Lozartan / Hydrochlorothiazide-Teva - instructions for use, dose, side effects, contraindications

Tablets 50 mg + 12.5 mg. 1 tablet contains: active substances: hydrochlorothiazide 12.5 mg, potassium losartan 50.0 mg; Excipients: lactose monohydrate 135.0 mg, microcrystalline cellulose 40.0 mg, pregelatinized starch 10.5 mg, magnesium stearate 2.0 mg; shell: Opadrai II 85F32410 yellow 8.0 mg (polyvinyl alcohol (partially hydrolyzed) 3,200 mg, titanium dioxide (E 171) 1,880 mg, macrogol-3350 1,616 mg, talc 1,184 mg, iron oxide yellow oxide (E 172) 0.120 mg).

Tablets of 100 mg + 25 mg. 1 tablet contains: active substances: hydrochlorothiazide 25.0 mg, potassium losartan 100.0 mg; Excipients: lactose monohydrate 270.0 mg, microcrystalline cellulose 80.0 mg, pregelatinized starch 21.0 mg, magnesium stearate 4.0 mg; shell: Opadrai II 85F32410 yellow 16.0 mg (polyvinyl alcohol (partially hydrolyzed) 6,400 mg, titanium dioxide (E 171) 3,760 mg, macrogol-3350 3,232 mg, talc 2,368 mg, ferric oxide yellow oxide (E 172) 0.240 mg).

Description:

Tablets 50 mg + 12.5 mg.

Oval biconvex tablets, covered with a film coating of yellow color, with a risk

on both sides and engraved "5" and "0" on one side. On the cross-section - the core is white or almost white.

Tablets of 100 mg + 25 mg.

Oval biconvex tablets, covered with a film coating of yellow color, with a risk

on both sides and engraved "1" and "00" on one side. On the cross-section - the core is white or almost white.

Pharmacotherapeutic group:hypotensive combined agent (angiotensin II receptor antagonist [ARA II] + diuretic).

ATX: & nbsp

C.09.D.A.01 Losartan in combination with diuretics

Pharmacodynamics:

Losartan / Hydrochlorothiazide-Teva combined antihypertensive drug with fixed doses of active components.

The active substances of the combination losartan / hydrochlorothiazide have an additive antihypertensive effect, reducing blood pressure (BP) more than each of the components individually. Due to the diuretic effect hydrochlorothiazide increases the activity of renin of blood plasma (ARP), stimulates the secretion of aldosterone, increases the concentration of angiotensin II and reduces the potassium content in the blood serum. The administration of losartan blocks all the physiological effects of angiotensin II and suppression effects

aldosterone helps to reduce the loss of potassium caused by the intake of a diuretic.

Losartan has a moderate and transient uricosuric effect.

Hydrochlorothiazide causes a slight increase in the concentration of uric acid in the blood; The combination of losartan and hydrochlorothiazide helps reduce the severity of hyperuricemia caused by a diuretic.

Losartan - Angiotensin II receptor antagonist (APA). Losartan and its pharmacologically active metabolite (E 3174) both in vitro and in vivo block all the physiological effects of angiotensin II, regardless of the source or route of synthesis. Losartan selectively binds to AT1 receptors and does not bind or block receptors of other hormones and ion channels that play an important role in regulating the function of the cardiovascular system. Besides, losartan does not inhibit the angiotensin-converting enzyme (ACE) -cininase II, and therefore does not interfere with the destruction of bradykinin, therefore side effects mediated by bradykinin (eg, angioedema) are rare.

When using losartan, the absence of negative feedback influence on renin secretion leads to an increase in ARP. Increased ARP leads to an increase in angiotensin II in blood plasma.However, antihypertensive activity and a decrease in plasma aldosterone concentration persist, indicating an effective blockade receptors of angiotensin II. Losartan and its active metabolite have a greater affinity for the angiotensin I receptors than for angiotensin II receptors. The active metabolite is 10-40 times more active than losartan. After a single oral intake, the antihypertensive effect (a decrease in systolic and diastolic blood pressure) peaks at 6 hours, then gradually decreases within 24 hours. The maximum antihypertensive effect develops in 3-6 weeks after the start of the drug.

