Hyzaar 50/12.5mg Organon treats hypertension and reduces the risk of cardiovascular disease (2 blisters x 14 tablets)

Losartan has been shown to excrete urinary uric acid at a light and transient level. Hydrochlorothiazide has been shown to cause a little increase in uric acid; The combination of Losartan and Hydrochlorothiazide tends to reduce hyperuricemia due to the effect of this diuretic.

Use combinations of Losartan and Hydrochlorothiazide increases anti -hypertension effect.

losartan

Losartan is an Angiotensin II receptor inhibitor (Type AT1) orally. Angiotensin II is linked to AT1 receptors that are found in many tissues (such as vascular smooth muscles, adrenal glands, kidneys and hearts) and promote many important biological activities, including vascular contractions and aldosterone secretions. Angiotensin II also stimulates smooth muscle cell proliferation. On the basis of cohesion and pharmacological biological tests, Angiotensin II selectively linked with AT1 receptors. In Vitro and In Vivo, both Losartan and carboxylic acid metabolites have its pharmacological activity (E-3174) blocking all related physiological activities of Angiotensin II, regardless of the source and synthetic root.

During the use of Losartan, the negative removal of Angiotensin II for the renin secretion will lead to increased lenin activity in plasma. Increasing lenin activity in plasma leads to an increase in angiotensin II in plasma. Even with these phenomena, the anti -hypertension activity and restraint of plasma aldosterone levels are still maintained, showing the ability to be effective for angiotensin II receptors.

Losartan is selected with AT1 receptor, and does not bind or blocked other hormones or other ion exchange channels that play an important role in the cardiovascular regulation. Moreover, Losartan does not inhibit ACE (Kininase II) - the enzyme degenerate Bradykinin. Therefore, the impacts that are not directly related to the AT1 receptor blockage such as the potential of intermediaries Bradykinin or edema (Losartan1.7%, Placeboo 1.9%) are not related to Losartan.

Losartan has been shown to prevent these response with angiotensin I and Angiotensin II without affecting Bradykinin response, this is a unified detection with the specific operating mechanism of Losartan. In contrast, ACE enzyme inhibitors have been shown to prevent response to angiotensin I and strengthen the response to Bradykinin without changing response to Angiotensin II, which is a sign of pharmacological distinctions between Losartan and ACE enzyme inhibitors.

hydrochlorothiazide

The mechanism of hypotension of the Thiazide group is not known. Thiazide usually does not have the effect of normal blood pressure.

Hydrochlorothiazide is a diuretic and hypotension. Effects on electrolyte reabsorption mechanism in the distance. Hydrochlorothiazide increases the excretion of sodium and chloride at approximately equal. Sodium output may be accompanied by a loss of potassium and bicarbonate.

After oral use, the diuretics began to work after 2 hours, reaching peak after about 4 hours and lasting for about 6 -12 hours.

Dynamic pharmacokinetics

absorption

Losartan: After oral use, Losartan is well absorbed and undergoing the first metabolic stage to form an active carboxylic acid metabolite and other non -active metabolites. Losartan's whole body bioavailability is approximately 33%. The average peak concentration is achieved after 1 hour (Losartan) and 3-4 hours (active metabolites). No significant clinical effect on Losartan's plasma concentrations when this drug is used with the same standard meal.

hydrochlorothiazide: After drinking, hydrochlorothiazide absorbs relatively quickly. The absorption level is about 65 - 75% of the dose of use, but this ratio can be reduced in patients with heart failure.

distribution

Losartan: Both Losartan and active metabolites are connected> 99% with plasma proteins, mainly albumin. Losartan distribution volume is 34 liters. Rat studies show that Losartan through cerebral blood membrane is very few, not even.

Hydrochlorothiazide passes through the placenta but does not pass through the cerebral blood and is secreted into breast milk.

transformation

Losartan: About 14% of Losartan dose uses intravenous or oral line converted into activated metabolites. After oral or oral use, Losartan Kali has a 14C marker, radioactive activity in circulating plasma is attributed to Losartan and its active metabolites. The minimum conversion of Losartan into an active metabolic substance is found in about 1% of the research individual. In addition to active metabolites, the formation of non-activity metabolites, including two main metabolites formed by hydroxylation of the butyl edge chain and a small metabolic substance, is a glucuronide N-2 Tetrazole.

