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

Auxiliary substances of the substance-granules: microcrystalline cellulose 41.00 mg, croscarmellose sodium 2.375 mg, povidone 1.50 mg, sodium lauryl sulfate 0.80 mg]

Excipients: mannitol 21.885 mg, magnesium stearate 4.50 mg, silicon dioxide colloid 1.00 mg

Film sheath: Opadrai II white * 3.50 mg, ferric oxide yellow oxide, E172 0.50 mg.

1 tablet of 5 mg + 160 mg contains:

Core: amlodipine besylate (amlodipine besylate) 6.94 mg, equivalent to amlodipine 5 mg, Valsartan A, substance-granules 251.35 mg

[Active substance of substance-granules: valsartan 160.00 mg. Auxiliary substances of granule substance: cellulose microcrystalline 82.00 mg, croscarmellose sodium 4.75 mg, povidone 3.00 mg, sodium lauryl sulfate 1.60 mg]

Excipients: mannitol 50.71 mg, magnesium stearate 9.00 mg, silicon dioxide colloid 2.00 mg

Film sheath: Opaprai II white * 7.00 mg, iron dye oxide yellow, E172 1,0 mg.

1 tablet 5 mg + 320 mg contains:

Core: amlodipine besylate (amlodipine besylate) 6.94 mg, equivalent to amlodipine 5 mg, Valsartan A, substance-granules 502.70 mg

[The active substance of the substance-granules: valsartan 320.00 mg Auxiliary substances of the substance-granules: microcrystalline cellulose 1,1mg, croscarmellose sodium 9.50 mg, povidone 6.00 mg, sodium lauryl sulfate 3.20 mg]

Excipients: mannitol 101.42 mg, magnesium stearate 18.00 mg, silicon dioxide colloid 4,00 mg

Film sheath: Opadrai II white * 14.00 mg, iron oxide yellow oxide, E172 1.80 mg, iron oxide red dye, E172 0.20 mg.

1 tablet of 10 mg + 160 mg contains:

Core: amlodipine besylate (amlodipine besylate) 13.88 mg, equivalent to amlodipine 10 mg, Valsartan A, substance-granules 251.35 mg

[The active substance of the granule substance: valsartan 160.00 mg Auxiliary substances of the substance-granules: microcrystalline cellulose 82,0 mg, croscarmellose sodium 4.75 mg, povidone 3.00 mg, sodium lauryl sulfate 1.60 mg]

Excipients: mannitol 43.77 mg, magnesium stearate 9.00 mg, silicon dioxide colloid 2.00 mg

Film sheath: Opadrai II white * 7.80 mg, ferric oxide yellow oxide, E172 0.20 mg.

1 tablet 10 mg + 320 mg contains:

Core: amlodipine besylate (amlodipine besylate) 13.88 mg, equivalent to amlodipine 10 mg, Valsartan A, substance-granules 502.70 mg

[The active substance of the substance-granules: valsartan 320.00 mg Auxiliary substances of the substance-granules: microcrystalline cellulose 164,0mg, croscarmellose sodium 9.50 mg, povidone 6.00 mg, sodium lauryl sulfate 3.20 mg]

Excipients: mannitol 101.42 mg, magnesium stearate 18.00 mg, silicon dioxide colloid 4,00 mg

Film sheath: Opaprai II white * 14.00 mg, iron colorant yellow oxide, E172 2.0 mg.

* Opapray II white is a mixture of polyvinyl alcohol (40.0%), titanium dioxide (25.0%) E171, macrogol (20.2%) and talc (14.8%).

Description:

Tablets 5 mg + 80 mg: Round, slightly biconvex tablets, covered with a film coat of brownish-yellow color with possible dark inclusions, with a facet.

Tablets 5 mg + 160 mg: Oval, biconvex tablets, covered with a film coat of brownish-yellow color with possible dark impregnations.

Tablets 5 mg + 320 mg: Capsules, biconvex tablets, covered with a film coat of orange-brown color.

Tablets 10 mg + 160 mg: Oval, biconvex tablets, covered with a film coat of a brownish-yellow color.

Tablets 10 mg + 320 mg: The capsule-shaped, biconvex tablets covered with a film coat of a brownish-yellow color.