The concentration of losartan and its active metabolite in the blood plasma, as well as the antihypertensive effect of losartan increase with increasing dose of the drug. As losartan and its active metabolite are antagonists of angiotensin II receptors, both of which contribute to the antihypertensive effect. Losartan does not affect vegetative reflexes and does not have a lasting effect on the concentration of noradrenaline in the blood plasma.

In patients with hypertension and left ventricular hypertrophy losartan, often in combination with hydrochlorothiazide, reduces the risk of cardiovascular morbidity and mortality.

Hydrochlorothiazide. The mechanism of hypotensive action of thiazide diuretics is unknown. Thiazide diuretics do not affect normal BP.

Hydrochlorothiazide is a diuretic and antihypertensive agent. It affects the reabsorption of electrolytes in the distal tubules of the kidneys. Hydrochlorothiazide approximately equally increases the excretion of sodium and chloride. Excretion of sodium can be accompanied by a small loss of potassium ions, bicarbonates and a delay in calcium ions in the body. When administered, the diuretic effect begins after 2 hours, reaches a maximum on average 4 hours and lasts from 6 to 12 hours.

Pharmacokinetics:

Pharmacokinetics losartan and hydrochlorothiazide with simultaneous reception does not differ from that for their separate application.

Suction

Losartan. Ingestion losartan is well absorbed from the gastrointestinal tract (GIT), is metabolized by "primary passage" through the liver, resulting in the formation of an active carboxylated metabolite and inactivemetabolites. Systemic bioavailability of losartan in the form of tablets is about 33%. The maximum concentration (C_m_Oh) in the blood plasma of losartan and its active metabolite are achieved after 1 h and 3-4 h, respectively. When losartan was taken during a meal, there was no clinically significant effect on the profile of losartan concentration in the blood plasma.

Hydrochlorothiazide. After ingestion, it is incomplete, but rather quickly absorbed from the digestive tract. 60-80%) of the dose is absorbed from the digestive tract. Time to reach C_m_Oh in blood plasma - 1,5-3 hours.

Distribution

Losartan. The binding of losartan and its active metabolite to blood plasma proteins (mainly albumin) is more than 99%. The volume of distribution is 34 liters. Studies in rats have shown that losartan practically does not penetrate the blood-brain barrier (BBB).

Hydrochlorothiazide. It penetrates the hematoplacental barrier, it is excreted into breast milk. Does not penetrate the BBB.

Metabolism

Losartan. After oral administration and intravenous (iv) administration of losartan, labeled with an isotope ¹⁴C, the radioactivity of the circulating blood plasma is associated with the presence in it of losartan and its active metabolite.

In addition to the active metabolite, biologically inactive are formed, incl.two major metabolites, formed as a result of the hydroxylation of the butyl side chain, and one secondary - N-2-tetrazole-glucuronide.

Hydrochlorothiazide.

Slightly is metabolized in the liver. At least 61% of the ingested dose is excreted unchanged for 24 hours.

Excretion

Losartan. The plasma clearance of losartan and its active metabolite is about 600 ml / min and 50 ml / min, respectively. The renal clearance of losartan and its active metabolite is approximately 74 ml / min and 26 ml / min, respectively. After oral administration losartan is excreted by the kidneys - about 4% unchanged and about 6% of the dose in the form of an active metabolite. After oral administration, the concentration of losartan and its active metabolite in the blood plasma is reduced polyexponentially with a finite half-life (T_1/2) about 2 hours and 6-9 hours, respectively.

With a single dose of 100 mg losartan, nor its active metabolite significantly accumulate in the blood plasma.

The excretion of losartan and its metabolites occurs through the intestine with bile and kidneys. In healthy volunteers after ingestion of losartan labeled with an isotope ¹⁴C, about 35% of the radioactive label is found in urine and 58% in feces.

Hydrochlorothiazide. Quickly excreted by the kidneys. T_1/2 ranged from 5.6 to 14.8 hours. At least 61% of the dose taken orally is excreted unchanged for 24 hours.

