Vamloset pills 5mg + 160mg, 90pcs

Composition

for 1 tablet 5 mg + 80 mg

Core:

Active ingredients:

Amlodipine besylate (amlodipine besylate) 6.94 mg, equivalent to amlodipine 5.00 mg Valsartan A, substance-granules 125.675 mg

[Active ingredient of the granulesubstance: Valsartan 80.00 mg

Excipients of the granule substance: microcrystalline cellulose, croscarmellose sodium, povidone K-25, sodium lauryl sulfate]

Auxiliary substances: mannitol, magnesium stearate, colloidal silicon dioxide

Film shell:

Opadray II white 1, iron oxide yellow dye (E172)

per 1 tablet 5 mg + 160 mg

Core:

Active ingredients:

Amlodipine besylate (amlodipine besylate) 6.94 mg, equivalent to amlodipine 5.00 mg Valsartan A, substance-granules 251.35 mg

[Active ingredient of the granulesubstance: Valsartan 160.00 mg

Excipients of the granule substance: microcrystalline cellulose, croscarmellose sodium, povidone K-25, sodium lauryl sulfate]

Auxiliary substances: mannitol, magnesium stearate, colloidal silicon dioxide

Film shell:

Opadray II white 1, iron oxide yellow dye (E172)

per 1 tablet 5 mg + 320 mg

Core:

Active ingredients:

Amlodipine Besylate (Amlodipine besylate) 6.94 mg, equivalent to amlodipine 5.00 mg

Valsartan A, substance-granules 502,70 mg

[Active ingredient of the granulesubstance: Valsartan 320.00 mg

Excipients of the granule substance: microcrystalline cellulose, croscarmellose sodium, povidone K-25, sodium lauryl sulfate]

Auxiliary substances: mannitol, magnesium stearate, colloidal silicon dioxide

Film shell:

Opadray II white 1, iron oxide dye yellow (E172), iron oxide dye Red (E172)

per 1 tablet 10 mg + 160 mg

Core:

Active ingredients:

Amlodipine Besylate (Amlodipine besylate) 13.88 mg, equivalent to Amlodipine 10.00 mg

Valsartan A, substance-granules 251.35 mg

[Active ingredient of the granulesubstance: Valsartan 160.00 mg

Excipients of the granule substance: microcrystalline cellulose, croscarmellose sodium, povidone K-25, sodium lauryl sulfate]

Excipients: mannitol, magnesium stearate, colloidal silicon dioxide

Film shell:

Opadray II white 1, iron oxide yellow dye (E172)

for 1 tablet of 10 mg + 320 mg

Core:

Active ingredients:

Amlodipine Besylate (Amlodipine besylate) 13.88 mg, equivalent to Amlodipine 10.00 mg

Valsartan A, substance-granules 502,70 mg

[Active ingredient of the granulesubstance: Valsartan 320.00 mg

Excipients of the granule substance: microcrystalline cellulose, croscarmellose sodium, povidone K-25, sodium lauryl sulfate]

Excipients: mannitol, magnesium stearate, colloidal silicon dioxide

Film shell:

Opadray II white 1, iron oxide yellow dye (E172)

1 Opadray II white: polyvinyl alcohol, titanium dioxide (E171), macrogol, talc.

Pharmacological action

antihypertensive combined agent (slow calcium channel blocker + angiotensin II receptor antagonist).

Clinical Pharmacology

Pharmacodynamics

Amlodipine, a dihydropyridine derivative, belongs to the class of “slow” calcium channel blockers (BMCC), valsartan-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 decrease in blood pressure compared to blood pressure when used separately.

Amlodipine

Amlodipine-a dihydropyridine derivative, BMCC, has an antianginal and antihypertensive effect. Inhibits the transmembrane supply of calcium ions to cardiomyocytes and vascular smooth muscle cells. The mechanism of antihypertensive action of amlodipine is due to a direct relaxing effect on vascular smooth muscles, which leads to a decrease in total peripheral vascular resistance (OPSS) and blood pressure.

