1.VASERETIC HISTORY
(How was Vaseretic discovered?)

Vaseretic is a product of Biovail Pharmaceuticals. 

Biovail's origins date back to the late 1980s when the Company (then Trimel Corporation) moved towards specialization in the field of controlled-release drug delivery technology. Biovail was one of the first companies in the world to recognize the potential of this emerging sector.

Biovail markets a range of advanced quality pharmaceutical products in a number of therapeutic categories, including cardiology, depression, central nervous system (consisting of the brain and spinal cord) and more.

Today, Biovail's portfolio includes more than 25 products, representing both NDA (branded) and ANDA (generic) medications. This portfolio includes products developed by Biovail, as well as in-licensed or acquired products, such as the Cardizem line of diltiazem medications. The Company has also established development and licensing agreements with leading pharmaceutical companies, including GlaxoSmithKline and Merck & Co. Inc. 

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

2.VASERETIC FACTS

Vaseretic is a combination of Enalapril and Hydrochlorothiazide.

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

3.ABOUT VASERETIC 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.

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.VASERETIC EFFECTIVENESS
(When is Vaseretic best taken?)

Following oral administration of Vaseretic dose, peak serum concentrations of Enalapril occur within about one hour. Based on urinary recovery, the extent of absorption of Enalapril is approximately 60 percent. Enalapril absorption is not influenced by the presence of food in the gastrointestinal tract.

Following absorption, Enalapril is hydrolyzed to enalaprilat, which is a more potent angiotensin converting enzyme inhibitor than Enalapril; enalaprilat is poorly absorbed when administered orally. Peak serum concentrations of enalaprilat occur three to four hours after an oral dose of enalapril maleate.

Excretion of Enalapril is primarily renal. Approximately 94 percent of the dose of enalapril is recovered in the urine and feces as enalaprilat or Enalapril. The principal components in urine are enalaprilat, accounting for about 40 percent of the dose of enalapril, and intact Enalapril. There is no evidence of metabolites of Enalapril, other than enalaprilat.

Hydrochlorothiazide is not metabolized. Its apparent volume of distribution is 3.6-7.8 L/kg, and its measured plasma protein binding is 67.9% The drug also accumulates in red blood cells, so that whole blood levels are 1.6-1.8 times those measured in plasma. 

5.VASERETIC EFFECTS ON SPECIAL POPULATION
(How do different people react to Vaseretic?)

Pregnancy:

Female patients of childbearing age should be told about the consequences of second- and third-trimester exposure to Vaseretic, and they should also be told that these consequences do not appear to have resulted from intrauterine ACE inhibitor exposure that has been limited to the first trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.

Nursing Mothers

Minimal amounts of unchanged Enalapril and of enalaprilat are excreted into the breast milk of lactating women treated with Vaseretic, so that a newborn child ingesting nothing but breast milk would receive less than 0.1 % of the maternal doses of enalapril and enalaprilat.

Hydrochlorothiazide, on the other hand, are definitely excreted into breast milk. Because of the potential for serious adverse reactions in nursing infants from Hydrochlorothiazide and the unknown effects of Enalapril in infants, a decision should be made whether to discontinue nursing or to discontinue Enalapril and of enalaprilat, taking into account the importance of the drug to the mother.

Geriatric Use

Of the total number of patients who received Vaseretic in U.S. clinical studies of Lotensin HCT, 19% were 65 or older while about 1.5% were 75 or older. Overall differences in effectiveness or safety were not observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Enalapril and enalaprilat are substantially excreted by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Pediatric Use

Safety and effectiveness of Vaseretic in pediatric patients have not been established.

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

Impaired Renal Function

Vaseretic should be used with caution in patients with severe renal disease. Hydrochlorothiazide may precipitate azotemia in such patients, and the effects of repeated dosing may be cumulative.

Impaired Hepatic Function

Vaseretic should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. In patients with hepatic dysfunction due to cirrhosis, levels of enalaprilat are essentially unaltered. No formal pharmacokinetic studies have been carried out in hypertensive patients with impaired liver function.

Intestinal Angioedema

Intestinal angioedema has occasionally been reported in patients treated with Vaseretic. These patients presented with abdominal pain; in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain. 

7.OTHER/ALTERNATE USES OF VASERETIC
(What else does Vaseretic treat?)

Vaseretic is usually used in combination with a diuretic medicine to treat heart failure.

8.ADVERSE/SIDE EFFECTS of VASERETIC
(What are the side effects of Vaseretic?)

Hypertension

Adverse experiences occurring in greater than one percent of patients with hypertension treated with Vaseretic in controlled clinical trials are shown in TABLE 1. In patients treated with Vaseretic, the maximum duration of therapy was three years; in placebo treated patients the maximum duration of therapy was 12 weeks.

