1.ZOCOR HISTORY
How was Zocor discovered?

Zocor is a product of Merck & Co.

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first.

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first.

Established in 1891, Merck discovers, develops, manufactures and markets vaccines and medicines in over 20 therapeutic categories.

Note: World-drugs.net sells generic version of Zocor

2.ZOCOR FACTS

Zocor is a time-tested, cholesterol-lowering medication, with over 160 million prescriptions filled in the past 11 years.

In patients with heart disease or diabetes, Zocor, along with a healthy diet, is proven to reduce the risk of heart attack and stroke, regardless of cholesterol level.

3.ABOUT ZOCOR MEDICATION
What is cholesterol and what does it have to do with heart disease?

Cholesterol is a waxy, fat-like material that is found in all parts of the body. It comes from two sources: the liver produces it, and we consume it in meat and dairy products.

Cholesterol is a chemical that can do both good and harm in the body. On the good side, cholesterol plays important roles in the structure of cells and in the production of hormones. But too much cholesterol in the blood can lead to heart and blood vessel disease. To complicate matters, not all cholesterol contributes to heart and blood vessel problems.

One type, called high-density lipoprotein (HDL) cholesterol, or "good cholesterol," actually lowers the risk of these problems. High-density lipoproteins (HDL) remove cholesterol from the bloodstream. The other type, low-density lipoprotein (LDL) cholesterol, or "bad cholesterol," is the type that threatens people's health. Low-density lipoproteins (LDL) deliver cholesterol to the body. To travel through the bloodstream, cholesterol must attach itself to a protein. The combination of a protein and a fatty substance like cholesterol is called a lipoprotein.

Many factors may contribute to the fact that some people have higher cholesterol levels than others. A diet high in certain types of fats is one factor. Medical problems such as poorly controlled diabetes, an under active thyroid gland, an overactive pituitary gland, liver disease or kidney failure also may cause high cholesterol levels. And some people have inherited disorders that prevent their bodies from properly using and eliminating fats. This allows cholesterol to build up in the blood.

Treatment for high cholesterol levels usually begins with changes in habits. By losing weight, stopping smoking, exercising more and reducing the amount of fat and cholesterol in the diet, many people can bring their cholesterol levels down to acceptable levels. However, some may need to use cholesterol-reducing drugs to reduce their risk of health problems.

While some cholesterol is needed for good health, too much cholesterol in your blood can raise your risk of having a heart attack or stroke.

The extra cholesterol in your blood may be stored in your arteries (blood vessels) and cause them to narrow. (This is called atherosclerosis.) Large deposits of cholesterol can completely block an artery, so the blood cannot flow through.

If an artery that supplies blood to your heart becomes blocked, a heart attack can occur. If an artery that supplies blood to your brain becomes blocked, a stroke can occur.

Cholesterol Levels:

Total cholesterol level

HDL cholesterol levels

•  60 or higher reduces your risk of heart disease.

What are Cholesterol Lowering agents?

Cholesterol-reducing drugs are medicines that lower the amount of cholesterol in the blood.

•  Bile acid sequestrants

They are drugs that act by binding with the bile produced by the liver. Bile helps the digestion and absorption of fats in the intestine. By blocking the digestion of fats, bile acid sequesterants prevent the formation of cholesterol. Drugs in this class include:

• Cholestyramine,
• Colestipol, and
• Colesevelam.
• HMG-CoA inhibitors, often called "statins,"

They are drugs that block an enzyme called "3-hydroxy-3-methyl-glutaryl-coenzyme A reductase." This blocks one of the steps in converting fat to cholesterol. These are the most effective cholesterol lowering agents available and in recent years have received increased attention for their benefits beyond helping patients with high cholesterol. In 2003, researchers reported that people with heart failure but no coronary artery disease received benefits after only 14 weeks of statin therapy. In addition, some research has connected the drugs to reduced risk for depression and dementia.

Drugs in this group include:

•  Fibric acid derivatives

They include

Although these drugs are less effective than the statins at lowering total cholesterol, they may be able to lower the low-density lipoprotein (LDL) cholesterol while raising the high-density lipoprotein (HDL) cholesterol. They probably act by inhibiting lipoprotein lipase activity.

4. Niacin, or vitamin B-3, also is effective in lowering cholesterol levels. Although the normal vitamin dose of niacin is only 20 mg, the dose required to reduce cholesterol levels is at least 500 mg each day. Niacin probably helps reduce cholesterol by inhibiting very low-density lipoprotein (VLDL) secretion in the bloodstream.

How does Zocor work?

Zocor decreases the production of LDL cholesterol by blocking the action of the enzyme in the liver (called HMG-CoA reductase) that is responsible for its production. This decreases the amount of cholesterol in the liver cells, which causes them to take up LDL cholesterol from the blood. The decreased cholesterol production and increased removal of LDL cholesterol from the blood ultimately results in lowered blood cholesterol levels.

As the body produces most cholesterol at night, statins are generally more effective if taken at night.

