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

Kernel: active substances: amlodipine besylate - 6.94 mg / 6.94 mg / 13.87 mg (corresponding to 5 mg / 5 mg / 10 mg amlodipine, respectively) and valsartan - 80 mg / 160 mg / 160 mg; auxiliary substances: cellulose microcrystalline - 54,06 mg / 109,06 mg / 108,13 mg, crospovidone -20,00 mg / 40,00 mg / 40,00 mg, magnesium stearate - 4.50 mg / 9.00 mg / 9 , 00 mg, silicon colloidal dioxide - 1.50 mg / 3.00 mg / 3.00 mg;

Sheath: Premix white (hypromellose, titanium dioxide, polyethylene glycol 4000, talc) - 4.40 mg / 7.15 mg / 11.93 mg; Premix yellow (hypromellose, iron oxide, yellow, polyethylene glycol 4000, talc) - 3.60 mg / 5.85 mg / 1.04 mg; Premix red (gynromellose, iron oxide red, polyethylene glycol, talc) (contained in tablets with a dosage of 10 mg / 160 mg) - 0.03 mg; purified water - enough.

Description:

Film-coated tablets, 5/80 mg: dark yellow, round with beveled edges, film-coated, with an overprint "NVR" on one side and "NV" another.

Film-coated tablets, 5/160 mg: dark yellow, oval with beveled edges, film-coated, with an overprint "NVR" on one side and "ECE" on the other.

The tablets covered with a film cover, 10/160 mg: light yellow color, oval with the oblique edges, covered with a film cover, with an overprint "NVR" on one side and "UIC" on the other.

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:

Exforge® is a combination of two antihypertensive components 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) and valsartan - to the class of angiotensin II receptor antagonists. The combination of these components has a mutually complementary antihypertensive effect, which leads to a more pronounced decrease in blood pressure compared to that of monotherapy with each drug.

Amlodipine

Amlodipine, which is part of the drug, inhibits transmembrannoe intake of calcium ions in cardiomyocytes and smooth muscle cells of blood vessels. The mechanism of antihypertensive action of amlodipine is associated with a direct relaxing effect on the smooth muscle of the vessels, which causes a decrease in peripheral vascular resistance and a decrease in blood pressure. Experimental data show that amlodipine binds both to dihydropyridine and non-dihydropyridine receptors. After taking in therapeutic doses in patients with hypertension amlodipine causes vasodilation, leading to a decrease in blood pressure (in the patient's position "lying" and "standing"). Decrease in blood pressure is not accompanied by a significant change in the heart rate (heart rate) and the concentration of catecholamines for prolonged use. With arterial hypertension in patients with normal renal function amlodipine in therapeutic doses leads to a decrease in the resistance of renal vessels, an increase in the glomerular filtration rate and effective renal plasma flow without changing the filtration fraction and the degree of proteinuria.

As with other BCCI, amlodipine treatment in patients with normal left ventricular function (LV) caused a change in hemodynamic parameters of heart function at rest and under physical exertion: there was a slight increase in the cardiac index, without significantly affecting the maximum rate of increase in pressure in the LV ( dP / dt) and end-diastolic pressure and LV volume. Hemodynamic studies in intact animals and humans showed that a 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 (5-adrenoblockers.

Amlodipine does not change the function of the sinoatrial node or atrioventricular conduction in intact animals and humans. When using amlodipine in combination with P-blockers in patients with arterial hypertension or with angina, a decrease in blood pressure is not associated with undesirable changes in ECG parameters.

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

Valsartan

Valsartan - an active and specific antagonist of angiotensin II receptors, intended for oral administration. It acts selectively on the AT1 subtype receptors which are responsible for the known effects of angiotensin II. Increased plasma concentration of free angiotensin II due to blockade of AT1 receptors under the influence of valsartan can stimulate unblocked AT2 receptors that counteract the effects of AT1 receptor stimulation. Valsartan does not have any expressed agonistic activity against AT1-receptors. The affinity of valsartan for the receptors of the AT1 subtype is about 20,000 times higher than for the AT2 subtype receptors.

