Simartan-N - instructions for use, dose, side effects, contraindications

Excipients: cellulose microcrystalline 100.0 mg, corn starch 40.5 mg. povidone (PVP K-30) 2.0 mg, silicon dioxide colloid 3.0 mg. magnesium stearate 2.0 mg, crospopidone 25.0 mg.

Shell composition: Rape brown: (hypromellose 5,400 mg, iron oxide red oxide 1,728 mg, macrogol 1.080 mg, titanium dioxide 0.792 mg) - 9.00 mg, propylene glycol 1,000 mg.

Description:Round biconvex tablets covered with a film coat of reddish-brown color with a risk on one side. On the cross section, the nucleus is white or almost white in color.

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:

Components of the preparation Simartan-H have an additive antihypertensive effect, reducing blood pressure (BP) more than each of the components separately. Due to the diuretic effect hydrochlorothiazide increases the activity of plasma renin (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, due to suppression of aldosterone effects, can help reduce the loss of potassium associated with taking a diuretic.

Losartan

Losartan is a specific antagonist of angiothezin II receptors (subtype AT1) for oral administration. Does not inhibit kinase II - an enzyme that catalyzes the reaction of the conversion of angiotensin I into angiotensin II.

Angiotensin II binds selectively to the AT1-receptor found in many tissues (smooth muscle tissues of blood vessels, adrenal glands, kidneys and the heart) and performs several important biological functions, including vasoconstriction and the release of aldosterone. Angiotensin II also stimulates proliferation of smooth muscle cells. 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 cardiovascular function.Besides, losartan does not inhibit angiotensin-converting enzyme (ACE) and, accordingly, does not interfere with the destruction of bradykinin, therefore side effects mediated by bradykinin (eg, angioneurotic edema) are rare. When using losartan, the absence of negative feedback influence on renin secretion leads to an increase in renin plasma activity. Increased renin activity leads to an increase in angiothezin II in blood plasma. However, antihypertensive activity and a decrease in plasma aldosterone concentration persist, indicating an effective blockade of angiothezin II receptors. Losartan and its active metabolite have a greater affinity for angiothezin I receptors than for angiothezin II receptors. The active metabolite is 10-40 times more active than losartan.

After a single oral intake, the antihypertensive effect (systolic and diastolic blood pressure decreases) reaches a maximum after 6 hours, then gradually decreases within 24 hours.

The maximum antihypertensive effect develops in 3-6 pellets after the start of the drug.

In patients with hypertension without concomitant diabetes mellitus with proteinuria (more than 2 g / day), the use of the drug significantly reduces proteinuria, albumin and immunoglobulin G excretion.

Losartan at a dose of 150 mg per day does not affect the concentration of triglycerides, total cholesterol and high-density lipoprotein cholesterol (HDL) in the blood serum in patients with hypertension. At the same dose losartan does not affect the concentration of glucose in the blood on an empty stomach.

Hydrochlorothiazide

The mechanism of antihypertensive action of thiazides is unknown. Thiazides usually do not affect normal BP.

Hydrochlorothiazide acts on the reabsorption of electrolytes in the distal tubules of the kidneys. Hydrochlorothiazide approximately equally increases the excretion of priests of sodium and chlorine. Sodium-sulfur may be accompanied by a small loss of potassium and bicarbonate ions. When ingestion the diuretic effect develops after 2 hours, reaches a maximum on average after 4 hours and lasts from 6 to 12 hours.

Pharmacokinetics:

Suction

Losartan

Ingestion losartan It is well absorbed and metabolized while "primary pass" through the liver, resulting in formation of the active carboxylated metabolite and inactive metabolites. Systemic bioavailability is approximately 33%. The average maximum concentrations of losartan and its active metabolite are reached after 1 hour and 3-4 hours, respectively. When losartan was taken with food, there was no clinically significant effect on the profile of losartan concentration in the blood plasma.

Hydrochlorothiazide

Ingestion hydrochlorothiazide quickly absorbed from the gastrointestinal tract. The time to reach the maximum concentration is 1.5-3 hours.

