1.ACEON HISTORY
(How was Aceon discovered?

Aceon is a product of Solvay Pharmaceuticals.

The FDA approved Aceon in August 2005.

Solvay Pharmaceuticals is one of the top 40 pharmaceutical companies in the world and its ambition is to speed up its development even further over the next few years.

Solvay holds a strong worldwide market position in carefully selected therapeutic areas and has a well-diversified portfolio of products in these areas.

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

2.ACEON FACTS

Aceon is a type of medicine called an ACE inhibitor.

Aceon works by blocking the action of a compound in the body called angiotensin-converting enzyme (ACE). Normally ACE produces another compound called angiotensin II, as part of the body's natural control of blood pressure. Angiotensin II has two actions. Firstly, it causes blood vessels to constrict and narrow, and secondly, it reduces the production of urine by the kidneys. Both these actions increase the pressure within the blood vessels.

As Aceon blocks the action of ACE, it reduces the production of angiotensin II. This means that the blood vessels are allowed to relax to widen and more urine is produced by the kidneys. The overall effect of this is a drop in blood pressure. Aceon can therefore be used to treat High blood pressure. 

3.ABOUT ACEON 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.

Some common ACE inhibitors include

•   Benazepril
•   Captopril
•   Enalapril
•   Fosinopril
•   Lisinopril
•   Perindopril
•   Quinapril
•   Ramipril

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. 

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 coarctations. 

4.ACEON EFFECTIVENESS
When is Aceon best taken?

Oral administration of Aceon results in its rapid absorption with peak plasma concentrations occurring at approximately 1 hour. The absolute oral bioavailability of Aceon is about 75%. Following absorption, approximately 30 to 50% of systemically available Aceon is hydrolyzed to its active metabolite, perindoprilat, which has a mean bioavailability of about 25%. Peak plasma concentrations of perindoprilat are attained 3 to 7 hours after Aceon administration. The presence of food in the gastrointestinal tract does not affect the rate or extent of absorption of perindopril but reduces bioavailability of perindoprilat by about 35%.

With 4, 8 and 16 mg doses of Aceon Tablets, Cmax and AUC of perindopril and perindoprilat increase in a linear and dose-proportional manner following both single oral dosing and at steady state during a once-a-day multiple dosing regimen.

Perindopril exhibits multiexponential pharmacokinetics following oral administration. The mean half-life of Aceon associated with most of its elimination is approximately 0.8 to 1.0 hours. At very low plasma concentrations of Aceon (<3 ng/mL), there is a prolonged terminal elimination half-life, similar to that seen with other ACE inhibitors, that results from slow dissociation of perindopril from plasma/tissue ACE binding sites. Aceon does not accumulate with a once-a-day multiple dosing regimen. Mean total body clearance of perindopril is 219 to 362 mL/min and its mean renal clearance is 23.3 to 28.6 mL/min. 

Aceon is extensively metabolized following oral administration, with only 4 to 12% of the dose recovered unchanged in the urine. Six metabolites resulting from hydrolysis, glucuronidation and cyclization via dehydration have been identified. These include the active ACE inhibitor, perindoprilat (hydrolyzed perindopril), perindopril and perindoprilat glucuronides, dehydrated perindopril and the diastereoisomers of dehydrated perindoprilat. In humans, hepatic esterase appears to be responsible for the hydrolysis of perindopril.

The active metabolite, perindoprilat, also exhibits multiexponential pharmacokinetics following the oral administration of Aceon Tablets. Formation of perindoprilat is gradual with peak plasma concentrations occurring between 3 and 7 hours. The subsequent decline in plasma concentration shows an apparent mean half-life of 3 to 10 hours for the majority of the elimination, with a prolonged terminal elimination half-life of 30 to 120 hours resulting from slow dissociation of perindoprilat from plasma/tissue ACE binding sites. During repeated oral once-daily dosing with perindopril, perindoprilat accumulates about 1.5 to 2.0 fold and attains steady state plasma levels in 3 to 6 days. The clearance of perindoprilat and its metabolites is almost exclusively renal.

Approximately 60% of circulating perindopril is bound to plasma proteins, and only 10 to 20% of perindoprilat is bound. Therefore, drug interactions mediated through effects on protein binding are not anticipated.

5.ACEON EFFECTS ON SPECIAL POPULATION
(How do different people react to Aceon?)

