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Hyzaar

Hyzaar
Hyzaar is a combined antihypertensive drug.

Brand: Losartan

Availability: In Stock
Average Delivery Time: 9 Days
Exp. Date: November 2023
Package Price Per pill Save Order
Hyzaar 50 mg
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30 pills - 50 mg $54.93 $1.83 No Add to cart
Hyzaar 12.5 mg
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Product description

Pharmacological action of the Hyzaar

Buy Hyzaar in Canada

Combined antihypertensive agent. Losartan and hydrochlorothiazide have an additive antihypertensive effect, lowering blood pressure to a greater extent than each of the components separately.

Losartan is a selective angiotensin II receptor antagonist (type AT1) for oral administration. In vivo and in vitro, losartan and its pharmacologically active metabolite E-3174 block all physiologically significant effects of angiotensin II on AT1 receptors, regardless of the pathway of its synthesis: it leads to an increase in blood plasma renin activity, reduces the concentration of aldosterone in blood plasma. Losartan indirectly causes the activation of AT2receptors by increasing the concentration of angiotensin II. Does not inhibit the activity of kininase II, an enzyme that is involved in the metabolism of bradykinin. Reduces systemic vascular resistance, pressure in the pulmonary circulation, reduces afterload on the myocardium, has a diuretic effect. Prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure (CHF). Taking losartan 1 time / day leads to a statistically significant decrease in systolic and diastolic blood pressure.

Losartan evenly controls blood pressure throughout the day, while the antihypertensive effect corresponds to the natural circadian rhythm. The decrease in blood pressure at the end of the dose of the drug was approximately 70-80% of the maximum effect of losartan, 5-6 hours after oral administration. There is no withdrawal syndrome.

Losartan has no clinically significant effect on heart rate, has a moderate and transient uricosuric effect.

Hydrochlorothiazide is a thiazide diuretic, the diuretic effect of which is associated with impaired reabsorption of sodium, chlorine, potassium, magnesium, water in the distal nephron; delays the excretion of calcium ions, uric acid. It has an antihypertensive effect, the action of which develops due to the expansion of arterioles. Has practically no effect on normal blood pressure. The diuretic effect occurs in 1-2 hours, reaches a maximum after 4 hours and lasts 6-12 hours. The maximum antihypertensive effect occurs in 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect.

Due to the diuretic effect, hydrochlorothiazide increases the activity of plasma renin, stimulates the secretion of aldosterone, increases the concentration of angiotensin II and reduces the concentration of potassium in the blood plasma. Taking losartan blocks all physiological effects of angiotensin II and, due to the suppression of the effects of aldosterone, may help reduce the loss of potassium associated with taking a diuretic. Hydrochlorothiazide causes a slight increase in the concentration of uric acid in the blood; the combination of losartan and hydrochlorothiazide helps to reduce the severity of diuretic-induced hyperuricemia.

Pharmacokinetics

The pharmacokinetics of losartan and hydrochlorothiazide with simultaneous use does not differ from that when used as monotherapy.

Losartan

After oral administration, losartan is well absorbed from the gastrointestinal tract. Undergoes significant metabolism during the "first pass" through the liver, forming a pharmacologically active carboxylated metabolite (E-3174) and inactive metabolites. Bioavailability is approximately 33%. Average Cmax of losartan and its active metabolite are reached after 1 hour and after 3-4 hours, respectively. Losartan and its active metabolite bind to blood plasma proteins (mainly albumin) by more than 99%. Vd losartan is 34 liters. It penetrates the BBB very poorly.

Losartan is metabolized to form an active (E-3174) metabolite (14%) and inactive ones, including two main metabolites formed by hydroxylation of the butyl group of the chain and a less significant metabolite, N-2-tetrazole glucuronide. Plasma clearance of losartan and its active metabolite is approximately 10 ml / sec (600 ml / min) and 0.83 ml / sec (50 ml / min), respectively. The renal clearance of losartan and its active metabolite is about 1.23 ml / sec (74 ml / min) and 0.43 ml / sec (26 ml / min). T1/2 of losartan and the active metabolite is 2 hours and 6-9 hours, respectively. It is excreted mainly with bile through the intestines - 58%, by the kidneys - 35%. Does not cumulate.

When taken orally in doses up to 200 mg, losartan and its active metabolite have linear pharmacokinetics.

Hydrochlorothiazide

After oral administration, absorption of hydrochlorothiazide is 60-80%. Cmax in blood plasma is reached within 1-5 hours after oral administration. Plasma protein binding - 64%. Penetrates the placental barrier. Excreted in breast milk. Hydrochlorothiazide is not metabolized and is rapidly excreted by the kidneys. T1/2 is 5-15 hours. At least 61% of the dose taken orally is excreted unchanged within 24 hours.