Elimination

Losartan: The clearance is about 600 ml/minute and its active metabolites are 50 ml/minute. Losartan's kidney clearance is about 74 ml/minute and its active metabolites are 26 mLL/min. When using Losartan oral, about 4% dose is secreted in urine in a constant form and about 6% of the dose is secreted through urine in the form of active metabolites. The pharmacokinetics of Losartan and its active metabolites linear with Losartan Kali taken at a dose from less to 200 mg. After oral use, Losartan's plasma concentration and its metabolites decrease many times with the end of the end of the end of the end of the end of the end of the end of the end of the end at about 2 hours (Losartan) and 6 - 9 hours (its metabolic).

Hydrochlorothiazide is not metabolized but quickly excreted in the kidneys. When the plasma level lasts for a minimum of 24 hours, the semi -cancellation time in plasma has been observed in the range of 5.6 -14.8 hours. At least 61 % of oral doses are eliminated in the form of unchanged within 24 hours.

No need to adjust the starting dose of Hyzaar 50/12.5mg for elderly patients. Do not use Losartan 100mg and Hydrochlorothiazide 25mg is the starting dose for this patient group.

Dosage to reduce the risk of cardiovascular disease and cardiovascular death in patients with hypertension with left ventricular hypertrophy:

What to do when overdose? Treatment is symptomatic and supportive. Need to stop Hyzaar immediately and carefully monitor patients. The proposed measures are vomiting if they have just taken Hyzaar, rehydration, electrolyte balance, liver coma treatment, handling of blood pressure loss according to normal processes.

losartan

Data on people overdose is limited. The most common manifestation of overdose is hypotension and tachycardia; Sometimes the heart is slow due to stimulation of the sympathetic cord (vagus nerve). When symptoms of hypotension occur, it is necessary to have supportive treatment.

cannot remove Losartan and the active metabolites of this drug with dialysis.

hydrochlorothiazide

The most common signs and symptoms of this diuretic overdose are the decrease in electrolytes (hypokalemia, hypoglycemic lower blood, blood sodium lower) and dehydration due to strong diuretic benefits. If combined with digitalis, the reduction of blood potassium can make the arrhythmia worse.

Not yet determined the degree of removal of hydrochlorothiazide by dialysis.

What to do when you forget 1 dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double dose to compensate for missed dose.

When experiencing side effects of the drug, it is necessary to stop using and notify the doctor or go to the nearest medical facility for timely treatment.

Be cautious when using

patients with a history of angioedema (swelling of the face, lips, throat, and/or tongue) should be closely monitored.

Symptomatic hypotension, especially after the first dose, may occur in patients with volume reduced and/or sodium reduction due to strong ureteral therapy, diet that limit salt, diarrhea or vomiting.

Electrolyte imbalance usually occurs in patients with renal failure, with or without diabetes and need to be treated. Therefore, it is necessary to strictly control the concentration of potassium in plasma and creatinine clearance, especially patients with heart failure and creatinine clearance from 30 - 50 ml/min. Do not simultaneously use potassium diuretic, potassium supplements and salt -containing substances containing potassium with losartan/hydrochlorothiazide.

As other vasodilators, especially cautious for patients with aortic valve stenosis or mitral valve, or congested cardiomyopathy.

Using Thiazide can reduce glucose tolerance. If necessary, adjust the dosage to treat diabetes, including insulin. Potential diabetes can be revealed during treatment with Thiazide.

Thiazide can reduce calcium secretion through urine and cause mild and interrupted serum calcium. Disclosed hypercalcemia may be the consequence of hidden parathyroid cysts. Need to stop using Thiazide before conducting tests on parathyroid function.

Use the diuretics may increase cholesterol and triglycerides. Thiazide can increase blood uric acid and/or cause gout in some people. Because Losartan reduces blood uric acid, Losartan coordinates with hydrochlorothiazide will reduce the increase in uric acid caused by this diuretic.

Be cautious when taking Thiazide in patients with liver function or liver disease, because it can cause bile stasis in the liver, and by minor changes of fluid balance and electrolyte can promote liver coma.

In Thiazide users, there are hypersensitivity reactions whether or not there is a history of allergies or bronchial asthma, having a system of drama or system activation of the system after using Thiazide.

The drug contains lactose. Patients with rare genetic diseases in tolerance Galactose, Lapp Lactase or Glucose-Galactose should not use this drug.

has not determined the safety and effectiveness of the drug with children. Babies have a history of Hyzaar exposure in the uterus: if the urinary or hypotension occurs, pay directly on the support of blood pressure and kidney perfusion. It may be necessary to transmit blood or fertilizer as a measure to reverse hypotension and/or instead of kidney function.

