Exototans - instructions for use, dose, side effects, contraindications

Active substances: Amlodipine besylate (in terms of amlodipine) - 6.94 mg (5.00 mg) or 6.94 mg (5 mg) or 13.87 mg (10 mg), valsartan - 80.00 mg or 160.00 mg or 160.00 mg.

Excipients: cellulose microcrystalline 21.71 mg or 43.43 mg or 43.43 mg, lactose monohydrate 11,60 mg or 24,13 mg or 23,20 mg, crospovidone (crospovidone CL-SF) - 25.05 mg or 50.10 mg or 50.10 mg, povidone (povidone K-30) 6.68 mg or 13.36 mg or 13.36 mg, croscarmellose sodium 8.35 mg or 16.70 mg or 16.70 mg, magnesium stearate 1.67 mg or 3.34 mg or 3.34 mg, silicon dioxide colloid (aerosil) 5.00 mg or 10.00 mg or 10.00 mg;

Sheath for doses (5 mg + 80 mg) or (5 mg + 160 mg): VIVACOAT® PA-2P-106 [hypromellose 6 cps (hydroxypropylmethylcellulose 6 cps) - 3.120 mg or 5.070 mg, titanium dioxide 0.376 mg or 0.611 mg, macrogol 3350 (polyethylene glycol 3350) 0.480 mg or 0.780 mg, talc 2.678 mg or 4,351 mg, polydextrose E1200 1,200 mg or 1,950 mg, iron coloration yellow oxide E172 0.144 mg or 0.234 mg, iron pigment oxide red E172 0.002 mg or 0.004 mg] 8.00 mg or 13.00 mg;

for dosage (10 mg + 160 mg): VIVACOAT® PA-1P-000 [hypromellose 6 cps (hydroxypropylmethylcellulose 6 cps) - 5,070 mg, titanium dioxide 3,900 mg, polydextrose E1200 1.950 mg, talc 1,300 mg, macrogol 3350 (polyethylene glycol-3350) -0.780 mg] -13, 00 mg.

Description:

Dosage (5 mg + 80 mg): tablets, covered with a film coating of dark yellow color, round biconvex. On the cut is white or almost white.

Dosage (5 mg + 160 mg): tablets, covered with a film shell of dark yellow color, oval biconvex with a risk. On the cut is white or almost white.

Dosage (10 mg +160 mg): tablets covered with a film coating of white or almost white color, oval biconvex with a risk. On the cut is white or almost white.

Pharmacotherapeutic group:Hypotensive combined agent (blocker of "slow" calcium channels + angiotensin II receptor antagonist)

ATX: & nbsp

C.08.C.A.01 Amlodipine

C.09.C.A.03 Valsartan

Pharmacodynamics:

Combined antihypertensive drug containing active substances with a complementary mechanism for controlling blood pressure (BP): amlodipine, a derivative of dihydropyridine, belongs to the class of blockers of "slow" calcium channels (BCCC) and valsartan - belongs to the class of angiotensin receptor antagonists II. The combination of these components has a mutually complementary antihypertensive effect, which leads to a more pronounced decrease in blood pressure compared to that of monotherapy with each drug.

Amlodipine

Amlodipine, which is part of the drug Exototans, inhibits transmembrannoe intake of calcium ions in cardiomyocytes and smooth muscle cells of blood vessels. The mechanism of antihypertensive action of amlodipine is associated with a direct relaxing effect on smooth muscle vessels, causing a decrease in overall peripheral vascular resistance and a decrease in blood pressure.

Experimental data show that amlodipine binds both to dihydropyridine and non-dihydropyridine receptors.

After taking in therapeutic doses in patients with hypertension amlodipine causes vasodilation, leading to a decrease in blood pressure (in the patient's position "lying" and "standing"). Decrease in blood pressure is not accompanied by a significant change in the heart rate (heart rate) and the concentration of catecholamines for prolonged use.

