Amlodipine + Valsartan - instructions for use, dose, side effects, contraindications

Excipients (core): cellulose microcrystalline - 76.76 mg, croscarmellose sodium - 7.00 mg, povidone-K25 - 5.00 mg, silicon dioxide colloid - 2.70 mg, magnesium stearate - 1.60 mg.

Auxiliary substances (shell): hypromellose - 3,42 mg, macrogol-4000 - 0,90 mg, titanium dioxide - 1,68 mg.

Amlodipine + Valsartan 5.0 mg + 160.0 mg contains:

Active substances: amlodipine besylate - 6.94 mg in terms of amlodipine - 5.00 mg, valsartan - 160.00 mg.

Excipients (core): cellulose microcrystalline - 160.46 mg, croscarmellose sodium - 14.00 mg, povidone-K25 - 10.00 mg, silicon dioxide colloid - 5.40 mg, magnesium stearate - 3.20 mg.

Auxiliary substances (shell): hypromellose - 6.84 mg, macrogol-4000 - 1.80 mg, iron dye red oxide - 0.12 mg, titanium dioxide - 3.24 mg.

Amlodipine + Valsartan 10.0 mg + 160.0 mg contains:

Active substances: amlodipine besylate - 13.88 mg in terms of amlodipine - 10.00 mg, valsartan - 160.00 mg.

Excipients (core): cellulose microcrystalline - 153.52 mg, croscarmellose sodium - 14.00 mg, povidone-K25 - 10.00 mg, silicon dioxide colloid - 5.40 mg, magnesium stearate - 3.20 mg.

Auxiliary substances (shell): hypromellose - 6.84 mg, macrogol-4000 - 1.80 mg, titanium dioxide - 3.36 mg.

Description:

Dosage 5 mg + 80 mg. Round biconvex tablets covered with a film coat of white or almost white color. On the fracture, two layers are visible: a white or almost white core and a film shell.

Dosage 5 mg + 160 mg. Round biconvex tablets, covered with a film coat from pink to light pink. On the fracture, two layers are visible: a white or almost white core and a film shell.

Dosage of 10 mg + 160 mg. Round biconvex tablets covered with a film coat of white or almost white color. On the fracture, two layers are visible: a white or almost white core and a film shell.

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:

The drug "Amlodipine + Valsartan" is a combination of two antihypertensive components with a complementary mechanism for monitoring blood pressure (BP): amlodipine, a dihydropyridine derivative, belongs to the group of "slow" calcium channel blockers (BCCC) and valsartan - to the group of angiotensin II receptor antagonists (ARAP). 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 component.

Amlodipine

Amlodipine, which is part of the drug Amlodipine + Valsartan, 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 the smooth muscle of the vessels, causing a decrease in total peripheral vascular resistance (OPSS) and a decrease in blood pressure.

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").Reduction of blood pressure is not accompanied by a significant change in the heart rate (heart rate) and the level of catecholamines for prolonged use.

The concentration of amlodipine in the blood plasma correlates with the clinical effect, both in young and elderly patients.

With arterial hypertension in patients with normal renal function amlodipine at therapeutic doses lead to a decrease in renal vascular resistance, increased glomerular filtration rate and effective renal plasma flow without changing filtration fraction and the degree of proteinuria.

As well as the application of other BCCI, amlodipine in patients with normal left ventricular function (LV) causes a change in hemodynamic parameters of cardiac function at rest and during exercise: noted a small increase in cardiac index without significant influence on the maximum rate of pressure rise in the left ventricle (dP/dt) and end-diastolic pressure and LV volume. Hemodynamic studies in intact animals and humans have shown that lowering blood pressure under the influence of amlodipine in the therapeutic dose range is not accompanied by a negative inotropic effect even while the use of beta-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 beta-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 AT1 subtype receptors, which are responsible for the known effects of angiotensin II. An increase in the plasma concentration of free angiotensin II due to blockade of AT1 receptors under the influence of valsartan can stimulate unblocked AT2 receptors that counteract the effects of stimulation of AT1 receptors. Valsartan does not have any expressed agonistic activity with respect to AT2 receptors. The affinity of valsartan for the receptors of the subtype AT1 approximately 20,000 times higher than to the AT2 subtype receptors.

