1.ATACAND HISTORY
(How was Atacand discovered?)

Atacand is a product of Astra-Zeneca International. 

The US FDA approved Atacand in November 2001.

Astra-Zeneca is one of the world's leading pharmaceutical companies with 60,000 people - 12,000 in the US alone - dedicated to the discovery, development, and marketing of new pharmaceutical solutions, to enrich the quality of people's lives all over the world.

The focused areas of research include:

• Cardiovascular
• Gastrointestinal
• Infection
• Neuroscience
• Oncology
• Respiratory

Astra-Zeneca discovers new medicines that are designed to improve the health and quality of life of patients around the world - medicines which are innovative, effective and which offer added benefits such as reduced side effects or better ways of taking the treatment. Astra-Zeneca also focuses on getting the best from every medicine they make by exploring all the ways it can be used or improved.

At AstraZeneca, innovation is about more than just research. 

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

2.ATACAND FACTS

Atacand contains the active ingredient candesartan cilexetil, which is a type of medicine called an angiotensin II antagonist. Atacand works by preventing the action of a hormone in the body called angiotensin II.

Angiotensin II normally acts on special receptors in the body, with two main results. Firstly, it causes the peripheral blood vessels to narrow, and secondly, it stimulates the production of another hormone called aldosterone. Aldosterone causes salt and water to be retained by the kidneys, which increases the volume of fluid in the blood vessels.

Atacand blocks the receptors that angiotensin II acts on, and so prevents its actions. The main result of this is that the peripheral blood vessels are allowed to widen, which means that there is more space and less resistance in these blood vessels. This lowers the pressure inside the blood vessels.

Blocking the actions of angiotensin II also reduces the action of aldosterone on the kidneys. The result of this is an increase in the amount of fluid removed from the blood by the kidneys. This decreases the amount of fluid in the blood vessels, which also lessens the resistance and pressure in the blood vessels. 

The combined overall effect of these changes is to lower the blood pressure. 

3.ABOUT ATACAND MEDICATION

What is High Blood Pressure (Hypertension)?

High blood pressure, also known as hypertension, is a serious disease affecting your heart and blood vessels. It occurs when the blood exerts too much pressure against the walls of the blood vessels. In fact, that is what the term hypertension means: "too much" (hyper) "pressure" (tension). It affects upwards of 58 million people nationwide.

High blood pressure is serious because it places you at risk for certain life threatening and disabling conditions. If left untreated, high blood pressure could lead to heart attack, kidney disease, and/or stroke.

This happens because as your blood continuously exerts too much pressure against the walls of the blood vessels, it places extra stress on the heart and blood vessels.

Blood pressure is measured in two numbers, systolic (top or higher number) and diastolic (lower number). The higher number is the maximum pressure, which occurs when the heart beats (systole), and the lower number is the lowest pressure measured when the heart relaxes between beats (diastole), just before the next contraction. A systolic reading of 140 or greater and a diastolic reading of 90 or greater is considered high.

The normal blood pressure is less than 120/80. In fact, for every 20/10 increase in blood pressure, your risk of cardiovascular events, such as heart attack or stroke, is DOUBLED.

 

Symptoms of High Blood Pressure

High blood pressure is sometimes called the "silent killer" because the symptoms are rarely seen or felt. So, even though it might be upsetting to be told that you have high blood pressure, it's good that your doctor has discovered it. Treatment can help avoid the serious, long-term effects of high blood pressure.

What are antihypertensives?

Antihypertensives are medications used to treat high blood pressure (hypertension). Although some patients do not need to take medication to control their high blood pressure, anyone who is prescribed medication needs to take it exactly as prescribed to avoid the serious medical problems associated with the condition. People taking Antihypertensives are also encouraged to make healthy lifestyle changes, such as quitting smoking, losing weight and getting regular exercise. Furthermore, they are encouraged to speak with their physician before taking any prescription medications, such as narcotics, or over-the-counter medications, such as diet pills.