With arterial hypertension in patients with normal renal function amlodipine in therapeutic doses leads to a decrease in the resistance of renal vessels, an increase in the glomerular filtration rate and effective renal blood flow of the plasma without changing the filtration fraction and the level of proteinuria.

Also, as with other BCCI, amlodipine treatment in patients with normal left ventricular function (LV) caused a change in hemodynamic parameters of heart function at rest and under physical exertion: there was a slight increase in cardiac index without significantly affecting the maximum rate of increase pressure in the LV (dP/dt) and end-diastolic pressure and LV volume. Hemodynamic studies in intact animals and humans showed that a decrease in blood pressure under the influence of amlodipine in the range of therapeutic doses is not accompanied by a negative inotropic effect even when used simultaneously with β-blockers. Amlodipine does not change the function of the sinoatrial node or atrioventricular conduction in intact animals and humans. When using amlodipine in combination with β-blockers in patients with arterial hypertension or with angina, a decrease in blood pressure is not accompanied by undesirable changes in ECG parameters.

The clinical efficacy of amlodipine in patients with chronic stable angina, vasospastic angina and angiographically confirmed coronary artery disease was demonstrated.

Valsartan

Valsartan - an active and specific antagonist of angiotensin II receptors, intended for oral administration. It acts selectively on the AT subtype receptors₁, which are responsible for the known effects of angiotensin II. Increase in plasma concentration of free angiotensin II due to blockade AT ₁-receptors under the influence of valsartan can stimulate unlocked AT₂-receptors that counteract the effects of stimulation AT₁receptors. Valsartan does not have any expressed agonistic activity against AT₁receptors. The affinity of valsartan for the receptors of the subtype AT₁ approximately 20,000 times higher than to the AT subtype receptors₂.

Valsartan does not inhibit angiotensin-converting enzyme (ACE), also known as kininase II, which converts angiotensin I into angiotensin II and causes destruction of bradykinin.

Since angiotensin II antagonists do not inhibit ACE and accumulate bradykinin or substance P, the development of a dry cough is unlikely.

In comparative clinical studies of valsartan with an ACE inhibitor, the incidence of dry cough was significantly lower (p <0.05) in patients who received valsartan (2.6% of patients who received valsartan, and in 7.9% - those who received the ACE inhibitor). In a clinical study involving patients who previously developed a dry cough in the treatment with an ACE inhibitor, this complication was observed in 19.5% of cases with valsartan, and in 19% of cases with a thiazide diuretic. At the same time, in the group of patients treated with an ACE inhibitor, cough was observed in 68.5% of cases (p <0.05). Valsartan does not interact and does not block the receptors of other hormones or ion channels that are important for the regulation of cardiovascular functions.

In the treatment of valsartan in patients with hypertension, there is a decrease in blood pressure, not accompanied by a change in heart rate.

Antihypertensive effect occurs within 2 hours in most patients after a single dose. The maximum decrease in blood pressure develops in 4-6 hours. After taking the drug, the duration of the hypotensive effect lasts more than 24 hours.With repeated application, the maximum reduction in blood pressure, regardless of the dose taken, is usually achieved within 2-4 weeks and is maintained at the achieved level during prolonged therapy. A sharp discontinuation of valsartan is not accompanied by a sharp increase in blood pressure or other undesirable clinical consequences. The use of valsartan in patients with chronic heart failure (CHF) II-IV functional class by classification NYHA leads to a significant decrease in the number of hospitalizations. This effect is most pronounced in patients who do not receive ACE inhibitors or β-blockers. With the use of valsartan in patients with left ventricular failure (stable clinical course) or with LV dysfunction after myocardial infarction, cardiovascular mortality is reduced.

Pharmacokinetics:

The pharmacokinetics of valsartan and amlodipine are characterized by linearity.

Amlodipine

Suction

After ingestion of amlodipine in therapeutic doses of C_m_Oh Amlodipine in blood plasma is achieved through 6-12 hours. The absolute bioavailability is on the average 64 - 80%.Eating food does not affect the bioavailability of amlodipine.