Valsartan does not inhibit the angiotensin-converting enzyme, also known as kininase II, which converts angiotensin I into angiotensin II and causes bradykinin to break down.

Since angiotensin II antagonists do not inhibit ACE and accumulate bradykinin or substance P, the development of a dry cough is unlikely. 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 after 4-6 hours. After taking the drug, the duration of the antihypertensive effect persists for more than 24 hours. When repeated, the maximum decrease in blood pressure, regardless of the dose taken, is usually achieved within 2-4 weeks and maintained at the reached 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 (according to the classification NYHA functional classes II-IV) leads to a significant decrease in the number of hospitalizations. This effect is most pronounced in patients who do not receive ACE inhibitors or beta-blockers. When taking valsartan in patients with left ventricular failure (stable clinical course) or with a violation of LV function after a previous myocardial infarction, there is a decrease in cardiovascular mortality.

Amlodipine / Valsartan

The combination of amlodipine and valsartan additively and dose-dependent in the therapeutic range of doses reduces blood pressure. When taking one dose of the amlodipine / valsartan combination, the hypotensive effect persists for 24 hours.

The clinical efficacy of the amlodipine / valsartan combination in patients with mild to moderate arterial hypertension (mean diastolic BP> 95 mmHg and <110 mmHg) without complications was compared with placebo.

Severity of blood pressure lowering in the "sitting" position with arterial hypertension with DB>> mm Hg. Art. and <120 mm Hg. Art. is comparable to the combination of an angiotensin-converting enzyme (ACE) inhibitor and a thiazide diuretic.

The hypotensive effect persists for a long time. Sudden withdrawal of the drug is not accompanied by a sharp increase in blood pressure (there is no "withdrawal" syndrome). The therapeutic effectiveness does not depend on the age, sex, race of the patient and body mass index.

When combined amlodipine / valsartan therapy is used, comparable blood pressure control is achieved with a lower probability of peripheral edema development in patients with previously achieved BP control and severe peripheral edema with amlodipine therapy.

Pharmacokinetics:

The pharmacokinetics of amlodipine and valsartan are characterized by linearity.

Amlodipine

Suction

After oral administration amlodipine slowly absorbed from the gastrointestinal tract (GIT).

After oral administration at therapeutic doses, the maximum concentration of amlodipine in the blood plasma is reached after 6-12 hours. The absolute bioavailability is on the average 64% - 80%.Eating food does not affect the bioavailability of amlodipine.

Distribution

The distribution volume 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.

Metabolism

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

Excretion

Excretion of amlodipine from plasma is biphasic with terminal half-life (T1/2) from about 30 to 50 hours. Equilibrium concentrations in the blood plasma are achieved after prolonged use for 7-8 days. 10% of unchanged amlodipine and 60% of amlodipine in the form of metabolites is excreted by the kidneys. Amlodipine is not excreted from the body by dialysis.

Valsartan

Suction

After oral administration of valsartan, the maximum concentration in the blood plasma is reached after 2-3 hours. The average absolute bioavailability is 23%.

The pharmacokinetic curve of valsartan has a downward multiexponential character (T1 / 2a<1 h and T1 / 2β about 9 h). When taking valsartan with food, there is a decrease in bioavailability (in terms of the area under the concentration-time curve, AUC) by 40% and the maximum concentration (C_mаx) in the blood plasma by almost 50%, although approximately 8 hours after taking the drug, valsartan plasma concentrations during ingestion with food and 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 in the equilibrium state after ingestion 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 pharmacologically active.

Excretion

Valsartan is excreted mainly unchanged through the intestine (about 83% of the dose) and with the kidneys (about 13% of the dose). T1 / 2 valsartan is 6 hours.

