Exforge, 28 pcs., 10 mg+160 mg, film-coated tablets

Compound

.

Description of the dosage form

Film-coated tablets, 5/80 mg: dark yellow, round with beveled edges, imprinted “NVR” on one side and “NV” on the other.

Film-coated tablets, 5/160 mg: dark yellow, oval with beveled edges, imprinted “NVR” on one side and “ECE” on the other.

Film-coated tablets, 10/160 mg: light yellow, oval with beveled edges, imprinted “NVR” on one side and “UIC” on the other.

Pharmacodynamics

Exforge® is a combination of 2 antihypertensive drugs with a complementary mechanism of blood pressure control: amlodipine, a dihydropyridine derivative, belongs to the class of “slow” calcium channel blockers (SCBC), valsartan belongs to the class of angiotensin II receptor antagonists. The combination of these components has a mutually complementary hypotensive effect, which leads to a more pronounced decrease in blood pressure compared to that during monotherapy with each drug.

Amlodipine

Amlodipine, which is part of the drug Exforge®, inhibits the transmembrane entry of calcium ions into cardiomyocytes and vascular smooth muscle cells. The mechanism of the antihypertensive effect of amlodipine is associated with a direct relaxing effect on vascular smooth muscle, causing a decrease in peripheral vascular resistance and a decrease in blood pressure.

When taken in therapeutic doses in patients with arterial hypertension, amlodipine causes vasodilation, leading to a decrease in blood pressure (in the patient’s “lying” and “standing” position). The decrease in blood pressure is not accompanied by a significant change in heart rate and catecholamine levels with long-term use.

Plasma concentrations of the drug correlate with 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, an increase in glomerular filtration rate and effective renal blood flow without changing the filtration fraction and the level of proteinuria.

As with the use of other BMCCs, taking amlodipine in patients with normal left ventricular (LV) function caused changes in hemodynamic parameters of cardiac function at rest and during exercise: there was a slight increase in cardiac index without a significant effect on the maximum rate of increase in pressure in the LV (dP /dt), final dBP and LV volume. Hemodynamic studies in intact animals and humans have shown that the decrease in blood pressure under the influence of amlodipine in the range of therapeutic doses is not accompanied by a negative inotropic effect, even when used simultaneously with beta-blockers.

Amlodipine does not alter sinoatrial node function or AV conduction in intact animals and humans. When amlodipine is used in combination with beta-blockers in patients with arterial hypertension or angina pectoris, a decrease in blood pressure is not accompanied by undesirable changes in ECG parameters.

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

Valsartan

Valsartan is an active and specific angiotensin II receptor antagonist intended for oral administration. It acts selectively on the AT1 receptor subtype, which is responsible for the known effects of angiotensin II. An increase in plasma concentrations of free angiotensin II due to AT1 receptor blockade under the influence of valsartan may stimulate unblocked AT2 receptors, which counteract the effects of AT1 receptor blockade. Valsartan does not have any pronounced agonistic 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 causes the destruction of bradykinin.

When using angiotensin II antagonists, ACE inhibition and accumulation of bradykinin or substance P do not occur, so the development of a dry cough is unlikely.

In comparative clinical studies of valsartan with an ACE inhibitor, the incidence of dry cough was significantly lower (p<0.05) in patients receiving valsartan (in 2.6% of patients receiving valsartan and in 7.9% of patients receiving an ACE inhibitor). 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 during treatment with valsartan, and in 19% of cases during treatment with a thiazide diuretic. At the same time, in the group of patients treated with an ACE inhibitor, cough was observed in 68.5% of cases (p<0.05). Valsartan does not interact with or block hormone receptors or ion channels that are important for regulating the functions of the cardiovascular system.

When treating patients with arterial hypertension with valsartan, a decrease in blood pressure is observed, not accompanied by a change in heart rate.

The antihypertensive effect appears within 2 hours in most patients after a single dose of the drug. The maximum reduction in blood pressure develops within 4–6 hours. After taking the drug, the antihypertensive effect persists for more than 24 hours. With repeated use, the maximum reduction in blood pressure, regardless of the dose taken, is usually achieved within 2–4 weeks and is maintained at this level during long-term therapy. Abrupt cessation 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 class II–IV) leads to a significant reduction in the number of hospitalizations. This effect is most pronounced in patients not receiving ACE inhibitors or beta-blockers. When taking valsartan in patients with left ventricular failure (stable clinical course) or with impaired LV function after myocardial infarction, a decrease in cardiovascular mortality is observed.

Amlodipine/Valsartan

In patients with arterial hypertension who received Exforge® once a day, the antihypertensive effect persisted for 24 hours.

The drug Exforge® in doses of 5/80 and 5/160 mg in patients with an initial SBP of 153–157 mm Hg. and dBP ≥95 and <110 mm Hg, reduces blood pressure by 20–28/14–19 mm Hg. (compared to 7–13/7–9 mmHg with placebo).

The drug Exforge® at a dose of 10/160 and 5/160 mg normalizes blood pressure (decrease in dBP in the sitting position <90 mm Hg) in 75 and 62% of patients with inadequate blood pressure control during monotherapy with valsartan at a dose of 160 mg/day. day

Exforge® at a dose of 10/160 mg normalizes blood pressure in 78% of patients with inadequate blood pressure control during monotherapy with amlodipine at a dose of 10 mg.

In patients with arterial hypertension, when combining valsartan at a dose of 160 mg with amlodipine at doses of 10 and 5 mg, an additional reduction in SBP and DBP by 6.0/4.8 mm Hg is achieved. and 3.9/2.9 mmHg. respectively, compared with patients who continued to receive valsartan 160 mg alone or amlodipine 5 and 10 mg alone.

When titrating the dose of Exforge® from 5/160 to 10/160 mg in patients with arterial hypertension with dBP ≥110 and <120 mmHg. There is a decrease in blood pressure in the sitting position by 36/29 mm Hg, comparable to a decrease in blood pressure when titrating the dose of a combination of an ACE inhibitor and a thiazide diuretic.

In two long-term studies with a long follow-up period, the effect of Exforge® was maintained for 1 year. Sudden cessation of taking Exforge® is not accompanied by a sharp increase in blood pressure.

In patients who achieved adequate blood pressure control, but developed severe edema during amlodipine monotherapy, when using combination therapy, comparable blood pressure control was achieved with a lower likelihood of developing edema.

The therapeutic effectiveness of Exforge® does not depend on the age, gender and race of the patient.