Distribution

Volume of distribution (Vd) is approximately 21 l / kg. In studies with amlodipine in vitro It is shown that in patients with arterial hypertension, approximately 97.5% of circulating amlodipine binds to plasma proteins. The concentration of amlodipine in the blood plasma correlates with the clinical effect, both in young and elderly patients.

Metabolism

Amlodipine is intensively (approximately 90%) metabolized in the liver with the formation of active metabolites.

Excretion

Excretion of amlodipine from plasma has a two-phase character with a half-life (T₁/₂) for about 30 to 50 hours. The equilibrium concentrations (C_ss) in blood plasma are achieved after prolonged use for 7-8 days. 10 % unchanged amlodipine and 60% of amlodipine in the form of metabolites is excreted by the kidneys.

Valsartan

Suction

After oral administration of valsartan C_m_Oh in blood plasma is achieved in 2-3 hours. The average absolute bioavailability is 23%. When taking valsartan at the same time as food intake, there is a decrease in bioavailability (by value, the area under the "concentration-time" curve - AUC) by 40% and C_m_Oh in blood plasma by almost 50%, although approximately 8 hours after taking the drug the concentrations of valsartan in the blood plasma in the group of patients taking it with food and in the group taking on an empty stomach are equalized. Decrease AUC, However, there is no clinically significant reduction in the therapeutic effect, so valsartan can be administered regardless of the time of ingestion.

Distribution

Volume of distribution (Vd) valsartan during the equilibrium period after intravenous administration was about 17 liters, indicating a lack of extensive distribution of valsartan in the tissues. Valsartan is largely associated with serum proteins (94 - 97%), mainly with albumins.

Metabolism

Valsartan does not undergo a pronounced metabolism (about 20% of the dose is determined in the form of metabolites). The hydroxyl metabolite is determined in blood plasma at low concentrations (less than 10% of AUC valsartan). This metabolite is not pharmacologically active.

Excretion

The pharmacokinetic curve of valsartan has a downward multiexponential character (T_1/2α<1 h and T _1/2β about 9 hours). Valsartan is excreted mainly unchanged through the intestine (about 83% of the dose) and kidneys (about 13% of the dose). After intravenous administration, the plasma clearance of valsartan is about 2 l / h and its renal clearance is 0.62 l / h (about 30% of the total clearance). T_1/2valsartan is 6 hours.

Amlodipine / valsartan

After ingestion of the combination amlodipine / valsartan C_m_Oh Valsartan and amlodipine are achieved after 3 and 6 to 8 hours, respectively. The speed and degree of absorption of the drug are equivalent to the bioavailability of valsartan and amlodipine when taken in each of them as separate tablets.

Pharmacokinetics in special clinical cases

Children and teenagers ≤18 years old

Pharmacokinetic features of the use of Exototans in children under 18 years of age have not been established.

Patients aged ≥65 years

Time to reach C_m_Oh Amlodipine in blood plasma in young and elderly patients is the same. In elderly patients the clearance of amlodipine is slightly reduced, which leads to an increase AUC and T_1/2.

In elderly patients, the systemic effect of valsartan was somewhat more pronounced than in young patients, however, this was not clinically significant.Since tolerability of the drug components in the elderly and in younger patients is equally good, it is recommended to use the usual dosing regimens.

Patients with impaired renal function

In patients with impaired renal function, the pharmacokinetic parameters of amlodipine do not change significantly. There was no correlation between renal function (creatinine clearance - CC) and systemic exposure to valsartan (AUC) in patients with varying degrees of impaired renal function. It is not required to change the initial dose in patients with mild and moderate impairment of renal function.

Patients with impaired hepatic function

Patients with impaired liver function have reduced clearance of amlodipine, which leads to an increase AUC approximately 40-60%. On average, patients with impaired liver function of the lung (5-6 points on the Child-Pugh scale) and moderate (7 - 9 on the Child-Pugh scale) bioavailability AUC) Valsartan is doubled in comparison with healthy volunteers (of the corresponding age, sex and body weight). Exototans should be used with caution in patients with impaired liver function, obstructive diseases of the biliary tract.

