Lorista ND - instructions for use, doses, side effects, contraindications

Active substances: hydrochlorothiazide 25.00 mg, potassium losartan 100.00 mg. Excipients: pregelatinized starch 69.84 mg, microcrystalline cellulose 175.40 mg, lactose monohydrate 126.26 mg, magnesium stearate 3.50 mg. SHELL FELT: hypromellose 10.00 mg, macrogol 4000 4000 mg, quinoline yellow (E104) dye 0.11 mg, titanium dioxide (E171) 2.89 mg, talc 1.00 mg.

Description:Oval, slightly biconvex tablets, covered with a film coat from yellow to yellow with a greenish tinge.

Pharmacotherapeutic group:hypotensive combined agent (angiotensin II receptor blocker + diuretic).

ATX: & nbsp

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

Pharmacodynamics:

Hydrochlorothiazide / losartan

Lorista ND is a combined preparation whose components have an additive antihypertensive effect and cause a more pronounced decrease in blood pressure (BP) compared to their separate use. Due to diuretic action hydrochlorothiazide increases the activity of renin plasma, aldosterone secretion, reduces serum potassium content and increases the concentration of angiotensin II in blood plasma. Losartan blocks the physiological effects of angiotensin II and by inhibiting the secretion of aldosterone can neutralize the loss of potassium ions caused by a diuretic. Losartan has a uricosuric effect. Hydrochlorothiazide causes a moderate increase in the concentration of uric acid, with the use of losartan simultaneously with hydrochlorothiazide decreases hyperuricemia caused by a diuretic. Antihypertensive effect combination hydrochlorothiazide / losartan persists for 24 hours. Despite a significant reduction in blood pressure, the use of combination hydrochlorothiazide / losartan has no clinically significant effect on the heart rate (heart rate). Combination hydrochlorothiazide / losartan is effective in men and women, as well as in patients younger (less than 65 years) and elderly (from 65 years and older) age.

Losartan

Losartan is an antagonist of angiotensin II receptors for ingestion of non-proteinaceous nature. Angiotensin II is a potent vasoconstrictor and the main hormone of the renin-angiotensin-aldosterone system (RAAS). Angiotensin II binds to AT1 receptors, which are found in many tissues (for example,vascular smooth muscle, adrenal gland, kidney and myocardium) and mediate the various biological effects of angiotensin II, including vasoconstriction and aldosterone release. In addition, angiotensin II stimulates proliferation of smooth muscle cells. Losartan selectively blocks AT1 receptors. In vivo and in vitro losartan and its biologically active carboxylic metabolite (EXP-3174) block all physiologically significant effects of angiotensin II on ATi-receptors, regardless of the route of its synthesis. Losartan does not possess agonism and does not block other hormonal receptors or ion channels that are important in the regulation of the cardiovascular system. Losartan does not suppress the activity of angiotensin-converting enzyme (ACE) (kininase II), which is involved in the metabolism of bradykinin. Accordingly, it does not cause an increase in the incidence of undesirable effects mediated by bradykinin.

Losartan indirectly causes the activation of AT2 receptors by increasing the concentration of angiotensin II in the blood plasma.

Suppression of regulation of renin secretion by angiotensin II by the mechanism of "negative feedback" in the treatment of losartan causes an increase in renin activity of blood plasma, which leads to an increase in the concentration of angiotensin II in blood plasma.However, the antihypertensive effect and suppression of aldosterone secretion persist, indicating an effective blockade of angiotensin II receptors. After cancellation of losartan, plasma renin activity and angiotensin II concentration decrease to initial values within 3 days.

Losartan and its main active metabolite have a significantly higher affinity for AT 1 receptors compared to AT2 receptors. The active metabolite is superior losartan by activity in 10 - 40 times. The frequency of cough development is comparable when applied losartan or hydrochlorothiazide and is significantly lower than with the use of an ACE inhibitor. In patients with arterial hypertension and proteinuria without diabetes mellitus, treatment with losartan significantly reduces proteinuria, albumin excretion and immunoglobulin G (IgG). Losartan supports glomerular filtration and reduces the filtration fraction. Losartan reduces the serum concentration of uric acid (usually less than 0.4 mg / dL) throughout the therapy. Losartan does not have an effect on vegetative reflexes and does not affect the concentration of noradrenaline in the blood plasma.