Finally, people with high blood pressure are urged to be patient as the type and level of their medication are adjusted for optimal results. This is especially important because the vast majority of patients have no symptoms, making hypertension the silent killer.

There are a wide variety of Antihypertensives and combinations of different medications that are available, and it may take some time before the ideal treatment has been found and finely tuned to the patients needs.

Antihypertensives include:

Diuretics ("water pills")
Diuretics are sometimes called "water pills" because they work in the kidney and flush excess water and sodium from the body.

Beta Blockers
Beta-blockers reduce nerve impulses to the heart and blood vessels. This makes the heart beat slower and with less force. Blood pressure drops and the heart works less hard.

Alpha Blockers
Alpha-blockers reduce nerve impulses to blood vessels, which allows blood to pass more easily, causing the blood pressure to go down.

Alpha-Beta Blockers
Alpha-beta-blockers work the same way as alpha-blockers but also slow the heartbeat, as beta-blockers do. As a result, less blood is pumped through the vessels and the blood pressure goes down.

Nervous System Inhibitors
Nervous system inhibitors relax blood vessels by controlling nerve impulses. This causes the blood vessels to become wider and the blood pressure to go down.

Angiotensin Converting Enzyme (ACE) Inhibitors
Angiotensin converting enzyme (ACE) inhibitors prevent the formation of a hormone called angiotensin II, which normally causes blood vessels to narrow. The ACE inhibitors cause the vessels to relax and blood pressure goes down.

Calcium Channel Blockers
CCBs keep calcium from entering the muscle cells of the heart and blood vessels. This causes the blood vessels to relax and pressure goes down.

Angiotensin Receptor Blockers (formal medical name angiotensin-2-receptor antagonists, known as "sartans" for short). These agents are sometimes prescribed together, for instance an ACE inhibitor along with a calcium channel blocker.

Angiotensin antagonists shield blood vessels from angiotensin II. As a result, the vessels become wider and blood pressure goes down. 

Some common Angiotensin receptor Blockers include

• Candesartan
• Eprosartan
• Irbesartan
• Losartan
• Telmisartan
• Valsartan  

Causes of High Blood Pressure

There are 2 main types of high blood pressure:

[1] Primary, Essential or Idiopathic. These 3 words all mean the same, & are medical terms for "unknown cause". 90% of cases of hypertension are of unknown cause.

There are a number of things that make it worse, one being stress & another being clogged arteries. Just like when a pipe is partly blocked with gunk it needs higher pressure to get fluid through it, so if your arteries are clogged with fat your heart steps up the pressure to get the blood through. A third factor is overweight. If you are too big you have a larger volume of small blood vessels so the heart has to pump harder & raise the pressure to supply them. A fourth is nicotine, a chemical in tobacco, which narrows arteries & so raises the pressure needed to get the blood through them. 

[2] Secondary hypertension. This means the high blood pressure is due to some known cause. Only 10% of cases have a known cause.

Some of these are:

[a] Kidney disease. If one of the kidneys has narrowing of the artery bringing its blood supply, or has damaged tubules, which can't handle your fluid & salt, you may get hypertension.

[b] Adrenal disease. The adrenal glands are a pair of small organs on the top of your kidneys. They produce lots of chemicals or hormones, which control salt & sugar in the body. One such hormone is aldosterone. This conserves salt, & if it conserves too much the blood pressure rises. Another is corticosteroid or steroid hormone. Too much of this will cause weight gain & grow too much body hair. This too can produce hypertension.

Another part of your adrenal gland produces adrenalin & nor-adrenalin. These are stress hormones, also called 'fight or flight' hormones. They will spit out adrenalin to make the heart pump faster, so more blood will go to your muscles ready for you to fight or run.

[c] Parathyroid disease . These are tiny glands in the neck, which produce a hormone controlling the calcium in your blood & bones. If they over act & pull too much calcium out of your bones into your blood, they may damage the kidneys or constrict your arteries causing high blood pressure.

[d] Other rare causes: The pituitary, a small gland at the base of the brain, produces growth hormone. Too much of this can make you grow to 7 feet or more [2.3 metres], or if it doesn't overact till late in life it can make your bones grow thicker instead of taller. It can also cause hypertension.