Indications:Arterial hypertension (for patients who are shown combined therapy).

Contraindications:

- Hypersensitivity to amlodipine, other dihydropyridine derivatives, valsartan, and other auxiliary components of the drug;

- hereditary angioedema, or edema in patients on the background of previous therapy with ARA II;

- pregnancy planning, pregnancy and the period of breastfeeding;

- severe (more than 9 points on the scale Child-Pugh) degree of violations of the liver, biliary cirrhosis, cholestasis;

- severe violations of kidney function (QC less than 30 ml / min), hemodialysis;

- severe arterial hypotension (systolic blood pressure less than 90 mm Hg); collapse, cardiogenic shock;

- hemodynamically unstable heart failure after acute myocardial infarction;

- obstruction of the outflow tract of the left ventricle (including severe aortic stenosis, hypertrophic obstructive cardiomyopathy);

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the preparation contains lactose);

- children under 18 years of age (safety and efficacy of the drug in this category of patients have not been established to date);

- simultaneous use with aliskiren and preparations containing aliskiren, in patients with diabetes mellitus and / or moderate or severe renal dysfunction (GFR less than 60 mL / min / 1.73 m²).

Carefully:

If you have one of these diseases, always consult a doctor before using the drug.

Care should be taken when using the drug in patients with hyperkalemia, a deficiency in the body of sodium and / or a decrease in the volume of circulating blood (BCC). Caution should be used in patients with impaired renal function of mild and moderate severity (QA 30-50 ml / min).

Caution should be exercised in patients on a diet with restriction of table salt.

Care should be taken when using the drug in patients with unilateral or bilateral stenosis of the renal arteries, or stenosis of the artery of a single kidney. The safety of the drug in patients after a recent transplantation of the kidney is not established.

Also, as with the use of other vasodilators, special care should be taken when prescribing amlodipine drug in patients with stenosis of the mitral or aortic valve of mild to moderate severity, as well as hypertrophic obstructive cardiomyopathy.

Caution should be used when using Exototans in patients with chronic heart failure III-IV functional class for NYHA, with acute coronary syndrome, after acute myocardial infarction, in patients with impaired liver function of mild and moderate severity (<9 on the Child-Pugh scale), obstructive diseases of the biliary tract.

Pregnancy and lactation:

Exototans is contraindicated in pregnancy and during breast feeding.

Like any other drug that directly affects the renin-angiotensin-aldosterone system (RAAS), Exototans should not be used in women planning a pregnancy. Patients of childbearing age should be informed of the possible risk to the fetus associated with the use of drugs that affect RAAS.

Given the mechanism of action of angiotensin II receptor antagonists, the risk to the fetus can not be ruled out.It is known that the appointment of ACE inhibitors that affect RAAS, pregnant in the II and III trimesters, leads to damage or death of the developing fetus. According to a retrospective analysis of the use of ACE inhibitors in the first trimester of pregnancy, the development of fetal and newborn pathology was accompanied. In case of unintended admission of valsartan in pregnant women, cases of spontaneous abortion, malignancy and renal dysfunction in newborns are described. Data on the use of amlodipine in pregnant women is not enough to judge its effect on the fetus.

If the pregnancy is diagnosed during the treatment with Exototans, the drug should be discontinued as soon as possible.

It is not known whether the valsartan and / or amlodipine in breast milk. Since in experimental studies, the isolation of valsartan with milk of lactating animals was noted, the use of Exfotans during breast-feeding is not recommended.

There is no data on the effect of amlodipine and valsartan on fertility.

Dosing and Administration:

The drug should be taken orally, washed down with a small amount of water, once a day, regardless of the time of ingestion.

The recommended daily dose is 1 Exototans tablet containing amlodipine / valsartan in a dose of 5 mg + 80 mg or 5 mg + 160 mg or 10 mg + 160 mg (maximum daily dose for amlodipine in the form of Exototans, film-coated tablets, 10 mg + 160 mg).