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

Amlodipine in therapeutic doses in patients with arterial hypertension causes dilation of blood vessels, which leads to a decrease in blood pressure (in the “lying” and “standing”positions). A decrease in blood pressure is not accompanied by a significant change in heart rate (HR) and the concentration of catecholamines in blood plasma with prolonged use of amlodipine.

In hypertensive 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 and degree of proteinuria.

Amlodipine, like other BMCs, in patients with normal left ventricular (LV) function causes a change in the hemodynamic parameters of heart function at rest and during exercise (or stimulation): there was a slight increase in the cardiac index, without a significant effect on the maximum rate of increase in LV pressure (dP/dt) and final diastolic pressure and final LV diastolic volume. Hemodynamic studies in intact animals and humans have shown that lowering blood pressure when using 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 atrioventricular conduction in intact animals and humans. The use of amlodipine in combination with beta-blockers in patients with arterial hypertension or angina pectoris was not accompanied by undesirable ECG changes.

The clinical efficacy of amlodipine has been demonstrated in patients with stable exertional angina, vasospastic angina pectoris and angiographically confirmed coronary artery disease.

Valsartan

Valsartan is an active and selective angiotensin II receptor antagonist (ARA II) for oral use, of a non-protein nature.

Selectively blocks AT1 subtype receptorsthat are responsible for the effects of angiotensin II. An increase in the plasma concentration of angiotensin II due to the blockade_ofAT1 receptors under the action of valsartan can stimulate unblocked AT2receptors, which counteract_{the effects of}AT1 receptor stimulation. Valsartan has no agonistic activity against AT1receptors. The affinity of valsartan for AT1 subtype receptors is approximately 20,000 times higher than for AT2 subtype receptors.

Valsartan does not inhibit the angiotensin-converting enzyme (ACE), also known as kininase II, which converts angiotensin I to angiotensin II and breaks down bradykinin. Due to the lack of influence on ACE, the effects of bradykinin or substance P are not potentiated, so the development of a dry cough is unlikely when taking ARA II.

In comparative clinical trials of valsartan with an ACE inhibitor, the incidence of dry cough was significantly lower (p In a clinical study that included patients who had previously developed a dry cough during treatment with an ACE inhibitor, this complication was noted in 19.5% of cases when treated with valsartan, and in 19.0% of cases when treated 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

Valsartan does not interact with or block other hormone receptors or ion channels that are important for regulating the functions of the cardiovascular system.

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

After oral use of a single dose of valsartan, the antihypertensive effect develops within 2 hours in most patients. The maximum reduction in blood pressure is achieved within 4-6 hours. The antihypertensive effect of valsartan persists for 24 hours after taking it. With repeated use of valsartan, the maximum reduction in blood pressure, regardless of the dose taken, is usually achieved after 2-4 weeks and maintained at the achieved level during long-term therapy. Sudden 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 (NYHA functional classes II-IV) leads to a significant reduction 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 insufficiency (stable clinical course) or with impaired LV function after a myocardial infarction, a decrease in cardiovascular mortality is noted.

Amlodipine/Valsartan

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

The clinical efficacy of the combination of amlodipine/valsartan in patients with mild to moderate arterial hypertension (mean diastolic blood pressure (DBP)) has been proven ≥ 95 mmHg and

The level of blood pressure reduction in the “sitting” position in arterial hypertension with DBP ≥ 110 mm Hg and

The antihypertensive effect persists for a long time. Sudden discontinuation of the drug is not accompanied by a sharp increase in blood pressure (there is no “withdrawal” syndrome).

Therapeutic efficacy is independent of the patient’s age, gender, race, and body mass index.

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

Pharmacokinetics

Linearity

The pharmacokinetics of amlodipine and valsartan are linear.

Amlodipine

Suction

After oral use of amlodipine in therapeutic doses, the maximum concentration (cmax) in blood plasma is reached in 6-12 hours. Absolute bioavailability averages 64-80%. Food intake does not affect the bioavailability of amlodipine.

