1.AVANDIA HISTORY
How was Avandia discovered?

Avandia is a product of GlaxoSmithKline (GSK) Pharmaceuticals.

GlaxoSmithKline (GSK) is a world leading research-based pharmaceutical company. Glaxo is headquartered in the UK and with operations based in the US ; the new company is one of the industry leaders, with an estimated seven per cent of the world's pharmaceutical market.

GSK also has leadership in four major therapeutic areas - anti-infectives, central nervous system (CNS), respiratory and gastro-intestinal/metabolic. In addition, it is a leader in the important area of vaccines and has a growing portfolio of oncology products.

Glaxo also has a Consumer Healthcare portfolio comprising over-the-counter (OTC) medicines; oral care products and nutritional healthcare drinks, all of which are among the market leaders. 

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

2.AVANDIA FACTS

Avandia is an anti-diabetic drug from the thiazolidinedione class.

Like other thiazolidinediones, its mechanism of action is by activation of the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPAR?.

Avandia is a pure ligand of PPAR?, and has no PPARa-binding action. Apart from its effect on insulin resistance, it appears to have an anti-inflammatory effect: nuclear factor kappa-B (NFaB) levels fall and inhibitor (IaB) levels increase in patients on Avandia.

 

 

3. ABOUT AVANDIA MEDICATION

What is Diabetes and what are its causes

Diabetes (diabetes mellitus): a condition characterized by hyperglycemia resulting from the body's inability to use blood glucose for energy. In type 1 diabetes, the pancreas no longer makes insulin and therefore blood glucose cannot enter the cells to be used for energy. In type 2 diabetes, either the pancreas does not make enough insulin or the body is unable to use insulin correctly.

Pre-diabetes : a condition in which blood glucose levels are higher than normal but are not high enough for a diagnosis of diabetes. People with pre-diabetes are at increased risk for developing type 2 diabetes and for heart disease and stroke. Other names for pre-diabetes are impaired glucose tolerance and impaired fasting glucose.

Type 1 diabetes : a condition characterized by high blood glucose levels caused by a total lack of insulin. Occurs when the body's immune system attacks the insulin-producing beta cells in the pancreas and destroys them. The pancreas then produces little or no insulin. Type 1 diabetes develops most often in young people but can appear in adults.

Type 2 diabetes : a condition characterized by high blood glucose levels caused by either a lack of insulin or the body's inability to use insulin efficiently. Type 2 diabetes develops most often in middle-aged and older adults but can appear in young people.

Other causes of diabetes

There are some other causes of diabetes, including certain diseases of the pancreas, but they are all very rare. Sometimes an accident or an illness may reveal diabetes if it is already there, but they do not cause it.

What are the symptoms of Diabetes?

The main symptoms of diabetes are:

Type 2 diabetes develops slowly and the symptoms are usually less severe. Some people may not notice any symptoms at all and their diabetes is only picked up in a routine medical check up. Some people may put the symptoms down to 'getting older' or 'overwork'.

Type 1 diabetes develops much more quickly, usually over a few weeks, and symptoms are normally very obvious.

In both types of diabetes, the symptoms are quickly relieved once the diabetes is treated. Early treatment will also reduce the chances of developing serious health problems.

What are the risk factors for Diabetes?

Age:

All people are vulnerable to the disease throughout their lives. However, the risk is higher as you grow older. There is a gradual increase in susceptibility, with slight peaks at puberty and during pregnancy, until we reach the age of 40. Then there is a rapid jump.

Heredity

If you have a family history of diabetes, especially parents or siblings with diabetes, then you're near the top of the list in terms of risk. Heredity is the most important predisposing factor for diabetes, especially for type-I diabetes.

Type 2 diabetes also tends to run in families, but since 80 to 85 percent of all cases occur among people who are over 40 and overweight, obesity is considered more important in the development of this form of the disease.

Obesity

80 to 85 percent of people with type 2 diabetes are overweight. It is true that not all overweight people have diabetes. But if you are obese, you may be setting yourself up for this disease 10 or 20 years from now. (You are considered obese, if you are more than 20 percent over ideal body weight.)

Race

In the United States the disease is more common among African-Americans, Hispanics and American Indians. More than 40% of Pima Indians in the United States have type 2 diabetes. However, that race alone does not predict diabetes; it must be combined with another factor, such as obesity.

Poverty

Researchers have uncovered a link between poverty and diabetes. In a survey in the USA , households with the lowest income-under $15,000- was found to have the highest incidence of diabetes.