It is recommended to start taking the drug at a dose of 5 mg + 80 mg once a day. You can increase the dose in 1 to 2 weeks after the start of therapy. The maximum dose of the drug is 10 mg + 320 mg per day.

Use in patients over 65 years of age

Correction of the dose is not required. In patients in this category, if necessary, it is possible to reduce the initial dose of Exototans to the lowest dose of amlodipine, i.e. one tablet containing amlodipine + valsartan in a dose of 5 mg + 80 mg or 5 mg + 160 mg (in the form of Exototans, film-coated tablets, 5 mg + 80 mg, 10 mg + 160 mg).

Use in children and adolescents under the age of 18 years

Since data on the safety and efficacy of Exototans in children of adolescents (under 18 years of age) is not sufficient, it is not recommended to use the drug in this category of patients.

Patients with impaired renal function

For patients with impaired renal function of mild and moderate severity (CK ≥ 30 ml / min), correction of the initial dose is not required.

Patients with impaired hepatic function

Exototans should be used with caution in patients with impaired liver function and obstructive diseases of the bile duct. In patients in this category, if necessary, it is possible to reduce the initial dose of Exototans to the lowest dose of amlodipine, i.e. one tablet containing amlodipine + valsartan in a dose of 5 mg + 80 mg or 5 mg + 160 mg (in the form of Exototans, film-coated tablets, 5 mg + 80 mg, 10 mg + 160 mg).

Side effects:

The following side effects are presented according to the following WHO frequency classification: very often (≥ 1/10), often (≥ 1/100 to <1/10), infrequently (≥ 1/1000 to <1/100 ), rarely (≥ 1/10000 to <1/1000), very rarely (<1/10000), frequency, unspecified (it is not possible to determine the frequency of occurrence according to available data). Within the limits of each group allocated according to the frequency of occurrence, adverse reactions are distributed in order of decreasing importance.

Infectious and parasitic diseases: often - nasopharyngitis, influenza.

From the immune system: rarely - hypersensitivity to the components of the drug.

From the side of metabolism and nutrition: often - hypokalemia, infrequently - anorexia, hypercalcemia, hyperuricemia, hyperlipidemia, hyponatremia.

Mental disorders: rarely - anxiety.

From the side of the central nervous system and the peripheral nervous system: often - headache; infrequently - dizziness, drowsiness, postural dizziness, paresthesia.

From the side of the organ of vision: rarely - visual impairment.

From the side of the hearing organ and labyrinthine disorders: infrequently - dizziness associated with impaired vestibular apparatus, rarely - tinnitus.

From the cardiovascular system: infrequently - tachycardia, palpitation, orthostatic hypotension; rarely - syncopal condition, marked decrease in blood pressure.

From the respiratory system, organs of the thorax and mediastinum: infrequently - cough, pain in the throat and larynx.

From the gastrointestinal tract: infrequently - diarrhea, nausea, abdominal pain, constipation, dryness of the oral mucosa.

From the skin and subcutaneous tissues: infrequently - skin rash, erythema; rarely - hyperhidrosis, exanthema, skin itching.

From the side of musculoskeletal and connective tissue: infrequently - swelling of the joints, back pain, arthralgia; rarely - muscle spasms, a feeling of heaviness in the whole body.

From the side of the kidneys and urinary tract: rarely - pollakiuria, polyuria.

From the genitals and mammary glands: rarely erectile dysfunction.

From the laboratory indicators: an increase in the concentration of urea nitrogen in the blood serum (more than 3.1 mmol / l) was observed only slightly more often in the groups receiving amlodipine / valsartan (5.5%) and valsartan in the form of monotherapy (5.5%), compared with the group receiving a placebo (4.5%).

Other: often - pastoznost, edema of the face, peripheral edema, increased fatigue, "tides" of blood to the face, asthenia, a feeling of heat.

The incidence of peripheral edema was significantly lower in patients receiving combination amlodipine with valsartan (5.8%) than in patients receiving amlodipine monotherapy (9%).

Undesirable effects reported earlier with each of the components may occur with Exototans, even if they have not been observed in clinical trials.