In patients with left ventricular failure losartan in doses of 25 mg and 50 mg has a positive hemodynamic and neurohumoral effects, characterized by an increase in the cardiac index and a decrease in the wedging pressure of pulmonary capillaries, a common peripheral vascular resistance (OPSS), mean blood pressure and heart rate and a decrease in plasma concentrations of aldosterone and norepinephrine. The risk of developing arterial hypotension in patients with heart failure depends on the dose of losartan. The use of losartan once a day in patients with mild and moderate essential hypertension causes a significant reduction in systolic and diastolic blood pressure. Antihypertensive action lasts for 24 hours while maintaining the natural circadian rhythm of blood pressure. The degree of BP decrease at the end of the dosing interval is 70-80% compared to the antihypertensive effect 5-6 hours after the administration of losartan.

Losartan is effective in men and women, as well as in elderly patients (65 years and older) and younger patients (under 65 years of age). The abolition of losartan in patients with arterial hypertension does not lead to a sharp increase in blood pressure (there is no "withdrawal" syndrome). Losartan does not have a clinically significant effect on heart rate.

Hydrochlorothiazide

Thiazide diuretic, the mechanism of antihypertensive action of which has not been finally established. Thiazides alter the reabsorption of electrolytes in the distal nephron and increase the excretion of sodium and chlorine ions approximately equally. The diuretic effect of hydrochlorothiazide leads to a decrease in the volume of circulating blood (BCC), an increase in plasma renin activity and aldosterone secretion, which leads to an increase in excretion of potassium and bicarbonate ions by the kidneys and a decrease in serum potassium content. The relationship between renin and aldosterone is mediated by angiotensin II, so the simultaneous use of an angiotensin II receptor antagonist suppresses the loss of potassium ions when treated with thiazide diuretics. After oral administration, the diuretic effect occurs after 2 hours, reaches a maximum in about 4 hours and persists for 6-12 hours; antihypertensive effect persists for 24 hours.

Pharmacokinetics:

The pharmacokinetics of losartan and hydrochlorothiazide at simultaneous reception does not differ from that at their separate application.

Suction

Losartan: after oral administration losartan well absorbed and metabolized under "primary pass through the liver with the formation of an active carboxyl metabolite (EXP-3174) and inactive metabolites.The systemic bioavailability is approximately 33% .The average maximum concentrations in blood plasma (C_m_Oh) of losartan and its active metabolite are achieved after 1 hour and 3-4 hours, respectively. Hydrochlorothiazide After oral intake of hydrochlorothiazide is 60-80%. FROM_m_Oh hydrochlorothiazide in blood plasma is achieved 1-5 hours after ingestion.

Distribution

Losartan: more than 99% of losartan and EXP-3174 binds to plasma proteins, mainly albumin. The volume of distribution of losartan is 34 liters. Very poorly penetrates the blood-brain barrier. Hydrochlorothiazide: the connection with plasma proteins is 64%; penetrates the placenta, but not through the blood-brain barrier and is excreted in breast milk.

Biotransformation

Losartan: approximately 14% of the dose of losartan administered intravenously orally is metabolized to form an active metabolite. After ingestion and / or intravenous administration ¹⁴C-losartan potassium, the circulating radioactivity of blood plasma was mainly determined by losartan and its active metabolite. In addition to the active metabolite, inactive metabolites are formed, including the two main metabolites formed by the hydroxylation of the butyl group of the chain, and the non-basic metabolite - N-2tetrazole glucuronide. The intake of the drug with food does not have a clinically significant effect on its serum concentrations. Hydrochlorothiazide not metabolized.

Excretion

Losartan: the plasma clearance of losartan and its active metabolite is 600 ml / min and 50 ml / min, respectively, the renal clearance of losartan and its active metabolite is 74 ml / min and 26 ml / min, respectively. After oral administration, only about 4% of the dose taken is excreted unchanged by the kidneys and about 6% - in the form of an active metabolite. Pharmacokinetic The parameters of losartan and its active metabolite when taken orally (in doses up to 200 mg) are linear. Half-life (T_1/2) of losartan and the active metabolite in the terminal phase of losartan and the active metabolite is 2 hours and 6-9 hours, respectively. Cumulation of losartan and its active metabolite when used in a dose of 100 mg once a day there. It is derived mainly through intestines with bile - 58%, kidneys - 35%. Hydrochlorothiazide: Quickly displayed through kidney. T1 / 2 is 5.6 - 14.8 hours. About 61% of the dose taken internally is excreted in unchanged form.