Pharmacological properties of the drug Exforge

Pharmacodynamics. Exforge contains two antihypertensive components with additional mechanisms for controlling blood pressure in patients with essential hypertension (arterial hypertension): amlodipine belongs to the class of calcium antagonists, and valsartan belongs to the class of angiotensin II antagonists. The combination of these ingredients has an additive antihypertensive effect, lowering blood pressure to a greater extent than either component alone. Amlodipine Amlodipine inhibits the transmembrane penetration of calcium ions into the smooth muscles of the heart and blood vessels. The mechanism of the antihypertensive effect of amlodipine is due to a direct relaxing effect on vascular smooth muscle, which causes a decrease in peripheral vascular resistance and leads to a decrease in blood pressure. Experimental data confirm that amlodipine binds at dihydropyridine and non-hydropyridine linkages. The process of contraction of cardiac muscle and vascular smooth muscle depends on the passage of extracellular calcium into the cell through specific ion channels. After administering a therapeutic dose to patients with essential hypertension (arterial hypertension), amlodipine causes vasodilation, which leads to a decrease in blood pressure in the supine and standing positions. This decrease in blood pressure is not accompanied by a significant change in heart rate or plasma catecholamine levels with prolonged use. The effect correlates with the concentration of the active substance in the blood plasma in young and elderly patients. In patients with normal renal function, a therapeutic dose of amlodipine leads to a decrease in renal vascular resistance and an increase in the level of glomerular filtration, as well as an improvement in renal blood flow without changes in the filtered fraction or proteinuria. Studies of cardiac hemodynamic function at rest and during exercise in patients with normal ventricular function receiving amlodipine therapy generally showed a slight increase in cardiac index without a significant effect on the change in pressure (dP/dt) in the left ventricle. Based on the results of studies conducted in animals and humans, amlodipine did not exhibit a negative inotropic effect when used in therapeutic doses, even when combined with beta-adrenergic blockers, and did not affect the function of the AV node or atrioventricular conduction. In clinical studies in patients with essential hypertension (arterial hypertension) or angina pectoris, no changes in ECG parameters were detected when amlodipine was used in combination with beta-adrenergic blockers. The use of amlodipine had a positive clinical effect in patients with chronic stable angina, vasospastic angina and coronary artery disease confirmed by angiography. Valsartan - (INN valsartanum - valsartan) Valsartan is an active and specific angiotensin II receptor antagonist, intended for oral use. It acts selectively on receptors of the AT1 subtype, which are rare and responsible for the effects of angiotensin II. Increased levels of angiotensin II due to blockade of AT1 receptors by valsartan can stimulate free AT2 receptors, which balances the effect of AT1 receptors. Valsartan does not have any partial agonist activity at the AT1 receptor and has a much greater (approximately 20,000-fold) affinity for the AT1 receptor than for the AT2 receptor. Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I to angiotensin II and destroys bradykinin, and no side effects due to bradykinin have been noted. In clinical trials where valsartan was compared with an ACE inhibitor, the incidence of dry cough was significantly lower (p≤0.05) in patients receiving valsartan than in patients receiving an ACE inhibitor (2.6% versus 7.9% respectively). In patients who were previously treated with an ACE inhibitor, a dry cough developed as a side effect. When treated with valsartan, this side effect was noted in 19.5% of cases, when treated with a thiazide diuretic - in 19%, while in the group of patients receiving an ACE inhibitor, cough was detected in 68.5% of cases (p≤0.05 ). Valsartan does not interact with or block other hormone receptors or ion channels, which are known to play an important role in regulating the function of the cardiovascular system. The use of the drug in patients with hypertension (arterial hypertension) leads to a decrease in blood pressure without affecting heart rate. In most patients, after oral administration of a single dose of valsartan, the onset of the antihypertensive effect is noted within 2 hours, and the maximum reduction in blood pressure is achieved within 4–6 hours. The antihypertensive effect persists for 24 hours after taking a single dose. With regular use of the drug, the maximum therapeutic effect is usually achieved within 2–4 weeks and is maintained at the achieved level during long-term therapy. Abrupt discontinuation of valsartan does not lead to resumption of hypertension or other adverse clinical effects. Valsartan has been found to significantly reduce hospitalization rates in patients with chronic heart failure (NYHA class II–IV). A more significant effect was achieved in patients who were not taking ACE inhibitors or beta-adrenergic blockers. It was also found that valsartan reduced cardiovascular mortality in clinically stable patients with left ventricular pathology or left ventricular dysfunction after myocardial infarction. Valsartan/amlodipine More than 1,400 patients with hypertension were treated with Exforge once daily in two placebo-controlled studies. The antihypertensive effect of a single dose of the drug lasted about 24 hours. Exforge (amlodipine besylate/valsartan) was studied in two placebo-controlled studies in patients with hypertension (arterial hypertension) and diastolic blood pressure between ≥95 and ≤110 mm Hg. Art. In the first stage of the study (initial blood pressure 153/99 mm Hg), Exforge in doses of 5/80 mg, 5/160 mg and 5/320 mg reduced blood pressure by 20–23/14–16 mm Hg. Art. compared to 7/7 mm Hg. Art. for placebo. In the second stage of the study (initial blood pressure 157/99 mm Hg), Exforge in doses of 10/160 mg and 10/320 mg reduced blood pressure by 28/18–19 mm Hg. Art. compared to 13/9 mm Hg. Art. for placebo. In a multicenter, randomized, double-blind, actively controlled study in parallel groups, normalization of blood pressure (diastolic blood pressure ≤90 mm Hg at the end of the trial) was established in 75% of patients using 10/160 mg of amlodipine/valsartan, in 62% of patients using 5/ 160 mg amlodipine/valsartan compared with 53% of patients using 160 mg valsartan alone. The simultaneous administration of 5 or 10 mg of amlodipine caused an additional reduction in systolic/diastolic blood pressure by 6/4.8 mm Hg. Art. and 3.9/2.9 mm Hg. Art. respectively, compared with patients using only 160 mg of valsartan. In a multicenter, randomized, double-blind, active-controlled, parallel-group study, normalization of blood pressure was established (diastolic blood pressure 90 mm Hg at the end of the trial) in 78% of patients using 10/160 mg amlodipine/valsartan compared with 67% of patients who continued to use only 10 mg amlodipine. The combined administration of 160 mg of valsartan caused an additional reduction in systolic/diastolic blood pressure by 2.9/2.1 mm Hg. Art. compared with patients using only 10 mg amlodipine. Exforge was studied in an actively controlled study in 130 patients with essential hypertension (arterial hypertension) and diastolic blood pressure between ≥110 and ≤120 mmHg. Art. In this study (baseline BP 171/113 mmHg), an Exforge dosing regimen of 5/160 mg to 10/160 mg reduced steady-state BP by 36/29 mmHg. Art. compared to 32/28 mm Hg. Art. when using the dosing regimen of lisinopril/hydrochlorothiazide 10/12.5 mg to 20/12.5 mg. In two long-term studies, it was proven that the effect of Exforge lasted 1 year. Sudden discontinuation of the drug did not lead to a rapid increase in blood pressure. In patients whose blood pressure is adequately controlled with amlodipine when peripheral edema occurs, combination therapy may provide similar blood pressure control while reducing the edema. Pharmacokinetics. Valsartan and amlodipine exhibit linear pharmacokinetics. Amlodipine After oral administration in a therapeutic dose, the maximum concentration of amlodipine in the blood plasma is achieved within 6–12 hours. The calculated absolute bioavailability is 64–80%. Food significantly affects the bioavailability of amlodipine. The volume of distribution is approximately 21 l/kg. In vitro studies of amlodipine have proven that in patients with essential hypertension (arterial hypertension), about 97.5% of the circulating drug is bound to plasma proteins. Amlodipine is intensively (about 90%) metabolized in the liver to inactive metabolites. The elimination of amlodipine from blood plasma is biphasic with a half-life of about 30–50 hours. Equilibrium plasma levels are achieved after continuous administration for 7–8 days. 10% of the original amlodipine and 60% of its metabolites are excreted in the urine. Valsartan After oral administration, the maximum concentration of valsartan in the blood plasma is achieved within 2–4 hours. The bioavailability of the drug averages 23%. The pharmacokinetic curve of valsartan has a descending multi-exponential character (half-life α ≤1 hour and β about 9 hours). Food reduces the exposure of valsartan AUC by approximately 40% and the maximum plasma concentration by 50%, although 8 hours after administration, the plasma concentration of valsartan is the same for the group of patients taking the drug on an empty stomach and the group of patients taking the drug after eating. A decrease in AUC is not accompanied by a clinically significant decrease in the therapeutic effect, so valsartan can be used regardless of food intake. The steady-state volume of distribution of valsartan after intravenous administration is about 17 L, which indicates that valsartan is not distributed intensively in tissues. Valsartan binds tightly to plasma proteins (94–97%), mainly to serum albumin. Valsartan is not significantly transformed, since only 20% of the dose is converted into metabolites. A hydroxymetabolite, which is pharmacologically inactive, has been identified in blood plasma at low concentrations (≤10% of valsartan). Valsartan is excreted primarily unchanged in feces (approximately 83% of the dose) and urine (approximately 13% of the dose). After intravenous administration, the plasma clearance of valsartan is approximately 2 l/h, and its renal clearance is about 0.62 l/h (about 30% of the total clearance). The half-life of valsartan is 6 hours. Valsartan/amlodipine After oral administration of Exforge, maximum plasma concentrations of valsartan and amlodipine are achieved within 3 hours and 6–8 hours, respectively. The rate and extent of absorption of Exforge are equivalent to the bioavailability of valsartan and amlodipine. Special groups of patients Patients with renal failure Impaired renal function does not significantly affect the pharmacokinetics of amlodipine. There is no real correlation between renal function (measured by creatinine clearance) and exposure (measured by AUC) when valsartan is used in patients with varying degrees of renal impairment. Therefore, patients with mild to moderate renal impairment take the usual starting dose. Patients with Hepatic Impairment In patients with hepatic impairment, the clearance of amlodipine is reduced, resulting in an increase in AUC of approximately 40–60%. In patients with mild to moderate hepatic impairment, exposure (as determined by AUC values) to valsartan is on average twice that of healthy volunteers (selected by age, sex and body weight). Patients with liver disease should be careful when using the drug.