There are other causes, like lead poisoning or aortic coarctation, but you will be getting sick of hearing about such rare conditions. 

4.ATACAND EFFECTIVENESS
(When is Atacand best taken?)

Atacand is rapidly and completely bioactivated by ester hydrolysis during absorption from the gastrointestinal tract to a selective AT1 subtype angiotensin II receptor antagonist. Atacand is mainly excreted unchanged in urine and feces (via bile). It undergoes minor hepatic metabolism by O-deethylation to an inactive metabolite. The elimination half-life of Atacand is approximately 9 hours. After single and repeated administration, the pharmacokinetics of candesartan are linear for oral doses up to 32 mg of Atacand. Atacand and its inactive metabolite do not accumulate in serum upon repeated once-daily dosing.

Following administration of Atacand, the absolute bioavailability of Atacand was estimated to be 15%. After tablet ingestion, the peak serum concentration (Cmax) is reached after 3 to 4 hours. Food with a high fat content does not affect the bioavailability of candesartan after Atacand administration. 

Metabolism and Excretion

Total plasma clearance of Atacand is 0.37 mL/min/kg, with a renal clearance of 0.19 mL/min/kg. When Atacand is administered orally, about 26% of the dose is excreted unchanged in urine. Following an oral dose of C-labeled Atacand, approximately 33% of radioactivity is recovered in urine and approximately 67% in feces. Following an intravenous dose of 14C-labeled candesartan, approximately 59% of radioactivity is recovered in urine and approximately 36% in feces. Biliary excretion contributes to the elimination of Atacand.

Distribution

The volume of distribution of Atacand is 0.13 L/kg. Candesartan is highly bound to plasma proteins (>99%) and does not penetrate red blood cells. The protein binding is constant at candesartan plasma concentrations well above the range achieved with recommended doses. In rats, it has been demonstrated that Atacand crosses the blood-brain barrier poorly, if at all. It has also been demonstrated in rats that Atacand passes across the placental barrier and is distributed in the fetus.

5.ATACAND EFFECTS ON SPECIAL POPULATION
(How do different people react to Atacand?)

Pediatric

The pharmacokinetics of Atacand have not been investigated in patients <18 years of age.

Geriatric and Gender

The pharmacokinetics of Atacand has been studied in the elderly (65 years) and in both sexes. The plasma concentration of Atacand was higher in the elderly compared to younger subjects administered the same dose. The pharmacokinetics of Atacand was linear in the elderly, and Atacand and its inactive metabolite did not accumulate in the serum of these subjects upon repeated, once-daily administration. No initial dosage adjustment is necessary. There is no difference in the pharmacokinetics of Atacand between male and female subjects. 

6.ATACAND EFFECTS ON MEDICAL CONDITIONS
How does Atacand affect your existing condition/ailment?

Renal Insufficiency

In hypertensive patients with renal insufficiency, serum concentrations of candesartan were elevated. After repeated dosing, the AUC and Cmax were approximately doubled in patients with severe renal impairment (creatinine clearance <30 mL/min/1.73m2) compared to patients with normal kidney function. The pharmacokinetics of Atacand in hypertensive patients undergoing hemodialysis are similar to those in hypertensive patients with severe renal impairment. Atacand cannot be removed by hemodialysis. No initial dosage adjustment is necessary in patients with renal insufficiency.

In heart failure patients with renal impairment, AUC0-72 was 36 % and 65 % higher in mild and moderate renal impairment, respectively. Cmax was 15% and 55 % higher in mild and moderate renal impairment, respectively.

Hepatic Insufficiency

The pharmacokinetics of Atacand dose were compared in patients with mild and moderate hepatic impairment to matched healthy volunteers following a single oral dose of Atacand 16 mg. The increase in AUC for Atacand was 30% in patients with mild hepatic impairment and 145% in patients with moderate hepatic impairment. The increase in Cmax for Atacand was 56% in patients with mild hepatic impairment and 73% in patients with moderate hepatic impairment. The pharmacokinetics after Atacand administration has not been investigated in patients with severe hepatic impairment. No initial Atacand dosage adjustment is necessary in patients with mild hepatic impairment. In hypertensive patients with moderate hepatic impairment, consideration should be given to initiation at a lower dose of Atacand.