Pharmacokinetics in special clinical cases. The concentrations of losartan and its active metabolite in blood plasma and the rate of absorption of hydrochlorothiazide in elderly patients with hypertension do not differ significantly from these indices in young patients with arterial hypertension. In patients with mild and moderate alcoholic cirrhosis of the liver, when taking the drug inside the concentration of losartan and its active metabolite in the blood plasma were respectively 5 and 1.7 times higher than in young male volunteers. Concentrations of losartan in blood plasma were 2 times higher in women with arterial hypertension compared with men with arterial hypertension. This apparent pharmacokinetic difference is not clinically significant. The concentrations of active metabolite in men and women did not differ.

With a creatinine clearance (CK) of more than 10 ml / min, the concentration of losartan in the blood plasma does not differ from that with normal kidney function.In patients on hemodialysis, the area under the concentration-time curve (AUC) losartan is approximately 2 times greater than in patients with normal renal function. The plasma concentrations of the active metabolite of losartan do not change in patients with impaired renal function or patients on hemodialysis. Losartan and its active metabolite can not be removed by hemodialysis.

Indications:

Arterial hypertension (patients who are shown combined therapy). Reduced risk of associated cardiovascular morbidity and mortality in patients with hypertension and hypertrophy left The ventricle, manifested by a cumulative reduction in the incidence of cardiovascular mortality, the incidence of stroke and myocardial infarction.

Contraindications:

Hypersensitivity to any of the components of the drug (as well as increased sensitivity to other drugs that are derivatives of sulfonamide); pregnancy; period breastfeeding; anuria; severe renal dysfunction (CC less than 30 ml / min); patients on hemodialysis; severe violations of the liver (more than 9 points on the scale Child-Pugh), cholestasis, refractory hypokalemia, symptomatic increase in the concentration of uric acid in the blood plasma, dehydration, children under 18 years. primary hyperaldosteronism; simultaneous use with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus and / or renal dysfunction (GFR less than 60 ml / mi / 1.73 m2) (see Interaction with other medicinal means);

lactose intolerance; deficiency of lactase; glucose-galactose malabsorption syndrome.

Carefully:Violations of the water-electrolyte balance (VEB) (decrease in the volume of circulating blood (BCC), hyponatremia, hypochloraemic alkalosis, hypomagnesemia, hypokalemia) that can develop against intercurrent diarrhea or vomiting; impaired renal function (QC more than 30 ml / min); violations of the liver (less than 9 points on the scale Child-Pugh); cardiac ischemia; cerebrovascular diseases; aortic stenosis; mitral stenosis; hypertrophic obstructive cardiomyopathy (GOKMP); bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney; diabetes; hypercalcemia, hyperuricemia and / or gout; weighed allergicanamnesis (in some patients angioedema has developed earlier with other medications, including ACE inhibitors); bronchial asthma; systemic connective tissue diseases, incl. systemic lupus erythematosus (SLE); hypovolaemia, incl. against a background of high doses of diuretics; and also with simultaneous administration with non-steroidal anti-inflammatory drugs (NSAIDs), incl. with inhibitors of cyclooxygenase-2 (COX-2).

Pregnancy and lactation:

Application Lozartan / Hydrochlorothiazide-Teva when pregnancy is contraindicated. It is known that drugs acting directly on the renin-angiotensin-aldosterone system (RAAS), when used in the II and III trimesters of pregnancy can cause developmental defects or even death of the developing fetus. Therefore, when diagnosing a pregnancy, the drug Lozartan / Hydrochlorothiazide-Teva should be discontinued as soon as possible. Women of reproductive age in the planning of pregnancy recommended the use of antihypertensive drugs with an established safety profile. As a result,that thiazide diuretics penetrate the hematoplacental barrier, their use in pregnant women is not recommended, as the risk of development of such adverse effects in the mother and fetus as embryonic jaundice, thrombocytopenia, VEB disturbances increases. Diuretics do not prevent the development of toxicosis of pregnancy, while there is no convincing evidence that they have a positive effect on the course of toxicosis. It is not known whether losartan with breast milk. Hydrochlorothiazide excreted in breast milk. The drug Losartan / Hydrochlorothiazide-Teva is contraindicated for use during breastfeeding.

Dosing and Administration:

Inside, regardless of food intake, with enough water. The initial and maintenance dose is 1 tablet of 50 mg + 12.5 mg once a day. For patients who can not achieve adequate control of blood pressure, the dose can be increased - 1 tablet of 100 mg + 25 mg once a day.

