Hyzaar: Medicine to treat high blood pressure
Hyzaar is indicated for the treatment of hypertension in patients suitable for this combination therapy and reduces the risk of cardiovascular disease and cardiovascular death in hypertensive patients with left ventricular hypertrophy.
Merck Sharp & Dohme.
Each tablet: Losartan potassium 50mg, hydrochlorothiazide 12.5mg.
Hyzaar (losartan potassium and hydrochlorothiazide) was the first to combine an angiotensin II receptor antagonist (type AT1) with a diuretic.
Losartan - Hydrochlorothiazide
The components of Hyzaar have been shown to have additive effects in lowering blood pressure, reducing blood pressure better than the individual components. This effect is thought to be the result of the synergistic effects of both ingredients. Furthermore, due to its diuretic effect, hydrochlorothiazide increases plasma renin activity, increases aldosterone secretion, decreases serum potassium, and increases angiotensin II levels. Administration of losartan will block all physiological effects of angiotensin II and through inhibition of aldosterone may predispose to diuretic-associated potassium loss.
Losartan has been shown to have a mild and transient urinary uric acid excretion effect. Hydrochlorothiazide has been shown to cause a slight increase in uric acid; The combination of losartan and hydrochlorothiazide tends to reduce hyperuricemia due to this diuretic effect.
The combined use of losartan and hydrochlorothiazide increases the antihypertensive effect.
The antihypertensive effect of Hyzaar is maintained for a period of 24 hours. In clinical studies lasting at least one year, efficacy in the treatment of hypertension was assured with continued therapy. Despite a significant reduction in blood pressure, the use of Hyzaar did not have a clinically significant impact on heart rate. In clinical studies, after 12 weeks of treatment with losartan 50 mg/hydrochlorothiazide 12.5 mg, trough diastolic blood pressure decreased by an average of 13.2 mmHg.
Hyzaar is effective in reducing blood pressure in both men and women, blacks and other races, and in both the young (<65 years) and the elderly (≥65 years), and is effective in all high blood pressure levels.
Losartan is an orally administered angiotensin II (type AT1) receptor blocker. Angiotensin II binds to the AT1 receptor found in many tissues (eg, vascular smooth muscle, adrenal gland, kidney, and heart) and promotes many important biological activities, including vasoconstriction and aldosterone secretion. Angiotensin II also stimulates smooth muscle cell proliferation. Based on binding and biopharmacological assays, angiotensin II selectively binds to the AT1 receptor. In vitro and in vivo, both losartan and its pharmacologically active carboxylic acid metabolite (E-3174) block all physiologically relevant activities of angiotensin II, regardless of synthetic source and origin.
During the use of losartan, the rejection of angiotensin II's negative feedback on renin secretion will result in increased plasma renin activity. Increased plasma renin activity leads to an increase in plasma angiotensin II. Even with these events, antihypertensive activity and suppression of plasma aldosterone concentrations were maintained, suggesting an effective blocker of the angiotensin II receptor.
Losartan binds selectively to the AT1 receptor and does not bind to or block other hormone receptors or other ion-exchange channels that are important in cardiovascular regulation. Furthermore, losartan does not inhibit ACE (kininase II), the enzyme that degrades bradykinin. Thus, effects that were not directly related to AT1 receptor blockade, such as bradykinin-mediated potentiation or edema generation (losartan 1.7%, placebo 1.9%) were not related. losartan.
Losartan has been shown to block responses to angiotensin I and angiotensin II without affecting bradykinin responses, a finding that is consistent with losartan's characteristic mechanism of action. In contrast, ACE inhibitors have been shown to block responses to angiotensin I and enhance responses to bradykinin without altering the response to angiotensin II, which is the hallmark Pharmacodynamics between losartan and ACE inhibitors.
In non-diabetic hypertensive patients with proteinuria, the administration of losartan potassium significantly reduced proteinuria, albumin, and IgG excretion fractions. Losartan maintains the glomerular filtration rate and reduces the filtration fraction. Overall, losartan causes a sustained decrease in serum uric acid (usually < 0.4 mg/dL) during chronic therapy.