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

ATX: & nbsp

C.08.C.A.01 Amlodipine

C.09.C.A.03 Valsartan

Pharmacodynamics:

Combined antihypertensive drug containing two active substances with a complementary mechanism for controlling blood pressure (BP). Amlodipine, a derivative of dihydropyridine, belongs to the class of blockers of "slow" calcium channels (BCCC), 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 as compared with AD in case of their separate application.

Pharmacodynamics

Amlodipine / Valsartan

The combination of amlodipine and valsartan additively dose-dependent in the therapeutic range of doses reduces blood pressure. When taking a single 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 blood pressure (DBP) ≥ 95 mm Hg. Art. and <110 mm Hg. ) without complications in comparison with placebo.

The level of blood pressure lowering in the "sitting" position with arterial hypertension with DBP ≥ 110 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.

Amlodipine

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

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

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

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

Amlodipine, like other BCCs, in patients with normal left ventricular function (LV) causes a change in hemodynamic parameters of heart function at rest and under physical exertion (or stimulation): a slight increase in the cardiac index, without significantly affecting the maximum rate of increase in pressure in the left ventricle (dP / dt) or end-diastolic pressure (LV CSF) or end-diastolic LV volume (LVEF). The use of amlodipine in the therapeutic range of doses does not cause a negative inotropic effect, even with simultaneous use with beta-blockers.

Amlodipine does not alter the function of the sinoatrial node or atrioventricular conduction in intact animals or humans. The use of amlodipine in combination with beta-blockers in patients with arterial hypertension or angina has not been associated with unwanted changes in the ECG.

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

Valsartan

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

Selectively blocks receptors of the subtype AT₁, which are responsible for the effects of angiotensin II. Increased plasma concentrations of angiotensin II due to blockade AT₁-receptors under the action of valsartan can stimulate unlocked subtype receptors AT₂, which counteract the effects of stimulation AT₁receptors. Valsartan has no agonistic activity in relation to AT₁receptors. The affinity of valsartan for the receptors of the subtype AT₁ approximately 20 000 times higher than to the receptors of the subtype AT₂.

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

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

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

Pharmacokinetics:

Linearity

The pharmacokinetics of amlodipine and valsartan is characterized by linearity.

Amlodipine / Valsartan

After ingestion of amlodipine / valsartan combination, the maximum concentrations of valsartan and amlodipine in the blood plasma (C_m_Oh) are achieved after 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

Suction: after oral administration amlodipine slowly absorbed from the gastrointestinal tract (GIT). FROM_m_Oh is achieved in 6-12 hours. Absolute bioavailability is 64 - 80%. Bioavailability does not depend on food intake.

Distribution: the volume of distribution is approximately 21 l / kg. According to in vitro: the connection with plasma proteins is 97.5%.

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

Excretion: amlodipine is derived from the blood plasma biphasic, with a terminal half-life (T_1/2) from 30 to 50 hours. Equilibrium concentrations in the blood plasma are achieved after prolonged oral administration for 7-8 days. 10% of unchanged amlodipine and 60% of amlodipine in the form of metabolites is excreted by the kidneys.

Valsartan

Suction: after taking valsartan inside C_m_Oh is achieved in 2-3 hours. The average absolute bioavailability is 23%. When taking valsartan with food, there is a decrease in bioavailability (by the value of the area under the curve "concentration-time" (AUC)) by about 40%, and C_m_Oh - approximately by 50%. Approximately 8 hours after ingestion, the plasma concentrations of valsartan in the group of patients taking with food and in the group taking on an empty stomach are equalized. Decrease AUC is not clinically relevant, so valsartan can be taken regardless of food intake.

Distribution: the volume of distribution of valsartan in the equilibrium period after intravenous administration is about 17 liters, indicating that there is no extensive distribution of valsartan in the tissues. Valsartan is largely associated with serum proteins (94 - 97%), mainly with serum albumin.

Biotransformation: valsartan does not undergo a pronounced metabolism. Only about 20% of the dose is determined in the blood plasma in the form of metabolites. Hydroxyl metabolite is determined in blood plasma at low concentrations (less than 10% of AUC valsartan). This metabolite is pharmacologically inactive.

Excretion: valsartan is output biphasically: α-phase with a half-life (T_1/2α) less than 1 hour and β-phase with T_1/2_β- about 9 hours. Valsartan is excreted mostly unchanged with bile through the intestine (about 83%) and kidneys (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). T_1/2valsartan is 6 hours.