Pharmacokinetics of individual groups patients:

Hydrochlorothiazide / losartan: Plasma concentrations of losartan and its active metabolite and hydrochlorothiazide in elderly patients with arterial hypertension is not reliably differed from those in patients young age. Losartan: In patients with mild and moderate alcoholic cirrhosis after admission inside losartan, concentration of losartan and an active metabolite in the blood plasma were 5 and 1.7 times higher than in young of male volunteers, respectively. Lozartan and its active metabolite are not are removed during hemodialysis.

Indications:

- Arterial hypertension (patients who are shown combined therapy).

- Reducing the risk of cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy.

Contraindications:

- Hypersensitivity to losartan, hydrochlorothiazide and other derivatives of sulfonamide, as well as to auxiliary substances;

- Anuria, severe renal failure (creatinine clearance (CK) less than 30 ml / min.);

- Severe hepatic insufficiency, cholestasis and obstructive diseases of the biliary tract;

- Simultaneous use with aliskiren in patients with diabetes mellitus or renal dysfunction (CC less than 60 ml / min);

- Age to 18 years (efficacy and safety of use not established);

- Hypokalemia or hypercalcaemia resistant to therapy;

- Refractory hyponatremia;

- Pregnancy, the period of breastfeeding;

- Deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome, because loritis is included in the drug Lorista ND.

Carefully:

FROM caution: pronounced hyponatremia and / or condition, accompanied by a decrease in BCC (incl. diet with restriction of table salt, diarrhea, vomiting, high-dose therapy diuretics), water- Electrolyte blood balance, diabetes mellitus, renal failure (QC 30-50 ml / min), liver dysfunction light and moderate severity chronic heart failure (CHF) III-IV functional class according to the NYHA classification and other conditions accompanied by activation of RAAS, bilateral stenosis of the renal arteries or stenosis of the single kidney artery, condition after kidney transplantation, primary hyperaldosteronism, ischemic heart disease and cerebrovascular disease, since excessive decrease in blood pressure can lead to the development of myocardial infarction and stroke; Stenosis of the aortic and / or mitral valve, hypertrophic obstructive cardiomyopathy (GOKMP), a burdened allergic anamnesis (in some patients, angioedema was developed earlier with the administration of other drugs, including ACE inhibitors) and bronchial asthma, symptomatic hyperuricemia / gout, systemic lupus erythematosus , acute myopia and secondary acute closed angle glaucoma.

Pregnancy and lactation:

The use of angiotensin II receptor antagonists in the first trimester of pregnancy is not recommended. The drug Lorista® ND should not be used during pregnancy, as well as in women planning pregnancy. When planning pregnancy, it is recommended that the patient be transferred Alternative antihypertensive therapy taking into account the safety profile. In case of pregnancy, stop taking Lorista® ND and, if necessary, translate to alternative hypotensive therapy. The drug Lorista® ND, as well as other agents having a direct effect on RAAS, can cause undesirable effects in the fetus (impaired renal function, delayed ossification of the fetal bones, oligihydramnion) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia). If nevertheless used the drug in II-III trimesters of pregnancy, it is necessary to conduct ultrasound examination of the kidneys and bones of the fetal skull.

Hydrochlorothiazide penetrates the placenta. With the use of thiazide diuretics in II-III trimester of pregnancy may reduce uteroplacental blood flow, the development of thrombocytopenia, jaundice, violations of water-electrolyte balance in the fetus or newborn.

Hydrochlorothiazide should not be used for treatment gestosis of the second half of pregnancy (edema, hypertension or preeclampsia

(nephropathy)) due to the risk of a decrease in bcc and a decrease in uteroplacental blood flow in the absence of a favorable effect on the course of the disease. Hydrochlorothiazide should not be used to treat essential hypertension in pregnant women for exception of rare cases when it is impossible to use alternative means.

Newborns, mothers who took the drug Lorista ND during pregnancy, should be monitored, because it is possible to develop an arterial hypotension in a newborn.

Breastfeeding period

The drug Lorista® ND is not recommended in period of breastfeeding, tk. no experience of application. It is recommended to use other antihypertensive drugs taking into account the safety profile. It is not known whether losartan with breast milk. Hydrochlorothiazide penetrates into the mother's breast milk in small amounts. Thiazide diuretics in high doses cause intense diuresis, thereby suppressing lactation.