Distribution

The volume of distribution (Vd) is approximately 21 l/kg. According to in vitro studies, approximately 97.5% of the circulating drug binds to plasma proteins in patients with arterial hypertension.

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

Metabolism

Amlodipine is extensively (about 90%) metabolized in the liver to form inactive metabolites.

Deduction

Elimination of amlodipine from blood plasma is biphasic with a half-life (T_1/2) of approximately 30 to 50 hours. Steady-state plasma concentrations are reached after prolonged oral use for 7-8 days. 10% of unchanged amlodipine and 60% of amlodipine as metabolites are excreted by the kidneys.

Valsartan

Suction

After oral use of valsartan, C_max in blood plasma is reached in 2-3 hours. The average absolute bioavailability is 23%. When taking valsartan with food, there is a decrease in bioavailability (according to the area under the concentration-time curve (AUC)) by 40%, and_cmax – by almost 50%, but approximately 8 hours after oral use, plasma concentrations of valsartan in the group of patients taking it with food and in the group taking it on an empty stomach are equal. The decrease in AUC is not accompanied by a clinically significant decrease in the therapeutic effect, so valsartan can be taken regardless of the meal time.

The distribution

of valsartan Vd at steady state after intravenous use was approximately 17 liters, indicating that there was no extensive distribution of valsartan in the tissues. Valsartan is largely bound to serum proteins (94-97%), mainly albumins.

Biotransformation

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

The

pharmacokinetic curve of valsartan is a descending multi-exponential one (T1_/2α < 1 hour and T1_/2β about 9 hours). Valsartan is mainly excreted unchanged through the intestines (about 83%) and kidneys (about 13%). After intravenous use, 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_1/2 of valsartan is 6 hours.

Amlodipine/Valsartan

After oral use of the amlodipine/valsartan combination, the_maximum plasma concentrations of valsartan and amlodipine are reached in 3 and 6-8 hours, respectively. The rate and degree of absorption are equivalent to the bioavailability of valsartan and amlodipine when taken separately.

Pharmacokinetics in selected groups of patients

Children and adolescents < 18 years of age

There are no pharmacokinetic data on the use of the drug in this group of patients.

Elderly patients (3 65 years)

The time to reach_cmax of amlodipine in blood plasma is the same in young and elderly patients. In elderly patients, the clearance of amlodipine is slightly reduced, which leads to an increase in AUC and T_1/2.

In elderly patients, the mean systemic exposure values (AUC) of valsartan are slightly more pronounced than in young patients. However, this was not clinically significant. Given the good tolerability of amlodipine and valsartan in elderly and younger patients, the usual dosage regimens are recommended.

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 (AUC) of valsartan in patients with varying degrees of renal impairment.

No changes in the initial dose are required in patients with mild to moderate renal impairment.

Impaired liver function

The experience of using the drug in patients with impaired liver function is limited. Patients with impaired liver function have a reduced clearance of amlodipine, which leads to an increase in AUC by about 40-60%. On average, in patients with mild (Child-Pugh score 5-6) and moderate (Child-Pugh score 7-9) hepatic impairment, the bioavailability (AUC) of valsartan doubles compared to healthy subjects (age, sex, and body weight appropriate). Vamloset® should be used with caution in patients with impaired liver function, obstructive biliary tract diseases.

Indications

Arterial hypertension (patients who are indicated for combination therapy).

Use during pregnancy and lactation

Pregnancy

The use of Vamloset® is contraindicated during pregnancy.

Given the mechanism of action of ARA II, it is impossible to exclude the risk to the fetus when using the drug in the first trimester of pregnancy.

Just like any other drug that has a direct effect on the renin-angiotensin-aldosterone system (RAAS), Vamloset®is a non-steroidal anti-inflammatory drug. it should not be used during pregnancy, as well as for women planning pregnancy. When using drugs that affect the RAAS, it is necessary to inform women of childbearing age about the potential risk of negative effects of these drugs on the fetus during pregnancy. When planning pregnancy, it is recommended to transfer the patient to alternative antihypertensive therapy, taking into account the safety profile. If pregnancy is diagnosed, Vamloset should be discontinued and, if necessary, switched to alternative antihypertensive therapy.