Pharmacokinetics in selected patient groups

Children (up to 18 years of age)

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

Patients of advanced age (over 65 years)

Time to reach C_m_Oh (TC_m_Oh) of amlodipine in blood plasma in young patients and elderly patients is the same. In elderly patients, clearance of amlodipine tends to decrease, which leads to an increase AUC and T_1/2.

In elderly patients, mean values of systemic exposure (AUC) Valsartan is somewhat more pronounced than in young patients. However, this was not clinically relevant. Given the good tolerability of amlodipine and valsartan in elderly patients and younger age, the usual dosing regimens are recommended.

Impaired renal function

In patients with renal insufficiency, the pharmacokinetic parameters do not change. Renal clearance of valsartan is only about 30% of the total clearance from blood plasma, so the correlation between kidney function and systemic exposure (by value AUC) valsartan was not detected.

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

Impaired liver function

The experience of using the drug in patients with impaired liver function is limited. Patients with impaired liver function have reduced clearance of amlodipine, which leads to an increase AUC by about 40 - 60%. On average, patients with impaired liver function are mild (5-6 points on the Child-Pugh scale) and moderate (7-9 points on the Child-Pugh scale) of the degree of bioavailability (by value AUC) Valsartan is doubled compared to healthy volunteers of the appropriate age, sex and body weight.

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

Contraindications:

Hypersensitivity to amlodipine, other dihydropyridine derivatives, valsartan, or other components of the drug;

Severe hepatic insufficiency (more than 9 points on the Child-Pugh scale), biliary cirrhosis and cholestasis;

Pregnancy and the period of breastfeeding;

Severe renal insufficiency (creatinine clearance (CK) less than 30 ml / min), use in patients on hemodialysis;

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 hypertrophic obstructive cardiomyopathy (GOKMP) and severe aortic stenosis);

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).

The safety of the drug Vamloset in patients after a kidney transplant, as well as children and adolescents under 18 years old is not established.

Carefully:

Dysfunction of the liver is light (5-6 points on the scale Child-Pugh) and moderate (7-9 points on the Child-Pugh scale) severity, as well as obstructive diseases of the biliary tract, violations of the kidneys 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, hyperkalemia, hyponatremia, diet with restriction of consumption of table salt, reduced volume of circulating blood (bcc) (incl.diarrhea, vomiting), use in patients with hereditary angioedema, or edema on the background of previous therapy with angiotensin II receptor antagonists (ARA II).

Also, as with the use of other vasodilators, special care should be taken when using in patients with mild to moderate aortic stenosis.

Pregnancy and lactation:

Pregnancy

The use of the drug Vamloset is contraindicated in pregnancy.

Given the mechanism of action of antagonists of angiotensin II receptors, one can not exclude the risk for the fetus when using the drug in the I trimester of pregnancy.

Like any other drug, has a direct impact on the renin-angiotensin-aldosterone system (RAAS), Vamloset drug should not be used during pregnancy, and women planning pregnancy. When using agents that affect RAAS, it is necessary to inform women of childbearing age of the potential risk of adverse effects of these drugs on the fetus during pregnancy. When planning pregnancy, it is recommended that the patient be transferred to alternative antihypertensive therapy, taking into account the safety profile.In case of pregnancy diagnosis, stop taking the drug Vamloset and, if necessary, transfer to alternative antihypertensive therapy.

The drug Vamloset, as well as other drugs that directly affect RAAS, is contraindicated in the FH trimesters of pregnancy, because it can cause fetotoxic effects (renal dysfunction, fetal bone decay, oligohydramnia) and neonatal toxic effects (renal failure, arterial hypotension , hyperkalemia) and fetal death. If nevertheless used the drug in the FH trimesters of pregnancy, then it is necessary to perform ultrasound examination of the kidneys and bones of the fetal skull. Newborns, whose mothers took the drug VAMOLOSET during pregnancy, should be under observation, as. it is possible to develop an arterial hypotension in a newborn.

Breastfeeding period.

It is not recommended to use Vamloset during breastfeeding. If you need to use the drug VAMOLOSET during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Inside, squeezed a small amount of water, regardless of the time of food intake 1 time per day.