Dosing and Administration:

Inside, regardless of food intake, drinking enough water, 1 tablet once a day. A drug

Lorista ND can be taken concomitantly with other antihypertensive drugs.

Arterial hypertension

The combination of hydrochlorothiazide / losartan is indicated in patients who, with hydrochlorothiazide or losartan in monotherapy adequate blood pressure control is not ensured. It is recommended to titrate the dose of losartan and hydrochlorothiazide before transferring the patient to therapy with Lorist® ND. If necessary (with inadequate control of blood pressure), the issue of patient transfer from therapy losartan for treatment with Lorist® ND.

As a rule, the drug Lorista® ND is prescribed to patients in the absence of adequate therapeutic (antihypertensive) effect on taking 1 tablet of Lorist® H (12.5 mg hydrochlorothiazide / 50 mg losartan). The maximum daily dose is 1 tablet of Lorista® ND (25 mg / 100 mg). Antihypertensive effect occurs immediately and increases within 3 weeks.

Special patient groups:

Patients with renal dysfunction or who are on hemodialysis: in patients with moderate renal dysfunction (CK 30-50 ml / min), correction of the initial dose of the drug is not required. Losartan and hydrochlorothiazide is not recommended for patients on hemodialysis.

Patients with low BCC: Before starting treatment with Lorist® ND, the BCC and / or maintenance should be restored sodium in blood plasma.

Older patients: dose adjustment is usually not required.

FROMThe risk of cardiovascular morbidity and mortality in patients with arterial hypertension and hypertrophy of the left ventricle

The standard initial dose of losartan is 50 mg once a day. Patients who failed to achieve target BP levels when taking Losartan 50 mg / day require treatment by a combination of losartan with low doses of hydrochlorothiazide (12.5 mg). If necessary, increase the dose of losartan up to 100 mg / day simultaneously with hydrochlorothiazide at a dose of 12.5 mg / day (Lorist® H can be used), further increase to 1 tablet of Lorist® ND (hydrochlorothiazide 25 mg / losartan 100 mg) once daily. If you need to further reduce blood pressure, you should add other antihypertensive drugs.

Side effects:

Classification of the frequency of development of side effects of the World Health Organization (WHO): very often >1/10

often from >1/100 to <1/10

infrequently from >1/1000 to <1/100

rarely from >1/10000 to <1/1000

very rarely from <1/10000

the frequency of the unknown can not be estimated from the available data.

Unwanted reactions with a combination of hydrochlorothiazide / losartan have been previously observed with the administration of losartan and / or hydrochlorothiazide.

Postmarketing application hydrochlorothiazide / losartan combination

Additional adverse reactions:

From the digestive system: rarely: hepatitis.

Laboratory data: rarely: hyperkalemia, increased activity of alanine aminotransferase (ALT).

Unwanted reactions that occurred when used in monotherapy with isosartan and hydrochlorothiazide and can be used with the combination hydrochlorothiazide / losartan:

Losartan

From the hematopoiesis: infrequently: anemia, purple Shenlaine-Genocha, ecchymosis, hemolysis; frequency unknown: thrombocytopenia.

From the cardiovascular system: infrequently: marked decrease in blood pressure, orthostatic hypotension, chest pain, angina pectoris, atrioventricular blockade (AV blockade) of the II degree, cerebrovascular accident, myocardial infarction (with excessive decrease in blood pressure), palpitation, arrhythmia (atrial fibrillation, sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation), vasculitis.

From the sense organs:

infrequently: vertigo, tinnitus, blurred vision, burning sensation / tingling sensations in the eyes, conjunctivitis, decreased visual acuity.

From the digestive system:

often: abdominal pain, nausea, diarrhea, indigestion;

infrequent: constipation, pain in the teeth, dryness of the oral mucosa, bloating, gastritis, vomiting, intestinal obstruction;

frequency unknown: pancreatitis, impaired liver function.

Allergic reactions:

rarely: hypersensitivity: anaphylactic reactions, angioedema, including laryngeal and pharyngeal edema, causing airway obstruction, and / or edema of the face, lips, pharynx and / or tongue; in some patients angioedema has also been noted in the history of treatment with other drugs, including ACE inhibitors.