The effect of the drug on driving and operating machinery

has not conducted research on the effect of driving and operating machinery. However, when driving or operating machinery, it should be noted that it may be dizzy or drowsiness when using anti -hypertension therapy, especially when starting treatment or when increasing the dose.

Use drugs for women during pregnancy and lactation

pregnancy:

Medicines directly acting on the Renin-Anotensin system can cause damage and developing pregnancy. When detecting pregnancy, Hyzaar must be stopped as soon as possible.

breastfeeding period:

There is no information related to the use of Hyzaar during breastfeeding, do not use Hyzaar, and if appropriate, should use alternative therapy that have set a safer profile during breastfeeding, especially when raising newborns or premature babies.

Small amount of hydrochlorothiazide is secreted into the mother's milk. High -dose Thiazide has strong diuretic can inhibit milk production. It is not recommended to use Hyzaar during breastfeeding. If using Hyzaar during the child, the lowest dose is possible.

Drug interaction

Losartan

In clinical dynamic trials, any clinical interactions have not been determined with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin. There have been reports on reducing the level of metabolites that are active of rifampin and fluconazole. The clinical value of these interactions has not been fully evaluated.

As with other drugs belonging to the Angiotensin II receptor inhibitor group or have the same effect, when used with potassium -keeping pills (such as Spironolacton, Triamteren, Amiloride), Potassium Supplements, Salt Supplies containing potassium, or drugs that can increase serum potassium (e.g., drugs containing trimethoprim), they can lead to increased serosology.

As well as other drugs that affect the excretion of sodium, can also reduce lithium excretion.

Therefore, if lithium salt is used with Angiotensin II receptor inhibitors, the test must monitor the amount of lithium in the serum. Non-steroid anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2 inhibitors (COX-2 inhibitors) may reduce the effect of diuretic and other hypertension drugs. Therefore, the lowering effect of the Angiotensin II receptor inhibitors may be impaired by NSAIDs, including COX-2 selective inhibitors.

In some patients with renal dysfunction (such as elderly patients or volume reduced, including patients being treated with diuretics) that have been treated with non-steroid anti-inflammatory drugs including cyclooxygenase-2 inhibitors, simultaneous use These effects are usually recovered. Therefore, it is necessary to be careful when using this combination in patients with renal dysfunction.

Renin-Anotensin-Aldosterone (RAAS) inhibitors by combining Angiotensin receptor inhibitors, ACE or Aliskiren inhibitors, which are accompanied by an increase in the risk of lowering blood pressure, fainting, hyperkalemia and changing renal function (including acute renal impairment) compared to the use of single therapy.

closely monitor blood pressure, kidney function and electrolyte on patients using Hyzaar and other drugs that affect RAAS. Do not use Aliskiren simultaneously with Hyzaar on diabetes patients. Avoid using Aliskiren with Hyzaar in patients with renal failure (GFR

hydrochlorothiazide

When coordinated, the following drugs may interact with the diuretic gums:

alcohol, barbiturate or addictive drug: aggravate the side effect of lowering the posture.

Hypogonodic drugs (insulin and oral medications): may need to adjust the dose of hypoglycemic drugs.

Other hypertension medications: Agreement effects.

Cholestyramine and Colestipol plastic: Reduce the absorption of hydrochlorothiazide when there is anion exchange plastic. The single dose of cholestyramine or Colestipol plastic combined with hydrochlorothiazide reduces the absorption of Thiazide through the digestive tube in the order of 85% and 43%.

corticoid, acth, or glycyrrhizin (found in licorice): increase power outages, especially hypokalemia.

Amines that cause vascular contractions (such as adrenaline): may reduce the response to the amino as a circuit, but there is not enough basis to stop using.

Non -reducing muscle relaxants (such as tuboCurarin): may increase response to muscle relaxants.

Lithium: The diuretic pills reduce the renal clearance of lithium and create a high risk of lithium toxicity, so it should not be coordinated.

Non-steroid anti-inflammatory (NSAID) including cyclooxygenase-2 inhibitors: In some people, using nonsteroidal anti-inflammatory drugs including cycloxygenase-2 inhibitors will reduce the effect of thiazide on diuretic benefits, sodium discharge and hypertension treatment.