Elderly Patients : Plasma concentrations of both perindopril and perindoprilat in elderly patients (>70 yrs) are approximately twice those observed in younger patients, reflecting both increased conversion of perindopril to perindoprilat and decreased renal excretion of perindoprilat. 

Pregnancy
When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, Aceon Tablets should be discontinued as soon as possible. 

Nursing Mothers:
Milk of lactating rats contained radioactivity following administration 14C-perindopril. It is not known whether perindopril is secreted in human milk. Because many drugs are secreted in human milk, caution should be exercised when Aceon Tablets is given to nursing mothers. 

Pediatric Use:
Safety and effectiveness of Aceon Tablets in pediatric patients have not been established.

Geriatric Use:
The mean blood pressure effect of Aceon was somewhat smaller in patients over 60 than in younger patients, although the difference was not significant. Plasma concentrations of both perindopril and perindoprilat were increased in elderly patients compared to concentrations in younger patients. No adverse effects were clearly increased in older patients with the exception of dizziness and possibly rash. Experience with Aceon Tablets in elderly patients at daily doses exceeding 8 mg is limited.

6.ACEON EFFECTS ON MEDICAL CONDITIONS
(How does Aceon affect your existing condition/ailment?)

Heart Failure Patients: Perindoprilat clearance is reduced in congestive heart failure patients, resulting in a 40% higher dose interval AUC. 

Patients with Renal Insufficiency: With Aceon doses of 2 to 4 mg, perindoprilat AUC increases with decreasing renal function. At creatinine clearances of 30 to 80 mL/min, AUC is about double that of 100 mL/min. When creatinine clearance drops below 30 mL/min, AUC increases more markedly.

In a limited number of patients studied, perindopril dialysis clearance ranged from 41.7 to 76.7 mL/min (mean 52.0 mL/min). Perindoprilat dialysis clearance ranged from 37.4 to 91.0 mL/min (mean 67.2 mL/min).

Patients with Hepatic Insufficiency: The bioavailability of perindoprilat is increased in patients with impaired hepatic function. Plasma concentrations of perindoprilat in patients with impaired liver function were about 50% higher than those observed in healthy subjects or hypertensive patients with normal liver function. 

7.OTHER/ALTERNATE USES OF ACEON
(What else does Aceon treat?)

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

8.ADVERSE/SIDE EFFECTS of ACEON
(What are the side effects of Aceon?)

Hypertension

Aceon Tablets has been evaluated for safety in approximately 3,400 patients with hypertension in U.S. and foreign clinical trials. Aceon Tablets was in general well-tolerated in the patient populations studied, the side effects were usually mild and transient. Although dizziness was reported more frequently in placebo patients (8.5%) than in perindopril patients (8.2%), the incidence appeared to increase with an increase in perindopril dose.

The data presented here are based on results from the 1,417 Aceon Tablets-treated patients who participated in the U.S. clinical trials. Over 220 of these patients were treated with Aceon Tablets for at least one year.

In placebo-controlled U.S. clinical trials, the incidence of premature discontinuation of therapy due to adverse events was 6.5% in patients treated with Aceon Tablets and 6.7% in patients treated with placebo. The most common causes were cough, headache, asthenia and dizziness.

Among 1,012 patients in placebo-controlled U.S. trials, the overall frequency of reported adverse events was similar in patients treated with Aceon Tablets and in those treated with placebo (approximately 75% in each group). Adverse events that occurred in 1% or greater of the patients and that were more common for perindopril than placebo by at least 1% (regardless of whether they were felt to be related to study drug) are shown in the first two columns below. Of these adverse events, those considered possibly or probably related to study drug are shown in the last two columns.  