Losartan does not affect autonomic reflexes and does not affect plasma norepinephrine.
In patients with impaired left ventricular function, doses of 25 mg and 50 mg of losartan have positive hemodynamic and neurohormonal effects characterized by an increase in cardiac index and a decrease in pulmonary capillary pressure, strength, and endurance. systemic vascular resistance, mean systemic arterial pressure and heart rate and decreased circulating aldosterone and norepinephrine levels. Hypotensive events are dose-dependent in these patients with heart failure.
Administration of losartan 50-100 mg once daily had a significantly higher antihypertensive effect than captopril 50-100 mg once daily. The antihypertensive effect of losartan 50 mg was similar to that of enalapril 20 mg once daily. The antihypertensive effect of losartan 50-100 mg once daily was comparable to atenolol 50-100 mg once daily. The effects of losartan 50-100 mg once daily were similar to those of felodipine 5-10 mg extended-release when used in elderly hypertensive patients (≥65 years) after 12 weeks of treatment.
Losartan is equally effective in hypertensive men and women and the young (<65 years) as well as the elderly (≥65 years). Although losartan is effective in lowering blood pressure in all races, as with other drugs acting on the rennin-angiotensin system, black hypertensive patients have a moderate response to losartan monotherapy was lower than in patients of other races.
The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study was a randomized, triple-blind, comparison-controlled study involving 9,193 subjects. hypertensive patients, ages 55 to 80 with evidence of left ventricular hypertrophy on electrocardiogram. Patients were randomized to losartan 50 mg or atenolol 50 mg once daily. If target blood pressure (<140/90 mmHg) is not achieved, first add hydrochlorothiazide (12.5 mg) and, as needed, increase the dose of losartan or atenolol to 100 mg orally once daily. When needed, other antihypertensive agents can be added to achieve the desired blood pressure, except ACE inhibitors, angiotensin II antagonists, or beta-blockers.
The mean follow-up was 4.8 years.
The primary composite endpoint of cardiovascular morbidity and mortality was assessed by reducing the combined rate of cardiovascular mortality, stroke, and myocardial infarction. Blood pressure decreased significantly to the same extent in both treatment groups. Treatment with losartan reduced the risk by 13.0% (p=0.021, 95% CI 0.77-0.98) compared with patients receiving atenolol in patients who met the primary endpoint. This is mainly due to reduced stroke rates. Treatment with losartan reduced the risk of stroke by up to 25% compared with atenolol (p=0.001, 95% CI 0.63-0.89). Cardiovascular mortality and myocardial infarction were not significantly different between the two treatment groups.
The mechanism of the antihypertensive action of the thiazide group is unknown. Thiazides generally do not affect normal blood pressure.
Hydrochlorothiazide is a diuretic and antihypertensive. It acts on the mechanism of electrolyte reabsorption in the distal tubule. Hydrochlorothiazide increases sodium and chloride excretion approximately equally. Sodium in urine, which may be accompanied by loss of potassium and bicarbonate.
After oral administration, diuretics begin to work after 2 hours, peak after about 4 hours, and last for about 6-12 hours.
Following oral administration, losartan is well absorbed and undergoes first-pass metabolism to the active carboxylic acid metabolite and other inactive metabolites. The systemic bioavailability of losartan is approximately 33%. Mean peak concentrations are reached after 1 hour (losartan) and 3-4 hours (active metabolite). There were no clinically significant effects on losartan plasma concentration data when this drug was administered with a standard meal.
After oral administration, hydrochlorothiazide is relatively rapidly absorbed. The extent of absorption is about 65-75% of the administered dose, however, this rate may be reduced in patients with heart failure.
Both losartan and the active metabolite are ≥99% bound to plasma proteins, mainly albumin. The volume of distribution of losartan is 34 liters. Studies in rats have shown that losartan crosses the blood-brain membrane very little, or even none.
Hydrochlorothiazide crosses the placenta but not the blood-brain membranes, and is secreted into breast milk.