Distribution

Losartan

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

Hydrochlorothiazide binds to blood plasma proteins for 40-60% penetrates through the placental (but not blood-brain barrier) and into breast milk.

Metabolism

Losartan

Approximately 14% of the dose of losartan, administered intravenously or by mouth, is converted to its active metabolite.

In addition to the active metabolite, as a result of hydroxylation of the butyl side

biologically inactive metabolites are formed, including two main

metabolite and one secondary - N-2-tetrazole-glucuronide.

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. When taking losartan, about 4% of the dose is excreted by the kidneys unchanged, and about 6% of the dose is in the form of an active metabolite. When taking losartan inside at doses up to 200 mg losartan and its active metabolite have linear pharmacokinetics. After oral administration, the plasma concentrations of losartan and its active metabolite are reduced by a polyexponential with a finite half-life of about 2 and 6-9 hours, respectively. With a single daily intake of the drug at a dose of 100 mg losartan, nor its active metabolite significantly accumulate in the blood plasma.

The excretion of losartan and its metabolites occurs with bile through the intestine and kidneys.

Hydrochlorothiazide

Hydrochlorothiazide is not metabolized and is rapidly excreted by the kidneys. Period

The elimination half-life ranges from 5.6 to 14.8 hours. At least 61% of the dose taken internally

is displayed unchanged for 24 hours.

Pharmacokinetics in selected patient groups

Losartan + hydrochlorothiazide

Elderly patients

The concentration of losartan and its active metabolite in blood plasma and the rate of absorption of hydrochlorothiazide in elderly patients with hypertension do not significantly differ from these indices in young patients with arterial hypertension.

Losartan

Floor

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.

Dysfunction of the liver and kidneys

When administered to patients with mild and moderate alcoholic cirrhosis of the liver, concentrations of losartan and its active metabolite in the blood plasma were, respectively, 5 to 1.7 times higher than in young male volunteers.Concentrations of losartan in the blood plasma in patients with creatinine clearance (CC) above 10 ml / min. did not differ from those in patients with a preserved function of the nights. When comparing the area under the curve "concentration-time" (AUC) in patients with normal renal function, AUC losartan in patients on hemodialysis, was approximately 2 times more. Plasma concentrations of the active metabolite 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). Reducing the risk of cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy.

Contraindications:

- Hypersensitivity to any of the components of the drug

- Hypersensitivity to sulfonamide derivatives.

- Anuria

- Severe renal impairment (QC less than 30 mL / min.)

- Severe violations of the liver (more than 9 points on the scale Child-Pugh), cholestasis.

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

- dehydration,

- refractory hypokalemia and hyperkalemia;

- hard-to-control diabetes mellitus;

- Addison's disease;

- primary hyperaldosteronism;

- pregnancy, the period of breastfeeding;

- Simultaneous use with aliskirnym and aliskirensoderzhaschimi drugs in patients with diabetes mellitus and / or renal dysfunction (glomerular filtration rate (GFR) less than 60 ml / min / 1.73 m2).

Carefully:

Patients with disturbed water-electrolyte balance of blood, for example, against diarrhea or vomiting (hyponatremia, hypochloraemic alkalosis, hypomagnesemia, hypokalemia).

Patients with renal insufficiency (KK 30-50 ml / min.); hepatic insufficiency (less than 9 on the Child-Pugh scale); bilateral stenosis of the renal arteries or stenosis of the artery of a single night; ischemic heart disease; heart failure with life-threatening arrhythmias; cerebrovascular diseases; aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy; diabetes mellitus, hypercalcemia; with a burdened allergic anamnesis and bronchial asthma; as well as in systemic diseases of connective tissue (including,systemic lupus erythematosus); hypovolemia (including the background of high doses of diuretics); and also, with simultaneous administration with non-steroidal anti-inflammatory drugs (NSAIDs), including inhibitors of cyclooxygenase-2 (COX-2); acute attack of myopia and secondary closed angle glaucoma; angioedema in history; symptomatic increase in the concentration of uric acid in the blood plasma, gout; state after kidney transplantation (no experience of use), chronic heart failure IV functional class according to NYHA classification; the use of Negroid race in patients.