The drug Vamloset®, like other drugs that have a direct effect on the RAAS, is contraindicated in the II-III trimesters of pregnancy, since it can cause fetotoxic effects (impaired renal function, slowing ossification of the fetal skull bones, oligohydramnion) and neonatal toxic effects (renal failure, hypotension, hyperkalemia) and fetal death. If the drug was still used in the II-III trimesters of pregnancy, then it is necessary to conduct an ultrasound examination of the kidneys and skull bones of the fetus. Newborns whose mothers have taken Vamloset® during pregnancy, should be under observation, because it is possible to develop hypotension in the newborn.

Breast-feeding period

It is not recommended to use Vamloset® during breastfeeding. If it is necessary to use Vamloset® during lactation, breast-feeding should be discontinued.

Experience with amlodipine shows that amlodipine is excreted in human breast milk. The average milk / plasma ratio for amlodipine concentration was 0.85 among 31 nursing women who suffered from pregnancy-related hypertension and received amlodipine at an initial dosage of 5 mg per day. The dosage of the drug was adjusted if necessary (depending on the average daily dose and weight: 6 mg and 98.7 mcg / kg, respectively). The estimated daily dose of amlodipine received by an infant through breast milk is 4.17 mcg/kg.

Recommendations for use

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

The recommended daily dose is 1 tablet of the 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. You can increase the dose 1-2 weeks after the start of therapy.

The maximum daily dose is 5 mg / 320 mg (based on valsartan) or 10 mg/160 mg (based on amlodipine) or 10 mg/320 mg.

In patients with impaired renal function (creatinine clearance >30 ml / min) correction of the initial dose of the drug is not required.

Patients with impaired liver function should use the drug with caution. The maximum daily dose of valsartan for mild to moderate hepatic insufficiency is 80 mg. The drug is contraindicated in patients with severe hepatic insufficiency, biliary cirrhosis and cholestasis.

No dose adjustment is required in elderly patients.

Contraindications

• Hypersensitivity to amlodipine, other dihydropyridine derivatives, valsartan, as well as to other auxiliary components of the drug.
• Hereditary angioedema, or edema in patients with previous ARA II therapy.

·  Severe liver failure (more than 9 points on the Child-Pugh scale), biliary cirrhosis and cholestasis.

·  Severe renal insufficiency (creatinine clearance less than 30 ml / min), use in patients undergoing hemodialysis.

• Pregnancy planning, pregnancy and breastfeeding period.

·  Severe arterial hypotension (systolic blood pressure less than 90 mm Hg), collapse, shock (including cardiogenic shock).

* Obstruction of the outflow tract of the left ventricle (including severe aortic stenosis).

* Hemodynamically unstable heart failure after acute myocardial infarction.

* Primary hyperaldosteronism.

• Concomitant use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and/or moderate to severe renal impairment (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2 of body surface area).
• Concomitant use with ACE inhibitors in patients with diabetic nephropathy.

The safety of using Vamloset® in patients after a kidney transplant, as well as in children and adolescents under 18 years of age, has not been established.

Interaction

Vamloset®

General drug interactions for Vamloset (amlodipine/valsartan)

Simultaneous use that requires attention

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

Drug interactions for amlodipine

Undesirable concomitant use

Grapefruit or grapefruit juice

Concomitant use is not recommended, given the possibility of increased bioavailability in some patients and increased antihypertensive effect.

Concomitant use that requires caution

Inhibitors of the CYP3A4 isoenzyme

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

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

With simultaneous use of inducers of the CYP3A4 isoenzyme, the concentration of amlodipine in blood plasma may vary. Therefore, blood pressure monitoring 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 to that of simvastatin monotherapy. Patients receiving amlodipine are recommended to use simvastatin at a dose of no more than 20 mg / day.