TABLE 1
	Vaseretic (n=2314) Incidence (discontinuation)	Placebo (n=230) Incidence
Body as a Whole
Fatigue	3.0 (<0.1)	2.6
Orthostatic Effects	1.2 (<0.1)	0.0
Asthenia	1.1 (0.1)	0.9
Digestive
Diarrhea	1.4 (<0.1)	1.7
Nausea	1.4 (0.2)	1.7
Nervous/Psychiatric
Headache	5.2 (0.3)	9.1
Dizziness	4.3 (0.4)	4.3
Respiratory
Cough	1.3 (0.1)	0.9
Skin
Rash	1.4 (0.4)	0.4

Heart Failure

Adverse experiences occurring in greater than one percent of patients with heart failure treated with Vaseretic are shown in TABLE 2. The incidences represent the experiences from both controlled and uncontrolled clinical trials (maximum duration of therapy was approximately one year). In the placebo treated patients, the incidences reported are from the controlled trials (maximum duration of therapy is 12 weeks). The percentage of patients with severe heart failure (NYHA Class IV) was 29 percent and 43 percent for patients treated with Vaseretic and placebo, respectively.

TABLE 2
	Vaseretic (n=673) Incidence (discontinuation)	Placebo (n=339) Incidence
Body as a Whole
Orthostatic Effects	2.2 (0.1)	0.3
Syncope	2.2 (0.1)	0.9
Chest Pain	2.1 (0.0)	2.1
Fatigue	1.8 (0.0)	1.8
Abdominal Pain	1.6 (0.4)	2.1
Asthenia	1.6 (0.1)	0.3
Cardiovascular
Hypotension	6.7 (1.9)	0.6
Orthostatic Hypotension	1.6 (0.1)	0.3
Angina Pectoris	1.5 (0.1)	1.8
Myocardial Infarction	1.2 (0.3)	1.8
Digestive
Diarrhea	2.1 (0.1)	1.2
Nausea	1.3 (0.1)	0.6
Vomiting	1.3 (0.0)	0.9
Nervous/Psychiatric
Dizziness	7.9 (0.6)	0.6
Headache	1.8 (0.1)	0.9
Vertigo	1.6 (0.1)	1.2
Respiratory
Cough	2.2 (0.0)	0.6
Bronchitis	1.3 (0.0)	0.9
Dyspnea	1.3 (0.1)	0.4
Pneumonia	1.0 (0.0)	2.4
Skin
Rash	1.3 (0.0)	2.4
Urogenital
Urinary Tract Infection	1.3 (0.0)	2.4

 

Other serious clinical adverse experiences occurring since the drug was marketed or adverse experiences occurring in 0.5 to 1.0 percent of patients with hypertension or heart failure in clinical trials are listed below and, within each category, are in order of decreasing severity.

Body as a Whole : Anaphylactoid reactions

Cardiovascular : Cardiac arrest; myocardial infarction or cerebrovascular accident, possibly secondary to excessive hypotension in high risk patients; pulmonary embolism and infarction; pulmonary edema; rhythm disturbances including atrial tachycardia and bradycardia; atrial fibrillation; palpitation; Raynaud's phenomenon.

Digestive : Ileus, pancreatitis, hepatic failure, hepatitis, melena, anorexia, dyspepsia, constipation, glossitis, stomatitis, dry mouth.

Musculoskeletal : Muscle cramps.

Nervous/Psychiatric: Depression, confusion, ataxia, somnolence, insomnia, nervousness, peripheral neuropathy (e.g., paresthesia, dysesthesia), dream abnormality.

Respiratory: Bronchospasm, rhinorrhea, sore throat and hoarseness, asthma, upper respiratory infection, pulmonary infiltrates, eosinophilic pneumonitis.

Skin: Exfoliative dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, pemphigus, herpes zoster, erythema multiforme, urticaria, pruritus, alopecia, flushing, diaphoresis, photosensitivity.

Special Senses: Blurred vision, taste alteration, anosmia, tinnitus, conjunctivitis, dry eyes, tearing.

Urogenital: Renal failure, oliguria, renal dysfunction, flank pain, gynecomastia, impotence.

Miscellaneous: A symptom complex has been reported which may include a positive ANA, an elevated erythrocyte sedimentation rate, arthralgia/arthritis, myalgia/myositis, fever, serositis, vasculitis, leukocytosis, eosinophilia, photosensitivity, rash and other dermatologic manifestations.

Angioedema : Angioedema has been reported in patients receiving Vaseretic, with an incidence higher in black than in non-black patients. Angioedema associated with laryngeal edema may be fatal. If angioedema of the face, extremities, lips, tongue, glottis and/or larynx occurs, treatment with Enalapril should be discontinued and appropriate therapy instituted immediately.

Hypotension : In the hypertensive patients, hypotension occurred in 0.9 percent and syncope occurred in 0.5 percent of patients following the initial dose or during extended therapy. Hypotension or syncope was a cause for discontinuation of therapy in 0.1 percent of hypertensive patients. In heart failure patients, hypotension occurred in 6.7 percent and syncope occurred in 2.2 percent of patients. Hypotension or syncope was a cause for discontinuation of therapy in 1.9 percent of patients with heart failure.

Fetal/Neonatal Morbidity and Mortality : Fetal/Neonatal Morbidity and Mortality