Amlodipine / Valsartan

After ingestion of the drug Amlodipine + Valsartan the maximum concentrations of valsartan and amlodipine are reached after 3 and 6-8 hours, respectively. The rate and extent of absorption of valsartan and amlodipine in the formulation Amlodipine + Valsartan are equivalent to the bioavailability of valsartan and amlodipine when taken separately.

Pharmacokinetics in special clinical cases Children

Pharmacokinetic features of the combination drug application amlodipine and valsartan in children under 18 years of age are not established.

Elderly patients

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 T1/₂.

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) and systemic exposure to valsartan (AUC) in patients with varying degrees of impaired renal function.

There is no need to change the initial dose in patients with initial and moderate impairment of renal function (creatinine clearance (CK) 30-50 ml / min).

Patients with impaired hepatic function

Patients with hepatic insufficiency have reduced clearance of amlodipine, which leads to an increase AUC approximately 40-60%.

On average, in patients with impaired hepatic function (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).

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

Contraindications:

Hypersensitivity to amlodipine, other derivatives of dihydropyridine, valsartan, as well as other auxiliary components of the drug.

Hereditary angioedema, or edema in patients on the background of previous therapy with angiotensin II receptor antagonists.

Severe hepatic insufficiency (> 9 on the Child-Pyo scale), biliary cirrhosis, cholestasis.

Severe renal dysfunction (CC less than 30 mL / min); use in patients on hemodialysis.

Pregnancy, use in planning pregnancy and the period of breastfeeding.

Severe arterial hypotension (systolic blood pressure less than 90 mm Hg).

Age to 18 years (effectiveness and safety not established).

Shock (including cardiogenic), collapse.

Obstruction of the left ventricular outflow tract (including hypertrophic obstructive cardiomyopathy (GOKMP)), severe aortic stenosis expression.

Hemodynamically unstable heart failure after acute myocardial infarction.

Primary hyperaldosteronism.

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

Safety of the drug Amlodipine + Valsartan in patients after the transplantation of the kidney is not established.

Carefully:impaired liver function of the lung (5-6 points on the Child-Pugh scale) and moderate (7-9 points on the Child-Pugh scale), severity, obstructive diseases of the biliary tract, renal failure of mild and moderate severity (QC 30-50 ml / min), unilateral or bilateral stenosis of the renal arteries or stenosis of the single kidney artery, chronic heart failure (CHF) III-IV functional class by classification NYHA, acute coronary syndrome, after myocardial infarction, hyperkalemia, hyponatremia, diet with restriction of salt intake, reduced circulating blood volume (bcc) (including diarrhea, vomiting), hypertrophic obstructive cardiomyopathy, simultaneous use of drugs containing angiotensin receptor antagonists II (ARAN), with other agents that inhibit the renin-angiotensin-aldosterone system, such as ACE inhibitors or aliskiren, including in patients with impaired renal function.

Pregnancy and lactation:

Like any other drug that affects the renin-angiotensin-aldosterone system (RAAS), the drug Amlodipine + Valsartan should not be used in women planning a pregnancy. When the drug is prescribed Amlodipine + Valsartan, as well as any other drug that affects RAAS, the doctor should inform women of reproductive age about the possible risk to the fetus,related to the use of the drug.

Application of the drug Amlodipine + Valsartan when pregnancy is contraindicated. 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 use of ACE inhibitors that affect RAAS, pregnant in the II and III trimesters, led to the development of fetotoxic effects (renal dysfunction, osteopenia of the fetal skull, oligohydramnios) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia) and the death of the developing fetus. According to a retrospective analysis of the use of ACE inhibitors during 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 pregnancy is diagnosed during drug therapy Amlodipine + Valsartan, the drug should be discontinued as soon as possible.

It is not known whether the valsartan and / or amlodipine in breast milk. Since in the experimental studies, the isolation of valsartan with milk of lactating animals was noted, it is not recommended to apply Amlodipine + Valsartan in the period of breastfeeding.

If you need to take the drug during lactation, you should stop breastfeeding.

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 tablet of the drug Amlodipine + Valsartan, containing amlodipine / valsartan in a dose of 5/80 mg, 5/160 mg, 10/160 mg. The recommended maximum daily dose is 10/160 mg.