Zocor also causes a small decrease in the production of other 'bad fats' in the blood called triglycerides, and a small increase in the level of HDL cholesterol. This results in lowered levels of 'bad fats' and raised levels of 'good fats' in the blood.

Statins have an important role in the prevention of coronary heart disease. They reduce the risk of excess cholesterol being deposited in the major blood vessels of the heart (atherosclerosis). Any blockage in the blood vessels limits the amount of blood and therefore oxygen being carried to the heart muscle. This can cause chest pain (angina) and in severe cases can result in a heart attack (myocardial infarction).

Zocor can also be used to reduce the risk of coronary heart disease in people who have already had a heart attack, or who suffer from angina or diabetes. In these people Zocor slows down hardening of the arteries, regardless of your cholesterol level. Zocor reduces the risk of needing procedures to improve blood supply to the heart, such as a balloon dilation of an artery or a heart bypass graft. It also reduces the risk of heart attack and death.

It is important to continue to follow a cholesterol-lowering diet and exercise regime while taking Zocor. Discuss this with your doctor.

4.ZOCOR EFFECTIVENESS
When is Zocor best taken?

Simvastatin is a lactone that is readily hydrolyzed in vivo to the corresponding (beta)-hydroxyacid, a potent inhibitor of HMG-CoA reductase. Inhibition of HMG-CoA reductase is the basis for an assay in pharmacokinetic studies of the (beta)-hydroxyacid metabolites (active inhibitors) and, following base hydrolysis, active plus latent inhibitors (total inhibitors) in plasma following administration of simvastatin.

Following an oral dose of Simvastatin in man, 13% of the dose was excreted in urine and 60% in feces. The latter represents absorbed drug equivalents excreted in bile, as well as any unabsorbed drug. Plasma concentrations of total radioactivity peaked at 4 hours and declined rapidly to about 10% of peak by 12 hours post dose. Absorption of Simvastatin, estimated relative to an intravenous reference dose, in each of two animal species tested, and averaged about 85% of an oral dose. In animal studies, after oral dosing, Simvastatin achieved substantially higher concentrations in the liver than in non-target tissues. Simvastatin undergoes extensive first-pass extraction in the liver, its primary site of action, with subsequent excretion of drug equivalents in the bile. As a consequence of extensive hepatic extraction of Simvastatin (estimated to be > 60% in man), the availability of drug to the general circulation is low. In a single-dose study in nine healthy subjects, it was estimated that less than 5% of an oral dose of Simvastatin reaches the general circulation as active inhibitors. Following administration of Simvastatin tablets, the coefficient of variation, based on between-subject variability, was approximately 48% for the area under the concentration-time curve (AUC) for total inhibitory activity in the general circulation.

Both Simvastatin and its (beta)-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins. Animal studies have not been performed to determine whether simvastatin crosses the blood-brain and placental barriers. However, when radiolabeled Simvastatin was administered to rats, Simvastatin-derived radioactivity crossed the blood-brain barrier.

In a study including 16 elderly patients between 70 and 78 years of age who received Zocor 40 mg/day, the mean plasma level of HMG-CoA reductase inhibitory activity was increased approximately 45% compared with 18 patients between 18-30 years of age. Clinical study experience in the elderly (n=1522), suggests that there were no overall differences in safety between elderly and younger patients.

Kinetic studies with another reductase inhibitor, having a similar principal route of elimination, have suggested that for a given dose level higher systemic exposure may be achieved in patients with severe renal insufficiency.

The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. Potent inhibitors of CYP3A4 can raise the plasma levels of HMG-CoA reductase inhibitory activity and increase the risk of myopathy.

5.ZOCOR EFFECTS ON SPECIAL POPULATION
How do different people react to Zocor?

Pregnancy

Zocor belongs to the Pregnancy Category X

Safety in pregnant women has not been established.

Zocor was not teratogenic in rats at doses of 25 mg/kg/day or in rabbits at doses up to 10 mg/kg daily. These doses resulted in 3 times (rat) or 3 times (rabbit) the human exposure based on mg/m 2 surface area. However, in studies with another structurally related HMG-CoA reductase inhibitor, skeletal malformations were observed in rats and mice.

Rare reports of congenital anomalies have been received following intrauterine exposure to HMG-CoA reductase inhibitors. In a review 5 of approximately 100 prospectively followed pregnancies in women exposed to Zocor or another structurally related HMG-CoA reductase inhibitor, the incidences of congenital anomalies, spontaneous abortions and fetal deaths/stillbirths did not exceed what would be expected in the general population. The number of cases is adequate only to exclude a 3 to 4 fold increase in congenital anomalies over the background incidence. In 89% of the prospectively followed pregnancies, drug treatment was initiated prior to pregnancies and was discontinued at some point in the first trimester when pregnancies was identified. As Safety in pregnant women has not been established and there is no apparent benefit to therapy with Zocor during pregnancy, treatment should be immediately discontinued as soon as pregnancy is recognized. Zocor should be administered to women of childbearing potential only when such patients are highly unlikely to conceive and have been informed of the potential hazards.