The maximum dose is 1 tablet of 100 mg + 25 mg once a day.

The maximum antihypertensive effect in most cases is achieved within 3-4 weeks from the start of treatment.In elderly patients, correction of the initial doses preparation

Losartan / Hydrochlorothiazide-Teva not required.

Lozartan / Hydrochlorothiazide-Teva is not recommended for use in patients under 18 years of age due to lack of efficacy and safety data for this age group.

Patients with moderate renal insufficiency (KK 30-50 ml / min) correction of the initial dose is not required.

Side effects:

In clinical studies with losartan / hydrochlorothiazide, no adverse events specific to this combination drug have been observed.

Undesirable effects were limited to those reported earlier with losartan and / or hydrochlorothiazide in monotherapy.

The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%, including isolated cases.

Losartan

From the side of the blood and lymphatic system: rarely - reduction of hemoglobin, decrease in hematocrit; very rarely oppression of bone marrow function, anemia, thrombocytopenia. leukopenia, neutropenia.agranulocytosis, hemolytic anemia, lymphadenopathy, eosinophilia.

From the endocrine system: rarely - a syndrome of inadequate secretion

antidiuretic hormone.

From the nervous system: often - headache, dizziness, fainting; infrequently - insomnia, anxiety, anxiety, confusion, depression, sleep disorder, drowsiness; rarely - memory impairment, paresthesia, peripheral neuropathy, tremor, migraine; an unknown frequency is dysgeusia.

From the side of the organ of vision: rarely - visual impairment, conjunctivitis, decreased visual acuity, a feeling of dryness and burning sensation in the eyes.

From the side of the hearing organ and labyrinthine disorders: infrequently - vertigo, noise in the ears.

From the cardiovascular system: often - marked decrease in blood pressure, orthostatic hypotension; infrequently - pain in the chest, stenocardia,

atrioventricular blockade of the II degree, cerebral blood flow disorder, myocardial infarction, palpitation, arrhythmia (atrial fibrillation, sinus bradycardia, tachycardia, ventricular fibrillation); unknown frequency, dose-dependent orthostatic effects.

From the respiratory system, chest and mediastinum: often - cough; infrequently - a rhinitis, zalozhennost a nose; very rarely - sinusitis, pharyngitis, laryngitis, dyspnea, bronchitis.

From the digestive system: often - nausea, diarrhea; infrequently - abdominal pain, constipation; rarely dryness of the oral mucosa. toothache, flatulence, vomiting, gastritis; very rarely - pancreatitis.

From the liver and bile ducts: infrequently - increased activity of "liver" transaminases, increased bilirubin concentration; very rarely - hepatitis.

From the skin and subcutaneous tissues: rarely - alopecia, psoriasis, dermatitis, dry skin; very rarely - pseudolymphoma.

Allergic reactions: infrequently - skin rash, itchy skin; rarely angioedema, swelling of the face, limbs, lips, tongue, vocal cords and / or larynx, dysphonia, urticaria; very rarely toxic epidermal necrolysis, Stevens-Johnson syndrome. erythema multiforme, photosensitivity.

From the side of the musculoskeletal and connective tissue: often - muscle spasm, back pain, leg pain, myalgia; infrequently - pain in the hands, arthralgia, musculoskeletal pain, stiffness and swelling of the joints.

From the urinary system: often - renal dysfunction; rarely uremia, acute renal failure; very rarely - oliguria, anuria.

On the part of the reproductive system: infrequently - impotence; rarely - gynecomastia.

Other: often - asthenia, fatigue, hyperkalemia; infrequent - increased body temperature, a slight increase in the concentration of urea and creatinine, hyperkalemia; rarely hyponatremia; very rarely - hyperglycemia, epistaxis, vasculitis. Hydrochlorothiazide

From the side of the blood and lymphatic system: rarely - non-neutropenia, agranulocytosis, thrombocytopenia,

aplastic anemia, hemolytic anemia, leukopenia, oppression of bone marrow function.

From the side of metabolism and nutrition: infrequently - aporexia, hyperglycemia, hyperuricemia, hypokalemia, hyponatremia, increased concentration of cholesterol and triglycerides, gout.

From the nervous system: often - depression, sleep disturbance; infrequently insomnia, paresthesia, dizziness.