The recommended daily dose is 1 tablet of the drug Vamloset, containing a combination of amlodipine / valsartan in a dose of 5/80 mg, 5/160 mg, 10/160 mg, 5/320 mg or 10/320 mg.

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

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

Special patient groups:

Amlodipine

Patients with impaired renal function: correction of the dose is not required.

Patients with impaired hepatic function: should be used with caution.

Older patients: dose adjustment and dosing regimen is not required.

Valsartan

Patients with impaired renal function: u patients with renal dysfunction / KK> 30 ml / min) correction of the initial dose is not required.

Patients with impaired hepatic function: valsartan contraindicated in patients with severe hepatic insufficiency, biliary cirrhosis and cholestasis. The maximum daily dose of valsartan for mild to moderate hepatic insufficiency is 80 mg. The drug Vamloset in a dose of 5/160 mg, 5/320 mg, 10/160 and 10/320 mg is contraindicated.

Older patients: correction of the dose is not required.

Side effects:

Classification of the frequency of development of side effects of the World Organization

Health (WHO):

Often ≥ 1/10

often from ≥1 / 100 to <1/10

infrequently from ≥1 / 1000 to <1/100

rarely from ≥1 / 10000 to <1/1000

very rarely from <1/10000

the frequency of the unknown can not be estimated from the available data.

The drug Vamloset

Infectious and parasitic diseases: often: nasopharyngitis, influenza.

Immune system disorders: rarely: hypersensitivity.

Disorders from the metabolism and nutrition: often: hypokalemia, infrequently: anorexia, hypercalcemia, hyperlipidemia, hyperuricemia, hyponatremia.

Disorders of the psyche: rarely: anxiety.

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

Disorders from the side of the organ of vision: infrequently: deterioration of vision; rarely: impaired vision.

Hearing disorders and labyrinthine disturbances: infrequently: vertigo; rarely: tinnitus.

Heart Disease: infrequent: palpitation, tachycardia; rarely: faint.

Vascular disorders: infrequently: orthostatic hypotension; rarely: marked decrease in blood pressure.

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

Disorders from the digestive system: infrequently: diarrhea, nausea, a feeling of discomfort in the abdomen, pain in the upper abdomen, constipation, dryness of the oral mucosa.

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

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

Disorders from the kidneys and urinary tract: rarely: pollakiuria, polyuria.

Violations of the genitals and breast: rarely: erectile dysfunction.

General disorders and disorders at the site of administration: often: asthenia, fatigue, face swelling, a sensation of "tidal" blood to the skin of the face, swelling, peripheral edema, pastoznost.

Additional Information

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

Amlodipine

Violation of the blood and lymphatic system: very rarely: leukopenia, thrombocytopenia sometimes with purpura.

Immune system disorders: very rarely: hypersensitivity.

Disorders from the metabolism and nutrition: very rarely: hyperglycemia.

Disorders of the psyche: infrequently: depression, insomnia / sleep disorders, mood lability, rarely: confusion.

Impaired nervous system: often: dizziness, headache, drowsiness; infrequently: a taste disorder, paresthesia, fainting, tremor, hypoesthesia; very rarely: muscle hypertonia, peripheral neuropathy, neuropathy; frequency unknown: extrapyramidal disorders.

Disorders from the side of the organ of vision: infrequent: vision impairment, visual impairment.

Hearing disorders and labyrinthine disturbances: infrequently: noise in the ears.

Heart Disease: often: palpitations; very rarely: arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction.

Vascular disorders: often: a sensation of a "tide" of blood to the skin of the face, a pronounced decrease in blood pressure; very rarely: vasculitis.

Disturbances from the respiratory system, organs of the thorax and mediastinum: infrequently: dyspnea, rhinitis; very rarely: cough.

Disorders from the digestive system: often: nausea, a feeling of discomfort in the abdomen, pain in the upper abdomen; infrequently: a change in stool, diarrhea, dryness of the oral mucosa, dyspepsia, vomiting; rarely: gastritis, gingival hyperplasia, pancreatitis.

Disorders from the liver and bile ducts: very rarely: increased "activity" of liver enzymes (more often with cholestasis), increased bilirubin concentration in the blood plasma, hepatitis, intrahepatic cholestasis, jaundice.

Disturbances from the skin and subcutaneous tissues: infrequently: alopecia, exanthema, erythema, photosensitivity reactions, itching, hyperhidrosis, purpura, skin rash, discoloration; very rarely: erythema multiforme, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, angioedema.