Approximately 14% of an intravenous or oral dose of losartan is converted to the active metabolite. Following oral or intravenous administration of 14C-labelled losartan potassium, the radioactivity in circulating plasma was attributed to losartan and its active metabolite. Minimal conversion of losartan to the active metabolite was seen in approximately 1% of subjects.
In addition to the active metabolite, inactive metabolites were formed, including two major metabolites formed by hydroxylation of the butyl side chain and a minor metabolite, an N-glucuronide. 2 tetrazoles.
The plasma clearance of losartan is approximately 600 mL/min and its active metabolite is 50 mL/min. The renal clearance of losartan is about 74 mL/min and its active metabolite is 26 mL/min. When losartan is administered orally, approximately 4% of the dose is excreted in the urine as an unchanged drug, and about 6% of the dose is excreted in the urine as the active metabolite. The pharmacokinetics of losartan and its active metabolite are linear with that of oral losartan potassium at doses ranging from less than 200 mg.
Following oral administration, plasma concentrations of losartan and its metabolite are reduced severalfold with terminal half-lives of approximately 2 hours (losartan) and 6-9 hours (its metabolite), respectively. . During once-daily dosing of losartan 100 mg, neither losartan nor its active metabolite accumulates appreciably in plasma.
Both biliary and renal excretion contribute to the elimination of losartan and its metabolites. Following oral administration of 14C-labelled losartan to humans, approximately 35% of the radioactivity was recovered intact in the urine and 58% in the feces.
Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidneys. When plasma levels persist for a minimum of 24 hours, the plasma half-life has been observed to range from 5.6-14.8 hours. At least 61% of an oral dose is eliminated unchanged within 24 hours.
Losartan - Hydrochlorothiazide
The plasma concentrations of losartan and its active metabolite and the absorption of hydrochlorothiazide were not significantly different in elderly hypertensive patients compared with younger patients.
Following oral administration in patients with mild and moderate alcoholic cirrhosis, plasma concentrations of losartan and its active metabolite were 5-fold (losartan) and 1.7-fold (losartan) active metabolism) compared with young healthy volunteers.
Neither losartan nor its active metabolite can be removed by hemodialysis.
Indications and usage
Hyzaar is indicated for the treatment of hypertension in patients suitable for this combination therapy.
Reducing the risk of cardiovascular disease and cardiovascular death in hypertensive patients with left ventricular hypertrophy.
Hyzaar is a combination of losartan (COZAAR) and hydrochlorothiazide. In patients with hypertension and left ventricular hypertrophy, losartan is often combined with hydrochlorothiazide, reducing the risk of cardiovascular events and deaths from these diseases such as overall cardiovascular mortality, stroke, and myocardial infarction in hypertensive patients with left ventricular hypertrophy (see also section 'Race').
Dosage and Administration
Hyzaar can be taken with other antihypertensive drugs.
Hyzaar can be taken with or without food.
The usual initial and maintenance dose is once daily, one Hyzaar 50/12.5 mg tablet (losartan 50 mg/hydrochlorothiazide 12.5 mg). For patients who do not respond adequately to Hyzaar 50/12.5 mg, the dose may be increased to losartan 100 mg and hydrochlorothiazide 25 mg orally once a day, or once daily, to 2 tablets of Hyzaar 50/12. ,5mg. The maximum dose is losartan 100 mg and hydrochlorothiazide 25 mg orally once a day, or once a day, 2 tablets of Hyzaar 50/12.5 mg each time. In general, the antihypertensive effect is achieved within the first three weeks of treatment.
Hyzaar should not be used in volume-depleted patients (eg, those treated with high-dose diuretics).
Hyzaar is not recommended for use in patients with severe renal impairment (creatinine clearance ≤30mL/min) or patients with hepatic impairment.
There is no need to adjust the starting dose of Hyzaar 50/12.5 mg for elderly patients. Losartan 100 mg and hydrochlorothiazide 25 mg should not be used as starting doses in this patient population.
