initial dose if verified to be due to another condition aside from statin use.

Pregnancy Risk Factor X

• Simvastatin contraindicated in pregnant women and those at risk of becoming pregnant
• Reports of genetic abnormalities have been reported after maternal HMG-CoA reductase inhibitions were administered to pregnant women.
• The available data are not easily understood due to the limitations of information on maternal disease, exposure rates, and variations in the agents used.
• Cholesterol biosynthesis is an important part of fetal development.
• As normal, pregnancy causes an increase in serum cholesterol and triglycerides.
• It is unlikely that the termination of lipid-lowering medication during pregnancy will have an impact on long-term outcomes of primary hypercholesterolemia treatment.
• Simvastatin should not be used if Simvastatin causes an unplanned pregnancy.
• Satisfactory contraception should be used if an HMG-CoA reductase inhibitor for females with reproductive potential is required.
• Females who are planning to have children should stop taking the HMG-CoA inhibitor for at least 1-2 months before trying to conceive.

Use during breastfeeding:

• It isn't known if simvastatin can be excreted in breastmilk.
• Manufacturers have declared that breastfeeding can cause serious adverse reactions in babies.

Dose in Kidney Disease:

• Mild to moderate impairment:
  • No dosage modifications required.
  • Simvastatin does not go through substantial renal excretion.
• Severe impairment:
  • Initial:
  • With close monitoring, 5 mg one time each day.

Dose in Liver disease:

• Contraindicated in active liver disease or in patients with mysterious continued increases of serum transaminases.

Side Effects of Simvastatin (Zocor):

• Cardiovascular:

  • Atrial Fibrillation
  • Edema

• Central Nervous System:

  • Headache
  • Vertigo

• Dermatologic:

  • Eczema

• Gastrointestinal:

  • Abdominal Pain
  • Constipation
  • Gastritis
  • Nausea

• Genitourinary:

  • Cystitis

• Hepatic:

  • Increased Serum Transaminases

• Neuromuscular & Skeletal:

  • Increased Creatine Phosphokinase In Blood Specimen
  • Myalgia

• Respiratory:

  • Upper Respiratory Infection
  • Bronchitis

Frequency of side effects not defined:

• Dermatologic:

  • Skin Rash

• Endocrine & Metabolic:

  • Increased Gamma-Glutamyl Transferase

• Gastrointestinal:

  • Diarrhea
  • Dyspepsia
  • Flatulence
  • Gastrointestinal Disease

• Hepatic:

  • Increased Serum Alkaline Phosphatase

• Neuromuscular & Skeletal:

  • Asthenia

Contraindications to Simvastatin (Zocor):

• Hypersensitivity to simvastatin and any component of the formulation
• Liver disease.
• Strangely, serum transaminases have been increasing in mysterious ways.
• Simultaneous use of strong CYP3A4 inhibitors (eg, clarithromycin, erythromycin, itraconazole, ketoconazole, nefazodone, posaconazole, voriconazole, protease inhibitors [including boceprevir and telaprevir], telithromycin, cobicistat-containing products), cyclosporine, danazol, and gemfibrozil.
• Women who are pregnant or may become pregnant.
• Breastfeeding

Warnings and precaution

• Diabetes mellitus:

  • Hyperglycemia can lead to an increase in HbA1c. The risk is outweighed by the benefits.

• Hepatotoxicity:

  • Continuous elevations in serum transaminases have been reported.
  • Transaminase levels are reverted back to or close to before therapy levels upon dose reduction, drug interruption or termination.
  • Reports of post-marketing fatalities and non-fatal liver failure have been made and are not common.
  • If severe hepatotoxicity is observed with clinical symptoms, hyperbilirubinemia, jaundice, or other signs during treatment, discontinue the treatment immediately.
  • If simvastatin isn't found in another cause, do not take simvastatin again.
  • It is important to perform liver enzyme tests at baseline and as often as it is clinically recommended.
  • Ethanol could increase the risk of adverse hepatic reactions.
  • To avoid excessive ethanol consumption, educate patients

• Myopathy and rhabdomyolysis

  • There have been reports of rhabdomyolysis, with or without severe renal failure secondary to myoglobinuria and myopathy.
  • Patients should be closely monitored.
  • The risk of developing this condition is dependent on the dose and can be increased by simvastatin 80 mg.
  • Concomitant use of strong CYP3A4 inhibitors (eg, clarithromycin, erythromycin, itraconazole, ketoconazole, nefazodone, posaconazole, voriconazole, protease inhibitors [including boceprevir and telaprevir], telithromycin, cobicistat-comprising products), cyclosporine, danazol, and gemfibrozil is contraindicated because of increased risk of myopathy.
  • Patients with uncontrolled hypothyroidism and patients who have taken other myopathy drugs (e.g. colchicine) >=65 years old should be monitored.
  • These patients are more likely to develop myopathy.
  • It has been reported that immuno-mediated necrotizing myopathy (IMNM), associated with HMG–CoA reductase inhibitors, is also possible.
  • Patients should be instructed to immediately report any unexplained pains, tenderness, weakness or brown urine, particularly if they are accompanied by malaise, fever, or other symptoms.
  • Stop treatment if CPK levels are elevated or myopathy is suspected/diagnosed.