Dantrolene (intravenous use)

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

Tacrolimus

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

Cyclosporine

Drug interaction studies with cyclosporine and amlodipine in healthy volunteers or other patient groups have not been conducted, except for patients who underwent kidney transplantation, who had variable minimum concentrations (average values: 0% -40%) of cyclosporine. When amlodipine is used concomitantly in patients undergoing kidney transplantation, the concentration of cyclosporine in blood plasma should be monitored, and if necessary, its dose should be reduced.

Clarithromycin

Clarithromycin is an inhibitor of the CYP3A4 isoenzyme. Concomitant use of amlodipine and clarithromycin increases the risk of hypotension. Careful medical monitoring of patients receiving amlodipine concomitantly with clarithromycin is recommended.

Mammalian mechanistic target inhibitors for rapamycin (tTOR)

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.

Simultaneous use that requires attention

Other services

In clinical studies, amlodipine has no significant interactions with thiazide diuretics, alpha-blockers, beta-blockers, ACE inhibitors, a long-acting nitrates, sublingual nitroglycerin for use, digoxin, warfarin, atorvastatin, sildenafilum, the Maalox (aluminum – or magnesium antacids, simethicone), cimetidine, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics and hypoglycemic agents for oral use.

Concomitant use of amlodipine and ethanol does not affect the pharmacokinetics of the latter.

Calcium supplements can reduce the effect of BMCC.

Concomitant use of BMCC with lithium preparations (no data available for amlodipine) may increase the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Glucocorticosteroids

Reduced antihypertensive effect (fluid retention and sodium ions as a result of corticosteroids).

Drug interactions for valsartan

Simultaneous use is contraindicated

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

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

Undesirable concomitant use

Lithium

Concomitant use with lithium preparations is not recommended, since a reversible increase in the concentration of lithium in blood plasma and the development of intoxication is possible. If concomitant 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 concomitantly with Vamloset® and diuretics.

Potassium-sparing diuretics, potassium preparations, potassium-containing dietary supplements, and other medications and substances that may increase serum potassium (for example, heparin)

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

Concomitant use

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

When used concomitantly, the antihypertensive effect may be weakened, the risk of developing impaired renal function may increase, and the potassium content in blood plasma may increase. At the beginning of therapy, it is recommended to assess kidney function, as well as correct violations of the water-electrolyte balance.

Carrier protein inhibitors

According to the results of an in vitro study, valsartan is a substrate for OATP1V1 and MRP2 transporter proteins. Concomitant use of valsartan with inhibitors of the OATP1B1 transporter protein (e. g. rifampicin, cyclosporine) and an inhibitor of the MRP2 transporter protein (e. g. 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 simultaneous therapy.

Double blockade of RAAS in the application ofARA II, ACE inhibitors or aliskiren

Concomitant use of ARA II with other drugs that affect the RAAS leads to an increase in the frequency of cases of arterial hypotension, hyperkalemia, and impaired renal function. It is necessary to monitor blood pressure, renal function, and plasma electrolyte levels when using Vamloset® with other drugs that affect the RAAS.

Other services

There were no clinically significant interactions with the following drugs during valsartan monotherapy: cimetidine, warfarin, furosemide, digoxin, atenolol, Indometacin, hydrochlorothiazide, amlodipine and glibenclamide.

How to take, course of use and dosage

Inside, with a small amount of water,1 time a day, regardless of the time of meal.

The recommended daily dose is 1 tablet of Vamloset® containing amlodipine / valsartan at a dose of 5/80 mg or 5/160 mg, or 10/160 mg, or 5/320 mg, or 10/320 mg.

The maximum daily dose is 5/320 mg (based on valsartan) or 10/160 mg (based on amlodipine) or 10/320 mg.

It is recommended to start taking Vamloset® with a dose of 5/80 mg once a day. You can increase the dose 1-2 weeks after the start of therapy.

Special patient groups

Elderly patients (over 65 years of age)

No dose adjustment is required in patients over 65 years of age. In patients of this category, if necessary, it is possible to reduce the initial dose of Vamloset® to the lowest dose of amlodipine, i. e. 1 tablet containing amlodipine/valsartan at a dose of 5/80 mg or 5/160 mg.