From the musculoskeletal system:

often: muscle cramps, back pain, leg pain, myalgia;

infrequently: pain in the hands, swelling of the joints, pain in the knees, musculoskeletal pain, pain in the shoulders, stiffness, arthralgia, arthritis, coxalgia, fibromyalgia, muscle weakness; frequency unknown: rhabdomyolysis.

From the nervous system: often: headache, dizziness, insomnia;

infrequent: nervousness, paresthesia, peripheral neuropathy, tremor, migraine, syncope, anxiety, anxiety disorder (excessive, uncontrolled and often irrational anxiety about everyday events), panic disorder (recurring panic attacks), confusion, depression, nightmares, sleep disorders, drowsiness, memory impairment;

From the genitourinary system: often: renal dysfunction, kidney failure;

infrequently: nocturia, rapidity urination, urinary tract infections;

On the part of the reproductive system: infrequently: decreased libido, erectile dysfunction / impotence.

From the respiratory system: often: cough, upper respiratory tract infections, nasal congestion, sinusitis, violation of upper airway patency; infrequently: a feeling of discomfort in the pharynx, pharyngitis, laryngitis, dyspnea, bronchitis, nosebleed, rhinitis, congestion in the respiratory tract;

From the skin: infrequently: alopecia, dermatitis, dry skin, erythema,sensation of "tides" of blood to the skin of the face, photosensitivity, skin itch, skin rash, urticaria, increased sweating.

Other: often: asthenia, fatigue, anorexia; infrequently: swelling of the face, swelling, fever; frequency unknown: flu-like symptoms, malaise.

Laboratory indicators: often: hyperkalemia, a slight decrease in hemoglobin and hematocrit, hypoglycemia; infrequently: a slight increase in serum concentrations of urea and creatinine; very rarely: increased activity of "liver" enzymes and bilirubin; frequency unknown: hyponatremia.

Hydrochlorothiazide

From the hematopoiesis: infrequently: agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, purpura, thrombocytopenia.

Allergic reactions: rarely: anaphylactic reaction.

From the side of metabolism: infrequently: anorexia, hyperglycemia, hyperuricemia, hypokalemia, hyponatremia.

From the nervous system: often: headache; infrequently: insomnia.

From the sense organs: infrequently: transitory violation visual perception, xantopsy; frequency unknown: acute myopia and acute closed angle glaucoma.

From the cardiovascular system: infrequently: necrotizing angiitis (vasculitis, cutaneous vasculitis).

From the respiratory system: infrequently: respiratory distress syndrome, including pneumonitis and pulmonary edema.

From the digestive system: infrequently: sialadenitis, spasm, irritation stomach, nausea, vomiting, diarrhea, constipation, jaundice (intrahepatic cholestasis), pancreatitis;

From the skin: infrequently: photosensitivity, hives, toxic epidermal necrolysis.

From the side of the locomotor system apparatus: infrequently: muscle cramps.

From the genitourinary system: infrequently: glucosuria, interstitial nephritis, impaired renal function, renal insufficiency.

Other: infrequently: fever, dizziness.

Overdose:

Lorista® ND

Information on combination overdose hydrochlorothiazide / losartan no.

Treatment: symptomatic and maintenance therapy. It is necessary to cancel the drug Lorista ND and carefully monitor the patient. If necessary: induce vomiting (if the patient has recently taken the drug), make up for the BCC, correction of water-electrolyte metabolism and marked decrease in blood pressure.

Losartan (data are limited) Symptoms: marked decrease in blood pressure, tachycardia; bradycardia due to parasympathetic (vagal) stimulation.

Treatment: symptomatic therapy, hemodialysis is ineffective.

Hydrochlorothiazide

Symptoms: the most frequent Symptoms are: hypokalemia, hypochloraemia, hyponatremia and Dehydration, as a result of excessive diuresis. With the simultaneous administration of cardiac glycosides, hypokalemia can aggravate the course of arrhythmia.

Treatment: symptomatic.

Interaction:

Losartan

Simultaneous application with aliskirenom in patients with diabetes mellitus or renal dysfunction (CC less than 60 ml / min) is contraindicated.

Rifampicin and fluconazole decreased the concentration of the active metabolite. The clinical significance of this interaction has not been studied. The simultaneous use of losartan, as well as other drugs that affect RAAS, with potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone), potassium preparations or substitutes for salts containing potassium ions, may lead to an increase in serum potassium content. Simultaneous application is not recommended.