Frequency of Adverse events (%) 

	All Adverse Events		Possibly– or Probably– Related Adverse Events
Aceon n=789	Placebo n=223	Aceon n=789	Placebo n=223
Cough	12	4.5	6	1.8
Back Pain	5.8	3.1	0	0
Sinusitis	5.2	3.6	0.6	0
Viral Infection	3.4	1.6	0.3	0
Upper Extremity Pain	2.8	1.4	0.2	0
Hypertonia	2.7	1.4	0.2	0
Dyspepsia	1.9	0.9	0.3	0
Fever	1.5	0.5	0.3	0
Proteinuria	1.5	0.5	1	0.5
Ear Infection	1.3	0	0	0
Palpitation	1.1	0	0.9	0

Of these, cough was the reason for withdrawal in 1.3% of Aceon and 0.4% of placebo patients. While dizziness was not reported more frequently in the perindopril group (8.2%) than in the placebo group (8.5%), it was clearly increased with dose, suggesting a causal relationship with perindopril. Other commonly reported complaints (1% or greater), regardless of causality, include: headache (23.8%), upper respiratory infection (8.6%), asthenia (7.9%), rhinitis (4.8%), low extremity pain (4.7%), diarrhea (4.3%), edema (3.9%), pharyngitis (3.3%), urinary tract infection (2.8%), abdominal pain (2.7%), sleep disorder (2.5%), chest pain (2.4%), injury, paresthesia, nausea, rash (each 2.3%), seasonal allergy, depression (each 2.0%), abnormal ECG (1.8%), ALT increase (1.7%), tinnitus, vomiting (each 1.5%), neck pain, male sexual dysfunction (each 1.4%), triglyceride increase, somnolence (each 1.3%), joint pain, nervousness, myalgia, menstrual disorder (each 1.1%), flatulence and arthritis (each 1.0%), but none of those was more frequent by at least 1% on perindopril than on placebo. Depending on the specific adverse event, approximately 30 to 70% of the common complaints were considered possibly or probably related to treatment.

Stable Coronary Artery Disease

A double-blind, placebo-controlled study in 12,218 patients with stable coronary artery disease. The overall rate of discontinuation was about 22% on drug and placebo. The most common medical reasons for discontinuation that were more frequent on Aceon than placebo were cough, drug intolerance and hypotension.

Below is a list (by body system) of adverse experiences reported in 0.3 to 1% of patients in U.S. placebo-controlled studies in hypertensive patients without regard to attribution to therapy. Less frequent but medically important adverse events are also included; the incidence of these events is given in parentheses.

Body as a Whole: malaise, pain, cold/hot sensation, chills, fluid retention, orthostatic symptoms, anaphylactic reaction, facial edema, angioedema (0.1%).

Gastrointestinal: constipation, dry mouth, dry mucous membrane, appetite increased, gastroenteritis.

Respiratory: posterior nasal drip, bronchitis, rhinorrhea, throat disorder, dyspnea, sneezing, epistaxis, hoarseness, pulmonary fibrosis (<0.1%).

Urogenital: vaginitis, kidney stone, flank pain, urinary frequency, urinary retention.

Cardiovascular: hypotension, ventricular extrasystole, myocardial infarction, vasodilation, syncope, abnormal conduction, heart murmur, orthostatic hypotension.

Endocrine: gout.

Hematology: hematoma, ecchymosis.

Musculoskeletal: arthralgia, myalgia.

CNS: migraine, amnesia, vertigo, cerebral vascular accident (0.2%).

Psychiatric: anxiety, psychosexual disorder.

Dermatology: sweating, skin infection, tinea, pruritus, dry skin, erythema, fever blisters, purpura (0.1%).

Special Senses : conjunctivitis, earache.

Laboratory: potassium decrease, uric acid increase, alkaline phosphatase increase, cholesterol increase, AST increase, creatinine increase, hematuria, glucose increase.

When Aceon Tablets was given concomitantly with thiazide Diuretics, adverse events were generally reported at the same rate as those for Aceon Tablets alone, except for a higher incidence of abnormal laboratory findings known to be related to treatment with thiazide diuretics alone (e.g., increases in serum uric acid, triglycerides and cholesterol and decreases in serum potassium). 

Potential Adverse Effects Reported with ACE Inhibitors: Other medically important adverse effects reported with other available ACE inhibitors include: cardiac arrest, eosinophilic pneumonitis, neutropenia/agranulocytosis, pancytopenia, anemia (including hemolytic and aplastic), thrombocytopenia, acute renal failure, nephritis, hepatic failure, jaundice (hepatocellular or cholestatic), symptomatic hyponatremia, bullous pemphigus, acute pancreatitis, exfoliative dermatitis and a syndrome which may include: arthralgia/arthritis, vasculitis, serositis, myalgia, fever, rash or other dermatologic manifestations, a positive ANA, leukocytosis, eosinophilia or an elevated ESR. Many of these adverse effects have also been reported for perindopril.