Valsartan does not inhibit angiotensin-converting enzyme (ACE), also known as kininase II, which converts angiotensin I to angiotensin II and causes the destruction of bradykinin.

Since angiotensin II receptor antagonists do not inhibit ACE and accumulate bradykinin or substance P, 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 who received valsartan (2.6% of patients who received valsartan, and in 7.9% of patients receiving an ACE inhibitor). In a clinical study involving patients who previously developed a dry cough in the treatment with an ACE inhibitor, this complication was observed in 19.5% of cases with valsartan, and in 19.0% of cases with a thiazide diuretic. At the same time, cough was observed in 68.5% of patients treated with an ACE inhibitor (p <0.05). Valsartan does not interact and does not block the receptors of other hormones or ion channels that are important for the regulation of cardiovascular functions.

In the treatment of valsartan in patients with hypertension, there is a decrease in blood pressure, not accompanied by a change in heart rate.

The antihypertensive effect occurs within 2 hours in most patients after a single oral intake of valsartan. The maximum decrease in blood pressure develops in 4-6 hours. After taking the drug, the duration of the hypotensive effect persists for more than 24 hours. With repeated application, the maximum reduction in blood pressure, regardless of the dose taken, is usually achieved within 2-4 weeks and is maintained at the reached level during prolonged therapy.A sharp discontinuation of valsartan is not accompanied by a sharp increase in blood pressure or other undesirable clinical consequences. The use of valsartan in patients with chronic heart failure (NYHA functional classes II-IV) leads to a significant reduction in the number of hospitalizations. This effect is most pronounced in patients who do not receive ACE inhibitors or β-blockers. With the use of valsartan in patients with left ventricular failure (stable clinical course) or with LV dysfunction after myocardial infarction, cardiovascular mortality is reduced.

Pharmacokinetics:

The pharmacokinetics of valsartan and amlodipine are characterized by linearity.

Amlodipine

Suction

After ingestion of amlodipine in therapeutic doses, the maximum concentration (Cmah) amlodipine in the blood plasma is achieved in 6-12 hours. The absolute bioavailability is on the average 64-80%. Eating food does not affect the bioavailability of amlodipine.

Distribution

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

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

Metabolism

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

Excretion

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

Valsartan

Suction

After oral administration of valsartan Cmax in blood plasma is achieved in 2-3 hours. The average absolute bioavailability is 23%.

When valsartan is taken with food, there is a decrease in bioavailability (by the value of the area under the concentration-time curve, AUC) by 40% and maximum concentration (Cmah) in blood plasma by almost 50%, although approximately 8 hours after taking the drug, valsartan plasma concentrations in the group of patients taking it with food and in the group taking on an empty stomach are equalized. The decrease in AUC, however, is not accompanied by a clinically significant decrease in the therapeutic effect, so valsartan can be administered regardless of the time of ingestion.

Distribution

The volume of distribution (Vd) of valsartan in the equilibrium period after intravenous administration was 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 albumins.

Metabolism

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

Excretion

The pharmacokinetic curve of valsartan has a downward multiexponential character (T1 / 2α <1 h and T1 / 2β about 9 h). Valsartan is excreted mainly unchanged through the intestine (about 83% of the dose) and kidneys (about 13% of the dose). After intravenous administration, the plasma clearance of valsartan is about 2 l / h and its renal clearance is 0.62 l / h (about 30% of the total clearance). T1/2 valsartan is 6 hours.

Amlodipine / Valsartan

After ingestion Exforge® Cmvalsartan and amlodipine are reached after 3 and 6-8 hours, respectively. The rate and extent of absorption of Exforge® are equivalent to the bioavailability of valsartan and amlodipine when taken in separate tablets.

Pharmacokinetics in special clinical cases

Children and teenagers <18 years old

Pharmacokinetic features of the use of Exforge ® in children under 18 years are not established.

Patients aged> 65 years

Time to reach Cmamlodipine in blood plasma in young and elderly patients is the same. In elderly patients, clearance of amlodipine is slightly reduced, which leads to an increase in AUC and T1/2.

