Vamloset

Vamloset®

The drug Vamloset®

Common drug interactions for Vamloset® (amlodipine/valsartan)

Concomitant use requiring attention

Other antihypertensive drugs (eg, alpha-blockers, diuretics) and drugs that have a hypotensive effect (eg, tricyclic antidepressants, alpha-blockers for the treatment of benign prostatic hyperplasia) may enhance the antihypertensive effect.

Drug interactions for amlodipine

Undesirable simultaneous use

Grapefruit or grapefruit juice

Concomitant use is not recommended due to the possibility of increased bioavailability in some patients and enhanced antihypertensive effects.

Concomitant use requiring caution

CYP3A4 isoenzyme inhibitors

Concomitant use with strong or moderate inhibitors of the CYP3A4 isoenzyme (protease inhibitors, verapamil or diltiazem, azole antifungals, macrolides such as erythromycin or clarithromycin) may lead to a significant increase in the systemic exposure of amlodipine. In elderly patients, these changes are of clinical significance, so medical supervision and dosage adjustment are necessary.

Inducers of the CYP3A4 isoenzyme (anticonvulsants (for example, carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin, herbal preparations containing St. John's wort)

With simultaneous use of inducers of the CYP3A4 isoenzyme, the concentration of amlodipine in the blood plasma may vary. Therefore, blood pressure control and dose adjustment of amlodipine are indicated both during treatment with inducers of the CYP3A4 isoenzyme and after their withdrawal, especially when using strong inducers of the CYP3A4 isoenzyme (for example, rifampicin, drugs containing St. John's wort).

Simvastatin

Simultaneous repeated use of amlodipine at a dose of 10 mg/day and simvastatin at a dose of 80 mg/day increases the exposure of simvastatin by 77% compared with that of simvastatin monotherapy. For patients receiving amlodipine, it is recommended to use simvastatin at a dose of no more than 20 mg/day.

Dantrolene (intravenous administration)

In animal experiments, cases of fatal ventricular fibrillation and cardiovascular failure associated with hyperkalemia were observed after oral administration of verapamil and intravenous administration of dantrolene. Given the risk of developing hyperkalemia, simultaneous use of slow calcium channel blockers, including amlodipine, should be avoided in patients prone to developing malignant hyperthermia.

Tacrolimus

When used concomitantly with amlodipine, there is a risk of increasing the concentration of tacrolimus in the blood plasma, but the pharmacokinetic mechanism of this interaction has not been fully studied. To prevent the toxic effect of tacrolimus when used concomitantly with amlodipine, the concentration of tacrolimus in the blood plasma should be monitored and the dose of tacrolimus should be adjusted if necessary.

Cyclosporine

Drug interaction studies have not been conducted with cyclosporine and amlodipine in healthy volunteers or other patient populations, except for renal transplant patients in whom variable trough concentrations (mean: 0%-40%) of cyclosporine were observed. With the simultaneous use of amlodipine in patients who have undergone kidney transplantation, the concentration of cyclosporine in the blood plasma should be monitored and, if necessary, its dose should be reduced.

Clarithromycin

Clarithromycin is an inhibitor of the CYP3A4 isoenzyme. With simultaneous use of amlodipine and clarithromycin, the risk of developing arterial hypotension is increased. Close medical monitoring of patients receiving amlodipine concomitantly with clarithromycin is recommended.

Mammalian target of rapamycin (mTOR) inhibitors

mTOR inhibitors such as sirolimus, temsirolimus and everolimus are substrates of the CYP3A isoenzyme. Amlodipine is a weak inhibitor of the CYP3A isoenzyme. When used concomitantly with mTOR inhibitors, amlodipine may increase their exposure.

Concomitant use requiring attention

Other

In clinical studies of amlodipine, there was no significant interaction with thiazide diuretics, alpha-blockers, beta-blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, Maalox (aluminum- or magnesium-containing antacids, simethicone) , cimetidine, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics and oral hypoglycemic agents.

Simultaneous use of amlodipine and ethanol

does not affect the pharmacokinetics of the latter.

Calcium preparations

may reduce the effect of BMCC.

With simultaneous use of BMCC with lithium preparations

(no data available for amlodipine) their neurotoxicity may increase (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Glucocorticosteroids

Decreased antihypertensive effect (retention of fluid and sodium ions as a result of action (retention of fluid and sodium ions as a result of the action of corticosteroids).

Drug interactions for valsartan

Concomitant use is contraindicated

Concomitant use of ARB II, including valsartan, with aliskiren and drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients.

Concomitant use of ARB II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Undesirable simultaneous use

Lithium

Simultaneous use with lithium preparations is not recommended, since a reversible increase in the concentration of lithium in the blood plasma and the development of intoxication are possible. If simultaneous use with lithium preparations is necessary, the concentration of lithium in the blood plasma should be carefully monitored. The risk of toxic effects associated with the use of lithium preparations may further increase when used simultaneously with Vamloset® and diuretics.

Potassium-sparing diuretics, potassium supplements, potassium-containing dietary supplements, and other drugs and substances that may increase serum potassium levels (eg, heparin)

If simultaneous use with drugs that affect potassium levels is necessary, it is recommended to monitor the potassium content in the blood plasma.

Concomitant use requiring caution

NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, acetylsalicylic acid in a dose of more than 3 g/day and non-selective NSAIDs

With simultaneous use, it is possible to weaken the antihypertensive effect, increase the risk of developing renal dysfunction and increase the potassium content in the blood plasma. At the beginning of therapy, it is recommended to assess renal function, as well as correct water and electrolyte imbalances.

Transport protein inhibitors

in vitro study results

valsartan is a substrate for the transporter proteins OATP1B1 and MRP2. Concomitant use of valsartan with OATP1B1 transporter protein inhibitors (eg, rifampicin, cyclosporine) and an MRP2 transporter protein inhibitor (eg, ritonavir) may increase the systemic exposure of valsartan (Cmax and AUC). This should be taken into account at the beginning and at the end of concomitant therapy.

Double blockade of the RAAS when using ARA II, ACE inhibitors or aliskiren

The simultaneous use of ARA II with other drugs that affect the RAAS leads to an increase in the incidence of cases of arterial hypotension, hyperkalemia, and renal dysfunction. It is necessary to monitor blood pressure, renal function, and the content of blood plasma electrolytes when using Vamloset® with other drugs that affect the RAAS.

Other

When monotherapy with valsargan, no clinically significant interactions were identified with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide.

A combined antihypertensive drug containing active substances with a complementary mechanism for blood pressure control. Amlodipine, a dihydropyridine derivative, belongs to the class of slow calcium channel blockers (SCBCs), valsartan belongs to the class of angiotensin II receptor antagonists. The combination of these components has a mutually complementary antihypertensive effect, which leads to a more pronounced reduction in blood pressure than when they are used separately.

Amlodipine/Valsartan

The combination of amlodipine and valsartan reduces blood pressure in an additive dose-dependent manner over the therapeutic dose range. When taking the amlodipine/valsartan combination in a single dose, the hypotensive effect persists for 24 hours.

The antihypertensive effect lasts for a long time. Sudden cessation of drug use is not accompanied by a sharp increase in blood pressure (there is no withdrawal syndrome).

Therapeutic effectiveness does not depend on the patient's age, gender, race and body mass index.

When using combination therapy with amlodipine/valsartan, comparable blood pressure control is achieved with a lower likelihood of developing peripheral edema in patients with previously achieved blood pressure control and severe peripheral edema during amlodipine therapy.

Amlodipine

Amlodipine is a dihydropyridine derivative, a slow calcium channel blocker, and has antianginal and antihypertensive effects. Inhibits the transmembrane entry of calcium ions into cardiomyocytes and vascular smooth muscle cells. The mechanism of the antihypertensive effect of amlodipine is due to a direct relaxing effect on vascular smooth muscle, which leads to a decrease in peripheral vascular resistance and blood pressure.

Amlodipine in therapeutic doses in patients with arterial hypertension causes dilation of blood vessels, which leads to a decrease in blood pressure (in the supine and standing position). A decrease in blood pressure with long-term use of amlodipine is not accompanied by a significant change in heart rate and the concentration of catecholamines in the blood plasma.

Plasma concentrations of amlodipine correlate with the clinical effect in both young and elderly patients.

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

Amlodipine, like other BMCCs, in patients with normal left ventricular function causes changes in hemodynamic parameters of cardiac function at rest and during exercise (or stimulation): a slight increase in cardiac index, without a significant effect on the maximum rate of increase in pressure in the left ventricle (dP/ dt) or end-diastolic pressure and end-diastolic volume of the left ventricle. The use of amlodipine in the therapeutic dose range does not cause a negative inotropic effect, even when used simultaneously with beta-blockers.

Amlodipine does not alter sinoatrial node function or AV conduction in intact animals or humans. The use of amlodipine in combination with beta-blockers in patients with arterial hypertension or angina pectoris was not accompanied by undesirable changes on the ECG.

The clinical effectiveness of amlodipine has been proven in patients with stable angina pectoris, vasospastic angina and angiographically confirmed lesions of the coronary arteries.

Valsartan

Valsartan is a selective angiotensin II receptor antagonist (AT1 type) for oral administration, of a non-protein nature.

Selectively blocks receptors of the AT1 subtype, which are responsible for the effects of angiotensin II. An increase in plasma concentrations of angiotensin II due to blockade of AT1 receptors by valsartan may stimulate unblocked AT2 receptors, which counteract the effects of AT1 receptor stimulation. Valsartan does not have agonist activity against AT1 receptors. The affinity of valsartan for receptors of the AT1 subtype is approximately 20,000 times higher than for receptors of the AT2 subtype.

Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I to angiotensin II and destroys bradykinin. Due to the lack of influence on ACE, the effects of bradykinin or substance P are not potentiated, therefore, when using angiotensin II receptor antagonists, the development of a dry cough is unlikely. It has been proven that the incidence of dry cough during treatment with valsartan is significantly lower than when using ACE inhibitors. Valsartan does not interact with or block receptors of other hormones or ion channels involved in the regulation of the functions of the cardiovascular system.

In the treatment of arterial hypertension, valsartan reduces blood pressure without affecting heart rate.

After oral administration of valsartan in a single dose, the hypotensive effect develops within 2 hours, and the maximum reduction in blood pressure is achieved within 4-6 hours. The antihypertensive effect of valsartan persists for 24 hours after its administration. With repeated use of valsartan, the maximum reduction in blood pressure, regardless of the dose, is achieved after 2-4 weeks and is maintained at the achieved level during long-term therapy. Sudden cessation of valsartan use is not accompanied by a significant increase in blood pressure or other adverse effects (withdrawal syndrome).

Pharmacokinetics

The pharmacokinetics of amlodipine and valsartan are linear.

Amlodipine/Valsartan

After oral administration of the amlodipine/valsartan combination, Cmax of valsartan and amlodipine in blood plasma is achieved after 3 hours and 6-8 hours, respectively. The rate and extent of absorption are equivalent to the bioavailability of valsartan and amlodipine when taken individually.

Amlodipine

Suction

After oral administration, amlodipine is slowly absorbed from the gastrointestinal tract. Cmax is reached within 6-12 hours. Absolute bioavailability is 64-80%. Bioavailability is independent of food intake.

Distribution

Vd is approximately 21 l/kg. According to in vitro data, binding to blood plasma proteins is 97.5%.

Css in blood plasma are achieved after prolonged oral use for 7-8 days.

Metabolism

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

Removal

Amlodipine is eliminated from blood plasma in a biphasic manner, with terminal T1/2 from 30 to 50 hours. 10% of unchanged amlodipine and 60% of amlodipine in the form of metabolites are excreted in the urine.

Valsartan

Suction

After taking valsartan orally, Cmax is achieved within 2-3 hours. The average absolute bioavailability is 23%. When taking valsartan with food, there is a decrease in bioavailability (according to AUC value) by approximately 40%, and Cmax by approximately 50%. Approximately 8 hours after oral administration, plasma concentrations of valsartan in the group of patients taking the drug with food and in the group taking the drug on an empty stomach level out. The decrease in AUC is not clinically significant, so valsartan can be taken without regard to meals.

Distribution

Vd of valsartan during the steady state period after intravenous administration is about 17 l, which indicates the absence of extensive distribution of valsartan in tissues. Valsartan is highly bound to serum proteins (94-97%), mainly to serum albumin.

Metabolism

Valsartan is not subject to significant metabolism. Only about 20% of the dose taken is determined in the blood plasma in the form of metabolites. The hydroxyl metabolite is detected in blood plasma in low concentrations (less than 10% of the AUC of valsartan). This metabolite is pharmacologically inactive.

Removal

Valsartan is excreted in two phases: α-phase with T1/2α less than 1 hour and β-phase with T1/2β - about 9 hours. Valsartan is excreted mainly unchanged with bile through the intestines (about 83%) and in urine (about 13%). ). 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). T1/2 of valsartan is 6 hours.

Pharmacokinetics in special groups of patients

There are no pharmacokinetic data on the use of the drug in children and adolescents under 18 years of age.

The time to reach Cmax of amlodipine in the blood plasma is the same in young patients and elderly patients. In elderly patients, the clearance of amlodipine tends to decrease, which leads to an increase in AUC and T1/2. In elderly patients, the mean systemic exposure (AUC) of valsartan is slightly higher than in younger patients. However, this was not clinically significant. Given the good tolerability of amlodipine and valsartan in elderly and younger patients, it is recommended to use the usual dosage regimens.

In patients with renal failure, pharmacokinetic parameters do not change. The renal clearance of valsartan is only approximately 30% of the total clearance from plasma, so there is no correlation between renal function and systemic exposure (as measured by AUC) of valsartan. No changes to the initial dose are required in patients with mild to moderate renal failure (creatinine clearance 30-50 ml/min).

Experience with the drug in patients with impaired liver function is limited. Patients with impaired liver function have reduced clearance of amlodipine, resulting in an increase in AUC of approximately 40-60%. On average, in patients with mild (5-6 Child-Pugh scores) and moderate (7-9 Child-Pugh scores) liver dysfunction, the bioavailability (AUC value) of valsartan is doubled compared to age-matched healthy volunteers , gender and body weight.

Vamloset 5mg+160mg, 90 film-coated tablets

Registration Certificate Holder

KRKA-RUS (Russia)

Dosage form

Medicine - Vamloset

Description

Film-coated tablets

brownish-yellow in color with possible dark inclusions, oval, biconvex.

1 tab.

amlodipine besilate 6.94 mg, which corresponds to the content of amlodipine 5 mg valsartan A granule substance 251.35 mg, which corresponds to the content of valsartan 160 mg

Excipients of the granule substance:

microcrystalline cellulose - 82 mg, croscarmellose sodium - 4.75 mg, povidone - 3 mg, sodium lauryl sulfate - 1.6 mg.

Excipients

: mannitol - 50.71 mg, magnesium stearate - 9 mg, colloidal silicon dioxide - 2 mg.

Film shell composition:

opadry II white - 7 mg (polyvinyl alcohol - 40%, titanium dioxide (E171) - 25%, macrogol - 20.2%, talc - 14.8%), iron dye yellow oxide (E172) - 1 mg.

7 pcs. — contour cell packaging (4) — cardboard packs.

Indications

arterial hypertension in patients who are indicated for combination therapy with amlodipine and valsartan.

Contraindications for use

severe liver failure (more than 9 points on the Child-Pugh scale);
biliary cirrhosis and cholestasis;
severe renal failure (creatinine clearance <30 ml/min);
use in patients on hemodialysis;
severe arterial hypotension (systolic blood pressure <90 mm Hg);
collapse, shock (including cardiogenic shock);
obstruction of the outflow tract of the left ventricle (including hypertrophic obstructive cardiomyopathy and severe aortic stenosis);
hemodynamically unstable heart failure after acute myocardial infarction;
simultaneous use with aliskiren in patients with diabetes mellitus or impaired renal function (creatinine clearance less than 60 ml/min);
primary hyperaldosteronism;
pregnancy;
lactation period (breastfeeding);
hypersensitivity to amlodipine, other dihydropyridine derivatives, valsartan or other components of the drug.

The safety of the drug in patients after kidney transplantation, as well as in children and adolescents under the age of 18 years, has not been established.
Carefully _

This combination should be prescribed for liver dysfunction of mild (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 dysfunction of mild to moderate severity (creatinine clearance 30-50 ml/min); unilateral or bilateral renal artery stenosis or stenosis of the artery of a single kidney; chronic heart failure FC III-IV according to NYHA classification; hyperkalemia; hyponatremia; following a diet with limited salt intake; decreased blood volume (including with diarrhea, vomiting); in patients with hereditary angioedema, or edema due to previous therapy with angiotensin II receptor antagonists; in patients with mild to moderate mitral and aortic stenosis.

pharmachologic effect

A combined antihypertensive drug containing: amlodipine (dihydropyridine derivative) and valsartan (angiotensin II receptor antagonist). The combination of these components has a mutually complementary hypotensive effect, which leads to a more pronounced decrease in blood pressure than when they are used separately.

The clinical effectiveness of the amlodipine/valsartan combination has been proven in patients with mild and moderate arterial hypertension (mean diastolic blood pressure ≥95 mm Hg and <110 mm Hg) without complications in comparison with placebo. The level of blood pressure reduction in the sitting position in arterial hypertension with diastolic blood pressure ≥110 mm Hg. Art. and <120 mm Hg. Art. comparable to the use of a combination of an ACE inhibitor and a thiazide diuretic. When using the combination of amlodipine/valsartan, comparable blood pressure control is achieved with a lower likelihood of developing peripheral edema in patients with previously achieved blood pressure control and severe peripheral edema during amlodipine therapy.

When taking the amlodipine/valsartan combination in a single dose, the hypotensive effect persists for 24 hours. The antihypertensive effect persists for a long time. Sudden cessation of drug use is not accompanied by a sharp increase in blood pressure (there is no withdrawal syndrome). Therapeutic effectiveness does not depend on the patient's age, gender, race or BMI.

Amlodipine

- a dihydropyridine derivative, a calcium channel blocker. Has antianginal and hypotensive effects. Inhibits the transmembrane transition of calcium ions into cardiomyocytes and smooth muscle cells of the vascular wall. The antihypertensive effect of amlodipine is due to a direct relaxing effect on the smooth muscle cells of the vascular wall. The mechanism of the antianginal action of amlodipine has not been fully studied, presumably it is associated with the following effects: causes dilation of peripheral arterioles, reducing peripheral vascular resistance (afterload), which leads to a decrease in myocardial oxygen demand; causes expansion of the coronary arteries and arterioles in both intact and ischemic areas of the myocardium, which increases the supply of oxygen to the myocardium, incl. in patients with Prinzmetal's angina. Amlodipine reduces the severity of left ventricular hypertrophy. It has no effect on myocardial contractility and conductivity, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases GFR, and has a weak natriuretic effect.

In patients with arterial hypertension, taking amlodipine 1 time per day provides a clinically significant decrease in blood pressure (lying and standing) within 24 hours. The antihypertensive effect develops slowly, and therefore the development of acute arterial hypotension is uncharacteristic. In patients with angina pectoris, taking amlodipine 1 time per day increases exercise tolerance, the time before the development of an angina attack and until ischemic depression of the ST segment, reduces the frequency of angina attacks and the need for taking nitroglycerin (short-acting forms).

The clinical effectiveness of amlodipine has been proven in patients with stable angina pectoris, vasospastic angina and angiographically confirmed lesions of the coronary arteries.

Amlodipine does not have any undesirable effects on lipid metabolism and does not cause changes in the lipid profile of the blood plasma. Amlodipine can be used in patients with bronchial asthma, diabetes mellitus and gout.

With a single oral dose, the effect of amlodipine begins within 2-4 hours and lasts for 24 hours. The maximum hypotensive effect is achieved no earlier than 4 weeks from the start of taking the drug. The hemodynamic effects of the drug remain unchanged with long-term use.

Valsartan

- a selective antagonist of angiotensin II receptors (type AT1) for oral administration. Selectively blocks receptors of the AT1 subtype, which are responsible for the effects of angiotensin II. An increase in plasma concentrations of angiotensin II due to blockade of AT1 receptors by valsartan may stimulate unblocked AT2 receptors, which counteract the effects of AT1 receptor stimulation. Valsartan does not have agonist activity against AT1 receptors. The affinity of valsartan for receptors of the AT1 subtype is approximately 20,000 times higher than for receptors of the AT2 subtype.