Reduced risk of cardiovascular disease and cardiovascular death in hypertensive patients with left ventricular hypertrophy
The usual starting dose is 50 mg of losartan taken once daily. If target blood pressure is not achieved with the 50 mg dose of losartan, the dose can be adjusted using a combination of losartan and hydrochlorothiazide at a low dose (12.5 mg) and, if necessary, increasing the dose to losartan 100. mg/hydrochlorothiazide 12.5 mg orally once a day. Hyzaar 50/12.5 mg and losartan 100 mg/hydrochlorothiazide 25 mg are suitable formulations in patients requiring losartan in combination with hydrochlorothiazide.
No specific information is available on the treatment of an overdose of Hyzaar. Treatment is symptomatic and supportive. Hyzaar should be discontinued immediately and the patient closely monitored. Suggested measures are induction of vomiting if Hyzaar has recently been taken, rehydration, electrolyte balance, management of hepatic coma, management of hypotension according to conventional procedures.
Human data on overdose is limited. The most common possible manifestations of Overdose are hypotension and tachycardia; There may also be bradycardia due to stimulation of the parasympathetic (vagal) nerves. When symptomatic hypotension occurs, supportive treatment is required.
Losartan and its active metabolites cannot be removed by dialysis.
This diuretic overdose's most common signs and symptoms are electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration due to potent diuresis. If combined with digitalis, hypokalemia may aggravate arrhythmias.
The extent of the elimination of hydrochlorothiazide by hemodialysis has not been determined.
Hypersensitivity to losartan, sulphonamide derivatives (such as hydrochlorothiazide), or to any of the ingredients in this product.
Hypokalemia or refractory hypercalcemia.
Severe liver failure; cholestasis and biliary obstruction disorders.
Hyponatremia is difficult to control.
Second and third trimesters of pregnancy.
Severe renal impairment (glomerular filtration rate <30 mL/min).
Concomitant use of Hyzaar with medicinal products containing aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (GFR <60 mL/min/1.73 m2).
Use in pregnant and lactating women
Drugs that act directly on the renin-angiotensin system can cause damage and death to the developing fetus. When pregnancy is discovered, Hyzaar must be discontinued as soon as possible.
Although there is no experience with the use of Hyzaar in pregnancy, animal studies with losartan potassium have demonstrated fetal and neonatal harm, and possibly death, a mechanism that has been implicated as through action on the renin-angiotensin system. In humans, fetal renal excretion is dependent on the development of the renin-angiotensin system starting in the second trimester of pregnancy; Thus, the risk to the fetus will increase, if the mother takes Hyzaar during the second and third trimesters of pregnancy.
Drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduce fetal renal function and increase morbidity and mortality in the fetus and neonate. The resulting oligohydramnios may be associated with pulmonary hypoplasia and fetal skeletal deformity. Possible adverse effects in the neonate include cranial hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is discovered, Hyzaar must be discontinued as soon as possible.
These adverse outcomes are commonly associated with the use of these drugs during the second and third trimesters of pregnancy. Most epidemiological studies examining fetal abnormalities following exposure to antihypertensives used during the first trimester of pregnancy have failed to distinguish drugs that affect the renin-angiotensin system from those that affect the renin-angiotensin system. other hypertension. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.
In the special case where there is no suitable alternative to drug therapy affecting the renin-angiotensin system for an individual patient, the mother should be informed of the potential risk. out for the fetus. A mass ultrasound examination should be performed to assess the intra-amniotic environment. Discontinue Hyzaar if oligohydramnios is observed unless it is considered life-saving for the mother. A pregnancy test may be appropriate, based on gestational age. However, the physician and patient should be aware that oligohydramnios may not manifest until after the fetus has sustained irreversible damage. Neonates with a history of intrauterine exposure to Hyzaar should be closely monitored for manifestations of hypotension, oliguria, and hyperkalemia.
Thiazides cross the placental barrier and appear in umbilical cord blood. The use of diuretics in healthy pregnant women is not recommended. This may expose both mother and fetus to unnecessary risks, such as fetal and neonatal jaundice, thrombocytopenia, and possibly Other adverse reactions observed in adults. Diuretics do not prevent the development of toxemia in pregnancy and there is no reliable evidence that diuretics are useful in the treatment of toxemia in pregnancy.