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

With simultaneous use of angiotensin II antagonists with non-steroidal anti-inflammatory drugs (NSAIDs) (for example, selective inhibitors of cyclooxygenase (COX) -2, and nonselective NSAIDs, high doses (more than 3 g / day) of acetylsalicylic acid) possible decrease in antihypertensive effect.

Simultaneous use of angiotensin II antagonists or diuretics with NSAIDs is accompanied by an increased risk of developing renal dysfunction, incl. development of acute renal disease deficiency, and an increase in serum potassium content (especially in patients with an existing history of renal dysfunction). At the same time, it should be used with NSAIDs with caution, especially in elderly patients. At the same time, it is necessary to adequately fill the BCC and periodically monitor the kidney function from the start of therapy and in the future. In some patients with impaired renal function, using NSAIDs, incl.selective inhibitors of COX - 2, the simultaneous use of the angiotensin II receptor antagonists can cause a further reversible renal impairment. Double blockade of RAAS: a double blockade of the RAAS; addition to ACE inhibitor therapy angiotensin II receptor antagonist, is only possible in individual cases under careful control of renal function. Patients with atherosclerosis, heart failure or diabetes with end-organ damage dual blockade of the RAAS (while the use of angiotensin II receptor antagonists, ACE inhibitors or aliskiren) is accompanied by an increased incidence of hypotension, syncope, hyperkalemia, and renal dysfunction (including acute renal insufficiency) in comparison with application of a preparation of one of the listed groups.

Other drugs that cause arterial hypotension, including tricyclic antidepressants, antipsychotics, baclofen, amifostine: simultaneous use of drugs that reduce blood pressure (the main or side effect), can increase the risk of developing arterial hypotension.

Hydrochlorothiazide

Ethanol, Barbiturates, general anesthetics or antidepressants: may potentiate the risk of developing orthostatic hypotension.

Hypoglycemic agents for ingestion and insulin: it may be necessary to correct the dose of hypoglycemic agents, t. hydrochlorothiazide affects glucose tolerance.

Metformin should be used with caution in connection with the risk of developing lactic acidosis against a background of kidney damage caused by hydrochlorothiazide.

Other antihypertensives: additive action.

Kolestyramine and colestipol: the absorption of hydrochlorothiazide decreases.

Colestramine and colestipol in a single dose bind hydrochlorothiazide and reduce its absorption in the gastrointestinal tract (GIT) by 85 and 43%, respectively. Corticosteroids, adrenocorticotropic hormone (ACTH): a marked decrease in the electrolyte content, especially hypokalemia.

Pressor amines (e.g., epinephrine and norepinephrine): a slight decrease in the severity of the response to the introduction of pressor amines is possible, but it does not exclude the possibility of their use.

Non-depolarizing muscle relaxants (e.g., tubocurarine): it is possible to enhance the effect of muscle relaxants.

Lithium: it is possible to reduce renal clearance of lithium and, accordingly, the risk of lithium intoxication. Therefore, simultaneous use is not recommended.

Drugs used to treat gout (probenecid, sulfinpirazone and allopurinol): may need to adjust the dose of uricosuric drugs, since hydrochlorothiazide may cause an increase in serum uric acid concentration. Thiazide diuretics can increase the incidence of hypersensitivity reactions by allopurinol.

Anticholinergic drugs (eg, atropine, biperidene): increase the bioavailability of thiazide diuretics due to a decrease in gastrointestinal motility.

Cytostatic drugs, for example, cyclophosphamide, methotrexate: increases mielopodavlivayuschee action due to slower excretion from the body.

Salicylates: when used simultaneously with salicylates (for example, acetylsalicylic acid) in high doses, it is possible to increase their toxic effect on the central nervous system.

Methyldopa: separate cases of hemolytic anemia are described with simultaneous application.

Simultaneous application cyclosporine increases the risk of hyperuricemia and exacerbation of gout;

Cardiac glycosides:

Hypokalemia and hypomagnesemia caused by the use of thiazide diuretics increase the risk of arrhythmias in the treatment of cardiac glycosides.