Pregnancy and lactation:

The use of the drug Simartan-N is contraindicated in pregnancy! The use of drugs that directly affect the renin-angiotensin-aldosterone system (RAAS) during the second and third trimesters of pregnancy can cause harm to the developing fetus or even cause its death. Immediately after the pregnancy is established, the intake of Simartan-H should be discontinued.

Despite the lack of data on the use of the drug Simartan-H in pregnant women,studies in animals have demonstrated that the use of losartan can cause harm to the fetus and the newborn and cause their death, which is probably due to the effect of the drug on the RLAS. In a human fetus, kidney perfusion, which depends on the development of RLAS, begins in the second trimester; Thus, the risk of impaired development and death of the fetus increases with the use of the drug Simartan-H during the second or third trimesters of pregnancy.

Thiazides penetrate the placental barrier and are detected in the blood of the umbilical cord. The use of diuretics in healthy pregnant women is not recommended, as this increases the risk of developing fetal adverse effects such as embryonic jaundice and jaundice of newborns, and the mother - thrombocytopenia. There is no evidence that losartan excreted in breast milk. It is known that thiazides penetrate the placental barrier and are determined by the blood of the umbilical cord. In connection with the risk of developing adverse events in infants, in all cases, a balanced decision should be made about taking the drug during the period of breastfeeding, taking into account the importance of therapy for the mother.

In the event that it is decided that you need to take the drug Simartan-H during lactation, breastfeeding should be discontinued.

Dosing and Administration:

The drug Simartan-N is taken orally, regardless of the time of ingestion.

Arterial hypertension - 1 tablet of the preparation Simartan-N once a day.

If there is no therapeutic effect for 2-4 weeks, the dose of Simartan-N can be increased to 2 tablets once a day. The maximum dose is 2 tablets of the preparation Simartan-N once a day. Typically, the antihypertensive effect is achieved within 3 pedl after the start of therapy.

Reducing the risk of cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy - 1 tablet once a day. In the absence of a therapeutic effect (the target values of blood pressure can not be reached on the background of taking 1 tablet), the dose of the preparation of Simartan-N can be increased to 2 tablets once a day. The maximum dose is 2 tablets once a day. It is not necessary to select an initial dose for elderly patients and patients with moderate-level renal insufficiency (KK 30-50 ml / mni).

The use of the drug in patients with reduced circulating blood volume (BCC) - Before beginning therapy with the drug, it is necessary to restore the BCC and / or the sodium content in the blood plasma.

Side effects:

The frequency 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 - 0.01%, including individual reports; frequency is not set (can not be calculated from available data).

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 hydrochlorothiazide alone.

In the post-marketing application of losartan / hydrochlorothiazide,

the following undesirable phenomena:

From the digestive system: rarely - hepatitis;

Laboratory indicators: rarely - hyperkalemia, increased activity of "liver" transaminases.

The following adverse events were observed with losartan and

hydrochlorothiazide alone.

Losartan

From the side of the blood and lymphatic system: infrequently - anemia, purpura Shenlaine-Henoch, ecchymosis, hemolytic anemia.

Allergic reactions: rarely - anaphylactic reactions, angioedema, hives.

From the side of metabolism and nutrition: anorexia, gout.

From the central nervous system: often - headache, dizziness, insomnia; infrequent anxiety, paresthesia, peripheral neuropathy, tremor, migraine, fainting, anxiety, anxiety disorders, panic disorder, confusion, depression, drowsiness, sleep disorder, memory impairment.

From the side of the organ of vision: infrequent - impaired vision, a feeling of dryness and burning in the eyes, conjunctivitis, reduced visual acuity.

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

From the respiratory system: often - nasal congestion, cough, upper respiratory tract infections (fever, sore throat, sinusopathy, sinusitis, pharyngitis); infrequently - pharyngitis, laryngitis, dyspnea, bronchitis, rhinitis, nosebleeds, discomfort in the pharyngeal region.

