The following additional side effects were reported
Laboratory Test findings
Each tablet contains Simvastatin 80 mg .
PATIENTS AT HIGH RISK OF CORONARY HEART DISEASE (CHD) OR WITH EXISTING CHD :
• In patients at high risk of CHD ( with or without hyperlipidemia ), i.e. Patients with diabetes , history of stroke or other cerebrovascular disease , peripheral vessel disease , or with existing CHD, CORVAST is indicated to :
- Reduce the risk of total mortality by reducing CHD deaths;
- Reduce the risk of major vascular events (a composite of non-fatal myocardial infarction , CHD death , stroke , or revascularization procedures);
- Reduce the risk of major coronary events ( a composite of non-fatal myocardial infarction or CHD deaths).
- Reduce the risk of stroke ;
- Reduce the need for coronary revascularization procedures
( including coronary artery bypass grafting and percutaneous
transluminal coronary angioplasty);
CORVAST is indicated as an adjunct to diet to reduce elevated total –C , LDL-C , TG and apolipoprotein B(apo B) , and to increase HDL-C in patients with primary hypercholesterolemia including heterozygous familial , non familial hypercholesterolemia , or combined ( mixed) hyperlipidemia , when response to diet and other nonpharmacological measures is inadequate CORVAST , therefore , lowers LDL-C/HDL-C and total –C / HDL –C ratios .
CORVAST is indicated for the treatment of patients with hypertriglyceridemia .
CORVAST is indicated for the treatment of patients with primary hyperlipoproteinemia .
1 tablet in the evening.
Patients at high risk of coronary heart disease (CHD)or with existing CHD
The usual starting dose of CORVAST is 20 mg / day in the evening for patients at high risk of CHD (with or without hyperlipidemia ) e.g. patients with diabetes , history of stroke or other cerebrovascular disease , peripheral vessel disease , or with existing CHD. Drug therapy can be initiated simultaneously with diet and exercise.
Patients with hyperlipidemia (Who are not in the risk Categories above)
The patient should be placed on a standard cholesterol-lowering diet before receiving CORVAST and should continue on this diet during treatment with CORVAST.
The usual starting dose is 20 mg/day in the evening, patients who require a large reduction in LDL-C (more than 45%) may be started at 40 mg/day.
Patients with homozygous familial hypercholesterolemia
40 mg in the evening or 80 mg/day in three divided doses of 20 mg, 20 mg and an evening dose of 40 mg.
- Hypersensitivity to any component of CORVAST .
- Active liver disease or unexplained persistent elevations of serum transaminases .
- pregnancy and lactation .
- pediatric use. - Porphyria
* Myopathy/ Rhabdomyolysis
Simvastatin , like other inhibitors of HMG-CoA reductase , occasionally causes myopathy manifested as muscle pain , tenderness or weakness with creatine kinase (CK) above 10X the upper limit of normal (ULN) , Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria , and rare fatalities have occurred . The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma.
The risk of myopathy/rhabdomyolysis is dose related . The incidence in clinical trials , in which patients were carefully monitored and some interacting drugs were excluded , has been approximately 0.4% at 80 mg dose.
- Many of patients who have developed rhabdomyolysis on therapy with simvastatin have had complicated medical histories , including renal insufficiency usually as a consequence of long-standing diabetes mellitus . Such patients merit closer monitroring . Therapy with simvastatin should be temporarily stopped a few days prior to elective major surgery and when any major medical or surgical conditions supervenes.
- It is recommended that LFTs be performed before treatment begins and thereafter when clinically indicated . Patients titrated to the 80-mg dose should receive an additional test prior to titration , 3 months after titration to the 80mg dose , and periodically thereafter (semi-annually) for the first year of treatment . Special attention should be paid to patients who develop elevated serum transaminase levels , and in these patients , measurements should be repeated promptly and then performed more frequently . If the transaminase levels show evidence of progression , particularly if they rise to 3x ULN and are persistent , the drug should be discontinued .
- The drug should be used with caution in patients who consume substantial quantities of alcohol and / or have a past history of liver disease . active liver diseases or unexplained transaminase elevations are contraindications to the use of simvastatin .
- As with other lipid –lowering agents , moderate (less than 3x ULN) elevations of serum transaminases have been reported following therapy with simvastatin . These changes appeared soon after initiation of therapy with simvastatin were often transient , were not accompanied by any symptoms and interruption of treatment was not required .
Concomitant administration of simvastatin with the following drugs , increase the risk of myopathy / Rhabdomyolysis :
HIV protease inhibitors
The risk of myopathy is also increased by the following lipid-lowering drugs , which can cause myopathy when given alone.
Niacin (nicothinic acid ) (≥ 1 g/day)
Amiodarone or verapamil : the risk of myopathy / rhadomyolysis is increased by concomitant administration of amiodarone or verapamil , but no calcium channel blockers other than verapamil
Drinking Grapefruit juice during simvastatin therapy , should be avoided
Drinking Grapefruit juice during simvastatin therapy , should be avoided
In patients taking coumarin anticoagulants , prothrombin time should be determined before starting simvastatin and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs. Once a stable prothrombin time has been documented , prothrombin times can be monitored at the intervals usually recommended for patients on coumarin anticogulants . simvastatin therapy has not been associated with bleeding or with changes in prothrombin time in patients not taking anticogulants.
CORVAST is generally well – tolerated ; for the most part , side effects have been mild and transient in nature . Less than 2% of patients were discontinued from controlled clinical studies due to side effects attributable to simvastatin . Adverse effects occurring with a frequency of 1% or more , are abdominal pain , constipation and flatulence . Other side effects occurring in 0.5-0.9% of patients were asthenia and headache .
Myopathy has been reported rarely
Nausea , diarrhea , rash , dyspepsia , pruritus, alopecia , dizziness , muscle cramps , myalgia, pancreatits , paresthesia , peripheral neuropathy vomiting and anemia . Rarely rhabdomyolysis and hepatitis / jaundice occurred . hypersensitivity syndrome has been reported rarely which has included some of the following features : angioedema , lupus –like syndrome , polymyalgia rheumatica , dermatomyositis , vasculitis , thrombocytopenia , eosinophilia , ESR increased , arthritis , arthralgia , urticaria , photosensitivity , fever , flushing , dyspnea , and malaise.
Liver funcation test abnormalities generally have been mild and transient. Increases in serum CK levels , derived from skeletal muscle , have been reported.
A few cases of overdosage have been reported ; no patients had any specific symptoms , and all patients recovered without sequelae . The maximum dose taken was 450 mg . General measure should be adopted.