Pharmacokinetics

The pharmacokinetics of valsartan and amlodipine are linear.

Amlodipine

Suction. After oral administration of amlodipine in therapeutic doses, the Cmax of amlodipine in the blood plasma is achieved within 6–12 hours. The absolute bioavailability averages 64–80%. Food intake does not affect the bioavailability of amlodipine.

Distribution. The apparent VSS is approximately 21 L/kg. In vitro studies with amlodipine have shown that in patients with arterial hypertension, approximately 97.5% of the circulating drug is bound to plasma proteins.

Metabolism. Amlodipine is extensively (approximately 90%) metabolized in the liver to form active metabolites.

Excretion. The elimination of amlodipine from plasma is biphasic with a T1/2 of approximately 30 to 50 hours. Equilibrium plasma concentrations are achieved after use for 7–8 days. 10% of unchanged amlodipine and 60% of amlodipine in the form of metabolites are excreted by the kidneys.

Valsartan

Suction. After oral administration of valsartan, Cmax in blood plasma is achieved within 2–3 hours. The average absolute bioavailability is 23%. The pharmacokinetic curve of valsartan has a descending multi-exponential character (T1/2α <1 hour and T1/2β - about 9 hours). When taking valsartan with food, there is a decrease in bioavailability (according to AUC value) by 40% and Cmax in the blood plasma by almost 50%, although approximately 8 hours after taking the drug, the concentration of valsartan in the blood plasma in the group of patients taking it with food and in group taking on an empty stomach are leveled off. The decrease in AUC, however, is not accompanied by a clinically significant decrease in the therapeutic effect, so valsartan can be prescribed regardless of the timing of meals.

Distribution. The VSS of valsartan at steady state after intravenous administration was approximately 17 L, indicating the absence of extensive tissue distribution of valsartan. Valsartan is highly bound to serum proteins (94–97%), mainly to albumin.

Metabolism. Valsartan is not subject to significant metabolism (about 20% of the dose taken is determined 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 active.

Excretion. Valsartan is excreted mainly unchanged through the intestines (about 83% of the dose) and by the kidneys (about 13% of the dose). After intravenous administration, plasma Cl of valsartan is about 2 l/h, renal Cl is 0.62 l/h (about 30% of total clearance). T1/2 of valsartan - 6 hours.

Amlodipine/Valsartan

After oral administration of the drug Exforge®, the Cmax of valsartan and amlodipine is achieved after 3 and 6–8 hours, respectively. The rate and extent of absorption of the drug is equivalent to the bioavailability of valsartan and amlodipine when each of them is taken in the form of separate tablets.

Pharmacokinetics in special clinical situations

The pharmacokinetic features of the use of Exforge® in children under 18 years of age have not been established.

Elderly patients. 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 T1/2.

In elderly patients, the systemic exposure to valsartan was slightly more pronounced than in younger patients, but these indicators were not clinically significant. Since the tolerability of the drug components in older and younger patients is equally good, it is recommended to use the usual dosage regimens.

Patients with impaired renal function. In patients with impaired renal function, the pharmacokinetic parameters of amlodipine do not change significantly. There was no correlation between renal function (clearance) and systemic exposure of valsartan (AUC) in patients with varying degrees of renal impairment. No change in the initial dose is required in patients with initial and moderate renal impairment (Cl creatinine - 30-50 ml/min).

Patients with Hepatic Impairment: Patients with hepatic impairment have reduced clearance of amlodipine, resulting in an increase in AUC of approximately 40–60%. On average, in patients with mild to moderate chronic liver disease, the bioavailability (AUC) of valsartan is doubled compared to healthy volunteers (matched for age, sex and body weight).

Exforge, film-coated tablets 10mg+160mg, 28 pcs.

Compound.

.

Description of the dosage form.

Film-coated tablets, 5/80 mg:

dark yellow, round with beveled edges, imprinted “NVR” on one side and “NV” on the other.

Film-coated tablets, 5/160 mg:

dark yellow, oval with beveled edges, imprinted “NVR” on one side and “ECE” on the other.

Film-coated tablets, 10/160 mg:

light yellow, oval with beveled edges, imprinted “NVR” on one side and “UIC” on the other.
Pharmachologic effect. Antihypertensive.

Pharmacodynamics.

Exforge® is a combination of 2 antihypertensive drugs with a complementary mechanism of blood pressure control: amlodipine, a dihydropyridine derivative, belongs to the class of “slow” calcium channel blockers (SCBC), valsartan belongs to the class of angiotensin II receptor antagonists. The combination of these components has a mutually complementary hypotensive effect, which leads to a more pronounced decrease in blood pressure compared to that during monotherapy with each drug.

Amlodipine

Amlodipine, which is part of the drug Exforge®, inhibits the transmembrane entry of calcium ions into cardiomyocytes and vascular smooth muscle cells. The mechanism of the antihypertensive effect of amlodipine is associated with a direct relaxing effect on vascular smooth muscle, causing a decrease in peripheral vascular resistance and a decrease in blood pressure.

When taken in therapeutic doses in patients with arterial hypertension, amlodipine causes vasodilation, leading to a decrease in blood pressure (in the patient’s “lying” and “standing” position). The decrease in blood pressure is not accompanied by a significant change in heart rate and catecholamine levels with long-term use.

Plasma concentrations of the drug correlate with 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, an increase in glomerular filtration rate and effective renal blood flow without changing the filtration fraction and the level of proteinuria.