Heart Failure

The pharmacokinetics of Atacand were linear in patients with heart failure (NYHA class II and III) after Atacand doses of 4, 8, and 16 mg. After repeated Atacand dosing, the AUC was approximately doubled in these patients compared with healthy, younger patients. The pharmacokinetics in heart failure patients is similar to that in healthy elderly volunteers. 

7.OTHER/ALTERNATE USES OF ATACAND
(What else does Atacand treat?)

Atacand may be used for other purposes as prescribed by your physician.

8.ADVERSE/SIDE EFFECTS of ATACAND
(What are the side effects of Atacand?)

Atacand has been evaluated for safety in more than 3600 patients/subjects, including more than 3200 patients treated for hypertension. About 600 of these patients were studied for at least 6 months and about 200 for at least 1 year. In general, treatment with Atacand was well tolerated. The overall incidence of adverse events reported with Atacand was similar to placebo.

The rate of withdrawals due to adverse events in all trials in patients (7510 total) was 3.3% (i.e, 108 of 3260) of patients treated with Atacand as monotherapy and 3.5% (i.e, 39 of 1106) of patients treated with placebo. In placebo-controlled trials, discontinuation of therapy due to clinical adverse events occurred in 2.4% (i.e, 57 of 2350) of patients treated with ATACAND and 3.4% (i.e, 35 of 1027) of patients treated with placebo.

The most common reasons for discontinuation of therapy with Atacand were headache (0.6%) and dizziness (0.3%).

The adverse events that occurred in placebo-controlled clinical trials in at least 1% of patients treated with Atacandand at a higher incidence in Atacand (n = 2350) than placebo (n = 1027) patients included back pain (3% vs. 2%), dizziness (4% vs. 3%), upper respiratory tract infection (6% vs. 4%), pharyngitis (2% vs. 1%), and rhinitis (2% vs. 1%).

The following adverse events occurred in placebo-controlled clinical trials at a more than 1% rate but at about the same or greater incidence in patients receiving placebo compared to Atacand: fatigue, peripheral edema, chest pain, headache, bronchitis, coughing, sinusitis, nausea, abdominal pain, diarrhea, vomiting, arthralgia, albuminuria.

Other potentially important adverse events that have been reported, whether or not attributed to treatment, with an incidence of 0.5% or greater from the 3260 patients worldwide treated in clinical trials with Atacand are listed below. It cannot be determined whether these events were causally related to Atacand.

Body as a Whole: asthenia, fever; Central and Peripheral Nervous System: paresthesia, vertigo; Gastrointestinal System Disorder: dyspepsia, gastroenteritis; Heart Rate and Rhythm Disorders: tachycardia, palpitation; Metabolic and Nutritional Disorders: creatine phosphokinase increased, hyperglycemia, hypertriglyceridemia, hyperuricemia; Musculoskeletal System Disorders: myalgia; Platelet/Bleeding-Clotting Disorders: epistaxis; Psychiatric Disorders: anxiety, depression, somnolence; Respiratory System Disorders: dyspnea; Skin and Appendages Disorders: rash, sweating increased; Urinary System Disorders: hematuria.

Other reported events seen less frequently included angina pectoris, myocardial infarction, and angioedema.

Adverse events occurred at about the same rates in men and women, older and younger patients, and black and non-black patients.

Post-Marketing Experience

The following have been very rarely reported in post-marketing experience:

Digestive
Abnormal hepatic function and hepatitis.

Hematologic
Neutropenia, leukopenia, and agranulocytosis.

Metabolic and Nutritional Disordershyperkalemia, hyponatremia.

Renal
renal impairment, renal failure.

Skin and Appendages Disorders
Pruritus and urticaria.

Rare reports of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers.