Why US FDA issued a warning on use of Simvastatin containing drug Zocor

“Simvastatin in high dose of 80 mg may cause muscle injury, severe kidney damage, kidney failure, may prove fatal.”

On March 19 US FDA took a remarkable step , by issuing a warning on use of drug called Zocor a drug containg simvastatin , a cholesterol lowering drug , US FDA after reveling the out come of a clinical trial which studied cardiovascular disease in patients prescribed with a dose of 80 milligrams of simvastatin in comparison with to those on dose of 20 milligrams.

Simvastatin have a side effect of inducing muscle injury, which may lead to a disease condition known as Rhabdomyolysis , In patient suffering with Rhabdomyolysis
Muscle damage occurs in rapid manner , which releases muscle tissue , cells and myoglobins in blood stream , which can harm patiens kidney , and can result in to kidney failure .Treatment for rhabdomyolysis is then left to hemofiltration or dialysis .

In 2001 a drug from statin group Cerivastatin Manufactured by Bayer A.G. was voluntarily withdrawn from the market worldwide, because reports of rhabdomyolysis.

Simvastatin is a drug of group called as statins,
statins lower cholesterol by following three mechanisms.

1.Direct inhibition of cholesterol synthesis :-
Competitive inhibition of HMG CoA reductase
Cholesterol is synthesized in our body from 3-hydroxy-3-methylglutaryl-coA
(read it as HMG co-enzyme A) and is written as (HMG coA), it is a precursor for cholesterol molecule.
For conversion of 3-hydroxy-3-methylglutaryl-coA to cholesterol , HMG coA first is converted to mavalonic acid and then to mevalonate, and then to cholesterol in series of biochemichal reaction , known as HMG CoA Path way.
Conversion of HMG coA to mavalonic acid requires an enzyme called as HMG CoA reductase ,
Statin owing to its molecular similarity to mavalonic acid . inhibits enzyme HMG CoA reductase , reversibly.

2. Increase in up take by liver and excretion of LDL , & VDL (bad cholesterol)

Statin first lowers cholesterol synthesis by competitive inhibition of enzyme HMG CoA reductase .
This results in to activation of our body’s feedback mechanism which activates absorption of cholesterol , LDL, VDL in liver and exaction in to bile.

Simvastatin is one of the preferred drug in group of patients which have high risk of heart blockage, and stroke,

US FDA has requested the sponsor of simvastatin change the product labeling to instruct healthcare professionals to avoid prescribing simvastatin doses greater than 40 mg daily when patients are taking the medication diltiazem, due to an increased risk for myopathy.

US FDA has published Simvastatin Dose Limitations which are as follows.

These limitations apply to ALL patients taking simvastatin.

Do not use simvastatin with these medications:


Itraconazole
Ketoconazole
Erythromycin
Clarithromycin
Telithromycin
HIV protease inhibitors
Nefazodone

Do not use more than 10mg of simvastatin with these medications:
Gemfibrozil
Cyclosporine
Danazol

Do not use more than 20mg of simvastatin with these medications:
Amiodarone
Verapamil

Do not use more than 40mg of simvastatin with this medication:
Diltiazem

Laboratory method for estimation of cholesterol

Following are some of articles which;will be useful for you in further understanding of aspects of sterile dosage form manufacturing and regulatory affairs in pharmaceutical industry

Pharmaceutical Validation , types of validation in pharmaceutical manufacturing
http://whoguideline.blogspot.com/2010/03/validation-in-pharmaceutical.html

Requirements of documents for validation of sterilisation process

http://whoguideline.blogspot.com/2009/11/us-fdas-requirements-of-documentation.html

How to investigate OOS out of specification results
http://whoguideline.blogspot.com/2009/09/how-to-investigate-out-of-specification.html

Determination of Phenol coeeficient of a disinfectant
http://whoguideline.blogspot.com/2009/04/determination-of-phenol-coefficient.html

Sterility testing
http://whoguideline.blogspot.com/2009/04/sterility-testing-of-pharmaceuticals.html

Cleen Room Classification
http://whoguideline.blogspot.com/2010/02/clean-room-classification-aspects-of.html

Time limitations in sterile pharmaceuticals processing
http://whoguideline.blogspot.com/2010/02/time-limitations-in-aseptic-process.html

Aspects of validation of manufacturing process in sterile pharmaceuticals
http://whoguideline.blogspot.com/2010/02/aspects-of-validation-of-aseptic_26.html

Good manufacturing practice in pharmaceutical industry
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