Amlodipine

From the side of the blood and lymphatic system: very rarely - leukopenia, thrombocytopenia.

From the immune system: very rarely - hypersensitivity reactions.

From the side of metabolism and nutrition: very rarely - hyperglycemia.

Mental disorders: infrequently - insomnia / sleep disorders, lability of mood.

From the side of the central nervous system and the peripheral nervous system: infrequently - tremor, hypoesthesia, dysgeusia; very rarely - muscle hypertonia, peripheral neuropathy.

From the side of the organ of vision: infrequently - diplopia;

From the cardiovascular system: very rarely - arrhythmia, bradycardia, ventricular tachycardia, atrial fibrillation, myocardial infarction, vasculitis.

From the respiratory system, chest and mediastinum: infrequently - shortness of breath, rhinitis.

From the gastrointestinal tract: infrequently - indigestion, vomiting; very rarely - gastritis, gingival hyperplasia, pancreatitis.

From the liver and biliary tract: very rarely - increased activity of "hepatic" enzymes (usually associated with cholestasis), hepatitis, jaundice.

From the skin and subcutaneous tissues: infrequently - alopecia, purpura, skin discoloration, photosensitization; very rarely - angioedema, urticaria, erythema multiforme, Stevens-Johnson syndrome.

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

From the side of the kidneys and urinary tract: infrequent - urination disorders, nocturia.

From the genitals and mammary glands: infrequently - gynecomastia.

Other: infrequent - weakness, pain in the chest, pain of different locations, increase or decrease in body weight.

Valsartan

From the side of the blood and lymphatic system: Unspecified frequency - reduction of hemoglobin and hematocrit, neutropenia, thrombocytopenia.

From the immune system: Unspecified frequency - hypersensitivity reactions, including serum sickness.

From the side of the hearing organ and labyrinthine disorders: infrequently - vertigo.

From the side of the vessels: unspecified frequency - vasculitis.

From the respiratory system, chest and mediastinum: infrequently - cough.

From the gastrointestinal tract: infrequently - abdominal discomfort, pain in the upper abdomen.

From the liver and bile ducts: Unspecified frequency - abnormal liver function, increased activity of "liver" enzymes, increased bilirubin concentration in blood plasma.

From the skin and subcutaneous tissues: unspecified frequency - angioedema, bullous dermatitis, skin itching, skin rash.

From the side of musculoskeletal and connective tissue: unspecified frequency - myalgia.

From the side of the kidneys and urinary tract: frequency, unspecified concentration of creatinine in the blood plasma, impaired renal function, including acute renal failure.

From the laboratory indicators: Unspecified frequency - an increase in the content of potassium in the blood plasma.

Other: infrequently - increased fatigue, asthenia.

Overdose:

There are no data on drug overdose cases at the present time.

Symptoms: with an overdose of valsartan, its main manifestation is a marked decrease in blood pressure, accompanied by dizziness. An overdose of amlodipine can lead to excessive peripheral vasodilation and possible reflex tachycardia. There was also reported the emergence of severe and prolonged systemic arterial hypotension until the development of shock with a lethal outcome.

Treatment: if the drug has been taken recently, induce vomiting or carry out gastric lavage. The use of activated carbon in healthy volunteers immediately or within 2 hours after taking amlodipine significantly reduced its absorption.In the absence of contraindications to restore vascular tone and blood pressure, it is possible to use (with caution) a vasoconstrictor. The excretion of valsartan and amlodipine during hemodialysis is unlikely.

Interaction:

Amlodipine

Simvastatin. Simultaneous long-term use of simvastatin in a daily dose of 80 mg and amlodipine in a daily dose of 10 mg leads to an increase in the exposure of simvastatin by 77%.

It is recommended to reduce the dose of simvastatin in patients taking amlodipine, up to 20 mg per day.