It is recommended to start taking the drug at a dose of 5/80 mg once a day. Increase the dose can be in 1-2 weeks from the start of therapy.

Use in patients over 65 years of age Correction of the dose is not required.

Use in patients with impaired renal function

For patients with initial or moderate renal dysfunction (CK> 30 ml / min), correction of the initial dose of the drug is not required.

Use in patients with impaired hepatic function

In severe hepatic insufficiency, the drug Amlodipine + Valsartan is contraindicated.

The maximum daily dose for valsartan for mild to moderate hepatic insufficiency is 80 mg, use of the drug Amlodipine + Valsartan in a dose of 5/160 mg, and 10/160 mg in these patients is contraindicated.

Side effects:

When assessing the incidence of side effects, the following criteria were used: the term "very often" is used if more than 10% of patients report adverse events; the notion of "often" - in 1% - 10%; the concept of "infrequently" - in 0.1% - 1%; the concept of "rare" - 0.001% - 0.1%; the term "in some cases" - less than 0.001% of patients, "frequency unknown" - can not be calculated from available data.

Combination of amlodipine and valsartan

Infectious and parasitic diseases: often - nasopharyngitis, influenza.

Immune system disorders: rarely - hypersensitivity.

Disorders from the side of the organ of vision: rarely - visual impairment.

Hearing disorders and labyrinthine disturbances: infrequently - vertigo; rarely - noise in the ears.

Disorders of the psyche: rarely - anxiety.

Impaired nervous system: often - headache; infrequently - dizziness, drowsiness, postural dizziness, paresthesia.

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

Disturbances from the respiratory system, chest and mediastinal organs: infrequently - cough, pain in the throat and larynx.

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

Disorders from the rut and subcutaneous tissues: infrequently - skin rash, erythema; rarely - hyperhidrosis (increased sweating), exanthema, skin itching.

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

Disorders from the urogenital system: rarely - pollakiuria, polyuria, erectile dysfunction.

General disorders: often - pastoznost, edema of the face, increased fatigue, asthenia, "tides" of blood to the skin of the face, peripheral swelling, a feeling of heat. Laboratory and instrumental data: increase in the concentration of urea nitrogen in the blood serum (more than 3.1 mmol / l).

Amlodipine

When using amlodipine in monotherapy, there were also other side effects:

Violations from the blood and lymphatic system: very rarely - leukopenia, thrombocytopenia.

Immune system disorders: very rarely - allergic reactions. Disorders from the metabolism and nutrition: very rarely - hyperglycemia. Disorders of the psyche: infrequently - insomnia, lability of mood.

Impaired nervous system: infrequently - taste disorders, hypoesthesia, tremor, dysgeusia; very rarely - muscle hypertonia, peripheral neuropathy. Disorders from the side of the organ of vision: infrequently it is diplopia.

Hearing disorders and labyrinthine disturbances: infrequently, noise in the ears. Heart Disease: very rarely - arrhythmias (including bradycardia, ventricular tachycardia, atrial fibrillation), myocardial infarction.

Vascular disorders: very rarely - vasculitis.

Disturbances from the respiratory system, chest and mediastinal organs: infrequently - shortness of breath, rhinitis.

Disorders from the digestive system: infrequently - indigestion, vomiting; very rarely - gastritis, gingival hyperplasia, pancreatitis.

Disorders from the liver and bile ducts: very rarely - hepatitis, jaundice.

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

Disturbances from the musculoskeletal system and connective tissue: infrequently - myalgia.

Disorders from the kidneys and urinary tract: infrequently - violations urination, nocturia.

Violations of the genitals and breast: infrequently - gynecomastia. General disorders: infrequently - weakness, pain in the chest, pain of different locations.

Laboratory and instrumental data: infrequently - increase or decrease in body weight; very rarely - increased activity of "liver" transaminases (usually associated with cholestasis).

Valsartan

Violations from the blood and lymphatic system: the frequency is unknown - a decrease in hemoglobin and hematocrit, neutropenia, thrombocytopenia.