From the side of the organ of vision: rarely transient focalization, xanthopsia.

From the organ of hearing: rarely - vertigo.

From the cardiovascular system: rarely - orthostatic hypotension.

From the respiratory system, chest and mediastinum: infrequently - respiratory distress syndrome, pneumonitis, pulmonary edema.

From the digestive system: rarely - sialadenitis, constipation, diarrhea, irritation of the gastrointestinal mucosa; very rarely - pancreatitis.

From the liver and bile ducts: infrequently, jaundice (intrahepatic cholestasis).

From the skin and subcutaneous tissues: rarely - photosensitivity; very rarely - urticaria, toxic epidermal necrolysis. Lyell's syndrome; unknown frequency - lupus-like erythema.

From the side of the musculoskeletal and connective tissue: infrequently - muscular spasm.

From the urinary system: infrequently - glucosuria, interstitial nephritis, renal failure.

Other: infrequently - fever, hyperkalemia. vasculitis.

Overdose:

Data on the specific treatment of an overdose there is no combination of losartan / hydrochlorothiazide. In case of an overdose, the drug Lozartan / Hydrochlorothiazide-Teva should be discontinued, the patient should ensure careful monitoring of vital signs, symptomatic therapy - induction of vomiting in If the drug is taken recently, as well as eliminating dehydration, electrolyte disorders, hepatic coma, and lowering blood pressure by standard methods.

Losartan. Data on the overdose of losartan in humans are limited.

The most likely symptoms overdose are a pronounced decrease in blood pressure and tachycardia; Bradycardia can be a consequence of parasympathetic (vagal) stimulation.

Treatment: In the case of a marked decrease in blood pressure, maintenance therapy is indicated. Losartan and its active metabolite are not excreted by hemodialysis.

Hydrochlorothiazide. The most frequent symptoms overdoses of hydrochlorothiazide are a consequence of a deficiency of electrolytes (hypokalemia, hypochloraemia,

hyponatremia) and dehydration due to excessive diuresis. With the simultaneous administration of cardiac glycosides, hypokalemia can aggravate the course of arrhythmias. It is not established to what extent

Hydrochlorothiazide can be removed from the body by hemodialysis.

Interaction:

Losartan. In clinical studies of pharmacokinetics, there was no clinically significant interaction of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine,phenobarbital, ketoconazole and erythromycin. According to reports, rifampicin and fluconazole reduce the concentration of the active metabolite, the clinical significance of this interaction has not been studied. The combination of losartan. as well as other agents blocking angiotensin II or its effects, with potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride, eplerenone (a derivative of spironolactone)), potassium-containing additives or potassium salts can lead to an increase in potassium in the blood serum.

If losartan is used simultaneously with lithium preparations, care should be taken because of a possible decrease in lithium excretion. NSAIDs, incl. selective inhibitors of COX-2, can reduce the effect of diuretics and other antihypertensive drugs. Therefore, the antihypertensive effect of angiotensin II receptor antagonists can be weakened by simultaneous application with NSAIDs (including COX-2 inhibitors). In some patients with impaired renal function (eg, elderly patients or patients with reduced BCC, including those receiving diuretics) who have received NSAID therapy (including COX-2 inhibitors),treatment with angiotensin II receptor antagonists or ACE inhibitors may cause further impairment of renal function, including acute renal failure (ARF), which is usually reversible.

The cases of double blockade of RAAS (for example, with simultaneous use of an ACE inhibitor, angiotensin II receptor antagonist or aliskiren) in patients with diagnosed atherosclerosis, heart failure, diabetes were more often accompanied by a marked decrease in blood pressure, syncope, hyperkalemia and renal dysfunction (including acute renal failure) compared with the use of one of the drugs that affects RAAS. With simultaneous use with tricyclic antidepressants, haloperidol. clopromazine, sulpiride. baclofen, amifostine increases the risk of a sharp decrease in blood pressure.

Hydrochlorothiazide. With simultaneous use of thiazide diuretics with barbiturates, narcotics analgesics, ethanol may increase the risk of developing orthostatic arterial hypotension. With simultaneous application, dose adjustment may be required hypoglycemic agents (for ingestion and insulin).In view of the risk of developing lactic acidosis due to possible renal dysfunction with hydrochlorothiazide metformin should be used with caution.