Inhibitor inhibitors CYP3A4. When amlodipine is used together with diltiazem, in elderly patients slowed metabolism of amlodipine, probably due to inhibition of the isoenzyme CYP3A4, which leads to an increase in the concentration of amlodipine in the blood plasma by approximately 50% and enhance the therapeutic effect. When using amlodipine together with strong inhibitors of isoenzymes CYP3A4 (eg, ketoconazole, itraconazole and ritonavir) a marked increase in the systemic exposure of amlodipine.

In connection with the inhibition of the isoenzyme SURCA4 with simultaneous administration with grapefruit juice, the bioavailability of amlodipine may increase.In a clinical study in healthy volunteers, however, there were no significant changes in pharmacokinetics when taking amlodipine at a dose of 10 mg with 240 ml of grapefruit juice.

Inductors of isoenzyme CYP3A4. Since the use of amlodipine together with isoenzyme inducers CYP3A4 (eg, carbamazepine, phenobarbital, phenytoin, phosphenytoin, primidon, rifampicin, grapefruit juice, herbal preparations containing Hypericum perforated), can lead to a marked decrease in its concentration in the blood plasma; when using amlodipine with isozyme inducers CYP3A4, it is necessary to control its therapeutic effect.

In monotherapy with amlodipine, no clinically significant interaction with thiazide diuretics, β-blockers, ACE inhibitors, long-acting nitrates, nitroglycerin for sublingual use, digoxin, warfarin, atorvastatin, sildenafil, magnesium hydroxide and aluminum hydroxide, simethicone, cimetidine, nonsteroidal anti-inflammatory drugs, antibiotics and oral hypoglycemic drugs.Simultaneous reception of amlodipine and ethanol does not affect the pharmacokinetics of the latter.

Valsartan

It was found that with monotherapy valsartan there is no clinically significant interaction with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.

Preparations and substances that affect the potassium content in blood serum. When used simultaneously with dietary supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other drugs that can cause an increase in potassium content in the blood (for example, with heparin), care should be taken and regular monitoring of potassium in the blood.

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of COX-2. The use of angiotensin II receptor antagonists concurrently with NSAIDs, including COX-2 inhibitors, can lead to a weakening of the hypotensive effect. In elderly patients, patients with reduced BCC (including those receiving diuretic therapy) or with renal dysfunction concurrent use of angiotensin II receptor antagonists and NSAIDs,including inhibitors of COX-2 may increase the risk of developing kidney dysfunction. At the beginning of therapy or when adjusting the dosing regimen in patients taking angiotensin II receptor antagonists and NSAIDs, including COX-2 inhibitors, regular monitoring of renal function is recommended.

Protein-carriers. The combined use of valsartan with inhibitors of the carrier protein OATP1B1 (rifampicin, ciclosporin) and with an inhibitor of carrier protein MRP2 (ritonavir) can lead to an increase in systemic bioavailability of valsartan.

Double blockade of RAAS with angiotensin II receptor antagonists, ACE inhibitors or aliskiren. Simultaneous use of an angiotensin II receptor blocker with other drugs that affect RAAS leads to an increase in the incidence of arterial hypotension, hyperkalemia, and renal dysfunction. The use of Exototans together with other drugs that directly affect RAAS should be addressed in each case individually, with careful monitoring of kidney function, electrolyte concentration in the blood, and blood pressure.Avoid concomitant use of drugs containing angiotensin II receptor antagonists, including Exototans, with other agents that affect RAAS in patients with type 2 diabetes and / or moderate or severe renal impairment (GFR less than 60 mL / min / 1 , 73 m²).

Contraindicated joint use of Exototans with aliskiren in patients with diabetes mellitus (see section "Contraindications"). It is necessary to avoid the joint use of Exototans and aliskiren in patients with impaired renal function.

Lithium preparations. With the simultaneous use of lithium preparations with ACE inhibitors and ARA II, a reversible increase in lithium serum levels was observed and, therefore, toxic effects were increased, therefore it is recommended to monitor the lithium content in serum. The risk of toxic manifestations associated with the use of lithium drugs may be further increased with simultaneous use with the drug Exototans and diuretics.