Immune system disorders: frequency is unknown - hypersensitivity reactions, including serum sickness.

Hearing disorders and labyrinthine disturbances: infrequently - vertigo. Vascular disorders: frequency is unknown - vasculitis.

Disturbances from the respiratory system, chest and mediastinal organs: infrequently - cough.

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

Disorders from the liver and bile ducts: the frequency is unknown - a violation of liver function, increased activity of "liver" enzymes, an increase in the concentration of bilirubin in the blood plasma.

Disturbances from the skin and subcutaneous fabrics: very rarely - angioedema, frequency unknown - itching, rash, bullous dermatitis.

Disturbances from the musculoskeletal system and connective tissue: frequency is unknown - myalgia.

Disorders from the kidneys and urinary tract: frequency unknown - increased creatinine concentration in blood plasma, impaired renal function, including acute renal failure.

General disorders: infrequently - increased fatigue, asthenia.

Laboratory and instrumental data: frequency unknown - increase the content of potassium in the blood plasma.

Overdose:

There are no data on drug overdose cases at the present time. With an overdose of valsartan, one can expect the development of 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: induce vomiting (if the drug was taken recently) or to wash the stomach. The use of activated carbon in healthy volunteers immediately or within 2 hours after taking amlodipine significantly reduced its absorption. With a clinically pronounced decrease in blood pressure caused by the drug Amlodipine + Valsartan, it is necessary to lay the patient, raise his legs, take active measures to support the activity of the cardiovascular system, including regular monitoring of heart and respiratory system function, bcc and the amount of excreted urine. In the absence of contraindications to restore vascular tone and blood pressure, it is possible to use (with caution)vasoconstrictor.

The excretion of valsartan and amlodipine during hemodialysis is unlikely.

Interaction:

Simvastatin. Simultaneous long-term use of simvastatin at a dose of 80 mg / day and amlodipine at a dose of 10 mg / day leads to a 77% increase in the exposure of simvastatin. It is recommended to reduce the dose of simvastatin in patients taking amlodipine, up to 20 mg / 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 an increase in the clinical effect. When using amlodipine together with strong inhibitors of isoenzyme CYP3A4 (eg, ketoconazole, itraconazole and ritonavir) a marked increase in the systemic exposure of amlodipine.

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 isoenzyme inducers CYP3A4, it is necessary to control its clinical effect. When monotherapy with amlodipine, there is no clinically significant interaction with thiazide diuretics, alpha-adrenoblockers, beta-blockers, ACE inhibitors, long-acting nitrates, nitroglycerin for sublingual use, digoxin, warfarin, atorvastatin, sildenafil, maalox (aluminum- or magnesium-containing antacids, simethicone), cimetidine, non-steroidal anti-inflammatory drugs, antibiotics and hypoglycemic agents for oral administration.

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.

Drugs and substances that affect the potassium content in blood serum: at simultaneous appointment with biologically active additives containing potassium, potassium-sparing diuretics,potassium-containing salt substitutes, or with other drugs that can cause an increase in potassium 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 cyclooxygenase-2 (COX-2): administration of receptor antagonists angiotensin II concomitantly with NSAIDs may lead to a weakening of the antihypertensive effect. In elderly patients, patients with BCC deficiency (including those receiving diuretic therapy) or with renal dysfunction, the simultaneous administration of angiotensin II receptor antagonists and NSAIDs may lead to an increased risk of impaired renal function. At the onset or change of the mode of simultaneous use by patients of angiotensin II receptor antagonists and NSAIDs, regular monitoring of kidney function is recommended.

Protein-carriers

The simultaneous 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 the use of ARAP, ACE inhibitor, aliskiren Simultaneous use of angiotensin II receptor antagonists with other drugs that affect RAAS leads to an increase in the incidence of arterial hypotension, hyperkalemia, and renal dysfunction. It is necessary to monitor the indices of blood pressure, kidney function, as well as the content of plasma electrolytes when applied preparation

Amlodipine +Valsartan with other drugs that affect RAAS.