Valsartan does not interact with or block receptors of other hormones or ion channels involved in the regulation of the functions of the cardiovascular system.

Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I to angiotensin II and destroys bradykinin. Due to the lack of influence on ACE, the effects of bradykinin or substance P are not potentiated, therefore, when using angiotensin II receptor antagonists, the development of a dry cough is unlikely. It has been proven that the incidence of dry cough during treatment with valsartan is significantly lower than when using ACE inhibitors. In the treatment of arterial hypertension, valsartan reduces blood pressure without affecting heart rate.

Drug interactions

Amlodipine/valsartan

Amlodipine

Concomitant use with grapefruit or grapefruit juice is not recommended, given the possibility of increased bioavailability in some patients and increased antihypertensive effects.

Concomitant use with strong or moderate inhibitors of the CYP3A4 isoenzyme (protease inhibitors, verapamil or diltiazem, azole antifungals, macrolide antibiotics such as erythromycin or clarithromycin) may lead to a significant increase in the systemic exposure of amlodipine. In elderly patients, these changes are of clinical significance, so medical supervision and dosage adjustment are necessary.

When used simultaneously with inducers of the CYP3A4 isoenzyme (anticonvulsants (for example, carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone), rifampicin, herbal preparations containing St. John's wort) caution should be exercised, because a decrease in the concentration of amlodipine in blood plasma is possible.

Simultaneous repeated use of amlodipine at a dose of 10 mg and simvastatin at a dose of 80 mg increases the exposure of simvastatin by 77% compared with that of simvastatin monotherapy. For patients receiving amlodipine, it is recommended to use simvastatin at a dose of no more than 20 mg/day.

In experimental studies in animals, cases of fatal ventricular fibrillation and cardiovascular failure associated with hyperkalemia were observed after oral administration of verapamil and intravenous administration of dantrolene. Given the risk of developing hyperkalemia, simultaneous use of calcium channel blockers, incl. amlodipine, in patients prone to the development of malignant hyperthermia.

Clinical studies revealed no significant interactions with thiazide diuretics, alpha-blockers, beta-blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, Maalox (aluminum- or magnesium-containing antacids, simethicone) , cimetidine, NSAIDs, antibiotics and oral hypoglycemic drugs.

Valsartan

The simultaneous use of angiotensin II receptor antagonists, including valsartan, or ACE inhibitors with aliskiren is contraindicated in patients with diabetes mellitus and impaired renal function (creatinine clearance less than 60 ml/min).

Simultaneous use with lithium preparations is not recommended, because a reversible increase in the concentration of lithium in the blood plasma and the development of intoxication is possible. If simultaneous use with lithium preparations is necessary, the concentration of lithium in the blood plasma should be carefully monitored.

If necessary, simultaneous use with drugs that affect potassium levels (potassium-sparing diuretics, potassium preparations, potassium-containing food supplements and other drugs and substances that can increase potassium levels in the blood serum (for example, heparin)), it is recommended to monitor the potassium level in the blood plasma .

When used simultaneously with NSAIDs, incl. selective COX-2 inhibitors, acetylsalicylic acid in a dose of more than 3 g/day and non-selective NSAIDs may weaken the antihypertensive effect, increase the risk of developing renal dysfunction and increase the potassium content in the blood plasma. At the beginning of therapy, it is recommended to evaluate renal function, as well as correct water and electrolyte imbalances.

According to the results of an in vitro study, valsartan is a substrate for the transporter proteins OATP1B1 and MRP2. Concomitant use of valsartan with OATP1B1 transporter protein inhibitors (eg, rifampicin, cyclosporine) and an MRP2 transporter protein inhibitor (eg, ritonavir) may increase the systemic exposure of valsartan (Cmax and AUC). This should be taken into account at the beginning and at the end of concomitant therapy.

Dosage regimen

The drug should be taken orally, 1 time/day, regardless of meals, with a small amount of water.

Recommended daily dose - 1 tablet. a drug containing a combination of amlodipine/valsartan at a dose of 5 mg/80 mg, 5 mg/160 mg, 10 mg/160 mg, 5 mg/320 mg or 10 mg/320 mg.

The initial dose of the drug is 5 mg/80 mg 1 time/day. The dose can be increased 1-2 weeks after the start of therapy.

The maximum daily dose is 5 mg/320 mg (in terms of valsartan) or 10 mg/160 mg (in terms of amlodipine) or 10 mg/320 mg.

In patients with impaired renal function (creatinine clearance >30 ml/min)

no adjustment of the initial dose of the drug is required.
Patients with impaired liver function
should use the drug with caution.
The maximum daily dose of valsartan for mild to moderate liver failure
is 80 mg.
The drug is contraindicated in patients with severe liver failure, biliary cirrhosis and cholestasis
.

In elderly patients

no dose adjustment is required.

Side effect

WHO classification of the incidence of side effects: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/100) 10,000 to <1/1000), very rare (<1/10,000), frequency unknown (cannot be estimated from available data).

Amlodipine/valsartan

Infectious and parasitic diseases:

often - flu.

From the side of metabolism:

often - hypokalemia; uncommon - hypercalcemia, hyperlipidemia, hyperuricemia, hyponatremia.

From the nervous system:

often - headache; uncommon - loss of coordination, dizziness, postural dizziness, paresthesia, drowsiness; rarely - anxiety.

From the side of the organ of vision:

infrequently - visual impairment; rarely - visual impairment.

Hearing and labyrinth disorders:

infrequently - vertigo; rarely - tinnitus.

From the cardiovascular system:

uncommon - palpitations, tachycardia, orthostatic hypotension; rarely - marked decrease in blood pressure, fainting.

From the respiratory system:

often - nasopharyngitis; infrequently - cough, pain in the pharynx and larynx.

From the digestive system:

uncommon - diarrhea, nausea, abdominal discomfort, pain in the upper abdomen, constipation, dry mouth.

For the skin and subcutaneous tissues:

infrequently - erythema, skin rash; rarely - exanthema, hyperhidrosis, itching.

From the musculoskeletal system:

infrequently - arthralgia, swelling of the joints; rarely - muscle spasms, a feeling of heaviness throughout the body.

From the urinary system:

rarely - pollakiuria, polyuria.

From the genital organs and breast:

rarely - erectile dysfunction.

Allergic reactions:

rarely - hypersensitivity.

General disorders and disorders at the injection site:

often - asthenia, increased fatigue, swelling of the face, a feeling of a rush of blood to the skin of the face, edema, peripheral edema, pastiness; infrequently - anorexia, back pain.

In patients receiving the amlodipine/valsartan combination, peripheral edema was less common (5.8%) than in patients receiving amlodipine therapy alone (9%).

Amlodipine

Often:

drowsiness, dizziness, palpitations, abdominal pain, nausea, swelling of the ankles.

Infrequently:

insomnia, mood lability (including anxiety), depression, tremor, taste disturbance, fainting, hypoesthesia, visual impairment (including diplopia), tinnitus, marked decrease in blood pressure, shortness of breath, rhinitis, vomiting, dyspepsia , alopecia, purpura, skin discoloration, hyperhidrosis, itching, exanthema, myalgia, muscle cramps, pain, urinary dysfunction, increased frequency of urination, impotence, gynecomastia, chest pain, malaise, weight gain, weight loss.

Rarely:

confusion.

Very rarely:

leukopenia, thrombocytopenia, allergic reactions, hyperglycemia, muscle hypertonicity, peripheral neuropathy, myocardial infarction, arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), vasculitis, pancreatitis, gastritis, gingival hyperplasia, hepatitis, jaundice, increased activity of liver enzymes (most often due to cholestasis), angioedema, erythema multiforme, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, photosensitivity.

Isolated cases of extrapyramidal syndrome have been described.
Valsartan
Frequency unknown:

decreased hemoglobin and hematocrit, neutropenia, thrombocytopenia, increased potassium content in the blood serum, increased activity of liver enzymes, increased concentration of bilirubin in the blood plasma, increased concentration of creatinine in the blood plasma, impaired renal function, including renal failure, angioedema, myalgia, vasculitis, hypersensitivity, including serum sickness.

special instructions

In patients with uncomplicated arterial hypertension receiving therapy with the amlodipine/valsartan combination, severe arterial hypotension was observed in 0.4% of cases.