Use in children and adolescents (under 18 years of age)

Since there are insufficient data on the safety and efficacy of Vamloset in children and adolescents (under 18 years of age), the drug is not recommended for use in patients of this category.

Patients with impaired renal function

No initial dose adjustment is required in patients with mild to moderate renal impairment (creatinine clearance ³ 30 ml / min).

Patients with impaired liver function

Due to the presence of valsartan and amlodipine, Vamloset should be used with caution in patients with impaired liver function and obstructive biliary tract diseases. In patients of this category, if necessary, it is possible to reduce the initial dose of Vamloset® to the lowest dose of amlodipine, i. e. 1 tablet containing amlodipine/valsartan at a dose of 5/80 mg or 5/160 mg.

Overdose

Symptoms

Data on overdose cases are currently unavailable. With an overdose of valsartan, you can expect the development of a pronounced decrease in blood pressure and dizziness. Overdose with amlodipine can lead to a marked decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (risk of severe and persistent hypotension, including shock and death).

Treatment

Treatment is symptomatic, the nature of which depends on the time that has elapsed since taking the drug, and on the severity of symptoms. In case of accidental overdose, you should induce vomiting (if the drug was taken recently) or perform gastric lavage. The use of activated charcoal in healthy volunteers immediately or within 2 hours after taking amlodipine led to a significant decrease in its absorption. With a marked decrease in blood pressure while taking Vamloset®, it is necessary to transfer the patient to the “lying” position on his back with raised legs, take active measures to maintain the activity of the cardiovascular system, including regular monitoring of the function of the heart and respiratory system, BCC and the volume of urine released. In the absence of contraindications, vasoconstrictors may be used (with caution) to restore vascular tone and blood pressure. To eliminate the blockage of calcium channels, intravenous use of a solution of calcium gluconate is possible.

Elimination of valsartan and amlodipine during hemodialysis is unlikely.

Description

Tablets 5 mg + 80 mg:

Round, slightly biconvex tablets, covered with a film-coated brownish-yellow color with possible dark inclusions, with a chamfer.

Tablets 5 mg + 160 mg:

Oval, biconvex tablets, covered with a film-coated brownish-yellow color with possible dark inclusions.

Tablets 5 mg + 320 mg:

Capsule-shaped, biconvex tablets, covered with a film-coated orange-brown color.

Tablets 10 mg + 160 mg:

Oval, biconvex tablets, covered with a film-coated brownish-yellow color.

Tablets 10 mg + 320 mg:

Capsule-shaped, biconvex tablets, covered with a film-coated brownish-yellow color.

Functional characteristics

The pharmacokinetics of amlodipine and valsartan are linear.

Amlodipine/Valsartan

After oral use of the amlodipine/valsartan combination, the_maximum plasma concentrations of valsartan and amlodipine are reached in 3 hours and 6-8 hours, respectively. The rate and degree of absorption are equivalent to the bioavailability of valsartan and amlodipine when taken separately.

Amlodipine

After oral use, amlodipine is slowly and almost completely absorbed from the gastrointestinal tract. Simultaneous food intake does not affect the absorption of amlodipine. C_max in blood plasma is reached in 6-12 hours after use. The average absolute bioavailability is 64-80%. _The average Vd is 21 l / kg of body weight, which indicates that most of the amlodipine is in the tissues, and less in the blood. Most of the amlodipine in the blood (97.5%) binds to plasma proteins. C_ss in blood plasma is reached after 7-8 days of continuous use of amlodipine. Amlodipine penetrates the BBB and placental barrier.

Amlodipine undergoes slow but active liver metabolism in the absence of a significant “first pass” effect through the liver. The metabolites do not have significant pharmacological activity.