Having impaired glucose tolerance

Having high blood pressure or high cholesterol levels (240 mg/dl or more)

In women, having a history of gestational diabetes or delivery of babies weighing more than 9 pounds

Complications of Diabetes

When you are not properly managing your type 2 diabetes, you greatly increase your risk of diabetes-related complications. Every one percent increase in your A1C level above 6 percent elevates the risk of diabetes-related complications, including stroke, heart attack, blindness and loss of limbs. Here are some of the more common risks associated with type 2 diabetes:

Heart Disease and Stroke

• Diabetes carries an increased risk for heart attack and stroke related to poor circulation.
• People with diabetes are two to four times more likely to suffer strokes.
• Two-thirds of the people with diabetes die of heart disease or stroke.

Kidney Disease

• The kidneys filter the waste products from the body.
• Diabetes can damage the kidneys, leading to failure.

Eye Complications

• Diabetes can cause eye problems and may lead to blindness.
• Every year up to 24,000 people lose their sight to diabetes.

Nerve Damage

• Diabetes can cause nerve damage (neuropathy), which can affect feelings in arms, hands, legs or feet, and cause you to lose sensitivity to pain.
• Severe nerve damage can lead to limb amputation.

Foot Complications

• Diabetes can cause foot ulcers, nerve damage to the feet, infections and loss of blood flow resulting in possible amputation.

Skin Complications

• Diabetes can cause a range of skin disorders, such as itching, diabetic blisters, bacterial and fungus infections.
• Although these conditions are serious, you can lower your risk of diabetes-related complications by managing your diabetes every day.

Treatment of Diabetes

An anti-diabetic drug or oral hypoglycemic agent is used to treat diabetes mellitus. They usually work by lowering the glucose levels in the blood. There are different types of anti-diabetic drugs, and their use depends on the nature of the diabetes, age and situation of the person, as well as other factors.

Insulin is the only non-oral antidiabetic drug. It is the mainstay of treatment in type I diabetes, in which insulin production is impaired. In type II diabetes, it is used when oral medication has become ineffective.

Antidiabetics

Sulfonylureas

Sulfonylureas were the first widely used oral hypoglycemic medications. They are insulin secretagogues, triggering insulin release by direct action on the KATP channel of the pancreatic beta cells. Seven types of these pills have been marketed in North America . Four, known as "first-generation" drugs, have been in use for some time, but not all remain available. Three "second-generation" drugs, are now more commonly used. They are stronger than first-generation drugs and have fewer side effects.

Sulfonylureas bind strongly to plasma proteins. Sulfonylureas are only useful in type II diabetes, as they work by stimulating endogenous release of insulin. They work best with patients over 40 years old, who have had diabetes mellitus for under ten years. They cannot be used with type I diabetes, or diabetes of pregnancy. They can be safely used with biguanides and glitazones. The toxicity of these drugs on the whole is relatively low.

First-generation agents

Second-generation agents

Meglitinides are related to sulfonylureas. The amplification of insulin release is shorter and more intense, and they are taken with meals to boost the insulin response to each meal.

Biguanides

Biguanides reduce hepatic glucose output. Although it must be used with caution in patients with impaired liver or kidney function, metformin has become the most commonly used agent for type 2 diabetes in children and teenagers.

Thiazolidinediones

Thiazolidinediones, also known as "glitazones," bind to PPAR?, a type of nuclear regulatory protein involved in transcription of numerous genes regulating glucose and fat metabolism. They act as "insulin sensitizers" without increasing insulin secretion.

Alpha glucosidase inhibitors

Alpha glucosidase inhibitors are "diabetes pills" but not technically hypoglycemic agents because they do not have a direct effect on insulin secretion or sensitivity. These agents slow the digestion of starch in the small intestine, so that glucose from the starch of a meal enters the bloodstream more slowly, and can be matched more effectively by an impaired insulin response or sensitivity. These agents are effective by themselves only in the earliest stages of impaired glucose tolerance, but can be helpful in combination with other agents in type 2 diabetes.

Experimental agents

Many other potential drugs are currently in investigation by pharmaceutical companies. Some of these are simply newer members of one of the above classes, but some work by novel mechanisms. For example, at least one compound that enhances the sensitivity of glucokinase to rising glucose is in the stage of animal research.

Insulin by mouth

The basic appeal of oral hypoglycemic agents is that most people would prefer a pill to an injection. Unlike all the oral drugs described in this article, insulin is a protein. Protein hormones, like meat proteins, are digested in the stomach and gut.