Nursing Mothers

It is not known whether Zocor is excreted in human milk. Because a small amount of another drug in this class is excreted in human milk and because of the potential for serious adverse reactions in nursing infants, women taking Zocor should not nurse their infants.

Pediatric Use

Safety and effectiveness of Zocor in patients 10-17 years of age with heterozygous familial hypercholesterolemia have been evaluated in a controlled clinical trial in adolescent boys and in girls who were at least 1 year post-menarche. Patients treated with Zocor had an adverse experience profile generally similar to that of patients treated with placebo. Doses greater than 40 mg have not been studied in this population. In this limited controlled study, there was no detectable effect on growth or sexual maturation in the adolescent boys or girls, or any effect on menstrual cycle length in girls.

Geriatric Use

A pharmacokinetic study with Zocor showed the mean plasma level of HMG-CoA reductase inhibitory activity to be approximately 45% higher in elderly patients between 70-78 years of age compared with patients between 18-30 years of age. In this study, Zocor significantly reduced total mortality and CHD mortality in elderly patients with a history of CHD.

6.ZOCOR EFFECTS ON MEDICAL CONDITIONS
How does Zocor affect your existing condition/ailment?

Myopathy

Zocor, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase above 10 × 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.

Liver Dysfunction

Persistent increases in serum transaminases have occurred in approximately 1% of patients who received Zocor in clinical studies. When drug treatment was interrupted or discontinued in these patients, the transaminase levels usually fell slowly to pretreatment levels. The increases were not associated with jaundice or other clinical signs or symptoms. There was no evidence of hypersensitivity.

7.OTHER/ALTERNATE USES OF ZOCOR
What else does Zocor treat?

Zocor is used to lower cholesterol in people who have high levels either due to genetics or as a result of diet and lifestyle. This thereby helps to reduce the risk of atherosclerosis, angina and heart attacks.

8.ADVERSE/SIDE EFFECTS of ZOCOR
What are the side effects of Zocor?

In the pre-marketing controlled clinical studies and their open extensions, 1.4% of patients were discontinued due to adverse experiences attributable to Zocor. Adverse reactions have usually been mild and transient. Zocor has been evaluated for serious adverse reactions in more than 21,000 patients and is generally well tolerated.

Clinical Adverse Experiences

In Adults

Adverse experiences occurring in adults at an incidence of 1% or greater in patients treated with Zocor, regardless of causality, in controlled clinical studies are shown in the table below

Clinical Adverse Experiences

The Clinical Studies involving 4,444 patients treated with 20-40 mg/day of Zocor (n=2,221) or placebo (n=2,223), the safety and tolerability profiles were comparable between groups over the median 5.4 years of the study. The clinical adverse experiences reported as possibly, probably, or definitely drug-related in >/= 0.5% in either treatment group are shown in the table below.

Heart Protection Study

Clinical Adverse Experiences

In the Clinical Studies, involving 20,536 patients treated with Zocor 40 mg/day (n=10,269) or placebo (n=10,267), the safety profiles were comparable between patients treated with ZOCOR and patients treated with placebo over the mean 5 years of the study. In this large trial, only serious adverse events and discontinuations due to any adverse events were recorded. Discontinuation rates due to adverse experiences were comparable (4.8% in patients treated with ZOCOR compared with 5.1% in patients treated with placebo). The incidence of myopathy was <0.1% in patients treated with Zocor.

The following effects have been reported with drugs in this class. Not all the effects listed below have necessarily been associated with Zocor therapy.

Skeletal : muscle cramps, myalgia, myopathy, rhabdomyolysis, arthralgias.

Neurological: dysfunction of certain cranial nerves (including alteration of taste, impairment of extra-ocular movement, facial paresis), tremor, dizziness, vertigo, memory loss, paresthesia, peripheral neuropathy, peripheral nerve palsy, psychic disturbances, anxiety, insomnia, depression.

Hypersensitivity Reactions : An apparent hypersensitivity syndrome has been reported rarely which has included one or more of the following features: anaphylaxis, angioedema, lupus erythematous-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, chills, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme, including Stevens-Johnson syndrome.

Gastrointestinal : pancreatitis, hepatitis, including chronic active hepatitis, cholestatic jaundice, fatty change in liver, and, rarely, cirrhosis, fulminant hepatic necrosis, and hepatoma; anorexia, vomiting.

Skin : alopecia, pruritus. A variety of skin changes (e.g., nodules, discoloration, dryness of skin/mucous membranes, changes to hair/nails) have been reported.

Reproductive : gynecomastia, loss of libido, erectile dysfunction.

Eye: progression of cataracts (lens opacities), ophthalmoplegia.

Laboratory Abnormalities : elevated transaminases, alkaline phosphatase, (gamma)-glutamyl transpeptidase, and bilirubin; thyroid function abnormalities.