Simvastatin is antihyperlipidic agent. Simvastatin is structural analog of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme). Like other agents, it inhibits the enzyme hydroxymethylglutaryl-CoA (HMG-CoA) reductase. It has an extremely high affinity for this enzyme and was considered the most potent agent of the HMG-CoA class until atorvastatin was approved. Simvastatin is inactive lactone prodrug and hydrolyzed in the gastrointestinal tract to the active ß hydroxy derivative. It was approved by the FDA in December 1991. It decreases total cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B, while increasing HDL.
Simvastatin also known as Synvinolin. . It is of Synthetic origin and belongs to Lactone. It belongs to HMGCoA reductase inhibitor pharmacological group on the basis of mechanism of action and also classified in Antilipemic Agent pharmacological group.The Molecular Weight of Simvastatin is 418.60.
Oral absorption of Simvastatin is found to be 42.5% ±42.5. Volume of distribution is found to be 98% and plasma protien binding is ~95%. Presystemic metabolism is noted to be 83% ±7 and metabolism is reported Hepatic. Renal Excretion accounts for 13% and plasma half life is 1.9 hr.
Simvastatin is known to interact with other drugs, the details of drug interactions is as follows:
Drug Details Severity Onset Management Amiodarone (HCl) Increased risk of myopathy when amiodarone is given with simvastatin. Major Avoid doses of simvastatin above 20 mg daily. Amprenavir Amprenavir possibly increases plasma concentration of Simvastatin. ADVICE: Avoid concomitant use. Major Atazanavir Atazanavir inhibits the hepatic metabolism of simvastatin results in increased plasma concentration. Major This combination is considered contraindicated. Patient should notify to physician if experience unexplained muscle pain, tenderness, or weakness, malaise or fever. Discontinue therapy if level of creatinine kinase is increased or if myopathy diagnosed. Bosentan Bosentan possibly reduces plasma concentration of Simvastatin. Ciprofibrate Colestipol (HCl) Danazol Concomitant administeration can lead to Rhabdomyolysis Digoxin Concomitant administerationn can slightly increase in digoxin level Eslicarbazepine Acetate can induce CYP3A4, decreasing plasma concentrations of
drugs that are metabolized by this isoenzyme use alternative Itraconazole Ketoconazole Linagliptin 10 mg of Linagliptin increases AUC by 34% and Cmax by 10% of simvastatin (40 mg) Mibefradil (Di HCl) Simeprevir co- administration may increased plasma concentrations of simvastatin use the lowest necessary dose Telithromycin Simvastatin levels were increased by Teicoplanin when used concurrently. Ticagrelor simvastatin is metabolised by CYP3A4 engzyme ( other e.g; Atorvastatin ) so ticagrelor may increase cmax of simvastatin by 81%, AUC 56% dose of Atorvastatin, symvastatin should be less than 40mg, greater than 40mg is not recommended Tocilizumab Toclizumab decreases exposure of simvastatin VORICONAZOLE Voriconazole may increase the serum concentration of simvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects Warfarin (Na) Simvastatin may enhance the anticoagulant effect of Warfarin. Moderate (Sequence important) Monitor for increased effects of Warfarin if Simvastatin is initiated/dose increased, or decreased effects if Simvastatin is discontinued/dose decreased. Dosage adjustments of Warfarin may be needed.
These interactions are sometimes beneficial and sometimes may pose threats to life. Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.
Interference in Pathology
Increased Alkaline Phosphatase Levels Elevaions in creatinine phosphokinase levels
The severe or irreversible adverse effects of Simvastatin, which give rise to further complications include Acute renal failure.
The symptomatic adverse reactions produced by Simvastatin are more or less tolerable and if they become severe, they can be treated symptomatically, these include Flatulence, Headache, Fatigue, Nausea, Diarrhea, Constipation, Abdominal pain, Elevation of liver enzymes, Myopathy, Rhabdomyolysis, Muscle tenderness, Increased intracranial pressure, Hepatitis, Pancreatitis.
Simvastatin's dosage details are as follows:
5 to 80 mg 42 (42.5) 24 hourly PO In evening, maintenance dose ranges 5-40 mg.
Paedriatic Dosage ( 20 Kg. )
Not recommended in this age group
Neonatal Dosage ( 3 Kg. )
Not recommended in this age group
High Risk Groups
Drug should not be given to Pregnant Mothers, patients suffering from Kidney dysfunction, and patients suffering from Liver Malfunction.
If prescribing authority justifies the benefits of the drug against the possible damages he/she should reevaluate them and consult the reference material and previous studies.
Warning / Precautions
Use simvastatin with caution in patients with liver disease, severe infection, kidney disease, heart disease, hypothyroidism, history of alcoholism or any allergy, especially drug allergies. Limit alcohol intake as it may aggravate side effects. Simvastatin should not be used during pregnancy or lactation.
Store Below 40°C. Protect from Sunlight and Moisture.
powered by Disqus. comments powered by