In elderly patients, the systemic effect of valsartan was somewhat more pronounced than in young patients, however, this was not clinically significant. Since tolerability of the drug components in the elderly and in younger patients is equally good, it is recommended to use the usual dosing regimens.

Patients with impaired renal function

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

Patients with impaired hepatic function

Patients with impaired hepatic function have reduced clearance of amlodipine, which leads to an increase in AUC of approximately 40-60%. On average, the degree of bioavailability (AUC) of valsartan is doubled in patients with liver disorders (5-6 on the Child-Pugh scale) and moderate (7-9 on the Child-Pugh scale) compared to healthy volunteers (of the corresponding age, sex and body weight). Exforge® should be used with caution in patients with impaired liver function, obstructive biliary tract disease.

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

Contraindications:

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

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

Severe (> 9 on Child-Pugh scale) degree of liver function abnormalities, biliary cirrhosis, cholestasis;

Severe violations of kidney function (QC less than 30 ml / min), hemodialysis;

Pregnancy, pregnancy planning and the period of breastfeeding;

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

Obstruction of the outflow tract of the left ventricle;

Hemodynamically unstable heart failure after acute myocardial infarction.

Simultaneous use with aliskiren in patients with type 2 diabetes mellitus.

Carefully:

If you have one of these diseases, always consult a doctor before using the drug.

Caution should be used to prescribe Exforge® to patients with hyperkalemia, a deficiency in the body of sodium, and / or a decrease in the volume of circulating blood (BCC).

Care should be taken when using the drug in patients with unilateral or bilateral stenosis of the renal arteries or arterial stenosis of a singlekidney. The safety of the drug in patients after a recent transplantation of the kidney is not established.

As with other vasodilators, special care should be taken when prescribing amlodipine drug in patients with mitral or aortic stenosis, and hypertrophic obstructive cardiomyopathy.

Caution should be exercised when using Exforge ® in patients with chronic heart failure III-IV functional class according to the NYHA classification, with acute coronary syndrome after acute myocardial infarction, in patients with hepatic impairment of less than 9 on the Child-Pugh scale, obstructive diseases of the biliary tract.

Also with caution should be the simultaneous use of drugs containing angiotensin II receptor antagonists, including Exforge®, with other agents that inhibit the renin-angiotensin-aldosterone system (RAAS), such as ACE inhibitors or aliskiren, including in patients with impaired renal function.

Pregnancy and lactation:

Like any other drug that affects RAAS, Exforge® should not be used in women who plan pregnancy. When prescribing Exforge®, like any other drug that affects RAAS, the doctor should inform women of childbearing age of the possible risk to the fetus associated with the use of the drug.

The use of Exforge® during pregnancy is contraindicated.

Given the mechanism of action of angiotensin II receptor antagonists, the risk to the fetus can not be ruled out. It is known that the appointment of ACE inhibitors that affect RAAS, pregnant in the II and III trimesters, leads to damage or death of the developing fetus. According to a retrospective analysis of the use of ACE inhibitors during the first trimester of pregnancy, the development of fetal and newborn pathology was accompanied. In case of unintended admission of valsartan in pregnant women, cases of spontaneous abortion, malignancy and renal dysfunction in newborns are described. Data on the use of amlodipine in pregnant women is not enough to judge its effect on the fetus. If the pregnancy is diagnosed during the treatment with Exforge®, the drug should be discontinued as soon as possible.

It is not known whether the valsartan and / or amlodipine in breast milk. Since in experimental studies noted the isolation of valsartan with milk lactating animals, it is not recommended to use the drug Exforge® during breastfeeding.

There is no data on the effect of amlodipine and valsartan on fertility.

Dosing and Administration:

The drug should be taken orally, washed down with a small amount of water, once a day, regardless of the time of ingestion. The recommended daily dose is 1 Exforge® tablet containing amlodipine / valsartan in a dose of 5/80 mg or 5/160 mg or 10/160 mg. It is recommended to start taking the drug at a dose of 5/80 mg once a day. You can increase the dose 1-2 weeks after the start of therapy. The maximum dose of the drug is 5/320 mg or 10/320 mg per day.