On the part of the organs of the gastrointestinal tract: often - nausea, diarrhea, dyspeptic phenomena, abdominal pain; infrequently - dryness of the oral mucosa, toothache, vomiting, flatulence, gastritis, constipation.

From the side of the musculoskeletal system: often - cramps, myalgia, back pain, in the legs; infrequently - arthralgia, pain in the hands, in the shoulder, knee, arthritis, fibromyalgia, muscle weakness, swelling of the joints, musculoskeletal pain.

From the cardiovascular system: infrequent - marked decrease in blood pressure, orthostatic hypotension (dose-dependent), palpitations, tachy- or bradycardia, arrhythmias, angina, chest pain, atrioventricular block II degree, cerebrovascular events, myocardial infarction, vasculitis.

From the genitourinary system: infrequently - nocturia, frequent urination, urinary tract infections, weakening of libido, impotence.

From the skin: infrequent - dry skin, erythema, "tides" of blood to the skin of the face, photosensitivity, itching, rash, increased sweating, alopecia, dermatitis.

Other: often - asthenia, increased fatigue; infrequently - swelling of the linden, fever.

Laboratory indicators: often - hyperkalemia, decrease in hematocrit and hemoglobin;

infrequently - increased concentrations of urea and creatinine; very rarely - increase

activity of "liver" transaminases.

HYDROCHLOROTHYASIDE

From the side of the blood and lymphatic system:

infrequently: agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, purpura, thrombocytopenia

Allergic reactions: - rarely: anaphylactic reactions

very rarely - urticaria, Stevens-Johnson syndrome, erythema multiforme, erythema, reversible pemphigoid reactions, exfoliative dermatitis, allergic alveolitis, eosinophilic pneumonia, angioedema, larynx, pharynx, tongue, face, lips, mucous membranes (including fatal) .

From the side of metabolism and nutrition:

Infrequent loss of appetite, hyperglycemia, hyperuricemia. violations of water-

electrolyte balance (in particular hypokalemia and hyponatremia, hypomagnesemia and

hypochloraemia, as well as hypercalcemia). Treatment with thiazides can reduce

tolerance to glucose, and latent diabetes mellitus may

manifest.

Very rarely - metabolic alkalosis.

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

From the side of the organ of vision:

Rarely is a decrease in the production of tear fluid, impaired vision. Very rarely - conjunctivitis.

Frequency not established-acute myopia, secondary closed angle glaucoma.

From the cardiovascular system: infrequently: necrotizing vasculitis.

On the part of the respiratory system:

infrequently: respiratory distress syndrome (including pneumonitis and non-cardiogenic pulmonary edema).

From the digestive system:

infrequently: sialodenitis, irritation of the mucous membrane of the gastrointestinal tract, nausea, vomiting, diarrhea, constipation, jaundice (intrahepatic cholestasis), pancreatitis.

From the skin and subcutaneous tissue:

infrequently: photosensitization, urticaria, toxic epidermal necrolysis,

lupus-like syndrome.

From the musculoskeletal system:

infrequently: muscle cramps.

From the urinary system:

infrequently: glucosuria, interstitial nephritis, impaired renal function, renal

failure.

Common violations:

infrequently: fever.

Overdose:

Symptoms: losartan - marked decrease in blood pressure, tachycardia, bradycardia (as a result of vagal stimulation).

Hydrochlorothiazide - loss of electrolytes (hypokalemia, hypochloraemia, hyponatremia); dehydration (excess diuresis).

Treatment: symptomatic and supportive therapy. If the drug is taken recently, the stomach should be washed; if necessary, correct the water-electrolyte disturbances. Losartan and its active metabolite are not removed by hemodialysis. It is not established to what extent hydrochlorothiazide can be removed from the body by hemodialysis.

Interaction:

LosartaMr.

In clinical studies of pharmacokinetics, there were no clinically significant interactions with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin. Rifampicin reduces the concentration of the active metabolite. The clinical significance of this interaction is not established.

