1.COZAAR HISTORY
(How was Cozaar discovered?)

Cozaar is a product of Merck & Co

The US FDA approved Cozaar in August 2001.

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.

Merck & Co. aims at helping to improve the health and well being of people everywhere by discovering, developing and bringing to market breakthrough medicines. Their priorities are focused on turning cutting-edge science into breakthrough medicines that address significant unmet needs, and thus have the potential to become important medical advances.

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

2.COZAAR FACTS

Cozaar is a type of medicine called an angiotensin II antagonist. Cozaar 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.

Cozaar 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 is the main mechanism by which the pressure in the blood vessels is lowered.

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.

3.ABOUT COZAAR 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.

Common Angiotensin Receptor blockers include:

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

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. 

4.COZAAR EFFECTIVENESS
(When is Cozaar best taken?)

Cozaar is an orally active agent that undergoes substantial first-pass metabolism by cytochrome P450 enzymes. Cozaar is converted, in part, to an active carboxylic acid metabolite that is responsible for most of the angiotensin II receptor antagonism that follows Cozaar treatment. Cozaar metabolites have been identified in human plasma and urine. In addition to the active carboxylic acid metabolite, several inactive metabolites are formed. Following oral and intravenous administration of 14C-labeled losartan potassium, circulating plasma radioactivity is primarily attributed to Cozaar and its active metabolite. In vitro studies indicate that cytochrome P450 2C9 and 3A4 are involved in the biotransformation of Cozaar to its metabolites. Minimal conversion of Cozaar to the active metabolite (less than 1% of the dose compared to 14% of the dose in normal subjects) was seen in about one percent of individuals studied. 

The terminal half-life of Cozaar is about 2 hours and of the metabolite is about 6-9 hours.

The pharmacokinetics of Cozaar and its active metabolite are linear with oral Cozaar doses up to 200 mg and do not change over time. Neither Cozaar nor its metabolite accumulate in plasma upon repeated once-daily dosing.

Following oral administration, Cozaar is well absorbed (based on absorption of radiolabeled losartan) and undergoes substantial first-pass metabolism; the systemic bioavailability of losartan is approximately 33%. About 14% of an orally-administered dose of Cozaar is converted to the active metabolite. Mean peak concentrations of Cozaar and its active metabolite are reached in 1 hour and in 3-4 hours, respectively. While maximum plasma concentrations of Cozaar and its active metabolite are approximately equal, the AUC of the metabolite is about 4 times as great as that of Cozaar. A meal slows absorption of losartan and decreases its Cmax but has only minor effects on Cozaar AUC or on the AUC of the metabolite (about 10% decreased).

Both Cozaar and its active metabolite are highly bound to plasma proteins, primarily albumin, with plasma free fractions of 1.3% and 0.2%, respectively. Plasma protein binding is constant over the concentration range achieved with recommended doses. Studies in rats indicate that Cozaar crosses the blood-brain barrier poorly, if at all.

5.COZAAR EFFECTS ON SPECIAL POPULATION
(How do different people react to Cozaar?)

Pediatric:
Pharmacokinetics of Cozaar and its active metabolite were generally similar in pediatrics and adults.

Geriatric and Gender:
Cozaar pharmacokinetics have been investigated in the elderly (65-75 years) and in both genders. Plasma concentrations of Cozaar and its active metabolite are similar in elderly and young hypertensives. Plasma concentrations of Cozaar were about twice as high in female hypertensives as male hypertensives, but concentrations of the active metabolite were similar in males and females. No dosage adjustment is necessary.

Race:
Pharmacokinetic differences due to race have not been studied.

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

Renal Insufficiency:

Following oral administration, plasma concentrations and AUCs of Cozaar and its active metabolite are increased by 50-90% in patients with mild or moderate renal insufficiency. In this study, renal clearance was reduced by 55-85% for both Cozaar and its active metabolite in patients with mild or moderate renal insufficiency. Neither Cozaar nor its active metabolite can be removed by hemodialysis. No dosage adjustment is necessary for patients with renal impairment unless they are volume-depleted.

Hepatic Insufficiency:

Following oral administration in patients with mild to moderate alcoholic cirrhosis of the liver, plasma concentrations of Cozaar and its active metabolite were, respectively, 5-times and about 1.7-times those in young male volunteers. Compared to normal subjects the total plasma clearance of Cozaar in patients with hepatic insufficiency was about 50% lower and the oral bioavailability was about 2-times higher. A lower starting dose is recommended for patients with a history of hepatic impairment.

7.OTHER/ALTERNATE USES OF COZAAR
(What else does Cozaar treat?)

Cozaar has also been shown to delay the progression of kidney disease in people with type 2 diabetes who have related kidney complications. If you have diabetic kidney disease you may be prescribed Cozaar for this reason, regardless of whether or not you also have High blood pressure.

8.ADVERSE/SIDE EFFECTS of COZAAR
(What are the side effects of Cozaar?)

Cozaar has been evaluated for safety in more than 3300 adult patients treated for essential hypertension and 4058 patients/subjects overall. Over 1200 patients were treated for over 6 months and more than 800 for over one year. In general, treatment with Cozaar was well-tolerated. The overall incidence of adverse experiences reported with Cozaar was similar to placebo.

In controlled clinical trials, discontinuation of therapy due to clinical adverse experiences was required in 2.3 percent of patients treated with Cozaar and 3.7 percent of patients given placebo.

The following table of adverse events is based on four 6- to 12-week, placebo-controlled trials involving over 1000 patients on various doses (10-150 mg) of losartan and over 300 patients given placebo. All doses of losartan are grouped because none of the adverse events appeared to have a dose-related frequency. The adverse experiences reported in =1% of patients treated with Cozaar and more commonly than placebo are shown in the table below.

	Cozaar (n=1075) Incidence %	Placebo (n=334) Incidence %
Musculoskeletal
Cramp, muscle	1	0
Pain, back	2	1
Pain, leg	1	0
Nervous System/Psychiatric
Dizziness	3	2
Respiratory
Congestion, nasal	2	1
Infection, upper respiratory	8	7
Sinusitis	1	0

The following adverse events were also reported at a rate of 1% or greater in patients treated with losartan, but were as, or more frequent, in the placebo group: asthenia/fatigue, edema/swelling, abdominal pain, chest pain, nausea, headache, pharyngitis, diarrhea, dyspepsia, myalgia, insomnia, cough, sinus disorder.

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

In the RENAAL study involving 1513 patients treated with Cozaar or placebo, the overall incidences of reported adverse experiences were similar for the two groups. Cozaar was generally well tolerated as evidenced by a similar incidence of discontinuations due to side effects compared to placebo (19% for Cozaar, 24% for placebo). The adverse experiences, regardless of drug relationship, reported with an incidence of =4% of patients treated with Cozaar and occurring more commonly than placebo, on a background of conventional antihypertensive therapy, are shown in the table below.

	Cozaar and Conventional Antihypertensive Therapy Incidence % (n=751)	Placebo and Conventional Antihypertensive Therapy Incidence % (n=762)
Body as a Whole
Asthenia/Fatigue	14	10
Chest Pain	12	8
Fever	4	3
Infection	5	4
Influenza-like disease	10	9
Trauma	4	3
Cardiovascular
Hypotension	7	3
Orthostatic hypotension	4	1
Digestive
Diarrhea	15	10
Dyspepsia	4	3
Gastritis	5	4
Endocrine
Diabetic neuropathy	4	3
Diabetic vascular disease	10	9
Eyes, Ears, Nose and Throat
Cataract	7	5
Sinusitis	6	5
Hemic
Anemia	14	11
Metabolic and Nutrition
Hyperkalemia	7	3
Hypoglycemia	14	10
Weight gain	4	3
Musculoskeletal
Back pain	12	10
Leg pain	5	4
Knee pain	5	4
Muscular weakness	7	4
Nervous System
Hypesthesia	5	4
Respiratory
Bronchitis	10	9
Cough	11	10
Skin
Cellulitis	7	6
Urogenital
Urinary tract infection	16	13

Post-Marketing Experience

The following additional adverse reactions have been reported in post-marketing experience:

Hypersensitivity: Angioedema, including swelling of the larynx and glottis, causing airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue has been reported rarely in patients treated with losartan; some of these patients previously experienced angioedema with other drugs including ACE inhibitors. Vasculitis, including Henoch-Schönlein purpura, has been reported. Anaphylactic reactions have been reported.

Digestive: Hepatitis

Musculoskeletal: Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers.

Respiratory: Dry cough

Hyperkalemia and hyponatremia have been reported.