Indications of active substances of the drug Hyzaar®

Hyzaar for hypertension

Arterial hypertension (for patients who are indicated for combination therapy); reducing the risk of cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy.

Dosage regimen

I take orally, regardless of food intake.

The recommended dose of the combination in terms of losartan is 50-100 mg 1 time / day. The maximum dose is 100 mg 1 time / day.

The maximum antihypertensive effect is achieved within 3 weeks of therapy.

Application during pregnancy and lactation

Use during pregnancy and lactation (breastfeeding) is contraindicated.

Application for violations of liver function

Contraindicated in severe violations of liver function.

With care when mild and moderate liver dysfunction.

Application for impaired renal function

Contraindicated in severe renal failure (CC <30 ml / min).

With caution in case of mild and moderate renal dysfunction (CC from 30-50 ml / min).

Use in children

The drug is contraindicated for use in children and adolescents under the age of 18 years

Use in elderly patients

The drug is approved for use in elderly patients

Special instructions

While using losartan, reversible renal dysfunctions, including renal failure, are possible, which disappear after losartan is discontinued. Drugs acting on the RAAS can lead to an increase in the concentration of urea and creatinine in the blood plasma in patients with bilateral renal artery stenosis or stenosis of a solitary kidney artery. These changes in renal function may be reversible and disappear after discontinuation of therapy.

In patients with impaired renal function treated with NSAIDs (including COX-2 inhibitors), therapy with angiotensin II receptor antagonists may further worsen renal impairment, including acute renal failure, which is usually reversible, and increase plasma potassium concentrations in patients with pre-existing renal impairment. This combination is recommended to be used with caution, especially in elderly patients. Patients should receive a sufficient amount of fluid, as well as monitor kidney function before and after starting treatment with this combination.

The condition of patients should be monitored in order to timely detect clinical signs of violations of water and electrolyte balance, for example, dehydration, hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia, which may develop against the background of concomitant diarrhea or vomiting. In such patients, it is necessary to monitor the content of electrolytes in the blood plasma.

Thiazide diuretic therapy can impair glucose tolerance. In some cases, it may be necessary to adjust the doses of hypoglycemic agents for oral administration and / or insulin.

Thiazides can reduce the excretion of calcium by the kidneys and cause a short-term and insignificant increase in the concentration of calcium in the blood plasma. Severe hypercalcemia may indicate latent hyperparathyroidism.

Due to the effect of thiazides on calcium metabolism, their use can distort the results of the study of the function of the parathyroid glands, therefore, before the study of the function of the parathyroid glands, the thiazide diuretic should be canceled.

An increase in the concentration of cholesterol and triglycerides in the blood may also be associated with therapy with thiazide diuretics.

In some patients, the use of thiazide diuretics can lead to hyperuricemia and / or the development of gout. Since losartan reduces the concentration of uric acid, its combination with hydrochlorothiazide reduces the severity of diuretic-induced hyperuricemia.

Hydrochlorothiazide is a sulfonamide that can cause an idiosyncratic reaction leading to the development of an acute attack of angle-closure glaucoma.

In patients receiving thiazide diuretics, hypersensitivity reactions can be observed even in the absence of a history of indications of allergic reactions or bronchial asthma. There are reports of the development of exacerbation or progression of systemic lupus erythematosus against the background of the use of thiazide diuretics.

Influence on the ability to drive vehicles and mechanisms

Care must be taken when driving vehicles and working with other technical devices that require increased concentration of attention and speed of psychomotor reactions.

Drug interaction

Simultaneous use with potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), potassium preparations or potassium-containing table salt substitutes, as well as the use of other drugs that increase the concentration of potassium in the blood plasma, increase the risk of hyperkalemia.

NSAIDs, incl. selective inhibitors of COX-2 can reduce the effect of diuretics and other antihypertensive drugs, including losartan.

The antihypertensive effect of losartan, like other antihypertensive drugs, can be reduced with the use of indomethacin.

Double blockade of RAAS, i.e. the addition of an ACE inhibitor to therapy with an angiotensin II receptor antagonist is possible only in individual cases under close monitoring of renal function.

In patients with atherosclerosis, heart failure or diabetes mellitus with damage to target organs, double blockade of the RAAS (with the simultaneous use of angiotensin II receptor antagonists, ACE inhibitors or aliskiren) is accompanied by an increased incidence of arterial hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure) in comparison with the use of a drug of one of the listed groups.