As with the use of other BMCCs, taking amlodipine in patients with normal left ventricular (LV) function caused changes in hemodynamic parameters of cardiac function at rest and during exercise: there was a slight increase in cardiac index without a significant effect on the maximum rate of increase in pressure in the LV (dP /dt), final dBP and LV volume. Hemodynamic studies in intact animals and humans have shown that the decrease in blood pressure under the influence of amlodipine in the range of therapeutic doses is not accompanied by a negative inotropic effect, even when used simultaneously with beta-blockers.

Amlodipine does not alter sinoatrial node function or AV conduction in intact animals and humans. When amlodipine is used in combination with beta-blockers in patients with arterial hypertension or angina pectoris, a decrease in blood pressure is not accompanied by undesirable changes in ECG parameters.

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

Valsartan

Valsartan is an active and specific angiotensin II receptor antagonist intended for oral administration. It acts selectively on the AT1 receptor subtype, which is responsible for the known effects of angiotensin II. An increase in plasma concentrations of free angiotensin II due to AT1 receptor blockade under the influence of valsartan may stimulate unblocked AT2 receptors, which counteract the effects of AT1 receptor blockade. Valsartan does not have any pronounced agonistic 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 causes the destruction of bradykinin.

When using angiotensin II antagonists, ACE inhibition and accumulation of bradykinin or substance P do not occur, so the development of a dry cough is unlikely.

In comparative clinical studies of valsartan with an ACE inhibitor, the incidence of dry cough was significantly lower (p<0.05) in patients receiving valsartan (in 2.6% of patients receiving valsartan and in 7.9% of patients receiving an ACE inhibitor). 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 during treatment with valsartan, and in 19% of cases during treatment with a thiazide diuretic. At the same time, in the group of patients treated with an ACE inhibitor, cough was observed in 68.5% of cases (p<0.05). Valsartan does not interact with or block hormone receptors or ion channels that are important for regulating the functions of the cardiovascular system.

When treating patients with arterial hypertension with valsartan, a decrease in blood pressure is observed, not accompanied by a change in heart rate.

The antihypertensive effect appears within 2 hours in most patients after a single dose of the drug. The maximum reduction in blood pressure develops within 4–6 hours. After taking the drug, the antihypertensive effect persists for more than 24 hours. With repeated use, the maximum reduction in blood pressure, regardless of the dose taken, is usually achieved within 2–4 weeks and is maintained at this level during long-term therapy. Abrupt cessation 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 class II–IV) leads to a significant reduction in the number of hospitalizations. This effect is most pronounced in patients not receiving ACE inhibitors or beta-blockers. When taking valsartan in patients with left ventricular failure (stable clinical course) or with impaired LV function after myocardial infarction, a decrease in cardiovascular mortality is observed.

Amlodipine/Valsartan

In patients with arterial hypertension who received Exforge® once a day, the antihypertensive effect persisted for 24 hours.

The drug Exforge® in doses of 5/80 and 5/160 mg in patients with an initial SBP of 153–157 mm Hg. and dBP ≥95 and <110 mm Hg, reduces blood pressure by 20–28/14–19 mm Hg. (compared to 7–13/7–9 mmHg with placebo).

The drug Exforge® at a dose of 10/160 and 5/160 mg normalizes blood pressure (decrease in dBP in the sitting position <90 mm Hg) in 75 and 62% of patients with inadequate blood pressure control during monotherapy with valsartan at a dose of 160 mg/day. day

Exforge® at a dose of 10/160 mg normalizes blood pressure in 78% of patients with inadequate blood pressure control during monotherapy with amlodipine at a dose of 10 mg.

In patients with arterial hypertension, when combining valsartan at a dose of 160 mg with amlodipine at doses of 10 and 5 mg, an additional reduction in SBP and DBP by 6.0/4.8 mm Hg is achieved. and 3.9/2.9 mmHg. respectively, compared with patients who continued to receive valsartan 160 mg alone or amlodipine 5 and 10 mg alone.

When titrating the dose of Exforge® from 5/160 to 10/160 mg in patients with arterial hypertension with dBP ≥110 and <120 mmHg. There is a decrease in blood pressure in the sitting position by 36/29 mm Hg, comparable to a decrease in blood pressure when titrating the dose of a combination of an ACE inhibitor and a thiazide diuretic.

In two long-term studies with a long follow-up period, the effect of Exforge® was maintained for 1 year. Sudden cessation of taking Exforge® is not accompanied by a sharp increase in blood pressure.

In patients who achieved adequate blood pressure control, but developed severe edema during amlodipine monotherapy, when using combination therapy, comparable blood pressure control was achieved with a lower likelihood of developing edema.

The therapeutic effectiveness of Exforge® does not depend on the age, gender and race of the patient.

Pharmacokinetics.

The pharmacokinetics of valsartan and amlodipine are linear.

Amlodipine

Suction.

After oral administration of amlodipine in therapeutic doses, the Cmax of amlodipine in the blood plasma is achieved within 6–12 hours. The absolute bioavailability averages 64–80%. Food intake does not affect the bioavailability of amlodipine.

Distribution.

The apparent VSS is approximately 21 L/kg.
In vitro
studies with amlodipine have shown that in patients with arterial hypertension, approximately 97.5% of the circulating drug is bound to plasma proteins.

Metabolism.

Amlodipine is extensively (approximately 90%) metabolized in the liver to form active metabolites.

Excretion.

The elimination of amlodipine from plasma is biphasic with a T1/2 of approximately 30 to 50 hours. Equilibrium plasma concentrations are achieved after use for 7–8 days. 10% of unchanged amlodipine and 60% of amlodipine in the form of metabolites are excreted by the kidneys.

Valsartan

Suction.

After oral administration of valsartan, Cmax in blood plasma is achieved within 2–3 hours. The average absolute bioavailability is 23%. The pharmacokinetic curve of valsartan has a descending multi-exponential character (T1/2α <1 hour and T1/2β - about 9 hours). When taking valsartan with food, there is a decrease in bioavailability (according to AUC value) by 40% and Cmax in the blood plasma by almost 50%, although approximately 8 hours after taking the drug, the concentration of valsartan in the blood plasma in the group of patients taking it with food and in group taking on an empty stomach are leveled off. The decrease in AUC, however, is not accompanied by a clinically significant decrease in the therapeutic effect, so valsartan can be prescribed regardless of the timing of meals.

Distribution.

The VSS of valsartan at steady state after intravenous administration was approximately 17 L, indicating the absence of extensive tissue distribution of valsartan. Valsartan is highly bound to serum proteins (94–97%), mainly to albumin.

Metabolism.

Valsartan is not subject to significant metabolism (about 20% of the dose taken is determined 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 active.

Excretion.

Valsartan is excreted mainly unchanged through the intestines (about 83% of the dose) and by the kidneys (about 13% of the dose). After intravenous administration, plasma Cl of valsartan is about 2 l/h, renal Cl is 0.62 l/h (about 30% of total clearance). T1/2 of valsartan - 6 hours.

Amlodipine/Valsartan

After oral administration of Exforge®, Cmax of valsartan and amlodipine is achieved after 3 and 6–8 hours, respectively. The rate and extent of absorption of the drug is equivalent to the bioavailability of valsartan and amlodipine when each of them is taken in the form of separate tablets.

Pharmacokinetics in special clinical situations

The pharmacokinetic features of the use of Exforge® in children under 18 years of age have not been established.

Elderly patients.

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 T1/2.

In elderly patients, the systemic exposure to valsartan was slightly more pronounced than in younger patients, but these indicators were not clinically significant. Since the tolerability of the drug components in older and younger patients is equally good, it is recommended to use the usual dosage regimens.