However, the potential market for an oral form of insulin is enormous and many laboratories have attempted to devise ways of moving enough intact insulin from the gut to the portal vein to have a measurable effect on blood sugar. One can find several research reports over the years describing promising approaches or limited success in animals, and limited human testing, but as of 2004, no products appear to be successful enough to bring to market.

4.AVANDIA EFFECTIVENESS
When is Avandia best taken?

Absorption

The absolute bioavailability of Avandia is 99%. Peak plasma concentrations are observed about 1 hour after dosing

Distribution:

The mean oral volume of distribution of Avandia is approximately 17.6 liters, based on a population pharmacokinetic analysis. Avandia is approximately 99.8% bound to plasma proteins, primarily albumin.

Metabolism:

Avandia is extensively metabolized with no unchanged drug excreted in the urine. The major routes of metabolism were N-demethylation and hydroxylation, followed by conjugation with sulfate and glucuronic acid. All the circulating metabolites are considerably less potent than parent and, therefore, are not expected to contribute to the insulin-sensitizing activity of rosiglitazone.

Excretion:

Following oral administration of Avandia, approximately 64% and 23% of the dose of Avandia was eliminated in the urine and in the feces, respectively. The plasma half-life of related material ranged from 103 to 158 hours.  

5.AVANDIA EFFECTS ON SPECIAL POPULATION
How do different people react to Avandia?

Age:

Results of the population pharmacokinetic analysis showed that age does not significantly affect the pharmacokinetics of Avandia.

Gender:

Results of the population pharmacokinetics analysis showed that the mean oral clearance of Avandia in female patients was approximately 6% lower compared to male patients of the same body weight.

As monotherapy and in combination with metformin, Avandia improved glycemic control in both males and females. In metformin combination studies, efficacy was demonstrated with no gender differences in glycemic response.

Race :

Results of a population pharmacokinetic analysis including subjects of Caucasian, black, and other ethnic origins indicate that race has no influence on the pharmacokinetics of Avandia.

Pediatric Use:

The safety and effectiveness of Avandia in pediatric patients have not been established.

6.AVANDIA EFFECTS ON MEDICAL CONDITIONS
How does Avandia affect your existing condition/ailment?

Hepatic Impairment:

Unbound oral clearance of Avandia was significantly lower in patients with moderate to severe liver disease compared to healthy subjects. Elimination half-life for Avandia was about 2 hours longer in patients with liver disease, compared to healthy subjects.

Therapy with Avandia should not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels at baseline. 

Renal Impairment:

There are no clinically relevant differences in the pharmacokinetics of rosiglitazone in patients with mild to severe renal impairment or in hemodialysis-dependent patients compared to subjects with normal renal function. No dosage adjustment is therefore required in such patients receiving Avandia. Since metformin is contraindicated in patients with renal impairment, co-administration of metformin with Avandia is contraindicated in these patients. 

7.OTHER/ALTERNATE USES OF AVANDIA
What else does Avandia treat?

Avandia is used, along with diet and exercise, in the treatment of type 2 diabetes.

Avandia may also be used with a sulfonylurea (e.g., Diabeta, Glucotrol, Micronase, others), metformin (Glucophage), or insulin when diet and exercise plus any one of these medicines alone do not result in adequate blood sugar control.

8.ADVERSE/SIDE EFFECTS of AVANDIA
What are the side effects of Avandia?

Heart failure. Avandia can cause your body to keep extra fluid (fluid retention), which leads to swelling and weight gain. Extra body fluid can make some heart problems worse or lead to heart failure.

Low blood sugar (hypoglycemia). Lightheadedness, dizziness, shakiness or hunger may mean that your blood sugar is too low. This can happen if you skip meals, if you use another medicine that lowers blood sugar, or if you have certain medical problems. Call your doctor if low blood sugar levels are a problem for you.

Weight gain. Avandia can cause weight gain that may be due to fluid retention or extra body fat. Weight gain can be a serious problem for people with certain conditions including heart problems. Call your doctor if you have an unusually fast increase in weight.

Low red blood cell count (anemia).

Ovulation (release of egg from an ovary in a woman) leading to pregnancy. Ovulation may happen in premenopausal women who do not have regular monthly periods. This can increase the chance of pregnancy.

Liver problems. It is important for your liver to be working normally when you take Avandia. Your doctor should do blood tests to check your liver before you start taking Avandia and during treatment as needed. Call your doctor right away if you have unexplained symptoms such as:

The most common side effects of Avandia included cold-like symptoms, injury, and headache.