When hydrochlorothiazide is used with other antihypertensive agents, an additive effect is observed. In the presence of anion-exchange resins, hydrochlorothiazide absorption is impaired. Kolestyramine or colestipol in single doses bind hydrochlorothiazide and reduce its absorption from the digestive tract by 85% and 43%, respectively.

The use of glucocorticosteroids, adrenocorticotropic hormone leads to a marked decrease in the electrolyte content, in particular, can cause hypokalemia.

It is possible to reduce the response to the introduction of pressor amines (eg, epinephrine).

It is possible to enhance the action of muscle relaxants of the non-depolarizing action type (for example, tubocurarine chloride).

Diuretics reduce renal clearance of lithium and increase the risk of its toxic effects; the combined use of diuretics and lithium preparations is not recommended.

In some cases, the use of NSAIDs (including selective inhibitors of COX-2) can reduce diuretic, natriuretic and antihypertensive effects of diuretics.In connection with the effect of thiazide diuretics on calcium metabolism, their administration may distort the results of the investigation of parathyroid gland function.

With simultaneous use with atropine, biperidenum, the bioavailability of thiazide diuretics increases due to decreased gastrointestinal motility and gastric emptying rate.

With simultaneous use, thiazide diuretics reduce renal excretion of methotrexate, cyclophosphamide and enhance their myelosuppressive effect. Thiazide diuretics can increase the toxic effects of salicylates on the central nervous system when used in high doses. Individual cases of development of hemolytic anemia with simultaneous use of thiazide diuretics and methyldopa have been reported.

With simultaneous application with cyclosporine, the likelihood of developing hyperuricemia and gout increases. Hypokalemia, like hyponatremia, caused by the use of thiazide diuretics, increases the risk of arrhythmias with concomitant use with cardiac glycosides.

Simultaneous use of thiazide diuretics with antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, ibutilide), some antipsychotic drugs (thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, amisulpride, sultopride, sulpiride, tiapride, limoside, haloperidol, droperidol) and other drugs (bepridil, cisapride, difemanyl, erythromycin. halofantrine, misolastine, pentamidine, terfenadine, wincamine, pentamidine) may be accompanied by the development of hypokalemia, which, in turn, can cause the development of piruet-type arrhythmias.

With simultaneous application with calcium preparations, there is a possibility of hypercalcemia, therefore it is necessary to control the calcium content in the blood serum. With simultaneous use with carbamazepine, there is a risk of developing hyponatremia.

With the development of dehydration against the background of the use of thiazide diuretics, there is a possibility of developing acute renal failure, especially with simultaneous application with iodine preparations.

Special instructions:Patients with an angioneurotic edema in the anamnesis (in general and in addition to the use of ACE inhibitors and ARA II) require careful monitoring.There have been reports that a number of patients taking Losartan / Hydrochlorothiazide-Teva, because of the suppression of the function of RAAS, observed changes in kidney function, including renal failure; these changes were reversible and disappeared after the abolition of therapy.

Like other agents that affect RAAS, application of preparation

Lozartan / hydrochlorothiazide-Teva in patients with bilateral renal artery stenosis and stenosis of the artery of a single kidney can lead to an increase in the concentration of urea and creatinine in the serum. These changes in kidney function were reversible and disappeared after therapy was discontinued. Simultaneous use of ACE inhibitors. ARA II or aliskiren increases the risk of developing arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure). Double blockade of RAAS with the use of ACE inhibitors. ARA II or aliskiren is not recommended (see section "Interaction with other drugs.") If a double blockade of RAAS is considered absolutely necessary, the treatment should only be performed under the supervision of specialists and should be accompanied by a thorough and regular monitoring of kidney function, electrolyte content and blood pressure.ACE inhibitors and ARA II should not be used simultaneously in patients with diabetic nephropathy. During treatment with the drug Losartan / Hydrochlorothiazide-Teva, as with any antihypertensive therapy, there may be a marked decrease in blood pressure. Patients should be examined for clinical signs of a reduction in bcc and water-electrolyte balance disorders, including hyponatremia, hypochloraemic alkalosis, hypomagnesemia, or hypokalemia that may occur as a result of diarrhea or vomiting, as a result of diuretic therapy, while limiting intake of table salt. Such patients need control of the content of electrolytes in the blood serum. Simultaneous use with potassium preparations, potassium-sparing diuretics is not recommended (see section "Interaction with other drugs"). In patients with impaired hepatic function (less than 9 on the Child-Pugh scale), the drug Losartan / Hydrochlorothiazide-Teva should be used with caution, since even minor disturbances of the water-electrolyte balance can lead to the development of hepatic coma. Have patients from primary hyperaldosteronism use of antihypertensive drugs that act on the RAAS, including drug Losartan / Hydrochlorothiazide Teva-ineffective.