Patients with impaired renal function.

In patients with impaired renal function, the pharmacokinetic parameters of amlodipine do not change significantly. There was no correlation between renal function (clearance) and systemic exposure of valsartan (AUC) in patients with varying degrees of renal impairment. No change in the initial dose is required in patients with initial and moderate renal impairment (Cl creatinine - 30-50 ml/min).

Patients with liver disorders.

Patients with hepatic impairment have reduced clearance of amlodipine, resulting in an increase in AUC of approximately 40–60%. On average, in patients with mild to moderate chronic liver disease, the bioavailability (AUC) of valsartan is doubled compared to healthy volunteers (matched for age, sex and body weight).

Indications.

Arterial hypertension (for patients for whom combination therapy is indicated).

Contraindications.

● hypersensitivity to amlodipine, valsartan and other components of the drug;

● pregnancy.

The safety of using Exforge® in patients with unilateral or bilateral renal artery stenosis or stenosis of the artery of a single kidney, in patients after a recent kidney transplant, as well as in children and adolescents under 18 years of age has not been established.

Carefully:

● liver diseases (especially with obstructive diseases of the biliary tract) - valsartan is excreted mainly unchanged in the bile, while amlodipine is intensively metabolized in the liver;

● severe renal dysfunction (Cl creatinine <10 ml/min) - because There are no data on the safety of the drug in such cases;

● mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy - as well as with the use of other vasodilators;

● hyperkalemia, sodium deficiency in the body and/or decrease in blood volume.

Use during pregnancy and breastfeeding.

Given the mechanism of action of angiotensin II receptor antagonists, a risk to the fetus cannot be excluded. It is known that the administration of ACE inhibitors, which affect the renin-angiotensin-aldosterone system (RAAS), to pregnant women in the second and third trimesters, leads to damage or death of the developing fetus. According to a retrospective analysis, the use of ACE inhibitors during the first trimester of pregnancy was accompanied by the development of pathology in the fetus and newborn. With the unintentional use of valsartan in pregnant women, cases of spontaneous abortion, oligohydramnios and renal dysfunction in newborns have been described.

Exforge®, like any other drug that directly affects the RAAS, should not be prescribed during pregnancy or to women wishing to become pregnant. Patients of childbearing age should be informed of the possible risk to the fetus associated with the use of drugs that affect the RAAS. If pregnancy is detected during treatment with Exforge®, the drug should be discontinued as soon as possible.

It is not known whether valsartan and/or amlodipine passes into breast milk. Since experimental studies have shown the excretion of valsartan into breast milk, it is not recommended to use Exforge® during breastfeeding.

Side effects.

The safety of Exforge® has been assessed in more than 2,600 patients.

Criteria for assessing the frequency of adverse reactions: very common (>10% of cases); often (1–10%); sometimes (0.1–1%); rarely (0.001–0.1%); in some cases (<0.001%). Within each group, identified by frequency of occurrence, adverse reactions are distributed in decreasing order of importance.

From the respiratory system:

often - nasopharyngitis, influenza.

Allergic and immunological reactions:

rarely - increased sensitivity.

From the senses:

rarely - visual impairment, tinnitus; sometimes - dizziness associated with dysfunction of the vestibular apparatus.

Mental disorders:

rarely - anxiety.

From the central nervous system and peripheral nervous system:

often - headache; sometimes - dizziness, drowsiness, orthostatic dizziness, paresthesia.

From the respiratory system:

sometimes - cough, pain in the pharynx and larynx.

From the cardiovascular system:

sometimes - tachycardia, palpitations, orthostatic hypotension; rarely - syncope, marked decrease in blood pressure.

From the digestive system:

sometimes - diarrhea, nausea, abdominal pain, constipation, dry mouth.

Dermatological reactions:

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

From the musculoskeletal system:

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

From the genitourinary system:

rarely - pollakiuria, polyuria, erectile dysfunction.

Other:

often - pastiness, facial swelling, peripheral edema, increased fatigue, flushing of the face, asthenia, feeling of heat.

In comparative and placebo-controlled clinical studies, the incidence of peripheral edema was significantly lower in patients receiving a combination of amlodipine with valsartan (5.8%) than in patients receiving amlodipine monotherapy (9%).

Laboratory indicators:

An increase in blood urea nitrogen (more than 3.1 mmol/l) was observed slightly more often in the groups receiving amlodipine/valsartan (5.5%) and valsartan monotherapy (5.5%), compared with the group receiving placebo (4 ,5%).

Adverse events previously reported with each of the components may occur with Exforge, even if they were not observed in clinical studies.

Amlodipine

In those clinical studies where amlodipine was used as monotherapy, other adverse events were also observed (regardless of their causal relationship with the drug being studied): most often - nausea; less often - alopecia, change in the frequency of defecation, dyspepsia, shortness of breath, rhinitis, gastritis, gum hyperplasia, gynecomastia, hyperglycemia, erectile dysfunction, increased urination, leukopenia, general malaise, mood lability, dry mouth, myalgia, peripheral neuropathy, pancreatitis, hepatitis, increased sweating, thrombocytopenia, vasculitis, angioedema, erythema multiforme.

In a long-term placebo-controlled study (PRAISE-2) in patients with heart failure of grades III and IV according to the NYHA classification of non-ischemic etiology, an increase in the incidence of pulmonary edema was observed when using amlodipine, with no significant differences in the incidence of worsening heart failure compared with placebo.

In rare cases, at the beginning of therapy with slow calcium channel blockers or with an increase in the dose of slow calcium channel blockers, especially in patients suffering from severe coronary artery disease, an increase in the frequency, duration and severity of angina or the development of acute myocardial infarction was observed. Also, during therapy with BMCC, cases of arrhythmia (including ventricular tachycardia and atrial fibrillation) were observed. It is not possible to distinguish the occurrence of these adverse events from the natural course of the underlying disease.

Valsartan

In clinical studies when using valsartan as monotherapy, the following adverse events were noted (regardless of their causal relationship with the drug under study): viral infections, upper respiratory tract infections, sinusitis, rhinitis, neutropenia, insomnia.

Neutropenia was detected in 1.9% of patients receiving valsartan and 1.6% of patients receiving an ACE inhibitor.

In controlled clinical trials, 3.9% and 16.6% of patients with heart failure treated with valsartan experienced increases in creatinine and blood urea nitrogen levels of more than 50%, respectively. For comparison, in patients receiving placebo, an increase in creatinine and urea nitrogen was observed in 0.9 and 6.3% of cases.

A doubling of serum creatinine was detected in 4.2% of patients after myocardial infarction receiving valsartan and in 3.4% of those receiving captopril.

In controlled clinical studies, 10% of patients with heart failure experienced an increase in serum potassium concentrations of more than 20%. For comparison, in patients receiving placebo, an increase in potassium concentration was observed in 5.1% of cases.

Interaction.

Amlodipine

When monotherapy with amlodipine there is no clinically significant interaction with thiazide diuretics, beta-blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, Maalox (aluminum hydroxide gel, magnesium hydroxide, simethicone), cimetidine, NSAIDs, antibiotics and oral hypoglycemic drugs.

Valsartan

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

When used concomitantly with dietary supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other drugs that may cause an increase in potassium concentrations in the blood (for example, heparin), caution and frequent monitoring of potassium concentrations in the blood should be exercised.

Method of administration and dose.

Inside,

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

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

The recommended maximum daily dose is 10/320 mg.