In patients with an activated RAAS (for example, in patients with dehydration and/or hyponatremia taking high doses of diuretics), symptomatic arterial hypotension may develop when taking angiotensin II receptor antagonists. Before starting treatment, sodium levels should be restored and/or BCC should be replenished, in particular by reducing the doses of diuretics, or therapy should be initiated under close medical supervision.

If a pronounced decrease in blood pressure develops, the patient should be transferred to a horizontal position with a low head and, if necessary, given an intravenous infusion of 0.9% sodium chloride solution. Therapy with the drug can be continued after stabilization of hemodynamic parameters.

Caution should be exercised when using potassium-sparing diuretics, potassium supplements, dietary supplements containing potassium, or other drugs that can increase plasma potassium levels (eg, heparin). It is necessary to regularly monitor the potassium content in the blood plasma.

The drug should be used with caution in patients with arterial hypertension against the background of unilateral or bilateral renal artery stenosis or stenosis of the artery of a single kidney, taking into account the possibility of increasing serum concentrations of urea and creatinine.

In patients with moderate renal impairment, it is recommended to monitor potassium levels and creatinine concentrations in the blood plasma.

Considering the damage to the RAAS in primary hyperaldosteronism, patients in this group should not be prescribed angiotensin II receptor antagonists, incl. valsartan.

Among patients with angioedema (including swelling of the larynx and vocal cords, causing obstruction of the airways and/or swelling of the face, lips, pharynx and/or tongue) during drug therapy, there was a history of the development of angioedema, including .h. to ACE inhibitors. If angioedema develops, the drug should be discontinued immediately and the possibility of repeated use should be excluded.

In patients whose renal function may depend on the activity of the RAAS (for example, in severe chronic heart failure), therapy with ACE inhibitors and angiotensin II receptor antagonists is accompanied by oliguria and/or an increase in azotemia, and in rare cases, acute renal failure and/or death . Similar outcomes have been described with valsartan. In patients with chronic heart failure or previous myocardial infarction, renal function should always be assessed.

In patients with chronic heart failure of non-ischemic etiology, class III-IV according to the NYHA classification, the use of amlodipine was accompanied by an increase in the incidence of pulmonary edema compared with placebo, with no significant difference in the incidence of worsening chronic heart failure between the two groups. Calcium channel blockers, incl. amlodipine should be used with caution in patients with chronic heart failure, because there may be an increased risk of cardiovascular complications and death.

The amlodipine/valsartan combination has been studied only in patients with arterial hypertension.
Effect on the ability to drive vehicles and operate machinery
When using the drug, care must be taken when driving vehicles and other technical devices that require increased concentration and speed of psychomotor reactions, because Dizziness, fatigue and nausea may develop.

Use during pregnancy and breastfeeding

Restrictions during pregnancy - Contraindicated. Restrictions when breastfeeding - Contraindicated.

The use of this combination is contraindicated during pregnancy and lactation.

Use for renal impairment

Restrictions for impaired renal function - With caution.

The use of the drug is contraindicated in severe renal failure (creatinine clearance <30 ml/min); in patients on hemodialysis.

This combination should be prescribed with caution for mild to moderate renal dysfunction (creatinine clearance 30-50 ml/min); unilateral or bilateral renal artery stenosis or stenosis of the artery of a single kidney.

The safety of the drug in patients after kidney transplantation has not been established.

Use for liver dysfunction

Restrictions for liver dysfunction - With caution.

The use of the drug is contraindicated in severe liver failure (more than 9 points on the Child-Pugh scale), biliary cirrhosis and cholestasis.

This combination should be prescribed with caution for mild (5-6 points on the Child-Pugh scale) and moderate (7-9 points on the Child-Pugh scale) liver dysfunction; obstructive diseases of the biliary tract.

Use in elderly patients

Restrictions for elderly patients - No restrictions.

In elderly patients, no dose adjustment is required.

Use in children

Restrictions for children - Contraindicated.

The safety of the drug in children and adolescents under 18 years of age has not been established.