Avoid concurrent use of ARAN-containing drugs, including Amlodipine + Valsartan, with other agents that affect RAAS in patients with diabetes mellitus and severe renal insufficiency.

Lithium preparations

With the simultaneous use of lithium preparations with ACE inhibitors and ARAN, a reversible increase in the lithium content in the blood serum and an increase in the toxic manifestations of lithium are therefore observed, therefore it is recommended to monitor the lithium content in the blood serum. The risk of toxic manifestations associated with the use of lithium drugs may be further increased with simultaneous use with the drug Amlodipine + Valsartan and diuretics.

Special instructions:

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

In patients with uncomplicated arterial hypertension, severe arterial hypotension was observed in 0.4% of cases. In patients with activated RAAS (eg, with a deficiency of bcc and / or sodium in patients receiving high doses of diuretics), with the administration of ARAP, symptomatic arterial hypotension may develop. Before starting treatment with the drug Amlodipine + Valsartan should adjust the sodium content in the body and / or BCC, or start therapy under close medical supervision. In case of development of arterial hypotension, the patient should be placed with raised legs, if necessary, an intravenous infusion of 0.9% sodium chloride solution. After stabilization of blood pressure treatment with the drug Amlodipine + Valsartan can be continued.

Hyperkalemia

With the simultaneous application of the drug with the biologically active additives containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes or other drugs that may cause increased potassium concentrations in the blood (e.g., heparin),care should be taken and regular monitoring of potassium 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, taking the drug Amlodipine + Valsartan may be accompanied by an increase in the concentration of urea and creatinine in the blood serum, so in such patients the drug should be used with caution.

Violations of the function of the nights

Patients with initial and moderate impairment of renal dosing correction function Amlodipine + Valsartan not required.

Dysfunction of the liver

Valsartan is excreted mainly unchanged through the intestines with bile, while amlodipine intensively metabolized in the liver. Care should be taken when using the drug Amlodipine + Valsartan in patients with liver disease (especially with obstructive diseases of the biliary tract), accompanied by impaired liver function.

Edema Quincke

Quincke's edema, 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 taking valsartan, some of these patients previously developed Quincke's edema on the background of the use of other drugs, including ACE inhibitors. Reception of the drug Amlodipine + Valsartan In case of development of the edema Quincke should be immediately canceled, the resumption of the use of the drug Amlodipine + Valsartan forbidden.

Heart failure, condition after myocardial infarction

It is recommended to use with caution the blockers of "slow" calcium channels (including amlodipine) in patients with chronic heart failure III-IV functional class by classification NYHA. In patients whose kidney function is depends on the activity of RAAS, therapy with ACE inhibitors and ARAP may be accompanied by the development of oliguria and / or progressive azotemia, and, in rare cases, acute renal failure and / or death. Evaluation of patients with heart failure or myocardial infarction should include evaluation of renal function.

Acute myocardial infarction

After the initiation of therapy (or increasing the dose) of amlodipine, angina may occur or a myocardial infarction may develop, especially in patients with severe coronary heart disease.

Mitral stenosis / aortic stenosis / hypertrophic obstructive cardiomyopathy

As with other vosodilating agents, caution should be exercised when using amlodipine in patients with stenosis of the aortic or mitral valve or with hypertrophic obstructive cardiomyopathy.

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 should be careful when driving vehicles or working with mechanisms.

Form release / dosage:

Tablets, film-coated 5.0 + 80.0 mg, 5.0 + 160.0 mg, 10.0 + 160.0 mg.

Packaging:

For 10, 20, 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 tablets in cans of polyethylene terephthalate. One jar or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 contour mesh packages together with the instruction for use are placed in a cardboard package.

It is allowed to bundle 2 or 3 cardboard packages (packs) into a group package (shipping container) from cardboard for consumer packaging.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002680

Date of registration:24.10.2014

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp24.10.2014

Illustrated instructions

Instructions

Amlodipine + Valsartan (Amlodipine + Valsartan)