It is possible to reduce the elimination of lithium ions. Therefore, with the simultaneous use of angiotensin II receptor antagonists with lithium salts, serum lithium concentrations should be carefully monitored.

When used simultaneously with thiazide diuretics, drugs such as ethanol, barbiturates and opioid analgesics may potentiate the risk of orthostatic hypotension.

With simultaneous use, it is possible to increase the hypoglycemic effect of oral hypoglycemic agents (sulfonylurea derivatives) and / or insulin in patients with diabetes mellitus; with such combinations, an increase in glucose tolerance is possible, which may require adjustment of doses of hypoglycemic agents for oral administration and / or insulin.

With simultaneous use with other antihypertensive drugs - an additive effect.

The absorption of hydrochlorothiazide is impaired in the presence of colestyramine and colestipol.

With simultaneous use with GCS, ACTH, there is a pronounced decrease in the content of electrolytes, in particular hypokalemia.

There is a decrease in the severity of the therapeutic effect of hydrochlorothiazide against the background of the use of pressor amines (for example, epinephrine (adrenaline), norepinephrine (norepinephrine)).

Hydrochlorothiazide enhances the effect of non-depolarizing muscle relaxants (for example, tubocurarine chloride).

Diuretics reduce the renal clearance of lithium and increase the risk of lithium toxicity. Simultaneous use is not recommended.

With simultaneous use with barbiturates, narcotic analgesics, antidepressants, ethanol, the risk of orthostatic hypotension increases.

Drugs used to treat gout (probenecid, sulfinpyrazone and allopurinol): hydrochlorothiazide can increase the serum concentration of uric acid, so a dose adjustment of uricosuric drugs may be required - an increase in the dose of probenecid or sulfinpyrazone. Concomitant use of thiazide diuretics may increase the frequency of hypersensitivity reactions to allopurinol.

Concomitant use with cyclosporine may increase the risk of hyperuricemia and exacerbate the course of gout.

Anticholinergics (eg, atropine, biperiden) increase the bioavailability of thiazide diuretics by reducing gastrointestinal motility and gastric emptying.

Thiazide diuretics can reduce the renal excretion of cytotoxic drugs (cyclophosphamide, methotrexate) and enhance their myelosuppressive effect.

In the case of the use of salicylates in high doses, hydrochlorothiazide may increase their toxic effect on the central nervous system.

There are limited data on the development of hemolytic anemia with the simultaneous use of hydrochlorothiazide and methyldopa.

Hypokalemia or hypomagnesemia caused by thiazide diuretics can lead to the development of arrhythmias with the use of cardiac glycosides.

Side effect

From the immune system: rarely - anaphylactic reactions, angioedema (including edema of the larynx and tongue, causing obstruction of the airways and / or edema of the face, lips, pharynx), urticarial rash.

On the part of the hematopoietic system: infrequently - anemia, Shenlein-Henoch purpura, ecchymosis, hemolysis, agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, thrombocytopenia.

From the nervous system: often - headache, dizziness, insomnia, increased fatigue; infrequently - migraine, anxiety, confusion, depression, sleep disturbances, memory impairment, drowsiness, nervousness, paresthesia, tremor, fainting.

From the side of the cardiovascular system: often - orthostatic hypotension (dose-dependent), palpitations, tachycardia; infrequently - AV block II degree, chest pain, myocardial infarction, arrhythmias; rarely - vasculitis.

From the respiratory system: often - cough, upper respiratory tract infections, sinusitis, swelling of the nasal mucosa, nasal congestion; infrequently - pharyngitis, laryngitis, rhinitis, dyspnea, bronchitis, epistaxis.

From the digestive system: often - diarrhea, dyspepsia, nausea, vomiting, abdominal pain; rarely - hepatitis, liver dysfunction.

From the urinary system: infrequently - urinary tract infections, frequent urination, nocturia, glucosuria.

From the reproductive system: infrequently - weakening of libido, decreased potency.

From the senses: infrequently - blurred vision, burning sensation in the eyes, conjunctivitis.

On the part of the skin: often - alopecia, dry skin, erythema, photosensitivity, increased sweating; infrequently - urticaria, itchy skin.

From the musculoskeletal system: often - myalgia, back pain; infrequently - arthralgia.

Others: often - asthenia, weakness, peripheral edema; infrequently - anorexia, exacerbation of the course of gout.

On the part of laboratory parameters: often - hyperkalemia, a slight decrease in the concentration of hemoglobin and hematocrit; infrequently - a moderate increase in the concentration of urea and creatinine in the blood plasma, hyperglycemia, hyperuricemia, disturbances in the water-electrolyte balance; rarely - increased ALT activity; very rarely - an increase in ACT activity and bilirubin concentration.