Drug Interaction:
HMG-COA reductase inhibitors include- Fluvastatin, Lovastatin, Pravastatin, Simvastatin
Refer - Lovastatin
Immunosuppressive drugs (cyclosporin), itraconazole, gemfibrozil, niacin, or erythromycin with concurrent simvastatin may increase risk of rhabdomyolysis & acute renal failure. Simvastatin may slightly enhance the anticoagulant effect of warfarin.
Prothrombin time must be closely monitored in patients taking statins with anticoagulants. Simvastatin may cause slight elevation of serum digoxin when used concurrently.
Cholestyramine or colestipol may decrease the bioavailabilty of simvastatin when used concurrently. It is suggested that simvastatin be given 4 hrs after cholestyramine or colestipol.
Indication:
Primary hypercholesterolaemias
HMG-COA reductase inhibitors include- Fluvastatin, Lovastatin, Pravastatin, Simvastatin
Approved by FDA in December 1991
New Drugs Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
1.Simvastatin Antihyperchlokesrterolemia September 1997
2.Simvasstatin 20mg 21-07-2009
+Ramipril 50mg
+HCTZ 12.5mg
+ Aspirin 100mg (EC Pellets)
capsules
For Secondary prevention of Coronary Heart Disease /stroke in patients
where use of such combination is appropiate
FIXED DOSE COMBINATIONS APPROVED BY DCG(I)
FROM JANUARY 1961 TILL NOVEMBER 2014
Name of Drug Indication Date of Approval
1.Simvastatin 10/20mg + 05-11-2005
Ezetimbe 10mg/10mg tablets
For primary Hypercholesteremia
2.Simvastatin 20mg +
Ramipril 5mg +
Atenolol 50mg +
HCTZ 12.5mg +
Aspirin 100mg (EC pelletes) capsules
For secondary prevention of Chronory Heart
disease/stroke in patients where use of such
combinations is appropriate
Patent Expiry Date of drugs (Ref - IDMA Publication)
Chemical Category Manufacturer/ US Patent
Ingredient- Marketer Expiration Date
Simvastatin Cardiovascular Merck & Co. 24-12-2005
INFORMATION UP DATE
STATINS : ADDITIONAL ADVERSE EFFECTS FOUND
Recent data suggests a number of additional side effects, namely;
-Treatment with any statins may be associated with depression, sleep disturbances,
memory loss and sexual dysfunction
-Statin therapy is associated with a slightly increased risk of development of diabetes
-Statins may rarely be associated with interstitial lung disease. Patients should be
adviced to seek medical attention if the symtoms such as dyspnoea, non-productive
cough or deterioration in general health( eg.fatigue, weight -loss and fever)
Simvastatin dose- (a) due to increased risk of serious , life threatening myopathy, no
patient should be initially started on 80mg dose
(b) use other treatments if patients LDL targets are not met with a 40mg daily dose
(c) patients concurrently on amidarone , or verapramil or diltiazem should not be
prescribed more than 10mg daily
(d) patients concurrently on amidopine or ranolazine must not receive more than 20mg
daily
(e) concurrent use of itraconazole , ketoconazole, posaconazole, erythromycin,
clarithromycin, telithromycin, HIV protease inhibitors , nefazodone, gemifibrozil,
cyclosporine and danazol is contraindicated (MIMS Feb 2014)
Adverse Reaction:
Adverse reactions are usually mild and transcient. These include headache, nausea, flatulance, heart burn, diarrhoea/constipation, abdominal pain, cramps, rarely myopathy features like myalgia, & muscle weakness have been reported.
Rhabdomyolysis with acute renal failure may also occur.
Elevation of the plasma concentration of the muscle isozyme of creatinine phosphokinase & serum transamminases reported. Hypersensitivity, lens opacities, blurring of vision, dizziness, loss of libido, erecetile dyfunction, depression, insomnia & upper respiratory symptoms, are also reported..
Contra-Indications:
Hypersensitivity, active liver disease or unexplained persistent elevations of serum transamminases.
Pregnacy and lactation.
Dosages/ Overdosage Etc:
Approved by FDA in December 1991
Primary hypercholesterolaemias
Dosage:
Initial dose- 5 to 10mg once daily in the evening. Consider starting dose of 5mg/day
Elderly- consider starting dose of 5mg/day.
Patient Information:
1. May cause photosentivity (sensitivity to sunlight) . Avoid prolonged exposure to the sun and othe ultraviolet light.
2. Use sunscreens and wear protective clothing until tolerance is determined
3. Promptly report unexplained muscle pain, tenderness or weakness, especially if accompanied by fever or malaise
4. Follow dietary recommendations.
5. Take lovastatin with meals, fluvastatin and simvastatin may be taken without regrads to meals.
Pharmacology/ Pharmacokinetics:
Pharmacology:
Simavastatin is an HMG-CoA reductase inhibitor derived synthetically from fermented product of Aspergillus terreus. It is a prodrug which is activated in the liver by hydrolysis to form the active beta-hydroxyacid derivative. This active form is a competitive and reversible inhibitor of HMG-CoA reductase, the enzyme responsible for conversion of HMG-CoA to mevalonic acid, an early and rate-limiting step in the biosynthesis of cholestrol.
Pharmacokinetics:
Folowing absoption from thr GIT, simvastatin undergoes extensive first pass metabolism in liver, its primary site of action. Consequently, the availability of the drug to the general circulation is low and variable. Under 5% of the oral dose has been reported to reach the circulation as the active metabolite. Both simvastin and its beta-hydoxyacid metabolite are highly protein bound (95%). Simvastin is eliminated 13% in urine and 60% via the rectal route.
Interaction with Food:
Simvastatin may be taken without regard to meals.
Pregnancy and lactation:
No data on pregnant women. Given to women of child bearing age only if they are highly unlikely to conceive.
Lactation:
Simvastatin is excreted in human breast milk. Because of the potential for serious adverse reactions in nursing infants, caution women taking these drugs not to nurse their infants.
Children:
Safety and efficacy in individuals below 18 years old have not been established
Manufacturer Details