Use in patients over 65 years of age

Correction of the dose is not required.

Use in children and adolescents under the age of 18 years

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

Patients with impaired renal function

For patients with mild and moderate renal dysfunction (CK> 30), correction of the initial dose is not required.

Patients with impaired hepatic function

Due to the presence of Exforge in the composition of valsartan and amlodipine® should be taken with caution to patients with impaired liver function and obstructive liver disease.

Side effects:

Safety of Exforge application® estimated more than 2,600 patients.

When assessing the incidence of side effects, the following grades are used: "very often" (> 1/10), "often" (from> 1/100 <1/10), "infrequently" (> 1/1000 <1/100) "rarely" (> 1/10000 <1/1000), "very rarely" (<1/10000), including individual messages.

Within the limits of each group allocated according to the frequency of occurrence, adverse reactions are distributed in order of decreasing importance.

Infectious and parasitic diseases Often: nasopharyngitis, influenza.

Immune system disorders Rarely: hypersensitivity.

Disorders from the visual organ Rarely: visual impairment.

Hearing impairments and labyrinthine infringements infrequently: vertigo; rarely: tinnitus. Disorders of the mind Rarely: anxiety.

Nervous system disorders Often: headache; infrequently: dizziness, drowsiness, postural dizziness, paresthesia.

Disorders from the heart Infrequent: tachycardia, palpitation, rarely: syncopal condition.

Vascular disturbances Infrequent: orthostatic hypotension; rarely: marked reduction in blood pressure.

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

Disturbances from the gastrointestinal tract Infrequent - diarrhea, nausea, abdominal pain, constipation, dryness of the oral mucosa.

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

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

Disorders from the kidneys and urinary tracts Rarely: pollakiuria, polyuria.

Violations of the genitals and mammary gland Rarely: erectile dysfunction.

Common disorders and irregularities at the injection site Often: pastosity, facial edema, peripheral edema, increased fatigue, "flushes" of blood to the face, asthenia, a feeling of heat.

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

Laboratory and instrumental data: an increase in the concentration of urea nitrogen in the blood (more than 3.1 mmol / L) was observed slightly more often in the groups receiving amlodipine / valsartan (5.5%) and valsartan in the form of monotherapy (5.5%), compared with the placebo group (4.5%).

Undesirable effects reported earlier with each of the components may occur with Exforge®, even if they have not been observed in clinical trials.

Amlodipine

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

Disorders from the immune system: very rarely - allergic reactions. Disorders from the metabolism and nutrition: very rarely - hyperglycemia.

Disorders of the psyche: infrequently - insomnia, lability of mood.

Disturbances from the nervous system: infrequently - tremor, hypesthesia, dysgeusia; very rarely - muscle hypertonia, peripheral neuropathy.

Disorders from the side of the organ of vision: infrequently - diplopia.

Disorders from the heart: very rarely - arrhythmia, bradycardia, ventricular tachycardia, atrial fibrillation, myocardial infarction.

Violations from the vessels: very rarely - vasculitis.

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

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

Disorders from the liver and biliary tract: very rarely - hepatitis, jaundice.

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

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

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

Violations of the genitals and breast: infrequently - gynecomastia.

General disorders and disorders at the injection site: infrequently - weakness, pain in the chest, pain of different localization.

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

Valsartan

Below are the AEs detected in patients with hypertension in clinical trials, as well as in clinical practice and laboratory studies. For AE revealed in clinical practice and in laboratory studies, it is not possible to establish frequency of occurrence, therefore for these PJ it is indicated: "frequency is unknown".

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

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

Hearing disorders and labyrinthine disturbances: infrequently, vertigo.

Violations from the vessels: the frequency is unknown - vasculitis.

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

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

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

Disturbances from the skin and subcutaneous tissues: the frequency is unknown - angioedema, bullous dermatitis, skin itching, rash.