The combination of losartan, as well as other means, blocking angiotensin II or its effects, with potassium-sparing diuretics (eg spironolactone, triamterene, amiloride, eplerenone), potassium-containing additives or potassium salts can lead to an increase in the potassium content in the blood serum.

As with the use of other agents that affect the excretion of lithium, treatment with losartan may be accompanied by a decrease in excretion and an increase in serum lithium concentration, so when treating with lithium preparations simultaneously, its serum concentration should be monitored.

NSAIDs, including selective inhibitors of COX-2, can reduce the effect of diuretics and other antihypertensive agents. Therefore, the antihypertensive effect of angiotensin II receptor antagonists can be reduced by NSAIDs, including COX-2 inhibitors.

In some patients with impaired renal function receiving NSAID therapy, including COX-2 inhibitors, treatment with angiotensin II receptor antagonists can cause further impairment of kidney function. These effects are usually reversible.

Double blockade of RAAS is the combined use of angiotensin II receptor antagonists. ACE inhibitors or aliskiren (direct renin inhibitor) - leads to a significant increase in the incidence of adverse events such as hypotension, syncope, hyperkalemia,impaired kidney function, acute renal failure, therefore, regular monitoring of blood pressure, kidney function and electrolyte content in blood in patients taking Simartan-N and other drugs that affect RAAS is necessary. The drug should not be used concomitantly with aliskiren in patients with diabetes mellitus. Avoid simultaneous use of the drug and aliskiren in patients with renal insufficiency (GFR less than 60 ml / min / 1.73 m²). The highest risk is in patients with established diagnosis of atherosclerosis, heart failure, diabetes mellitus (with any complication). The question of the application of the double blockade of RAAS

(eg, by simultaneous administration of an ACE inhibitor and an angiotensin II receptor antagonist) should be addressed in each case individually with careful monitoring of renal function.

Fluconazole, isoenzyme inhibitor CYP2C9, reduces plasma concentrations of the active metabolite and increases the concentration of losartan, however, the pharmacodynamic significance of this phenomenon has not been established. It was shown that in patients not metabolizing losartan in the active metabolite, there is a very rare and specific defect of the isoenzyme CYP2C9. Hydrochlorothiazide

With the simultaneous administration of hydrochlorothiazide with ethanol, barbiturates, narcotic analgesics, the risk of orthostatic hypotension increases;

- with hypoglycemic agents for ingestion and insulin may require dose adjustment for hypoglycemic agents;

- with other antihypertensive agents, additive effect is possible;

-with colestyramine and colestinol-impaired absorption of hydrochlorothiazide. A single dose of colestyramine or colestipol can reduce the absorption of hydrochlorothiazide in the gastrointestinal tract by 85% and 43%, respectively.

With the simultaneous administration of hydrochlorothiazide with glucocorticosteroids, adrenocorticotronic hormone, glycyrrhizic acid (found in the licorice root), amphotericin B may increase the loss of electrolytes, aggravation of hypokalemia;

- with pressor amines (norepinephrine, epinephrine), a slight decrease in the effect of pressor amines is possible, which does not prevent their use;

- with nondepolarizing muscle relaxants - strengthening their action;

- with NSAIDs (including COX-2 inhibitors), a decrease in the diuretic, natriuretic, antihypertensive action of diuretics is possible.

Do not apply simultaneously with lithium preparations, because diuretics reduce renal clearance of lithium and increase the risk of lithium intoxication.

Drugs used to treat gout (probenecid, sulfinpyrazone and allopurinol) - a dose adjustment (an increase in the dose of probenecid and sulfinpyrazone) may be required, since hydrochlorothiazide can increase the concentration of uric acid in the serum. The combined use of thiazide diuretics can increase the incidence of hypersensitivity reactions to allopurinol.

Anticholinergics (for example, atropine, biperidene) - increased bioavailability of thiazide diuretics due to a decrease in the motility of the gastrointestinal tract and the rate of gastric emptying.