When prescribed to elderly patients, patients with initial or moderate renal impairment (Cl creatinine >30 ml/min), impaired liver function or liver disease, with symptoms of cholestasis:

no change in dosage regimen is required.

Overdose.

There are currently no data on cases of drug overdose.

Symptoms:

with an overdose of valsartan, one can expect the development of a pronounced decrease in blood pressure and dizziness. Overdose of amlodipine can lead to excessive peripheral vasodilation and possible reflex tachycardia. Severe and prolonged systemic arterial hypotension has also been reported, leading to the development of shock with a fatal outcome.

Treatment:

in case of accidental overdose, induce vomiting (if the drug was taken recently) or perform gastric lavage. The use of activated charcoal in healthy volunteers immediately or 2 hours after taking amlodipine significantly reduced its absorption.

In case of clinically significant arterial hypotension caused by the drug Exforge®, the patient should be placed with his legs elevated, and active measures should be taken to maintain the activity of the cardiovascular system, including frequent monitoring of the function of the heart and respiratory system, blood volume and the amount of urine excreted. In the absence of contraindications, in order to restore vascular tone and blood pressure, it is possible to use (with caution) a vasoconstrictor. IV calcium gluconate may be effective in reversing calcium channel blockade. Removal of valsartan and amlodipine during hemodialysis is unlikely.

Special instructions.

If it is necessary to discontinue β-blockers before starting Exforge® therapy, the dose of β-blockers should be reduced gradually. Since amlodipine is not a β-blocker, the use of Exforge® does not prevent the development of withdrawal syndrome that occurs when treatment with β-blockers is abruptly stopped.

Sodium deficiency in the body and/or decrease in blood volume.

In placebo-controlled studies in patients with uncomplicated arterial hypertension, severe arterial hypotension was observed in 0.4% of cases. In patients with an activated renin-angiotensin-aldosterone system (for example, with BCC and/or sodium deficiency in patients receiving high doses of diuretics), symptomatic arterial hypotension may develop when taking angiotensin receptor blockers. Before starting treatment with Exforge®, sodium levels in the body and/or blood volume should be corrected or therapy should be initiated under close medical supervision. If arterial hypotension develops, the patient should be placed with legs elevated and, if necessary, given an intravenous infusion of saline solution. After stabilization of blood pressure, treatment with Exforge® can be continued.

Hyperkalemia.

When using the drug simultaneously with dietary supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other drugs that may cause an increase in the concentration of potassium in the blood (for example, heparin), caution should be exercised and regular monitoring of the concentration of potassium in the blood should be carried out.

Impact on the ability to drive vehicles and operate machinery.

There is no data on the effect of the drug on the ability to drive vehicles and operate machinery. Due to the possible occurrence of dizziness or increased fatigue, caution should be exercised when driving vehicles or operating machinery.

Release form.

Film-coated tablets, 5 mg/80 mg, 5 mg/160 mg or 10 mg/160 mg.

7, 10 or 14 pcs. in a blister; 1, 2, 4, 8, 14 or 40 blisters of 7 tablets; 3, 9 or 28 blisters of 10 tablets; 1. 2, 4, 7, or 20 blisters of 14 tablets are placed in a cardboard box.

Film-coated tablets, 5 mg + 320 mg or 10 mg + 320 mg.

7 or 14 tablets in a PVC/PVDC blister. 1 blister of 7 tablets; 1, 2, 4, 7 blisters of 14 tablets each are placed in a cardboard box.

Manufacturer.

Film-coated tablets, 5 mg/80 mg, 5 mg/160 mg or 10 mg/160 mg.

Novartis Pharma AG, Switzerland.

Produced

Novartis Pharma Stein AG, Switzerland.

or

Novartis Pharmaceuticals S.A., Spain.

Novartis Pharma AG, Switzerland.

Manufactured by Novartis Pharma Stein AG, Switzerland.

or Novartis Pharmaceutica SA, Spain.

Film-coated tablets, 5 mg + 320 mg or 10 mg + 320 mg.

Novartis Pharma AG, Switzerland.

Produced

Novartis Pharma Stein AG, Switzerland.

Lichtstrasse 35, 4056 Basel, Switzerland.

Novartis Pharma AG, Switzerland.

Manufactured by Novartis Pharma Stein AG, Switzerland.

Lichtstrasse 35, 4056 Basel, Switzerland.

For all dosages

Additional information about the drug can be obtained at

115035, Moscow, Sadovnicheskaya st., 82/2.

Tel.; fax: (495) 967-12-68.

Conditions for dispensing from pharmacies.

On prescription.

Contraindications

hypersensitivity to amlodipine, valsartan and other components of the drug;

pregnancy.

The safety of using Exforge® in patients with unilateral or bilateral renal artery stenosis or stenosis of the artery of a single kidney, in patients after a recent kidney transplant, as well as in children and adolescents under 18 years of age has not been established.

Carefully:

liver diseases (especially with obstructive diseases of the biliary tract) - valsartan is excreted mainly unchanged in the bile, while amlodipine is intensively metabolized in the liver;

severe renal dysfunction (creatinine Cl <10 ml/min) - because There are no data on the safety of the drug in such cases;

mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy - as well as with the use of other vasodilators;

hyperkalemia, sodium deficiency in the body and/or decrease in blood volume.

Use during pregnancy and breastfeeding

Given the mechanism of action of angiotensin II receptor antagonists, a risk to the fetus cannot be excluded. It is known that the administration of ACE inhibitors, which affect the renin-angiotensin-aldosterone system (RAAS), to pregnant women in the second and third trimesters, leads to damage or death of the developing fetus. According to a retrospective analysis, the use of ACE inhibitors during the first trimester of pregnancy was accompanied by the development of pathology in the fetus and newborn. With the unintentional use of valsartan in pregnant women, cases of spontaneous abortion, oligohydramnios and renal dysfunction in newborns have been described.

Exforge®, like any other drug that directly affects the RAAS, should not be prescribed during pregnancy or to women wishing to become pregnant. Patients of childbearing age should be informed of the possible risk to the fetus associated with the use of drugs that affect the RAAS. If pregnancy is detected during treatment with Exforge®, the drug should be discontinued as soon as possible.

It is not known whether valsartan and/or amlodipine passes into breast milk. Since experimental studies have shown the excretion of valsartan into breast milk, it is not recommended to use Exforge® during breastfeeding.

Reviews of Exforge

Reviews about Exforge are both positive and negative. Many patients note its effectiveness. Some, however, say that they experienced side effects that forced them to stop taking the drug.

In fact, no specialist can rule out the occurrence of undesirable effects in advance. The drug is much more effective than taking amlodipine or valsartan alone, but its use should be well controlled. For many, in addition, it is more profitable to buy analogs of Exforge.

Reviews of Co-Exforge are generally positive. Patients note the undoubted effectiveness of this remedy and recommend it to others.

Side effects

The safety of Exforge® has been assessed in more than 2,600 patients.

Criteria for assessing the frequency of adverse reactions: very common (>10% of cases); often (1–10%); sometimes (0.1–1%); rarely (0.001–0.1%); in some cases (<0.001%). Within each group, identified by frequency of occurrence, adverse reactions are distributed in decreasing order of importance.

From the respiratory system: often - nasopharyngitis, influenza.

Allergic and immunological reactions: rarely - hypersensitivity.

From the senses: rarely - visual impairment, tinnitus; sometimes - dizziness associated with dysfunction of the vestibular apparatus.

Mental disorders: rarely - anxiety.

From the central nervous system and peripheral nervous system: often - headache; sometimes - dizziness, drowsiness, orthostatic dizziness, paresthesia.

From the respiratory system: sometimes - cough, pain in the pharynx and larynx.

From the cardiovascular system: sometimes - tachycardia, palpitations, orthostatic hypotension; rarely - syncope, marked decrease in blood pressure.

From the digestive system: sometimes - diarrhea, nausea, abdominal pain, constipation, dry mouth.

Dermatological reactions: sometimes - skin rash, erythema; rarely - hyperhidrosis, exanthema, itching.

From the musculoskeletal system: sometimes - swelling of the joints, back pain, arthralgia; rarely - muscle spasms, a feeling of heaviness throughout the body.

From the genitourinary system: rarely - pollakiuria, polyuria, erectile dysfunction.

Other: often - pastiness, facial swelling, peripheral edema, increased fatigue, flushing of the face, asthenia, feeling of heat.

In comparative and placebo-controlled clinical studies, the incidence of peripheral edema was significantly lower in patients receiving a combination of amlodipine with valsartan (5.8%) than in patients receiving amlodipine monotherapy (9%).

Laboratory parameters: an increase in blood urea nitrogen (more than 3.1 mmol/l) was observed slightly more often in the groups receiving amlodipine/valsartan (5.5%) and valsartan monotherapy (5.5%) compared with the group receiving placebo (4.5%).

Adverse events previously reported with each of the components may occur with Exforge, even if they were not observed in clinical studies.

Amlodipine

In those clinical studies where amlodipine was used as monotherapy, other adverse events were also observed (regardless of their causal relationship with the drug being studied): most often - nausea; less often - alopecia, change in the frequency of defecation, dyspepsia, shortness of breath, rhinitis, gastritis, gum hyperplasia, gynecomastia, hyperglycemia, erectile dysfunction, increased urination, leukopenia, general malaise, mood lability, dry mouth, myalgia, peripheral neuropathy, pancreatitis, hepatitis, increased sweating, thrombocytopenia, vasculitis, angioedema, erythema multiforme.

In a long-term placebo-controlled study (PRAISE-2) in patients with heart failure of grades III and IV according to the NYHA classification of non-ischemic etiology, an increase in the incidence of pulmonary edema was observed when using amlodipine, with no significant differences in the incidence of worsening heart failure compared with placebo.

In rare cases, at the beginning of therapy with slow calcium channel blockers or with an increase in the dose of slow calcium channel blockers, especially in patients suffering from severe coronary artery disease, an increase in the frequency, duration and severity of angina or the development of acute myocardial infarction was observed. Also, during therapy with BMCC, cases of arrhythmia (including ventricular tachycardia and atrial fibrillation) were observed. It is not possible to distinguish the occurrence of these adverse events from the natural course of the underlying disease.

Valsartan

In clinical studies when using valsartan as monotherapy, the following adverse events were noted (regardless of their causal relationship with the drug under study): viral infections, upper respiratory tract infections, sinusitis, rhinitis, neutropenia, insomnia.

Neutropenia was detected in 1.9% of patients receiving valsartan and 1.6% of patients receiving an ACE inhibitor.

In controlled clinical trials, 3.9% and 16.6% of patients with heart failure treated with valsartan experienced increases in creatinine and blood urea nitrogen levels of more than 50%, respectively. For comparison, in patients receiving placebo, an increase in creatinine and urea nitrogen was observed in 0.9 and 6.3% of cases.

A doubling of serum creatinine was detected in 4.2% of patients after myocardial infarction receiving valsartan and in 3.4% of those receiving captopril.

In controlled clinical studies, 10% of patients with heart failure experienced an increase in serum potassium concentrations of more than 20%. For comparison, in patients receiving placebo, an increase in potassium concentration was observed in 5.1% of cases.

Side effects of the drug Exforge

The following adverse reactions are classified by organ, system and frequency of occurrence, with the most common listed first. Classification of the frequency of occurrence of adverse reactions: very often (≥1/10); often (1/100, ≤1/10); sometimes (1/1000, ≤1/100); rare (1/10,000, ≤1/1000); very rare (≤1/10,000), including isolated reports. For each frequency group, adverse reactions are listed in order of increasing severity.

Additional information regarding components Exforge may cause adverse reactions previously reported for one of the components of the drug, even if such reactions were not noted in clinical trials. Amlodipine The following additional adverse reactions were observed in clinical trials with amlodipine monotherapy, regardless of causal relationship to the drug studied. The most commonly reported adverse reaction was vomiting. Sometimes the following adverse reactions were identified: alopecia, constipation, dyspepsia, shortness of breath, rhinitis, gastritis, gingival hyperplasia, gynecomastia, hyperglycemia, impotence, increased frequency of urination, leukopenia, mood changes, peripheral neuropathy, pancreatitis, hepatitis, thrombocytopenia, vasculitis, angioedema, erythema, pulmonary edema. Valsartan In clinical trials with valsartan monotherapy, regardless of the cause-and-effect relationship with the study drug, the following additional side effects were noted: viral infections, upper respiratory tract infections, sinusitis, rhinitis, neutropenia, insomnia, increased levels of creatinine in the blood, urea nitrogen.

Interaction

Amlodipine

When monotherapy with amlodipine there is no clinically significant interaction with thiazide diuretics, beta-blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, Maalox (aluminum hydroxide gel, magnesium hydroxide, simethicone), cimetidine, NSAIDs, antibiotics and oral hypoglycemic drugs.

Valsartan

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

When used concomitantly with dietary supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other drugs that may cause an increase in potassium concentrations in the blood (for example, heparin), caution and frequent monitoring of potassium concentrations in the blood should be exercised.

Directions for use and doses

Orally, with a small amount of water, 1 time per day, regardless of meal time.

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

The recommended maximum daily dose is 10/320 mg.

When prescribed to elderly patients, patients with initial or moderate renal impairment (Cl creatinine >30 ml/min), impaired liver function or liver disease, with symptoms of cholestasis: no change in dosage regimen is required.

Use of the drug Exforge

Patients whose blood pressure is inadequately regulated by one of the monodrugs (amlodipine or valsartan) can be transferred to combination therapy with Exforge. Recommended dose - 1 tablet per day; It is recommended to take the drug with water. Patients taking valsartan and amlodipine separately can be switched to Exforge, which contains the same doses of components. For elderly patients, the usual dosing regimens are recommended. The maximum daily dose is 1 tablet of Exforge 5/80 mg, or 1 tablet of Exforge 5/160 mg, or 1 tablet of Exforge 10/160 mg (the maximum permissible doses of the drug components are 10 mg for amlodipine content, 160 mg for valsartan content).

Overdose

There are currently no data on cases of drug overdose.

Symptoms: with an overdose of valsartan, you can expect the development of a pronounced decrease in blood pressure and dizziness. Overdose of amlodipine can lead to excessive peripheral vasodilation and possible reflex tachycardia. Severe and prolonged systemic arterial hypotension has also been reported, leading to the development of shock with a fatal outcome.

Treatment: in case of accidental overdose, induce vomiting (if the drug was taken recently) or perform gastric lavage. The use of activated charcoal in healthy volunteers immediately or 2 hours after taking amlodipine significantly reduced its absorption.