Angiotensin II receptor antagonists (AIIRAs)
As no information is available regarding the use of Hyzaar during lactation, Hyzaar should not be used and, if appropriate, alternative therapy that has established a safer profile during lactation breastfeeding, especially when nursing a newborn or premature baby.
Small amounts of hydrochlorothiazide are secreted into breast milk. High doses of thiazides are potent diuretics that can inhibit milk production. Hyzaar is not recommended during lactation. If Hyzaar is used during lactation, the lowest possible dose should be used.
In clinical pharmacokinetic trials, no clinically significant interactions with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital have been identified (see section "Hydrochlorothiazide: Alcohol, barbiturates or narcotic drugs below") ), ketoconazole, and erythromycin There have been reports of reductions in the levels of the active metabolites of rifampin and fluconazole. The clinical value of these interactions has not been fully evaluated.
As with other drugs of the angiotensin II receptor blocker or similar effect, when administered with potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium supplements, salt substitutes containing potassium, which can lead to hyperkalemia
As with other drugs affecting sodium excretion, lithium excretion may also be reduced. Therefore, if lithium salts are used together with angiotensin II receptor blockers, serum lithium levels should be closely monitored.
Nonsteroidal anti-inflammatory drugs (NSAIDs) including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors) may reduce the effect of diuretics and other antihypertensive agents. Therefore, the antihypertensive effect of angiotensin II receptor blockers may be attenuated by NSAIDs, including selective COX-2 inhibitors.
In some patients with renal dysfunction (e.g. elderly or volume-depleted patients, including patients on diuretic therapy) who have been treated with nonsteroidal anti-inflammatory drugs including selective inhibitors of cyclooxygenase-2, concomitant use of angiotensin II receptor blockers may lead to further deterioration of renal function. These effects are usually reversible. Therefore, caution should be exercised when this combination is used in patients with impaired renal function.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) by the combination of angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with an increased risk of hypotension, syncope, and hyperkalemia, and changes in renal function (including acute renal failure) compared with monotherapy. Closely monitor blood pressure, renal function, and electrolytes in patients receiving Hyzaar and other drugs that affect RAAS. Concomitant use of aliskiren with Hyzaar in diabetic patients is contraindicated. Avoid the use of aliskiren with Hyzaar in patients with renal impairment (GFR <60mL/min).
When combined, the following drugs may interact with thiazide diuretics:
Alcohol, barbiturates, or narcotics: exacerbation of orthostatic hypotension.
Hypoglycaemic drugs (insulin and oral medications): dosage adjustment of hypoglycaemic drugs may be necessary.
Other antihypertensive agents: synergistic effects.
Cholestyramine and colestipol resin: reduce the absorption of hydrochlorothiazide in the presence of anion exchange resins. Single doses of cholestyramine or colestipol resin in combination with hydrochlorothiazide reduced gastrointestinal absorption of thiazides by 85% and 43%, respectively.
Corticosteroids, ACTH, or glycyrrhizin (found in licorice): increase electrolyte loss, especially hypokalemia.
Vasoconstrictor amines (e.g. adrenaline): may decrease response to vasoconstrictor amines, but there is insufficient evidence to discontinue use.
Non-depolarizing muscle relaxants (eg tubocurarine): may increase response to muscle relaxants.
Lithium: diuretics reduce renal clearance with lithium and pose a high risk of lithium toxicity, so the combination should not be used. Read the instructions for lithium use carefully before taking these products.
Nonsteroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2 inhibitors: in some people, taking non-steroidal anti-inflammatory drugs including selective cyclooxygenase-2 inhibitors will reduce the thiazide diuretic effect. , remove sodium and treat hypertension.
Interact with lab tests
Because of their effects on calcium metabolism, thiazides may interact with tests of parathyroid function.
The following adverse events are classified by system organ class and frequency according to the following convention: Very common: ≥1/10; Common: ≥1/100, <1/10; Uncommon: ≥1/1,000, <1/100; Rare: ≥1/10,000, <1/1,000; Very rare: <1/10,000; Unknown: cannot be judged from available data.
In clinical trials with losartan potassium and hydrochlorothiazide, no adverse reactions specific to this combination were observed. Adverse reactions were limited to those seen for losartan alone, and/or for hydrochlorothiazide alone.
In the controlled idiopathic hypertension clinical trial, dizziness was the only adverse event occurring with an incidence of 1% or slightly higher in the placebo group in patients treated with losartan and hydrochlorothiazide.
These adverse events are known for the individual components of this combination and are likely to occur with the losartan potassium/hydrochlorothiazide combination.
In controlled clinical trials, clinically significant changes in standard laboratory parameters were less likely to be associated with the use of Hyzaar. There were 0.7% of patients experiencing hyperkalemia (serum potassium >5.5 mEq/l), but in these trials, there was no need to discontinue Hyzaar due to hyperkalemia. ALT elevations are rare and usually reversible upon discontinuation of the drug.
Patients with a history of angioedema (swelling of the face, lips, throat, and/or tongue) should be monitored closely.
Lower blood pressure and decrease intravascular volume
Symptomatic hypotension, especially after the first dose, may occur in volume- and/or sodium-depleted patients due to potent diuretic therapy, dietary salt restriction, diarrhea, or vomiting. . These conditions need to be corrected before starting Hyzaar.
Electrolyte imbalances commonly occur in patients with renal failure, with or without diabetes, and should be addressed. Therefore, it is necessary to closely monitor the plasma potassium concentration and creatinine clearance, especially in patients with heart failure and creatinine clearance between 30-50mL/min.
Do not take potassium-sparing diuretics, potassium supplements, and salt substitutes containing potassium with losartan/hydrochlorothiazide.
Decreased liver function
Based on pharmacokinetic data showing significantly increased plasma concentrations of losartan in patients with cirrhosis, Hyzaar should be used with caution in patients with a history of mild to moderate hepatic impairment. There is no treatment experience with losartan in patients with severe hepatic impairment. Therefore, the use of Hyzaar is contraindicated in patients with severe hepatic impairment.
Decreased kidney function
As a consequence of inhibition of the renin-angiotensin-aldosterone system, changes in renal function have been reported, including renal failure (especially in patients with renal function dependent on the renin-angiotensin-aldosterone system). , such as patients with severe heart failure, or pre-existing renal dysfunction).
As with other drugs acting on the renin-angiotensin-aldosterone system, elevations in blood urea and serum creatinine have been reported in patients with bilateral renal artery stenosis or renal artery stenosis in individuals with only one kidney. This change in renal function is reversible upon discontinuation of the drug. Losartan should be used with caution in patients with bilateral renal artery stenosis or renal artery stenosis in patients with only one kidney.
There is no treatment experience in patients who have recently received a kidney transplant.
Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs acting through inhibition of the renin-angiotensin system. Therefore, Hyzaar should not be used in these patients.
Coronary heart disease and cerebrovascular disease
As with any antihypertensive agent, excessive hypotension in patients with ischemic cardiovascular disease and cerebrovascular disease can lead to myocardial infarction or stroke.
As with drugs that act on the renin-angiotensin system, there is a risk of severe arterial hypotension, and (often acute) renal failure in patients with heart failure, with or without renal failure.
Aortic and mitral stenosis, obstructive hypertrophic cardiomyopathy
As with other vasodilators, special caution should be exercised in patients with aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.
As observed for angiotensin-converting enzyme inhibitors, losartan and other angiotensin antagonists appear to be less effective in reducing blood pressure in blacks than in non-blacks, possibly because low renin levels are often It is more common in the black population to have hypertension.
Angiotensin II receptor antagonists (AIIRA) should not be used during pregnancy. Unless continuation of AIIRA therapy is deemed necessary, patients planning pregnancy should be switched to other antihypertensive therapy that has an established safety profile for use during pregnancy. pregnant. When pregnancy is detected, treatment with AIIRAs should be stopped immediately, and, if appropriate, an alternative therapy initiated.
Dual blocker of the renin-angiotensin-aldosterone system (RAAS)
There is evidence that concomitant use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of hypotension, hyperkalemia, and decreased renal function (including acute renal failure). Therefore, dual inhibition of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is not recommended.
If the dual blockade is considered absolutely necessary, it should be administered only under professional supervision and with frequent close monitoring of renal function, electrolytes, and blood pressure. Concomitant use of ACE inhibitors with angiotensin II receptor blockers is not recommended in patients with diabetic nephropathy.
Hypotension and fluid/electrolyte imbalance
As with all antihypertensive agents, symptomatic hypotension may occur in some patients. Patients should be observed for clinical signs of fluid or electrolyte imbalance such as volume depletion, hyponatremia, hypochloremic alkalosis, hypomagnesemia, or hypokalemia that may occur during diarrhea. or vomiting occurs again and again. Serum electrolytes should be tested regularly at appropriate intervals in these patients. Dilution-induced hyponatremia may occur in patients with edema in hot weather.
Metabolic and endocrine effects
Taking thiazides may decrease glucose tolerance. If necessary, adjust the dose of antidiabetic drugs, including insulin. Latent diabetes mellitus may manifest during thiazide treatment.
Thiazides may decrease urinary calcium excretion and cause mild and intermittent hypercalcemia. Marked hypercalcemia may be the result of latent hyperparathyroidism. Thiazides should be discontinued prior to conducting tests of parathyroid function.
Taking thiazide diuretics can increase cholesterol and triglycerides.
Thiazides may increase blood uric acid and/or cause gout in some people. Because losartan reduces blood uric acid, the combination of losartan and hydrochlorothiazide will reduce the increase in uric acid caused by this diuretic.
Thiazides should be used with caution in patients with impaired liver function or advanced liver disease, because of possible intrahepatic cholestasis, and because minor changes in fluid and electrolyte balance may precipitate hepatic coma.
Hyzaar is contraindicated in patients with severe hepatic impairment.
In patients taking thiazides, hypersensitivity reactions with or without a history of allergies or bronchial asthma have been reported. Exacerbations or activation of systemic lupus erythematosus has been reported following thiazide administration.
The drug contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase, or glucose-galactose malabsorption should not take this medicine.
Use in children
The safety and efficacy of the drug in children have not been established.
Newborns with a history of Hyzaar exposure in uero
If oliguria or hypotension occurs, direct attention should be paid to supporting blood pressure and renal perfusion. Transfusion or dialysis may be necessary as a means of reversing hypotension and/or replacing impaired renal function.
Use in the elderly
In clinical studies, no significant differences in the effectiveness and safety of Hyzaar were observed between the elderly (≥65 years of age) and younger subjects (<65 years of age).
According to the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, no conclusions could be made regarding benefit on cardiovascular morbidity and mortality from cardiovascular disease in the losartan group compared with the atenolol group in black patients with hypertension and left ventricular hypertrophy, although both BP-lowering effects were achieved in both treated black groups. Overall, in the LIFE population as a whole (n=9,193), in the losartan group, the composite of primary events, including cardiovascular mortality, stroke, and myocardial infarction, 13.0% reduction (p=0.021) compared with the atenolol group. In this study, compared with atenolol, losartan reduced the risk of cardiovascular disease and cardiovascular death in non-black hypertensive patients with left ventricular hypertrophy (n=8.660) as measured by variable Primary events included cardiovascular mortality, stroke, and myocardial infarction (p=0.003). However, in this study, black patients treated with atenolol had a lower risk of primary events than black patients treated with losartan (p=0.03). In the black subgroup (n=533; 6% in the LIFE study), there were 29 primary events among 263 patients treated with atenolol (11%, 25.9 per 1000 patient-years). ) and 46 primary events among 270 patients (17%, 41.8 per 1000 patient-years) treated with losartan.
Effects on ability to drive and use machinery
Studies on the effects on the ability to drive and use machines have not been conducted. However, when driving a vehicle or operating machinery, it should be borne in mind that dizziness or drowsiness may occur with antihypertensive therapy, especially at the start of treatment or when the dose is increased.
Do not store above 30°C. Store in original packaging to protect from light and moisture.
Presentation and packaging
Film-coated tablets: Box of 2 blisters x 15 tablets.