Thiazide diuretics can reduce renal excretion of cytotoxic drugs (for example, cyclophosphamide, methotrexate) and enhance their myelosuppression 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 have been reported with simultaneous use of hydrochlorothiazide and methyldopa.

Concomitant treatment with cyclosporine may increase the risk of hyperuricemia and gout.

Hypokalemia or hypomagnesemia caused by the use of thiazide diuretics can promote the development of arrhythmias with simultaneous use with cardiac glycosides.

Simultaneous use of thiazide diuretics with antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), some antipsychotic drugs (neuroleptics) (thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopyride, amisulpride, tiapride, pimozide, 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 lead to the development of piruet-type arrhythmias.Thiazide diuretics can lead to hypercalcemia as a result of a decrease in its excretion, so it is necessary to monitor the calcium content in the serum. And the connection with the effect of thiazide diuretics on calcium metabolism, their administration may distort the results of the study of parathyroid gland function.

With simultaneous use with carbamazepine, there is a risk of symptomatic hyponatraemia.

With the development of dehydration against the background of the use of diuretics, there is a chance of developing acute renal failure, especially when used with iodine preparations.

Ethanol, barbiturates and narcotic analgesics can potentiate the risk of developing orthostatic hypotension.

Special instructions:

The drug Simartan-N can be administered in combination with other antihypertensive drugs.

Losartan

Due to the inhibition of the renin-angiotensin-aldosterone system, some susceptible patients experienced changes in kidney function, including renal failure; These changes were reversible and disappeared after discontinuation of therapy.

Perhaps the manifestation of such a symptom of hypersensitivity as angioedema, so patients with an angioedema in the anamnesis (swelling of the face, lips, pharynx / larynx and / or tongue) require careful monitoring of the drug.

Simartan-H, like some drugs that have an effect on RAAS, can increase the concentration of blood urea and serum creatinine in patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney. These changes in kidney function were reversible and disappeared after therapy was discontinued. Pharmacokinetic data indicate that the concentration of losartan in the blood plasma in patients with cirrhosis of the liver is significantly increased, so patients with a history of liver disease should use the drug in a lower dose. During treatment with the drug Simartan-H, as with any antihypertensive therapy, there may be a marked decrease in blood pressure. Patients should be examined for the purpose of identifying clinical signs of a decrease in bcc and violations of the water-electrolyte balance, including hyponatremia, hypochloraemic alkalosis, hypomagnesemia or hypokalemia,which can arise from episodes of diarrhea or vomiting, as a result of diuretic therapy, while limiting intake of table salt. Such patients need control of the content of plasma electrolytes. Simultaneous use with potassium preparations, potassium-sparing diuretics is not recommended (see the section "Interaction with other medicinal products").

In patients with primary hyperaldosteronism, the use of antihypertensive drugs that affect RAAS, including the preparation of Simartan-H, is ineffective.

A sharp decrease in blood pressure when treated with Simartan-H, as well as other antihypertensive drugs, in patients with ischemic cardiovascular and cerebrovascular diseases can lead to the development of acute myocardial infarction or stroke.

In patients with heart failure, both with a deficiency of kidney function, and without it, the use of the preparation Simartan-H, as well as other agents that affect the RAAS. increases the risk of a sharp decline in blood pressure and the development of acute renal failure.

Caution should be exercised when using Simartan-H in patients with aortic stenosis, mitral stenosis, and hypertrophic obstructive cardiomyopathy.

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.

Hydrochlorothiazide

As in the case of taking any antihypertensive drugs, some patients may experience symptomatic hypertension. In some patients hydrochlorothiazide can increase water-electrolyte imbalance (decrease in bcc, hyponatremia, hypochloraemic alkalosis, hypomagnesemia, hypokalemia), impair glucose tolerance, reduce calcium excretion by the kidneys, cause a transient slight increase in calcium in the blood plasma, increase the concentration of cholesterol and triglycerides, provoke the occurrence of hyperuricemia and / or gout (since losartan reduces the concentration of uric acid, the severity of hyperuricemia caused by a diuretic is reduced). Can give positive results in the conduct of doping control. Hydrochlorothiazide in connection with the impact on calcium metabolism, can distort the results of parathyroid function analysis.