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

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

General disorders and disorders at the injection site: infrequently - fatigue, asthenia.

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

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

There are no data on drug overdose cases at the present time. With an overdose of valsartan, the main manifestation is a marked decrease in blood pressure, accompanied by dizziness.

An overdose of amlodipine can lead to excessive peripheral vasodilation and possible reflex tachycardia.There was also reported the emergence of severe and prolonged systemic arterial hypotension until the development of shock with a lethal outcome.

Treatment: If the drug has been taken recently, induce vomiting or rinse the stomach. The use of activated carbon in healthy volunteers immediately or within 2 hours after taking amlodipine significantly reduced its absorption.

In the absence of contraindications to restore vascular tone and blood pressure, it is possible to use (with caution) a vasoconstrictor.

The excretion of valsartan and amlodipine during hemodialysis is unlikely.

Interaction:

Amlodipine

Simvastatin. A joint long-term use of simvastatin 80 mg / day and amlodipine at a dose of 10 mg / day leads to a 77% increase in the exposure of simvastatin. It is recommended to reduce the dose of simvastatin in patients taking amlodipine, up to 20 mg / day.

Inhibitors of the isoenzyme CYP3A4. When amlodipine is used concomitantly with diltiazem, in elderly patients, amlodipine metabolism is slowed, probably due to inhibition of the CYP3A4 isoenzyme, which leads to an increase in the concentration of amlodipine in the blood plasma by approximately 50% andstrengthening the therapeutic effect. When using amlodipine concomitantly with strong inhibitors of CYP3A4 (for example, ketoconazole, itraconazole and ritonavir) a marked increase in the systemic exposure of amlodipine.

Inductors of isoenzyme CYP3A4. Since the use of amlodipine concurrently with inducers of the isoenzyme CYP3A4 (for example, carbamazepine, phenobarbital, phenytoin, phosphenytoin, primidon, rifampicin, grapefruit juice, herbal preparations containing Hypericum perforated), can lead to a marked decrease in its concentration in the blood plasma; when prescribing amlodipine with inducers of the isoenzyme CYP3A4, its therapeutic effect should be monitored.

In monotherapy with amlodipine, there is no clinically significant interaction with thiazide diuretics, (3-adrenoblockers, ACE inhibitors, long-acting nitrates, nitroglycerin for sublingual use, digoxin, warfarin, atorvastatin, sildenafil, maalox (aluminum hydroxide gel, magnesium hydroxide, simethicone), cimetidine, non-steroidal anti-inflammatory drugs, antibiotics and hypoglycemic drugs for oral administration.

Valsartan

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

Drugs and substances that affect the potassium content in blood serum: when administered simultaneously with dietary supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other drugs that can cause an increase in potassium in the blood (for example, with heparin), care should be taken and regular monitoring of potassium in the blood.

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2): the appointment of angiotensin II receptor antagonists concomitantly with NSAIDs may lead to a weakening of the hypotensive effect. In elderly patients, patients with reduced BCC (including those receiving diuretic therapy) or with renal dysfunction, the simultaneous use of receptor antagonists for angiotensin II and NSAIDs may increase the risk of renal dysfunction.At the beginning of therapy or when adjusting the dosage regimen, regular monitoring of kidney function is recommended in patients taking antagonists of angiotensin II and NSAID receptors.

Protein-carriers. Co-administration of valsartan with inhibitors of the carrier protein OATP1B1 (rifampin, ciclosporin) and with an inhibitor of the transporter protein MRP2 (ritonavir) may lead to an increase in systemic bioavailability of valsartan.

Double blockade of RAAS with the use of angiotensin II receptor antagonists, ACE inhibitors or aliskiren.

Simultaneous use of angiotensin II receptor antagonists with other drugs that affect RAAS leads to an increase in the incidence of arterial hypotension, hyperkalemia, and renal dysfunction. It is necessary to monitor blood pressure, kidney function, and the content of plasma electrolytes when prescribing Exforge® with other drugs that affect RAAS. Avoid concomitant use of drugs containing angiotensin II receptor antagonists, including Exforge®, with other agents that affect RAAS in patients with type 2 diabetes and severe renal failure.