Drugs that can cause side effects when the serum potassium content is changed:

Recommended periodically control the potassium content in the blood serum and ECG with simultaneous use with cardiac glycosides and drugs that extend the interval QT (risk of developing ventricular tachycardia such as "pirouette"):

- I A class of antiarrhythmic drugs (for example, quinidine, disopyramide);

- III class of antiarrhythmic agents (eg, amiodarone, sotalol, dofetilide);

- Some antipsychotics (for example, thioridazine, chlorpromazine, levomepromazine, trifluoperazine, sulpiride, amisulpride, tiapride, haloperidol, droperidol);

- Other drugs (for example, cisapride, diphemanyl methyl sulfate, erythromycin for intravenous administration, halofantrine, ketanserin, mizolastin, terfenadine, sparfloxacin, wincamine for intravenous administration).

Vitamin D and calcium salts: simultaneous use of thiazide diuretics with vitamin D or calcium salts increases the serum calcium content, because decreased excretion of calcium. If you need calcium or vitamin D, you should monitor the calcium level in the blood serum and, possibly, adjust the dose of these drugs.

Carbamazepine: risk of development symptomatic hyponatremia.

Need to monitor AD, clinical signs of disturbed water-electrolyte metabolism. It should also be monitored periodically serum electrolyte content. Hydrochlorothiazide may increase the risk of developing acute renal failure, especially with the simultaneous use of high doses iodine containing contrast agents. Before their application it is necessary to restore BCC.

Amphotericin B (for intravenous administration), laxative stimulant or ammonium glycyrrhizinate (contained in licorice): hydrochlorothiazide can enhance violations of water-electrolyte balance, especially hypokalemia.

Non-steroidal anti-inflammatory drugs (NSAIDs)

NSAIDs (for example, selective inhibitors of COX-2, and nonselective NSAIDs, high doses (more than 3 g / day) of acetylsalicylic acid) can reduce the diuretic and antihypertensive effects of thiazide diuretics.

Special instructions:

Losartan

Angioedema

Patients with angioneurotic edema (face, lips, throat and / or throat) in a history should be carefully monitored

Arterial hypotension and hypovolemia (dehydration)

In patients with hypovolemia (dehydration) and / or reduced sodium in the blood plasma, against the background of diuretic therapy, restriction of consumption of table salt, diarrhea or vomiting, the development of symptomatic arterial hypotension, especially after taking the first dose of Lorist® ND. Before using the drug should be restored BCC and / or sodium content in blood plasma.

Violations of the water-electrolyte balance

Violations of water-electrolyte balance are often found in patients with impaired renal function, especially against diabetes mellitus. In this regard, it is necessary to carefully monitor the potassium content in the blood plasma and QC, especially in patients with heart failure and KK 30-50 ml / min.Simultaneous use with potassium-sparing diuretics, potassium preparations, substitutes for table salt containing potassium, or other agents that can increase the potassium content in the blood plasma (eg, heparin) is not recommended.

Impaired liver function

The concentration of losartan in the blood plasma increases significantly in patients with cirrhosis of the liver, so the drug Lorista ND should be administered with caution to patients with mild or moderate impairment of liver function.

Impaired renal function

Possible development of renal dysfunction, including renal failure, due to inhibition of RAAS (especially in patients whose kidney function depends on RAAS, for example, with severe heart failure or renal dysfunction in history).

Stenosis of the renal artery

In patients with bilateral renal artery stenosis, as well as stenosis of the artery of a single functioning kidney, preparations that affect RAAS, including angiotensin II receptor antagonists, can reversibly increase urea and creatinine concentrations in the blood plasma. Losartan should be used with caution in patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney.

Kidney Transplantation

Experience with the drug Lorista ND in patients who have recently undergone kidney transplantation, absent.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are resistant to antihypertensive drugs that affect RAAS, so such patients are not recommended for using Lorista® ND.

Ischemic heart disease (CHD) and cerebrovascular diseases

As with any antihypertensive drug, excessive BP reduction in patients with ischemic heart disease or cerebrovascular disease can lead to the development of myocardial infarction or stroke.

Heart failure

In patients whose renal function depends on the state of RAAS (eg, in chronic heart failure III-IV functional class by classification NYHA, accompanied or not accompanied by impaired renal function), therapy with drugs that affect RAAS may be accompanied by severe arterial hypotension, oliguria and / or progressive azotemia, and in rare cases acute renal failure. It is impossible to exclude the development of these disorders due to the suppression of RAAS activity against the background of angiotensin II receptor antagonists.

Stenosis of aortic and / or mitral valves, GOKMP

The drug Lorista® ND, as well as other vasodilators, is necessary with use caution in patients with hemodynamically significant stenosis of the aortic and / or mitral valves, or with GOKMP.