Special instructions:

Deficiency in the body of sodium and / or decrease in BCC

In placebo-controlled studies in patients with uncomplicated hypertension of 0.4 % of cases, pronounced arterial hypotension was observed. In patients with activated RAAS (eg, with a deficiency of bcc and / or sodium in patients receiving high doses of diuretics), with the admission of angiotensin receptor blockers, it is possible to develop symptomatic arterial hypotension. Before beginning treatment with Exototans, you should adjust the sodium content in the body and / or BCC, or begin therapy under close medical supervision.

In case of significant decrease in blood pressure, the patient should be placed with raised legs, if necessary, an intravenous infusion of 0.9 % solution of sodium chloride. After stabilization of blood pressure, Exototans treatment can be continued.

Hyperkalemia

With simultaneous use of the drug with dietary supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other drugs that can cause an increase in the potassium concentration in the blood (for example, with heparin), care should be taken and regular monitoring of potassium concentration in the blood .

Stenosis of the renal artery

In patients with unilateral or bilateral stenosis of the renal artery, or stenosis of the artery of a single kidney, the use of Exototans may be accompanied by an increase in the concentration of urea and creatinine in the serum, so Exfoltans should be used with caution in such patients.

Renal impairment

Patients with initial and moderate impairment of kidney function (CK 30-50 ml / min) are not required to correct the dose of ExFotanz.

Dysfunction of the liver

Valsartan is excreted mainly unchanged through the intestines with bile, while amlodipine intensively metabolized in the liver. Caution should be exercised when prescribing Exototans for patients with liver disease (especially with obstructive diseases of the biliary tract), accompanied by impaired liver function.

Angioedema, including angioedema

Angioedema, including swelling of the larynx and vocal cords leading to airway obstruction, and / or swelling of the face, lips, pharynx, and / or tongue edema, occurred in patients who received valsartan, some of these patients had angioedema earlier with other drugs, including AG1F inhibitors. The use of Exototans in the case of angioedema development should be immediately canceled, the resumption of taking the drug is contraindicated.

Heart failure, condition after myocardial infarction It is recommended to use with caution the blockers of "slow" calcium channels (including, amlodipine) in patients with CHF III-IV functional class for NYHA. In patients whose renal function depends on the state of RAAS (eg, patients with CHF III-IV functional class for NYHA), therapy with ACE inhibitors and angiotensin II receptor antagonists was accompanied by oliguria and / or progressive azotemia, and in rare cases led to acute renal failure and / or death. The examination of patients with circulatory failure and patients who underwent myocardial infarction should include a study of kidney function.

Acute myocardial infarction

After the start of therapy (or increasing the dose) of amlodipine, there may occur an attack of angina or develop myocardial infarction,especially in patients with severe ischemic heart disease.

The drug is not intended for use in patients with diabetes mellitus.

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

There are no data on the effect of the drug on the ability to drive vehicles and work with mechanisms. In connection with the possible occurrence of dizziness or increased fatigue, care should be taken when driving vehicles or working with mechanisms.

Form release / dosage:

Tablets, film-coated, 5 mg + 80 mg, 5 mg + 160 mg, 10 mg + 160 mg.

Packaging:

For 14 tablets in a polyvinylchloride or PVC / PVDC / PVC / PVC / Polyethylene / PVDC jig and foil of aluminum printed lacquered 2, 4 or 6 contour squares, together with the instruction for use, they are placed in a pack of cardboard.

For 14 or 28 tablets in a polymer tube with a cap - compensator. Tubu together with instructions for use are placed in a pack of cardboard.

Storage conditions:

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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003718

Date of registration:11.07.2016

Expiration Date:11.07.2021

The owner of the registration certificate:PHARMSTANDART-TOMSKHIMFARM, OJSC PHARMSTANDART-TOMSKHIMFARM, OJSC Russia

Manufacturer: & nbsp

PHARMSTANDART-TOMSKHIMFARM, OJSC Russia

Information update date: & nbsp13.09.2016

Illustrated instructions

Instructions

Exototans (Exfotans)