Losartan N tablets p / o 50 + 12.5mg, No. 30
Expiration Date: 05/2027
Russian Pharmacy name:
Лозартан Н таблетки п/о 50+12,5мг, №30
Ј Arterial hypertension (for patients for whom combination therapy is indicated);
Ј Reducing the risk of cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy.
The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.
I take it orally, regardless of the meal.
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.
Active ingredients:
losartan potassium - 50 mg,
hydrochlorothiazide - 12.5 mg
Excipients: lactose monohydrate (milk sugar) - 64.25 mg, microcrystalline cellulose - 47.5 mg, sodium carboxymethyl starch - 9.5 mg, povidone K25 - 3.8 mg, colloidal silicon dioxide - 0.95 mg, magnesium stearate - 1.5 mg.
The composition of the film shell: hypromellose - 2.9 mg, macrogol-4000 - 0.70 mg, titanium dioxide - 1.33 mg, iron dye yellow oxide - 0.07 mg.
Anuria;
severe renal failure (CC <30 ml / min);
severe liver dysfunction;
pregnancy;
lactation period (breastfeeding);
children and adolescents up to 18 years old;
hypersensitivity to drug components;
hypersensitivity to sulfonamide derivatives.
Carefully
Violations of the water and electrolyte balance of the blood (hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), bilateral stenosis of the renal arteries, stenosis of the artery of the only functioning kidney, condition after kidney transplantation, hypercalcemia, hyperuricemia and / or gout, aggravated allergic diseases, asthma connective tissue (including systemic lupus erythematosus), simultaneous use of NSAIDs, including COX-2 inhibitors, diabetes mellitus, liver dysfunction, renal dysfunction (CC from 30-50 ml / min), hypovolemia (including against the background of taking diuretics in high doses), an acute attack of angle-closure glaucoma.
Description:
Film-coated tablets of light yellow or light yellow color with a beige tint, round, biconvex; on the cross-section of the tablet, two layers are visible: an almost white core and a film shell.
Composition:
Active ingredients:
losartan potassium - 50 mg,
hydrochlorothiazide - 12.5 mg
Excipients: lactose monohydrate (milk sugar) - 64.25 mg, microcrystalline cellulose - 47.5 mg, sodium carboxymethyl starch - 9.5 mg, povidone K25 - 3.8 mg, colloidal silicon dioxide - 0.95 mg, magnesium stearate - 1.5 mg.
The composition of the film shell: hypromellose - 2.9 mg, macrogol-4000 - 0.70 mg, titanium dioxide - 1.33 mg, iron dye yellow oxide - 0.07 mg.
Clinical and pharmacological group: Antihypertensive drug
Pharmaco-therapeutic group: Antihypertensive combined agent (angiotensin II receptor blocker + diuretic)
pharmachologic effect
Combined antihypertensive agent. Losartan and hydrochlorothiazide have an additive antihypertensive effect, lowering blood pressure to a greater extent than each of the components alone.
Losartanis a selective antagonist of angiotensin II receptors (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 AT2 receptors 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 OPSS, 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 the 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 they are used with 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 of losartan is 34 liters. Very poorly penetrates the BBB.
Losartan is metabolized to form an active (E-3174) metabolite (14%) and inactive, 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, the absorption of hydrochlorothiazide is 60-80%. Cmax in blood plasma is achieved 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
Ј Arterial hypertension (for patients for whom combination therapy is indicated);
Ј Reducing the risk of cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy.
Dosage regimen
The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.
I take it orally, regardless of the meal.
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.
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, 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 - II degree AV block, 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.
On the part of 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 the activity of ACT and the concentration of bilirubin.
Contraindications for use
Anuria;
severe renal failure (CC <30 ml / min);
severe liver dysfunction;
pregnancy;
lactation period (breastfeeding);
children and adolescents up to 18 years old;
hypersensitivity to drug components;
hypersensitivity to sulfonamide derivatives.
Carefully
Violations of the water and electrolyte balance of the blood (hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), bilateral stenosis of the renal arteries, stenosis of the artery of the only functioning kidney, condition after kidney transplantation, hypercalcemia, hyperuricemia and / or gout, aggravated allergic diseases, asthma connective tissue (including systemic lupus erythematosus), simultaneous use of NSAIDs, including COX-2 inhibitors, diabetes mellitus, liver dysfunction, renal dysfunction (CC from 30-50 ml / min), hypovolemia (including against the background of taking diuretics in high doses), an acute attack of angle-closure glaucoma.
Application during pregnancy and lactation
Use during pregnancy and lactation (breastfeeding) is contraindicated.
Application for violations of liver function
Contraindicated in severe liver dysfunction.
With caution for mild and moderate liver dysfunctions.
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).
Application 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
Against the background of the use of losartan, reversible renal dysfunction, including renal failure, which disappear after losartan is discontinued, are possible. Drugs affecting 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 levels 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, monitoring of the content of electrolytes in the blood plasma is necessary.
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 interactions
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.
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ѕри одновременном применении с тиазидными диуретиками такие лекарственные средства, как этанол, барбитураты и опиоидные анальгетики могут потенцировать риск развити¤ ортостатической гипотензии.
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ѕри одновременном применении с другими гипотензивными средствами - аддитивный эффект.
¬сасывание гидрохлоротиазида нарушаетс¤ в присутствии колестирамина и колестипола.
ѕри одновременном применении с v —, ј “v наблюдаетс¤ выраженное снижение содержани¤ электролитов, в частности гипокалиеми¤.
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vидрохлоротиазид усиливает эффект миорелаксантов недепол¤ризующего типа действи¤ (например, тубокурарина хлорида).
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ѕрепараты, примен¤емые дл¤ лечени¤ подагры (пробенецид, сульфинпиразон и аллопуринол): гидрохлоротиазид способен повышать сывороточную концентрацию мочевой кислоты, поэтому может потребоватьс¤ коррекци¤ дозы препаратов урикозурического действи¤ - повышение дозы пробенецида или сульфинпиразона. ќдновременное применение тиазидных диуретиков может повышать частоту реакций повышенной чувствительности к аллопуринолу.
ќдновременное применение с циклоспорином может повышать риск развити¤ гиперурикемии и привести к обострению течени¤ подагры.
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“иазидные диуретики могут снижать почечную экскрецию цитотоксических препаратов (циклофосфамид, метотрексат) и усиливать их миелосупрессивный эффект.
¬ случае применени¤ салицилатов в высоких дозах гидрохлоротиазид может усиливать их токсическое воздействие на ?Ќ—.
»меютс¤ ограниченные данные о развитии гемолитической анемии при одновременном применении гидрохлоротиазида и метилдопы.
¬ызванна¤ тиазидными диуретиками гипокалиеми¤ или гипомагниеми¤ может приводить к развитию аритмии на фоне применени¤ сердечных гликозидов.
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