Ethnic Features

Lozartan (as well as other drugs that affect RAAS) has a less pronounced antihypertensive effect in patients of the Negroid race compared with representatives of other races, possibly due to a higher incidence of giporenemia in patients with hypertension.

Hydrochlorothiazide

Arterial hypotension and disturbance of water-electrolyte metabolism

It is necessary to monitor blood pressure, clinical signs of disturbance of water-electrolyte metabolism, including dehydration, hyponatremia, hypochloraemic alkalosis, hypomagnesemia or hypokalemia, which can develop against diarrhea or vomiting. Periodically monitor the serum content of electrolytes.

Metabolic and endocrine effects

Caution is needed in all patients receiving treatment with hypoglycemic agents for ingestion or insulin, since hydrochlorothiazide can weaken their action.Against the background of therapy with thiazide diuretics, latent diabetes mellitus can manifest. Thiazide diuretics, including hydrochlorothiazide, can cause a disturbance of the water-electrolyte balance (hypercalcemia, hypokalemia, hyponatremia, hypomagnesemia and hypokalemic alkalosis). Thiazide diuretics can reduce the excretion of calcium by the kidneys and cause a temporary and insignificant increase in the calcium content in the blood plasma. Expressed hypercalcemia may be a sign of latent hyperparathyroidism. Before the study of the function of parathyroid glands, thiazide diuretics should be discontinued. Against the background of treatment with thiazide diuretics, it is possible to increase the concentration of cholesterol and triglycerides in the blood serum.

Therapy with thiazide diuretics in some patients may exacerbate hyperuricemia and / or aggravate the course of gout.

Losartan reduces the concentration of uric acid in the blood plasma, so its use in combination with hydrochlorothiazide neutralizes Hyperuricemia caused by a thiazide diuretic.

Impaired liver function

Thiazide diuretics should be used with caution in patients with impaired liver function or progressive liver disease, since they can cause intrahepatic cholestasis, and even minimal disturbances of the water-electrolyte balance can contribute to the development of the hepatic coma.

The drug Lorista® ND is contraindicated in patients with severe liver dysfunction, since there is no experience of using the drug in this category of patients.

Acute myopia and secondary acute closed angle glaucoma

Hydrochlorothiazide is a sulfonamide that can cause an idiosyncratic reaction leading to the development of transient acute myopia and acute closed-angle glaucoma. Symptoms include: sudden reduction in visual acuity or eye pain, which usually appears within a few hours or weeks of initiating hydrochlorothiazide therapy. In the absence of treatment, acute closed-angle glaucoma can lead to persistent loss of vision.

Treatment: as soon as possible stop taking hydrochlorothiazide. If intraocular pressure remains uncontrolled, immediate medical treatment or surgery may be required. Risk factors for the development of acute closed-angle glaucoma are: an allergic reaction to sulfonamide or benzylpenicillin in the anamnesis.

Are common

In patients taking thiazide diuretics, hypersensitivity reactions can develop both in the presence and in the absence of a history of an allergic reaction or bronchial asthma, but are more likely if there are any in the history. There are reports of an exacerbation of the systemic lupus erythematosus with the use of thiazide diuretics.

Special information on auxiliary substances

The drug Lorista® ND contains lactose, therefore the drug is contraindicated in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

Effect on the ability to drive transp. cf. and fur:

At the beginning of therapy, the drug Lorista ND can cause a decrease in blood pressure and dizziness or drowsiness, thus indirectly affect the psychoemotional state. For safety reasons, before starting activities requiring increased attention, patients should first assess their response to ongoing treatment.

Form release / dosage:

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

Packaging:

For 7, 10 or 14 tablets in a blister (contour mesh packaging) from the combined material PVC / PVDH / - foil aluminum.

By 2, 4, 8, 12 or 14 blisters (contour cell packings) of 7 tablets, or 3, 6 or 9 blisters (contour cell packs) of 10 tablets, or 1, 2, 4, 6 or 7 blisters contour packs) of 14 tablets together with instructions for use are placed in a cardboard pack.

Storage conditions:At temperatures not higher than 30 ° C, in the original packaging. Keep out of the reach of children.

Shelf life:

5 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002031/08

Date of registration:21.03.2008

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, d.d. Slovenia

KRKA-RUS, LLC Russia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp02.02.2016

Illustrated instructions

Instructions

Lorista® ND (Lorista® HD)