The sharp decrease in blood pressure when therapy with Losartan / Hydrochlorothiazide Teva, as for the treatment of other antihypertensive drugs in patients with ischemic cardiovascular and

cerebrovascular diseases can lead to the development of myocardial infarction or stroke.

In patients with heart failure as a failure of kidney function, and without it, the use of the drug Losartan / Hydrochlorothiazide Teva-how and other means of acting on the RAAS, increases the risk of a sharp decline in blood pressure and the development of acute renal failure. Care should be taken when applying preparation

Losartan / Hydrochlorothiazide Teva, in patients with aortic stenosis, mitral stenosis and GOKMP.

Therapy drug Losartan / Hydrochlorothiazide-Teva can lead to impaired glucose tolerance. In some cases, it may be necessary to correct the dose of hypoglycemic agents (including insulin).

Application Lozartan / Hydrochlorothiazide-Teva can reduce the excretion of calcium by the kidneys and cause an episodic and insignificant increase in the serum calcium level. Expressed hypercalcemia may indicate about latent hyperparathyroidism.

The drug Losartan / Hydrochlorothiazide-Teva should be discontinued before examining the functions of parathyroid glands.

An increase in the concentration of cholesterol and triglycerides in blood plasma can also be associated with the use of the drug Losartan / Hydrochlorothiazide-Teva. In some patients, taking Losartan / Hydrochlorothiazide-Teva may lead to hyperuricemia and / or exacerbation of gout. Because the losartan reduces the concentration of uric acid, its combination with hydrochlorothiazide reduces the severity of hyperuricemia caused by a diuretic.

In patients receiving the drug Losartan / Hydrochlorothiazide-Teva. reactions of hypersensitivity can be observed even in the absence of an indication of the presence of an allergy or bronchial asthma in an anamnesis. There are reports of the development of exacerbation or progression of SLE in the presence of thiazide diuretics.

It should be borne in mind that angiotensin II receptor antagonists, including losartan, are less effective for the treatment of hypertension when used in patients of the Negroid race than in other patients.

When admission The drug Lozartan / Hydrochlorothiazide-Teva can be obtained a positive result in doping control, tk. it includes hydrochlorothiazide.

Effect on the ability to drive transp. cf. and fur:When using the drug Losartan / Hydrochlorothiazide-Teva, caution should be exercised when driving vehicles and working with machinery requiring increased attention and speed of psychomotor reactions, due to the possible development of unwanted side effects from the nervous system (dizziness, drowsiness).

Form release / dosage:

Tablets, film-coated 50 mg + 12.5 mg, 100 mg + 25 mg.

Packaging:

For 7 tablets in a blister of PVC / PE / PVDC and aluminum foil or PVC / Aklar and aluminum foil. 2, 4, 8 or 12 blisters together with instructions for use in a cardboard box.

For 10 tablets in a blister of PVC / PE / PVDC and aluminum foil or PVC / Aklar and aluminum foil. 3, 5, 6, 9 or 28 blisters together with instructions for use in a cardboard box.

For 14 tablets in a blister of PVC / PE / PVDC and aluminum foil or PVC / Aklar and aluminum foil. 1, 2, 4 or 6 blisters together with instructions for use in a cardboard box.

Storage conditions:Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001671

Date of registration:20.04.2012

Date of cancellation:2017-04-20

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Works Private, Ltd. Co. Hungary

Representation: & nbspTeva Teva Israel

Information update date: & nbsp23.12.2015

Illustrated instructions

Instructions

Losartan / Hydrochlorothiazide-Teva (Losartan / Hydrochlorothiazide-Teva)