• Hepatic impairment, ethanol and/or ethanol abuse:

  • Active hepatic injury is contraindicated. Patients with a history of liver disease or alcoholics should be cautious.

• Renal impairment

  • Take care. Pay attention. modify dose as required.

Simvastatin: Drug Interaction

Monitoring parameters:

ACC/AHA Blood Cholesterol Guideline recommendations:

Lipid panel (total cholesterol, HDL, LDL, triglycerides):

• Before starting therapy, lipid profile (fasting or nonfasting).
• The fasting lipid profile should be rechecked 4-12 weeks after initiating treatment later after every 3-12 months.
• If 2 consecutive LDL levels are below 40 mg/dL, the dose may be increased.

Hepatic transaminase levels:

• Obtain baseline levels of hepatic transaminase levels (AST and ALT).
• During treatment, measure AST, ALT, total bilirubin, and alkaline phosphatase
• Watch for any symptoms of liver damage (eg, unusual fatigue or weakness, anorexia, abdominal pain, dark-colored urine, or yellowing of skin or sclera).

CPK:

• In patients with a family background of statin intolerance or muscle disease, clinical presentation, on medication that may increase the risk of myopathy baseline CPK should be obtained.
• May obtain CPK in any patient with symptoms indicative of myopathy (pain, tenderness, stiffness, cramping, weakness, or generalized fatigue).
• Regular routine check-up of CPK is not required.
• During treatment, evaluate for new-onset diabetes mellitus.

How to administer Simvastatin (Zocor)?

• Suspension:
  • Take without food at night
• Tablets:
  • Take regardless of food.
  • More effective if taken at night.

Mechanism of action of Simvastatin (Zocor):

• Simvastatin is a methylated derivative of lovastatin, it competitively inhibits the rate-limiting enzyme in the production of cholesterol, the 3-hydroxy-3methylglutaryl-coenzyme A (HMG-CoA) reductase.
• HMG-CoA reductase inhibits lower levels of high-sensitivity, C-reactive protein. They also improve endothelial function and reduce inflammation at the site.

Onset of action:

• >3 days

Peak effect:

• 2 weeks

LDL-C reduction:

• 20-40 mg/day:
• 35%-41% (for each doubling of this dose, LDL-C is lowered ~6%)

Average HDL-C increase:

• 5%-15%
• Average triglyceride reduction:
• 7%-30%

Absorption:

• Although 85% is absorbed following administration, <5% reaches the general circulation due to an extensive first-pass effect

Protein binding:

• ~95%

Metabolism:

• Hepatic via CYP3A4.
• Extensive first-pass effect

Bioavailability:

• <5%

Half-life elimination:

• Unknown

Time to peak:

• 1.3-2.4 hours

Excretion:

• Feces (60%).
• Urine (13%)

International Brand Names of Simvastatin:

• FloLipid
• Zocor
• ACT Simvastatin
• AG-Simvastatin
• APO-Simvastatin
• Auro-Simvastatin
• BCI Simvastatin
• DOM-Simvastatin
• JAMP-Simvastatin
• Mar-Simvastatin
• MINT-Simvastatin
• MYLAN Simvastatin
• PHARMA-Simvastatin
• PHL-Simvastatin
• PMS-Simvastatin
• RAN-Simvastatin
• RIVA-Simvastatin
• SANDOZ Simvastatin
• Simvastatin-10
• Simvastatin-20
• Simvastatin-40
• Simvastatin-80
• TARO-Simvastatin
• TEVA-Simvastatin
• Zocor
• Alkor
• Allesta
• Antex
• Avastinee
• Bestatin
• Biosim
• Cazet
• Cholemed
• Cholestat
• Clinfar
• Colesken
• Corstat
• Cotritev
• Covastin
• Decrelip
• Ecuvas
• Esvat
• Ethicol
• Eucor
• Forcad
• Husimba
• Ifistatin
• Klonastin
• Lesvatin
• Lipaco
• Lipecor
• Lipex
• Lipidoff
• Lipinorm
• Liponorm
• Lipovas
• Lochol
• Lodales
• Luoqi
• Mersivas
• Nimicor
• Nor-Vastina
• Orovas
• Priacin
• Pulsar AT
• Pusarat
• Ransim
• Rechol
• Recol
• Rezostatin
• Roco
• Simaspen
• Simastin
• Simaz
• Simbado
• Simchol
• Simlo
• Simovil
• Simplaqor
• SimStatin
• Simtan
• Simtin
• Simva
• Simvacor
• Simvahex
• Simvahexal
• Simvalord
• Simvar
• Simvart
• Simvast
• Simvastan
• Simvata
• Simvatin
• Simvaxon
• Simver
• Simvor
• Sinty
• Sinvacor
• Sivacor
• Sivas
• Sivastin
• Statin
• Stavid
• Torio
• Tulip
• Valemia
• Vascor
• Vasilip
• Vasotenal
• Vastin
• Vidastat
• Viscor
• Zeid
• Zetina
• Zimmex
• Zimstat
• Zocor
• Zocor HP
• Zocord
• Zokor
• Zorced
• Zostin
• Zovast

Simvastatin Brand Names in Pakistan: