1.HYZAAR HISTORY
(How was Hyzaar discovered?)

Hyzaar is a product of Merck Pharmaceuticals.

The US FDA approved Hyzaar on April 21, 2005.

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 Hyzaar

2.HYZAAR FACTS

Hyzaar is a combination of Losartan and Hydrochlorothiazide

Hydrochlorothiazide is a type of medicine known as a thiazide diuretic. Thiazide diuretics act in the kidney, where they increase the production of urine. They work by causing the kidneys to increase the amount of salts, such as potassium and sodium, which are filtered out of the blood and into the urine. When these salts are filtered out of the blood by the kidneys, water is also drawn alongside. As Hydrochlorothiazide increases the removal of salts from the blood, it also causes more water to be drawn out of the blood and into the urine. Removing water from the blood decreases the volume of fluid circulating through the blood vessels, which lowers the pressure within the blood vessels, i.e lowers blood pressure. It also decreases the effort required by the heart to pump the blood around the body.

Losartan is a type of medicine called an angiotensin II receptor antagonist. It 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. It causes the peripheral blood vessels to narrow, and it also 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. Losartan 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 helps lower blood pressure.

The combination of these two medicines is particularly useful in treating High blood pressure

3.ABOUT HYZAAR 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, but you will be getting sick of hearing about such rare conditions. 

4.HYZAAR EFFECTIVENESS
(When is Hyzaar best taken?)

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

Both Hyzaar 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 of Hyzaar. Studies in rats indicate that Hyzaar crosses the blood-brain barrier poorly, if at all.

5.HYZAAR EFFECTS ON SPECIAL POPULATION
(How do different people react to Hyzaar?)

Pediatric:
Hyzaar pharmacokinetics have not been investigated in patients <18 years of age. 

Geriatric and Gender:
Hyzaar pharmacokinetics has been investigated in the elderly (65-75 years) and in both genders. Plasma concentrations of Hyzaar and its active metabolite are similar in elderly and young hypertensives. Plasma concentrations of Losartan were about twice as high in female hypertensives as male hypertensives, but concentrations of the active metabolite were similar in males and females.

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

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

Renal Insufficiency

Losartan:

Following oral administration, plasma concentrations and AUCs of Losartan 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 Losartan and its active metabolite in patients with mild or moderate renal insufficiency. Neither Losartan nor its active metabolite can be removed by hemodialysis. 

Hydrochlorothiazide:

Following oral administration, the AUC for Hydrochlorothiazide is increased by 70 and 700% for patients with mild and moderate renal insufficiency, respectively. In this study, renal clearance of Hydrochlorothiazide decreased by 45 and 85% in patients with mild and moderate renal impairment, respectively.

The usual regimens of therapy with Hyzaar may be followed as long as the patient's creatinine clearance is >30 mL/min. In patients with more severe renal impairment, loop Diuretics are preferred to thiazides, so Hyzaar is not recommended.

Hepatic Insufficiency:

Following oral administration in patients with mild to moderate alcoholic cirrhosis of the liver, plasma concentrations of Hyzaar 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 Hyzaar in patients with hepatic insufficiency was about 50% lower, and the oral bioavailability was about 2 times higher. The lower starting dose of Losartan recommended for use in patients with hepatic impairment cannot be given using Hyzaar. Its use in such patients as a means of Losartan titration is, therefore, not recommended. 

7.OTHER/ALTERNATE USES OF HYZAAR
(What else does Hyzaar treat?)

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

8.SIDE EFFECTS of HYZAAR
(What are the side effects of Hyzaar?)

Hyzaar has been evaluated for safety in 858 patients treated for essential hypertension. In clinical trials with Losartan potassium-Hydrochlorothiazide, no adverse experiences peculiar to this combination have been observed. Adverse experiences have been limited to those that were reported previously with Losartan potassium and/or Hydrochlorothiazide. The overall incidence of adverse experiences reported with the combination was comparable to placebo.

In general, treatment with Hyzaar was well tolerated. For the most part, adverse experiences have been mild and transient in nature and have not required discontinuation of therapy. In controlled clinical trials, discontinuation of therapy due to clinical adverse experiences was required in only 2.8% and 2.3% of patients treated with the combination and placebo, respectively.

In these double-blind controlled clinical trials, the following adverse experiences reported with Hyzaar occurred in >1 percent of patients, and more often on drug than placebo, regardless of drug relationship:

The following adverse events were also reported at a rate of 1% or greater, but were as, or more, common in the placebo group: asthenia/fatigue, diarrhea, nausea, headache, bronchitis, pharyngitis.

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

A patient with known hypersensitivity to aspirin and penicillin, when treated with Losartan potassium, was withdrawn from study due to swelling of the lips and eyelids and facial rash, reported as angioedema, which returned to normal 5 days after therapy was discontinued.

Superficial peeling of palms and hemolysis were reported in one subject treated with Losartan potassium.

Other adverse experiences that have been reported due to Losartan, without regard to causality, are listed below:

Body as a Whole: chest pain, facial edema, fever, orthostatic effects, syncope;

Cardiovascular: angina pectoris, arrhythmias including atrial fibrillation, sinus bradycardia, tachycardia, ventricular tachycardia and ventricular fibrillation, CVA, hypotension, myocardial infarction, second degree AV block;

Digestive: anorexia, constipation, dental pain, dry mouth, dyspepsia, flatulence, gastritis, vomiting;

Hematologic: anemia;

Metabolic: gout;

Musculoskeletal : arm pain, arthralgia, arthritis, fibromyalgia, hip pain, joint swelling, knee pain, leg pain, muscle cramps, muscle weakness, musculoskeletal pain, myalgia, shoulder pain, stiffness;

Nervous System/Psychiatric: anxiety, anxiety disorder, ataxia, confusion, depression, dream abnormality, hypesthesia, insomnia, libido decreased, memory impairment, migraine, nervousness, panic disorder, paresthesia, peripheral neuropathy, sleep disorder, somnolence, tremor, vertigo;

Respiratory : dyspnea, epistaxis, nasal congestion, pharyngeal discomfort, respiratory congestion, rhinitis, sinus disorder;

Skin : alopecia, dermatitis, dry skin, ecchymosis, erythema, flushing, photosensitivity, pruritus, sweating, urticaria;

Special Senses : blurred vision, burning/stinging in the eye, conjunctivitis, decrease in visual acuity, taste perversion, tinnitus;

Urogenital : impotence, nocturia, urinary frequency, urinary tract infection.

Other adverse experiences that have been reported due to Hydrochlorothiazide, without regard to causality, are listed below:

Body as a Whole: weakness;

Digestive: pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation;

Hematologic: aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia;

Hypersensitivity: purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema;

Metabolic : hyperglycemia, glycosuria, hyperuricemia;

Musculoskeletal : muscle spasm; Nervous

System/Psychiatric : restlessness;

Renal : renal failure, renal dysfunction, interstitial nephritis;

Skin : erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis;

Special Senses : transient blurred vision, xanthopsia.

Post-Marketing Experience

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

Digestive : Hepatitis has been reported rarely in patients treated with Hyzaar.

Hemic : Thrombocytopenia has been reported rarely with Hyzaar.

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 with Losartan. Anaphylactic reactions have been reported.

Metabolic and Nutrition: Hyperkalemia, hyponatremia have been reported with Hyzaar.

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

Respiratory: Dry cough (see above) has been reported with Hyzaar.