Disturbances from the musculoskeletal and connective tissue: often: swelling of the ankles; infrequently: arthralgia, back pain, muscle spasms, myalgia.

Disorders from the kidneys and urinary tract: infrequently: violation of urination, nocturia, pollakiuria.

Violations of the genitals and breast: infrequently: erectile dysfunction, gynecomastia.

General disorders and disorders at the site of administration: often: increased fatigue, peripheral edema; infrequently: asthenia, discomfort, malaise, non-cardiogenic pain in the heart, pain.

Laboratory and instrumental data. infrequently: decrease / increase in body weight.

Valsartan

Violation of the blood and lymphatic system: frequency unknown: decreased hemoglobin and hematocrit, leukopenia, neutropenia, thrombocytopenia sometimes with purpura;

Immune system disorders: very rarely: hypersensitivity.

Hearing disorders and labyrinthine disturbances: infrequently: vertigo.

Vascular disorders: frequency unknown: vasculitis.

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

Disorders from the digestive system: infrequently: a feeling of discomfort in the abdomen, pain in the upper abdomen;

Disorders from the liver and bile ducts: frequency is unknown: increased "activity" of hepatic enzymes, increased bilirubin concentration in blood plasma;

Disturbances from the skin and subcutaneous tissues: frequency unknown: itching, skin rash, angioedema.

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

Disorders from the kidneys and urinary tract: the frequency is unknown: an increase in the concentration of creatinine in the blood plasma, a violation of kidney function, including acute renal failure.

General disorders and disorders at the site of administration: infrequently: increased fatigue.

Laboratory and instrumental data: frequency is unknown: an increase in serum potassium

Further information on the components of the preparation

Undesirable effects reported earlier in the use of each component may occur with the use of the Vamloset drug, even if they have not been observed in clinical trials.

Amlodipine

often: drowsiness, dizziness, palpitations, abdominal pain, nausea, swelling of the ankles; infrequently: insomnia, mood lability (incl.anxiety), depression, tremor, taste disorder, fainting, hypoesthesia, visual impairment (including diplopia), tinnitus, marked decrease in blood pressure, dyspnea, rhinitis, vomiting, dyspepsia, alopecia, purpura, discoloration, hyperhidrosis , skin itching, exanthema, myalgia, muscle cramps, pain, urination disorder, frequency of urination, impotence, gynecomastia, chest pain, malaise, weight gain, weight loss; rarely: confusion;

very rarely: leukopenia, thrombocytopenia, allergic reactions, hyperglycemia, muscle hypertonia, peripheral neuropathy, myocardial infarction, arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), vasculitis, pancreatitis, gastritis, gingival hyperplasia, hepatitis, jaundice, hepatic activity "enzymes (most often due to cholestasis), angioedema, erythema multiforme, urticaria, exfoliative dermatitis, Stevens-Johnson syndrome, photosensitivity. Separate cases of extrapyramidal syndrome are described.

Valsartan

frequency unknown: decreased hemoglobin and hematocrit, neutropenia, thrombocytopenia, increased serum potassium levels, increased "activity" of liver enzymes, increased bilirubin concentration in the blood plasma, increased serum creatinine concentration, impaired renal function including renal insufficiency, angioedema, myalgia, vasculitis, hypersensitivity, including serum sickness .

Overdose:

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

Treatment: Symptomatic, the nature of which depends on the time elapsed since the time of taking the drug, and on the severity of the symptoms. In case of an accidental overdose, you should 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 led to a significant decrease in its absorption.In case of a marked decrease in blood pressure during the administration of the drug, WAMOLOSET needs to move the patient to the "lying" position on the back with raised legs, take active measures to support the cardiovascular system, including regular monitoring of heart function and respiratory system, BCC and volume of excreted urine. In the absence of contraindications to restore vascular tone and blood pressure, it is possible to use (with caution) vasoconstrictors. To eliminate calcium channel blockade, intravenous administration of calcium gluconate solution is possible.

The excretion of valsartan and amlodipine during hemodialysis is unlikely.

Interaction:

The drug Vamloset

General drug interactions for the drug Vamloset (amlodipine / valsartan)

Simultaneous application requiring attention

Other antihypertensive drugs (eg, alfa-adrenoblockers, diuretics) and drugs that have antihypertensive effects (eg, tricyclic antidepressants, alfa-adrenoblockers for the treatment of benign prostatic hyperplasia), can enhance the hypotensive effect.

Drug Interactions for Amlodipine

Unwanted simultaneous application

Grapefruit or grapefruit juice: simultaneous use is not recommended, given the possibility of increasing bioavailability in some patients and enhancing hypotensive effects.

Concurrent use requiring caution

Inhibitor inhibitors CYP3A4

Simultaneous application with strong or moderate isoenzyme inhibitors CYP3A4 (protease inhibitors, verapamil or diltiazem, azole antifungal drugs, macrolides such as erythromycin or clarithromycin) can lead to a significant increase in the systemic exposure of amlodipine. In elderly patients, these changes are of clinical importance, so medical supervision and dose adjustment are necessary. Inductors of isoenzyme CYP3A4 (anticonvulsants (for example, carbamazepine, phenobarbital, phenytoin, phosphenytoin, primidon), rifampicin, herbal preparations containing St. John's Wort (perforated)): Care should be taken with caution. with simultaneous application possible decrease in the concentration of amlodipine in the blood plasma.

Simvastatin

Simultaneous re-use of amlodipine in a dose of 10 mg and simvastatin in a dose of 80 mg increases the exposure of simvastatin by 77% compared with that of monotherapy with simvastatin. Patients receiving amlodipine, it is recommended to apply simvastatin in a dose of no more than 20 mg / day.

Dantrolene (intravenous): in experiments on animals after oral administration of verapamil and intravenous dantrolene, cases of ventricular fibrillation with a lethal outcome and cardiovascular insufficiency associated with hyperkalemia were observed. Given the risk of hyperkalemia, simultaneous use of blockers of "slow" calcium channels should be avoided, including. amlodipine, in patients prone to developing malignant hyperthermia.

Simultaneous application requiring attention

Other: in clinical trials amlodipine no significant interaction with thiazide diuretics, alpha-adrenoblockers, beta-adrenoblockers, ACE inhibitors, long-acting nitrates, nitroglycerin for sublingual use, digoxin, warfarin, atorvastatin, sildenafil, maalox (aluminum-or magnesium-containing antacid preparations, simethicone), cimetidine, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics and hypoglycemic agents for prima inward.

Drug Interactions for valsartan

Simultaneous use is contraindicated

The simultaneous use of ARA II, including valsartan, or ACE inhibitors with aliskiren is contraindicated in patients with diabetes mellitus and renal dysfunction (CC less than 60 ml / min).

Unwanted simultaneous application

Lithium

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

Potassium-sparing diuretics, potassium preparations, potassium-containing food additives and other medicines and substances that can increase serum potassium (for example, heparin)

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

Concurrent use requiring caution

NSAIDs, including selective inhibitors of cyclooxygenase-2 (COX-2), acetylsalicylic acid in a dose of more than 3 g / day and nonselective NSAIDs With simultaneous use, it is possible to reduce the hypotensive effect, increase the risk of kidney dysfunction and increase the potassium content in the blood plasma. At the beginning of therapy it is recommended to evaluate the function of the kidneys, as well as adjust the violations of the water-electrolyte balance.

Protein Transfer Inhibitors

By the results of the study in vitro Valsartan is a substrate for the OATP1B1 carrier proteins and MRP2. The simultaneous use of valsartan with inhibitors of the OATP1B1 carrier protein (for example, rifampicin, ciclosporin) and an inhibitor of the carrier protein MRP2 (eg, ritonavir) can increase the systemic exposure of valsartan (C_m_Oh and AUC). This should be taken into account at the beginning and at the end of the simultaneous therapy.

Others: when monotherapy with valsartan did not reveal clinically significant interactions with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide.

Special instructions:

Patients with hyponatraemia and / or a decrease in BCC

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

In patients with activated RAAS (eg, in patients with dehydration and / or hyponatremia, taking diuretics in high doses), with the intake of angiotensin II receptor antagonists, symptomatic arterial hypotension may develop. Before the start of treatment, it is recommended to restore the sodium content and / or replenish the BCC, in particular, by reducing the dose of diuretics or starting therapy under close medical supervision. With the development of a pronounced reduction in blood pressure: the patient should be placed in a horizontal position with raised legs and, if necessary, intravenously infused 0.9% solution of sodium chloride. Therapy with Vamloset can be continued after stabilization of hemodynamic parameters.