There are reports of the development of exacerbation or progression of systemic lupus erythematosus on the background of thiazide diuretics.

Thiazide diuretics should be used with caution in patients with impaired liver function or progressive liver disease, this can lead to the development of intrahepatic cholestasis, which, in combination with a violation of the water-electrolyte balance, can lead to the development of a "hepatic" coma. Thiazide therapy may impair glucose tolerance, in some cases, a dose adjustment of hypoglycemic agents, including insulin, may be required. Expressed hypercalcemia may indicate latent hyperparathyroidism. In connection with the effect of thiazides on calcium metabolism, their administration can distort the results of the investigation of parathyroid gland function, before the study of parathyroid gland function, the thiazide diuretic should be canceled.

Acute myopic attack and angle-closure glaucoma

Against the background of the use of hydrochlorothiazide there have been cases of transient myopia and acute development of closed-angle glaucoma. Risk factors for the acute development of an angle-closure glaucoma may be anamnestic data on allergic reactions to sulfonamide derivatives and penicillin.Symptoms: sudden onset, sudden drop in vision or pain in the eye, usually occurring between a few hours and a week after the start of therapy. An untreated attack of angle-closure glaucoma can lead to persistent loss of vision. The first step is to stop taking hydrochlorothiazide. If intraocular pressure does not decrease after hydrochlorothiazide cancellation, medical or surgical treatment may be required.

Kidney transplantation. The experience of using hydrochlorothiazide + losartan in patients who have recently undergone kidney transplantation is absent.

Ischemic heart disease (IHD) and cerebrovascular disease. As with any antihypertensive drug, an excessive reduction in blood pressure in patients with ischemic heart disease or cerebrovascular disease can lead to the development of myocardial infarction or stroke.

Heart failure. Patients whose renal function depends on the state of RAAS (eg, XCH III-IV functional class by classification NYIIA, 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 taking ARA II.

Stenosis of the aortic and / or mitral valve, hypertrophic obstructive cardiomyopathy. Simartan-N, like other vasodilators, should be used with caution in patients with hemodynamically significant stenosis of the aortic and / or mitral valves, or with hypertrophic obstructive cardiomyopathy.

Interaction with drugs that affect RAAS. Double blockade of RAAS with angiotensin II receptor antagonists, ACE inhibitors, or aliskiren-containing drugs is associated with an increased risk of arterial hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared with monotherapy. It is necessary to monitor blood pressure, kidney function and electrolyte content in patients who simultaneously use several drugs that affect RAAS. Not recommended joint use of aliskiren with preparations containing hydrochlorothiazide + losartan in patients with diabetes mellitus and in patients with renal disease deficiency (GFR <60 ml / min / 1.73 m²).

Effect on the ability to drive transp. cf. and fur:Some of the side effects of the drug, such as dizziness, weakness, drowsiness and impaired vision, can adversely affect the ability to drive vehicles and can drive and tractor and perform potentially hazardous activities requiring increased concentration and speed of psychomotor reactions. At the beginning of therapy with the drug (the duration of this period is determined individually), it is recommended to refrain from driving vehicles and performing work that requires a high concentration of attention and speed of psychomotor reactions (due to the possible development of dizziness and drowsiness), and further caution should be exercised.

Form release / dosage:

Tablets, film-coated 12.5 mg + 25.0 mg

Packaging:

10 tablets per blister of PVDC. For 3 blisters in a cardboard box with instructions for medical use.

Storage conditions:In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002963

Date of registration:21.04.2015

Date of cancellation:2020-04-21

The owner of the registration certificate: Simpex Pharma Pvt Ltd. Simpex Pharma Pvt Ltd. India

Manufacturer: & nbsp

SIMPEX PHARMA, Pvt. Ltd. India

Representation: & nbspKORAL-MED, CJSCKORAL-MED, CJSC

Information update date: & nbsp18.12.2015

Illustrated instructions

Instructions

Simartan-N (Simartan-N)