Lithium preparations. With the simultaneous use of lithium preparations with ACE inhibitors and angiotensin II receptor antagonists, a reversible increase in lithium serum levels was noted and, therefore, toxic effects were increased, therefore, it is recommended to control the lithium content in serum. The risk of toxic manifestations associated with the use of lithium drugs may be further increased with simultaneous use with Exforge® and diuretics.

Special instructions:

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

In placebo-controlled studies in patients with uncomplicated arterial hypertension, severe arterial hypotension was observed in 0.4% of cases. In patients with activated RAAS (eg, with a deficiency of bcc and / or sodium in patients receiving high doses of diuretics), the development of symptomatic arterial hypotension is possible with angiotensin receptor antagonists. Before starting treatment with Exforge ®, you should adjust the sodium content in the body and / or BCC, or start therapy under close medical supervision.In case of significant decrease in blood pressure, the patient should be placed with raised legs, if necessary, an intravenous infusion of 0.9% sodium chloride solution. After stabilization of blood pressure, Exforge® treatment can be continued.

Hyperkalemia

With simultaneous use of the drug with dietary supplements containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other drugs that can cause an increase in the potassium content in the blood (for example, with heparin), care should be taken and regular monitoring of the potassium content in the blood .

Stenosis of the renal artery

In patients with unilateral or bilateral stenosis of the renal artery or stenosis of the artery of a single kidney, the use of Exforge® may be accompanied by an increase in serum levels of urea and creatinine, so Exforge® should be used with caution in such patients.

Renal impairment

Patients with initial and moderate impairment of renal function are not required to adjust the dose of Exforge®.

Dysfunction of the liver

Valsartan is excreted mainly unchanged through the intestines with bile, while amlodipine intensively metabolized in the liver. Caution should be exercised when prescribing Exforge® to patients with liver disease (especially with obstructive diseases of the biliary tract), accompanied by impaired liver function.

Edema Quincke

Quincke's edema, including swelling of the larynx and vocal cords, leading to airway obstruction, and / or swelling of the face, lips, pharynx, and / or tongue edema, occurred in patients who received valsartan, some of these patients previously developed Quincke's edema on the background of taking other drugs, including ACE inhibitors. Taking Exforge10 in case of development of Quincke's edema should be immediately canceled, resumption of Exforge® is prohibited.

Heart failure, condition after myocardial infarction

It is recommended to use with caution the blockers of "slow" calcium channels (including, amlodipine) in patients with chronic heart failure III-IV functional class according to the NYHA classification.In patients whose renal function depends on the state of RAAS (eg, patients with heart failure), therapy with ACE inhibitors and receptor antagonists angiotensin II was accompanied by oliguria and / or progressive azotemia, and in rare cases led to acute renal failure and / or death. The examination of patients with circulatory failure and patients who underwent myocardial infarction should include a study of kidney function.

Acute myocardial infarction

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

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

There are no data on the effect of the drug on the ability to drive vehicles and work with mechanisms. In connection with the possible occurrence of dizziness or increased fatigue should be careful when driving vehicles or working with mechanisms.

Form release / dosage:

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

Packaging:Film-coated tablets, 5 mg / 80 mg, 5 mg / 160 mg or 10 mg / 160 mg: 7, 10 or 14 pcs.in the blister; 1, 2, 4, 8, 14 or 40 blisters of 7 tablets; 3, 9 or 28 blisters for 10 tablets; 1. 2, 4, 7, or 20 blisters for 14 tablets together with instructions for use in a cardboard bundle.

Storage conditions:

In a dry place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

The drug should not be used after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002605/07

Date of registration:07.09.2007

The owner of the registration certificate:Novartis Pharma AGNovartis Pharma AG Switzerland

Manufacturer: & nbsp

NOVARTIS PHARMA STEIN, AG Switzerland

Information update date: & nbsp28.10.2014

Illustrated instructions

Instructions

Exforge® (Exforge®)