Hyperkalemia

With the simultaneous use of potassium-sparing diuretics, potassium preparations, dietary supplements containing potassium or other drugs that can increase the potassium content in the blood plasma (for example,heparin) should be careful. It is necessary to regularly monitor the content of potassium ions in the blood plasma.

Stenosis of the renal artery

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

Condition after kidney transplantation

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

Impaired liver function

Valsartan is mostly excreted unchanged with bile. Patients T_1/2lengthens, and AUC - increases. Caution should be exercised when using the drug VAMOLOSET in patients with mild (5-6 points on the Child-Pugh scale) or moderate (7-8 on the Child-Pugh scale), a violation of liver function or obstructive diseases of the biliary tract.

Impaired renal function

Correction of the dose of the drug Vamloset in patients with mild and moderate renal dysfunction is not required.In patients with moderate renal impairment, control of potassium and creatinine concentrations in blood plasma is recommended. The simultaneous use of ARA II, including valsartan, or ACE inhibitors with aliskirenom is contraindicated in patients with impaired renal function (CC less than 60 ml / min).

Primary hyperaldosteronism

Given the defeat of RAAS in primary hyperaldosteronism, these patients should not be prescribed angiotensin II receptor antagonists, including valsartan.

Angioedema

Among patients with angioneurotic edema (including swelling of the larynx and vocal cords causing airway obstruction and / or swelling of the face, lips, pharynx and / or tongue) against the background of therapy with the Vamloset drug, there have been cases of angioedema development in the anamnesis, including and on ACE inhibitors. When developing angioedema, immediately discontinue the drug and exclude the possibility of repeated use.

Heart failure / previous myocardial infarction

In patients whose renal function may depend on the activity of RAAS (eg, in severe CHF),therapy with ACE inhibitors and angiotensin II receptor antagonists is accompanied by oliguria and / or augmentation of azotemia, and in rare cases acute renal failure and / or lethal outcome. Similar outcomes were described with the use of valsartan. In patients with CHF or a history of myocardial infarction, renal function should always be evaluated. In patients with CHF of III-IV non-ischemic etiology of the NYHA classification class, the use of amlodipine was associated with an increase in the incidence of pulmonary edema compared with placebo in the absence of a significant difference in the incidence of worsening CHF between the two groups. Blocks of "slow" calcium channels, incl. amlodipine, should be used with caution in patients with CHF, as there may be an increased risk of developing cardiovascular complications and death.

Stenosis of aortic valve of mild to moderate degree and mitral valve

As with any vasodilator, care should be taken in patients with mitral stenosis and aortic stenosis of mild to moderate severity. The combination of amlodipine / valsartan was studied only in patients with arterial hypertension.

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

When using the drug Vamloset, care must be taken when driving vehicles and other technical devices that require a high concentration of attention and speed of psychomotor reactions. possibly the appearance of dizziness, fatigue and nausea.

Form release / dosage:

Tablets, film-coated, 5 mg + 80 mg, 5 mg + 160 mg, 5 mg + 320 mg, 10 mg + 160 mg, 10 mg + 320 mg.

Packaging:

Tablets 5 mg + 80 mg, 5 mg + 160 mg, 5 mg + 320 mg, 10 mg + 160 mg, 10 mg + 320 mg: 10 tablets in a contour mesh package made of the combined material OPA / Al / PVC and aluminum foil.

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

Tablets 5 mg + 80 mg: 14 tablets in a contour mesh package made of a combined material OPA / Al / PVC and aluminum foil.

1, 2, 4 or 7 contour mesh packages together with the instruction 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 in a contour mesh package made of the combined material OPA / Al / PVC and aluminum foil.

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

Storage conditions:

At a temperature of no higher than 30 ° 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-002283

Date of registration:23.10.2013 / 18.01.2016

Expiration Date:23.10.2018

The owner of the registration certificate:KRKA-RUS, LLC KRKA-RUS, LLC Russia

Manufacturer: & nbsp

KRKA-RUS, LLC Russia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp20.01.2017

Illustrated instructions

Instructions

Vamloset® (Vamloset®)