After a single dose of amlodipine, T_1/2 varies from 35 to 50 hours, with repeated use it is approximately 45 hours. About 60% of the oral dose is excreted by the kidneys mainly in the form of metabolites,10% – unchanged,20-25% – through the intestines with bile. The total clearance of amlodipine is 0.116 ml / s / kg (7 ml / min / kg,0.42 l / h/kg). Amlodipine is not removed by hemodialysis.

Prolongation of T_1/2 in patients with hepatic insufficiency suggests that with prolonged use, the accumulation of amlodipine in the body will be higher (increases up to 60 hours).

Valsartan

After taking valsartan orally_{, max} is reached in 2-3 hours. The average absolute bioavailability is 23%. When taking valsartan with food, there is a decrease in bioavailability (in terms of AUC) by about 40%, and with_max-by about 50%. Approximately 8 hours after oral use, 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 are aligned. The decrease in AUC is not clinically significant, so valsartan can be taken regardless of food intake.

The_{vd of} valsartan at steady state after intravenous use is about 17 liters, which indicates that there is no extensive distribution of valsartan in the tissues. Valsartan is largely bound to serum proteins (94-97%), mainly to serum albumin.

Valsartan does not undergo a pronounced metabolism. 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 at low concentrations (less than 10% of the AUC of valsartan). This metabolite is pharmacologically inactive.

Valsartan is excreted in two phases: alpha-phase with_t1/2α less than 1 h and beta-phase with_t1/2β-about 9 h. Valsartan is mainly excreted unchanged through the intestine (about 83%) and kidneys (about 13%). After intravenous use, 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_1/2 of valsartan is 6 hours.

On average, in patients with mild (Child-Pugh score 5-6) and moderate (Child-Pugh score 7-9) hepatic impairment, the bioavailability (AUC) of valsartan doubles compared to healthy subjects of the appropriate age, sex, and body weight.

Special instructions

Mild (Child-Pugh score 5-6) and moderate (Child-Pugh score 7-9) hepatic impairment, as well as obstructive biliary tract diseases, unilateral or bilateral renal artery stenosis or stenosis of the artery of a single kidney, chronic heart failure (CHF) of NYHA functional class III-IV, acute coronary syndrome, after acute myocardial infarction, hyperkalemia, hyponatremia, high blood pressure diet. reduced intake of table salt, reduced circulating blood volume (BCC) (including diarrhea, vomiting).

As with other vasodilators, special care should be taken when used in patients with mild to moderate mitral or aortic stenosis and hypertrophic obstructive cardiomyopathy (HOCMP).

Since there are insufficient data on the safety and efficacy of Vamloset in children and adolescents (under 18 years of age), the drug is not recommended for use in patients of this category.

Patients with impaired renal function

No initial dose adjustment is required in patients with mild to moderate renal impairment (creatinine clearance ³ 30 ml / min).

Patients with impaired liver function

Due to the presence of valsartan and amlodipine, Vamloset should be used with caution in patients with impaired liver function and obstructive biliary tract diseases. In patients of this category, if necessary, it is possible to reduce the initial dose of Vamloset® to the lowest dose of amlodipine, i. e. 1 tablet containing amlodipine/valsartan at a dose of 5/80 mg or 5/160 mg.

Elderly patients (over 65 years of age)

No dose adjustment is required in patients over 65 years of age. In patients of this category, if necessary, it is possible to reduce the initial dose of Vamloset® to the lowest dose of amlodipine, i. e. 1 tablet containing amlodipine/valsartan at a dose of 5/80 mg or 5/160 mg.

Patients with hyponatremia and / or reduced BCC

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

Patients with activated RAAS (for example, patients with dehydration and/or hyponatremia taking high-dose diuretics) may develop symptomatic hypotension when taking ARA II. Before starting treatment, it is recommended to restore the sodium content and / or replenish the BCC, in particular, by reducing the doses of diuretics or starting therapy under close medical supervision.

If a marked decrease in blood pressure develops, the patient should be placed in a horizontal position with raised legs and, if necessary, an intravenous infusion of 0.9% sodium chloride solution should be performed. Therapy with Vamloset® can be continued after stabilization of hemodynamic parameters.