In case of clinically significant arterial hypotension caused by the drug Exforge®, the patient should be placed with his legs elevated, and active measures should be taken to maintain the activity of the cardiovascular system, including frequent monitoring of the function of the heart and respiratory system, blood volume and the amount of urine excreted. In the absence of contraindications, in order to restore vascular tone and blood pressure, it is possible to use (with caution) a vasoconstrictor. IV calcium gluconate may be effective in reversing calcium channel blockade. Removal of valsartan and amlodipine during hemodialysis is unlikely.

special instructions

If it is necessary to discontinue β-blockers before starting Exforge® therapy, the dose of β-blockers should be reduced gradually. Since amlodipine is not a β-blocker, the use of Exforge® does not prevent the development of withdrawal syndrome that occurs when treatment with β-blockers is abruptly stopped.

Sodium deficiency in the body and/or decrease in blood volume. In placebo-controlled studies in patients with uncomplicated arterial hypertension, severe arterial hypotension was observed in 0.4% of cases. In patients with an activated renin-angiotensin-aldosterone system (for example, with BCC and/or sodium deficiency in patients receiving high doses of diuretics), symptomatic arterial hypotension may develop when taking angiotensin receptor blockers. Before starting treatment with Exforge®, sodium levels in the body and/or blood volume should be corrected or therapy should be initiated under close medical supervision. If arterial hypotension develops, the patient should be placed with legs elevated and, if necessary, given an intravenous infusion of saline solution. After stabilization of blood pressure, treatment with Exforge® can be continued.

Hyperkalemia. When using the drug simultaneously with dietary supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other drugs that may cause an increase in the concentration of potassium in the blood (for example, heparin), caution should be exercised and regular monitoring of the concentration of potassium in the blood should be carried out.

Impact on the ability to drive vehicles and operate machinery. There is no data on the effect of the drug on the ability to drive vehicles and operate machinery. Due to the possible occurrence of dizziness or increased fatigue, caution should be exercised when driving vehicles or operating machinery.

Special instructions for the use of Exforge

Patients with a deficiency in the body of sodium and/or bcc In patients with uncomplicated hypertension (arterial hypertension), excessive hypotension was detected. In patients with an activated renin-angiotensin system (with a reduced sodium content in the blood and/or circulating volume and receiving diuretics in high doses) while taking angiotensin receptor blockers, symptomatic hypotension may occur. This condition should be corrected before using Exforge and the patient should be closely monitored at the start of therapy. If hypotension occurs when using Exforge, the patient should be placed in a horizontal position and, if necessary, given an intravenous infusion of physiological solution. Continue treatment until blood pressure stabilizes. Hyperkalemia Caution should be exercised during concomitant treatment with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium or other drugs that may increase potassium levels (heparin, etc.), as well as regular monitoring of blood potassium levels. Withdrawal of beta-adrenergic blockers Amlodipine is not a beta-adrenergic blocker and therefore does not protect against the danger of sudden withdrawal of beta-adrenergic blockers, so the dose of drugs in this group should be reduced gradually. Renal artery stenosis There are no data on the use of Exforge in patients with unilateral or bilateral renal artery stenosis. Kidney transplantation There is no experience with the safe use of Exforge in patients with a recent kidney transplant. Impaired liver function Valsartan is excreted mainly unchanged in bile, while amlodipine is extensively metabolized in the liver. Particular caution is required when using Exforge in patients with impaired liver function or obstructive disorders of the gallbladder. Impaired renal function For patients with mild to moderate renal impairment, there is no need to adjust the dose of Exforge. For patients with severe renal impairment (creatinine clearance ≤10 ml/min), there are no data on the use of the drug, so it is recommended to prescribe the drug with caution to this category of patients. Aortic or mitral valve stenosis, obstructive hypertrophic cardiomyopathy As with other vasodilators, the drug should be used with extreme caution in patients diagnosed with aortic or mitral valve stenosis, or obstructive hypertrophic cardiomyopathy. The drug should be used with caution in cases of unstable angina. Use during pregnancy or breastfeeding Considering the mechanism of action of angiotensin II antagonists, a risk to the fetus cannot be excluded. It has been reported that the use of ACE inhibitors, a specific class of drugs acting on the renin-angiotensin-aldosterone system, in the second and third trimester of pregnancy can cause damage and death of the fetus. In addition, based on available retrospective data, the use of ACE inhibitors in the third trimester of pregnancy is associated with a potential risk of developing congenital defects in the fetus. Spontaneous miscarriages, oligohydramnios, and renal dysfunction in newborns have been reported if a woman inadvertently took valsartan during pregnancy. Like any drug that directly affects the renin-angiotensin-aldosterone system, Exforge is not used during pregnancy or in women planning pregnancy. A physician prescribing any drug that acts on the renin-angiotensin-aldosterone system should warn a woman planning a pregnancy about the potential risk of taking these drugs to the unborn child. If pregnancy occurs during therapy, Exforge should be stopped immediately. It is unknown whether valsartan and/or amlodipine passes into breast milk, so it is not recommended to use the drug during breastfeeding. If drug therapy is necessary for the mother, breastfeeding should be stopped. Children Studies on the use of this drug in children under 18 years of age have not been conducted. Therefore, until more complete information is obtained, Exforge is not recommended for the treatment of this category of patients. The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Studies regarding the effect of the drug on the ability to drive vehicles and work with potentially dangerous mechanisms have not been conducted. However, patients who experience dizziness or a feeling of weakness after taking the drug should refrain from driving vehicles or operating potentially dangerous machinery.

Release form

Film-coated tablets, 5 mg/80 mg, 5 mg/160 mg or 10 mg/160 mg. 7, 10 or 14 pcs. in a blister; 1, 2, 4, 8, 14 or 40 blisters of 7 tablets; 3, 9 or 28 blisters of 10 tablets; 1. 2, 4, 7, or 20 blisters of 14 tablets are placed in a cardboard box.

Film-coated tablets, 5 mg + 320 mg or 10 mg + 320 mg. 7 or 14 tablets in a PVC/PVDC blister. 1 blister of 7 tablets; 1, 2, 4, 7 blisters of 14 tablets each are placed in a cardboard box.

Exforge price, where to buy

The price of Exforge is considered quite high. You can buy this product in Moscow and other Russian cities for, on average, 1,400–1,800 rubles.

The price of Co-Exforge, on average, is about 2000 rubles.

• Online pharmacies in RussiaRussia
• Online pharmacies in KazakhstanKazakhstan

LuxPharma* special offer

• Exforge table
  10 mg/160 mg No. 28 RUR 1,590 order
• Exforge tab. 5 mg/160 mg No. 28

  1650 rub. order

ZdravCity

• Co-exforge tab. p.p.o. 5mg+160mg+12.5mg n28Novartis Pharma Stein AG/Novartis Pharmaceuticals S.A

  RUB 2,785 order

• Co-exforge tab. p.p.o. 10mg+160mg+12.5mg n28Novartis Pharmaceutica SA

  RUB 2602 order

• Exforge tablets p.p.o. 5mg+80mg 28 pcs. Novartis Pharmaceutica SA

  RUB 1,899 order

Pharmacy Dialogue

• Exforge (tablet p/o 10mg+160mg No. 28)Novartis

  RUB 2,127 order

• Co-exforge (0.01+0.16/0.0125 No. 28)Novartis

  RUR 2,478 order

• Exforge (tablet p/o 5mg+80mg No. 28)Novartis

  RUR 1,855 order

• Exforge (tablet p/o 5mg+160mg No. 28)Novartis

  RUB 2,136 order

• Co-exforge (0.005+0.16/0.0125 No. 28)Novartis

  RUB 2,514 order

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