Primary hypercholesterolemia (type IIa and IIb) in patients who have not responded adequately to diet and other appropriate measures. Also indicated in coronary heart disease and elevated plasma cholesterol levels.

Simvastatin is a cholesterol-lowering agent. It works by inhibiting HMG-CoA reductase, leading to an increase in LDL receptor density on liver cells, which enhances the removal of LDL cholesterol from the plasma and increases its breakdown. It also reduces very low-density lipoprotein (VLDL) cholesterol and decreases the formation of LDL from VLDL. Simvastatin is extensively metabolized in the liver, which is also its primary site of action.

The patient should be placed on a standard cholesterol-lowering diet before receiving Simvastatin and should continue on this during treatment with Simvastatin. The usual starting dose is 10 mg/day given as a single dose in the evening. Adjustment of dosage, if required, should be made at intervals of not less than four weeks, to a maximum of 40 mg daily given as a single dose in the evening. If LDL-cholesterol levels fall below 2 mmol/L or total plasma cholesterol levels fall below 3.5 mmol/L, consideration should be given to reducing the dose of Simvastatin. In hypercholesterolemia, the recommended starting dose is 5-10 mg once a day in the evening and the recommended dosing range is 5-40 mg per day as a single dose in the evening. In patients with coronary heart disease and hypercholesterolemia, the starting dose should be 20 mg once a day in the evening. Because Simvastatin does not undergo significant renal excretion, modification of dosage should not be necessary in patients with renal insufficiency. Safety and effectiveness in children and adolescents have not been established.

Digoxin: Concomitant use of Simvastatin and Digoxin in healthy individuals resulted in a slight increase (less than 0.3 µg/mL) in plasma digoxin levels compared to placebo with digoxin.

Coumarin derivatives: May slightly enhance the anticoagulant effect of Warfarin (mean increase in prothrombin time less than two seconds) in patients maintained on low therapeutic anticoagulation.

Others: In clinical studies, Simvastatin has been co-administered with ACE inhibitors, beta-blockers, calcium channel blockers, diuretics, and NSAIDs without evidence of clinically significant adverse interactions.

Simvastatin should not be used in:

• Patients with active liver disease
• Pregnant or breastfeeding women
• Women of childbearing potential unless adequately protected by contraception
• Patients with known hypersensitivity to any component of the formulation
• Patients with homozygous familial hypercholesterolemia who lack functional LDL receptors

Simvastatin is generally well tolerated. Common adverse effects include headache, fatigue, insomnia, and gastrointestinal symptoms such as nausea, constipation, diarrhea, flatulence, dyspepsia, and abdominal cramps. Muscle-related effects such as myalgia, myositis, and myopathy have also been reported. Rare cases of rhabdomyolysis with secondary acute renal failure due to myoglobinuria have been observed. Other reported effects include hepatitis, pancreatitis, rash, and angioedema. No potentially life-threatening adverse effects have been commonly reported.

Category X: Evidence from animal and human studies indicates fetal abnormalities and clear risk to the fetus. The potential risks of use in pregnant women outweigh any possible benefits. This drug is contraindicated in women who are pregnant or may become pregnant.

• Use with caution in patients with a history of liver disease
• Caution is advised in individuals who consume excessive alcohol
• Liver function tests should be performed before starting therapy and periodically during treatment
• If serum transaminases increase to three times the upper limit of normal, therapy should be discontinued
• Pregnancy should be avoided during treatment and for one month after stopping the drug

No specific data are available regarding overdose. There is no known antidote. General supportive measures should be implemented and liver function should be monitored.

Other Anti-anginal & Anti-ischaemic drugs, Statins

Store in a cool, dry place. Protect from light. Keep out of the reach of children.