Hyperkalemia

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

Renal artery stenosis

Vamloset should be used with caution in hypertensive patients with unilateral or bilateral renal artery stenosis or stenosis of the artery of a single kidney, taking into account the possibility of increasing serum urea and creatinine concentrations.

Post-kidney transplant status

The safety of using the amlodipine/valsartan combination in patients who have recently undergone a kidney transplant has not been established.

Impaired liver function

Valsartan is mainly excreted unchanged in the bile. In patients, T_1/2 lengthens and AUC increases. Caution should be exercised when using Vamlocet® in patients with mild (Child-Pugh score 5-6) or moderate (Child-Pugh score 7-9) hepatic impairment or obstructive biliary tract diseases.

Impaired renal function

No dose adjustment of Vamloset is required in patients with mild to moderate renal impairment. In patients with moderate renal impairment, monitoring of potassium and creatinine levels in blood plasma is recommended. Concomitant use of ARA II, including valsartan, or ACE inhibitors with aliskiren is contraindicated in patients with impaired renal function (creatinine clearance less than 60 ml / min).

Primary hyperaldosteronism

Given the involvement of RAAS in primary hyperaldosteronism, these patients should not be prescribed ARA II, including valsartan.

Angioedema

A history of angioedema, including angioedema of the larynx and vocal cords that causes airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue, has been reported in patients treated with Vamloset, including patients treated with ACE inhibitors. If angioedema develops, the drug should be discontinued immediately and the possibility of repeated use should be excluded.

Heart failure/previous myocardial infarction

In patients whose renal function may depend on the activity of the RAAS (for example, in severe CHF), therapy with ACE inhibitors and ARA II is accompanied by oliguria and/or increased azotemia, and in rare cases – acute renal failure and / or death. Similar outcomes have been reported with valsartan. Renal function should always be evaluated in patients with CHF or previous myocardial infarction.

In patients with non-ischemic heart failure of NYHA functional class III-IV, the use of amlodipine was accompanied by an increase in the incidence of pulmonary edema compared to placebo, and there was no significant difference in the frequency of CHF deterioration between the two groups. Slow calcium channel blockers, including amlodipine, should be used with caution in patients with CHF, as the risk of developing cardiovascular complications and death may increase.

Mild to moderate aortic valve and mitral valve stenosis, HOCMP

As with all vasodilators, caution should be exercised in patients with mild-to-moderate mitral and aortic stenosis, HOCMP. The combination of amlodipine/valsartan was studied only in patients with arterial hypertension.

When using Vamloset®, care should be taken when driving vehicles and other technical devices that require increased concentration of attention and speed of psychomotor reactions, as dizziness, fatigue and nausea may occur.

Form of production

Film-coated tablets,5 mg + 80 mg,5 mg + 160 mg,5 mg + 320 mg,10 mg + 160 mg,10 mg + 320 mg.

Tablets 5 mg + 80 mg,5 mg + 160 mg,5 mg + 320 mg,10 mg + 160 mg,10 mg + 320 mg:

10 tablets each in a contour cell package made of combined OPA/Al/PVC material and aluminum foil.

3,6,9 or 10 contour cell packages together with the instructions for use are placed in a pack of cardboard.

Tablets 5 mg + 80 mg:

14 tablets each in a contour cell package made of combined OPA/Al/PVC material and aluminum foil.

1,2,4 or 7 contour cell packages together with the instructions for use are placed in a pack of cardboard.

Tablets 5 mg + 160 mg,5 mg + 320 mg,10 mg + 160 mg,10 mg + 320 mg:

7 tablets each in a contour cell package made of combined OPA/Al/PVC material and aluminum foil.

2,4,8 or 14 contour cell packages together with the instructions for use are placed in a pack of cardboard.

Storage conditions

At a temperature not exceeding 25 °C, in the original packaging.

Keep out of reach of children.

Shelf life

3 years

Do not use the drug after the expiration date.

Active ingredient

Amlodipine, Valsartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets