Universal reference book for medicines
Product name: EXFORGE ®

Active substance: amlodipine, valsartan

Type: Antihypertensive drug

Manufacturer: NOVARTIS PHARMA (Switzerland) manufactured by NOVARTIS PHARMA STEIN (Switzerland)
Composition, form of production and packaging
The tablets, covered with a film shell of
dark yellow color, round with bevelled edges, with an overprint "NVR" on one side and "NV" on the other.

1 tab.

amlodipine besylate 6.94 mg,

which corresponds to the content of amlodipine 5 mg

valsartan 80 mg

Excipients: microcrystalline cellulose - 54.06 mg, crospovidone - 20 mg, magnesium stearate - 4.5 mg, silicon dioxide colloid - 1.5 mg.

The composition of the film shell: premix white (hypromellose, titanium dioxide, polyethylene glycol 4000, talc) - 4.4 mg, premix yellow (hypromellose, iron oxide yellow, polyethylene glycol 4000, talc) - 3.6 mg, purified water qs

7 pcs.
- blisters (2) - packs of cardboard.
14 pcs.
- blisters (2) - packs of cardboard.
The tablets covered with a film shell of dark yellow color, oval with oblique edges, with an overprint "NVR" on one side and "ECE" on the other.

1 tab.

amlodipine besylate 6.94 mg,

which corresponds to the content of amlodipine 5 mg

valsartan 160 mg

Excipients: microcrystalline cellulose - 109.06 mg, crospovidone - 40 mg, magnesium stearate - 9 mg, silicon dioxide colloid - 3 mg.

The composition of the film shell: premix white (hypromellose, titanium dioxide, polyethylene glycol 4000, talc) - 7.15 mg, premix yellow (hypromellose, iron oxide yellow, polyethylene glycol 4000, talc) - 5.85 mg, purified water qs

7 pcs.
- blisters (2) - packs of cardboard.
14 pcs.
- blisters (2) - packs of cardboard.
The tablets covered with a film cover of light yellow color, oval with oblique edges, with an overprint "NVR" on one side and "UIC" on the other.

1 tab.

amlodipine besylate 13.87 mg,

which corresponds to the content of amlodipine 10 mg

valsartan 160 mg

Excipients: cellulose microcrystalline - 108.13 mg, crospovidone - 40 mg, magnesium stearate - 9 mg, silicon dioxide colloid - 3 mg.

The composition of the film shell: premix white (hypromellose, titanium dioxide, polyethylene glycol 4000, talc) - 11.93 mg, premix yellow (hypromellose, iron oxide yellow, polyethylene glycol 4000, talc) - 1.04 mg, premix red (hypromellose, iron osside red, polyethylene glycol, talc) - 0.03 mg, purified water - qs

7 pcs.
- blisters (2) - packs of cardboard.
14 pcs.
- blisters (2) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2013.

PHARMACHOLOGIC EFFECT

Combined antihypertensive drug containing active substances with a complementary mechanism for monitoring blood pressure.
Amlodipine, a derivative of dihydropyridine, belongs to the class of slow calcium channel blockers (BCCC), valsartan - to the class of angiotensin II receptor antagonists. The combination of these components has a mutually complementary antihypertensive effect, which leads to a more pronounced decrease in blood pressure compared to that of monotherapy with each drug.
Amlodipine

Amlodipine, part of Exforge, 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 reduction in OPSS and a decrease in blood pressure.
After taking in therapeutic doses in patients with arterial hypertension, amlodipine causes vasodilation, leading to a decrease in blood pressure (in the position of the patient lying down and standing).
Decrease in blood pressure is not accompanied by a significant change in heart rate and catecholamine levels with prolonged use.
The concentration of the drug in the blood plasma correlates with the clinical effect in both young and elderly patients.

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

As with other BCCI, amlodipine treatment in patients with normal left ventricular function 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 left ventricle, of course diastolic pressure and volume of the left ventricle.
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 with simultaneous application with beta-blockers.
Amlodipine does not change the function of the sinoatrial node or AV-conduction in intact animals and in humans.
When using amlodipine in combination with beta-blockers in patients with arterial hypertension or with angina, a decrease in blood pressure is not accompanied by 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 AT 1 receptor subtype, which is responsible for the known effects of angiotensin II. An increase in the plasma concentration of free angiotensin II due to blockade of AT 1 -receptors under the influence of valsartan can stimulate unblocked AT 2 receptors, which counteract the effects of stimulation of AT 1 -receptors. Valsartan does not have any marked agonistic activity against AT 1 -receptors. The affinity of valsartan for AT 1 subtype receptors is about 20,000 times higher than for AT 2 receptor subtypes.
Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I into angiotensin II and causes destruction of bradykinin.

Because
when angiotensin II antagonists are used, there is no inhibition of ACE and accumulation of 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 receiving valsartan (2.6% of patients receiving valsartan and 7.9% receiving 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 patients with valsartan, and in 19% of cases with a thiazide diuretic. At the same time, cough was observed in 68.5% of cases in the group 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, which are important for the regulation of the functions of the cardiovascular system.
In the treatment of valsartan in patients with arterial hypertension, a decrease in blood pressure is noted, not accompanied by a change in heart rate.

Antihypertensive effect occurs within 2 hours in most patients after a single dose.
The maximum decrease in blood pressure develops after 4-6 hours. After taking the drug, the duration of the hypotensive effect persists for more than 24 hours. When repeated, the maximum decrease in blood pressure, regardless of the dose taken, is usually achieved within 2-4 weeks. and maintained at the achieved level during long-term 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 class II-IV functional class according to the NYHA classification) leads to a significant reduction in the number of hospital admissions. This effect is most pronounced in patients who do not receive ACE inhibitors or beta-blockers. With the use of valsartan in patients with left ventricular failure (stable clinical course) or with left ventricular dysfunction after a previous myocardial infarction, there is a decrease in cardiovascular mortality.
Amlodipine / valsartan

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

Exforge in doses of 5/80 mg and 5/160 mg in patients with baseline systolic BP 153-157 mm Hg.
Art. and diastolic blood pressure is 95 mm Hg. and less than 110 mm Hg. reduces blood pressure by 20-28 / 14-19 mm Hg. (compared with 7-13 / 7-9 mmHg when taking placebo).
Exforge at a dose of 10/160 mg and 5/160 mg normalizes blood pressure (a decrease in diastolic blood pressure in a sitting position less than 90 mm Hg at the end of the study) in 75% and 62% of patients with inadequate BP control against valsartan monotherapy in a dose 160 mg / day.

Exforge at a dose of 10/160 mg normalizes blood pressure in 78% of patients with inadequate blood pressure control amlodipine monotherapy with a dose of 10 mg.In patients with arterial hypertension with a combination of valsartan 160 mg with amlodipine at doses of 10 mg and 5 mg, an additional reduction in systolic and diastolic blood pressure is achieved at 6.0 / 4.8 mm Hg.
and 3.9 / 2.9 mm Hg. respectively, compared with patients who continued to receive only valsartan at a dose of 160 mg or only amlodipine at a dose of 5 and 10 mg.
When titrating the Exforge dose from 5/160 mg to 10/160 mg in patients with arterial hypertension with diastolic blood pressure of? 110 mm Hg.
and less than 120 mm Hg. there was a decrease in blood pressure in the sitting position by 36/29 mm Hg, comparable with a decrease in blood pressure when titrating the dose of the combination of an ACE inhibitor and a thiazide diuretic.
In two long-term studies with a long observation period, Exforge's effect persisted for 1 year.
A sudden stopping of Exforge's intake is not accompanied by a sharp increase in blood pressure.
In patients with an adequate control of blood pressure, but developed pronounced swelling with amlodipine monotherapy, combined therapy was used to achieve comparable control of blood pressure with a lower probability of edema development.

The therapeutic efficacy of Exforge does not depend on the age, sex and race of the patient.

PHARMACOKINETICS

The pharmacokinetics of valsartan and amlodipine are characterized by linearity.

Amlodipine

Suction

After ingestion of amlodipine in therapeutic doses of Cmax, amlodipine in blood plasma is achieved after 6-12 hours. The absolute bioavailability is on the average 64-80%.
Eating food does not affect the bioavailability of amlodipine.
Distribution

V d 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.
Metabolism

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

Excretion

The removal of amlodipine from plasma is biphasic with T 1/2 approximately 30 to 50 hours.
C ss in 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 ingestion of valsartan C max in blood plasma is achieved after 2-3 hours. The average absolute bioavailability is 23%.
The pharmacokinetic curve of valsartan has a downward multiexponential character (T 1/2? <1 h and T 1/2? About 9 h). When valsartan is taken with food, there is a decrease in bioavailability (by AUC value) by 40% and C max 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, equalize. 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

V d of valsartan in the equilibrium state after intravenous administration was about 17 liters, indicating a lack of extensive distribution of valsartan in the tissues.Valsartan largely binds to 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 not pharmacologically active.
Excretion

Valsartan is excreted mainly unchanged through the intestine (about 83% of the dose) and kidneys (about 13% of the dose).
After iv introduction, the plasma clearance of valsartan is about 2 l / h and its renal clearance is 0.62 l / h (about 30% of the total clearance). T 1/2 of valsartan is 6 hours.
Amlodipine / valsartan

After ingestion of Exforge C max, valsartan and amlodipine are reached after 3 hours and 6-8 hours, respectively.
The speed and degree of absorption of Exforge are equivalent to the bioavailability of valsartan and amlodipine when taken in each of them as separate tablets.
Pharmacokinetics in special clinical cases

Pharmacokinetic features of Exforge application in children under 18 years of age have not been established.

The time to achieve C max amlodipine in blood plasma in young and elderly patients is the same.
In elderly patients, the clearance of amlodipine is slightly reduced, which leads to an increase in AUC and T 1/2 .
In elderly patients, the systemic effect of valsartan was somewhat more pronounced than in young patients, but 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.
In patients with impaired renal function, the pharmacokinetic parameters of amlodipine do not change significantly.
There was no correlation between renal function (CC) 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 kidney function (QA 30-50 ml / min).
Patients with hepatic insufficiency have a reduced clearance of amlodipine, which leads to an increase in AUC of approximately 40-60%.
On average, in patients with chronic liver diseases of mild to moderate degree, valsartan's bioavailability (AUC) is doubled compared to healthy volunteers (of the appropriate age, sex, and body weight).
INDICATIONS

- Arterial hypertension (for patients who are shown combined therapy).

DOSING MODE

The drug should be taken orally, washed down with a small amount of water, 1 time / day, regardless of the time of ingestion.

The recommended daily dose is 1 tablet.
in a dose of 5/80 mg or 5/160 mg or 10/160 mg.
When appointing elderly patients, patients with initial or moderate renal dysfunction (CK> 30 ml / min), with impaired liver function or with liver disease, with cholestasis , a change in the dosing regimen is not required.

SIDE EFFECT

Safety of Exforge application is estimated more than in 2600 patients.

Criteria for assessing the frequency of adverse reactions: very often - more than 10% of cases;
often - 1-10%; sometimes - 0.1-1%; rarely - 0.001-0.1%; in some cases - less than 0.001%. Within the limits of each group allocated according to the frequency of occurrence, adverse reactions are distributed in order of decreasing importance.
On the part of the respiratory system: often - nasopharyngitis, influenza;
sometimes - cough, pain in the throat and larynx.
From the senses: rarely - visual impairment, tinnitus;
sometimes - dizziness associated with impaired vestibular apparatus.
From the side of the central nervous system and peripheral nervous system: often - headache;
sometimes - dizziness, drowsiness, orthostatic dizziness, paresthesia;rarely - anxiety.
From the cardiovascular system: sometimes - tachycardia, palpitation, orthostatic hypotension;
rarely - syncopal condition, 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 - puffiness of the joints, back pain, arthralgia;
rarely - muscle spasms, a feeling of heaviness in the whole body.
From the urinary system: rarely - pollakiuria, polyuria.

On the part of the reproductive system: rarely - erectile dysfunction.

Other: often - pastovnost, edema of the face, 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 significantly lower in patients treated with amlodipine versus valsartan (5.8%) than in patients receiving amlodipine monotherapy (9%).

On the part of laboratory indicators: an increase in blood urea nitrogen (more than 3.1 mmol / L) was observed only slightly in the groups receiving amlodipine / valsartan (5.5%) and valcartan as monotherapy (5.5%), compared with the placebo group (4.5% ).

Allergic reactions: rarely - hypersensitivity to the components of the drug.

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

Amlodipine

In those clinical studies where amlodipine was used as a monotherapy, other adverse events were also noted (regardless of their causal relationship with the study drug): most often nausea;
less often - alopecia, changes in the frequency of defecation, dyspepsia, dyspnea, rhinitis, gastritis, gingival mucosa, gynecomastia, hyperglycemia, erectile dysfunction, increased urination, leukopenia, general malaise, mood laxity, dry mouth, myalgia, peripheral neuropathy, pancreatitis, hepatitis , increased sweating, thrombocytopenia, vasculitis, angioedema, erythema multiforme.
For continuous placebo-controlled study (PRAISE-2) in patients with heart failure III and IV functional class classification NYHA nonischemic etiology, when applying amlodipine showed an increase in frequency of lung edema in the absence of significant differences in the incidence of worsening of heart failure as compared with placebo.
In rare cases, the beginning of therapy of calcium channel blockers slow (BCCI) or with increasing doses BCCI, particularly in patients suffering from severe coronary artery disease was noted increase in frequency, duration and severity of acute angina pectoris or myocardial infarction. Cases of arrhythmia (including ventricular tachycardia and atrial fibrillation) have also been observed on the background of BCCI therapy. It is not possible to distinguish the occurrence of adverse events data from the main flow of the natural disease.
Valsartan
in clinical trials when used as monotherapy valsartan, noted the following adverse events (irrespective of causal relationship to the study drug): viral infections, upper respiratory tract infection, sinusitis, rhinitis, neutropenia, insomnia.
Neutropenia was present in 1.9% of patients receiving valsartan, and 1.6% of patients receiving ACE inhibitor.
In controlled clinical trials in 3.9% and 16.6% of patients with heart failure treated with valsartan, it noted increased creatinine and blood urea nitrogen more than 50%, respectively. For comparison - in patients who received placebo, increased creatinine and urea nitrogen were observed in the 0.9% and 6.3% of cases.
A doubling of serum creatinine were observed in 4.2% of patients after myocardial infarction treated with valsartan and 3.4% treated with captopril.
In controlled clinical studies, 10% of patients with heart failure, there was an increase in serum potassium concentration greater than 20%. For comparison, in patients treated with placebo, increasing the concentration of potassium was observed in 5.1% of cases.
CONTRAINDICATIONS

- Pregnancy;

- Hypersensitivity to the components of the drug.

Safety of application of Exforge in patients with unilateral or bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, patients with recent myocardial kidney transplantation, as well as children and adolescents under 18 years of age has not been established.
With caution prescribers with: human liver (especially in obstructive diseases of biliary tract); severe renal impairment (creatinine clearance <10 mL / min); patients with mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy; with hyperkalemia, sodium deficiency in the body and / or reduction of BCC.
PREGNANCY AND LACTATION

Exforge, like any other drug, has a direct impact on the RAAS, should not be given during pregnancy and women wishing to become pregnant. If pregnancy is detected during treatment with Exforge, the drug should be discontinued as soon as possible.
Female patients of childbearing age must be informed about the possible risk to the fetus associated with the use of drugs affecting RAAS.
Considering the mechanism of action of angiotensin II receptor antagonists, we can not exclude the risk to the fetus. It is known that administration of ACE inhibitors that affect the RAAS in pregnant trimesters II and III, leading to damage or destruction of the developing fetus. According to a retrospective analysis of ACE inhibitors in I trimester accompanied by the development of the fetus and newborn pathology. Accidental reception valsartan pregnant described cases of spontaneous abortion, oligohydramnios and renal impairment in newborns.
It is not known whether valsartan are isolated and / or amlodipine with breast milk. Since pilot studies noted selection valsartan breast milk, apply Exforge lactation (breast-feeding) is not recommended.
APPLICATION FOR FUNCTIONS OF THE LIVER

Patients with initial and moderate renal impairment Exforge correction dose is not required. Caution must be exercised when administering the drug to patients with severe renal impairment (creatinine clearance <10 mL / min), since data on safety of the drug in such cases is not obtained.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Care must be taken when assigning Exforge patients with liver disease (especially in obstructive disorders of the biliary tract). Valsartan is derived mostly unchanged in the bile, whereas amlodipine is extensively metabolized in the liver.
APPLICATION FOR CHILDREN

Safety of application of Exforge in children and adolescents under 18 years of age has not been established.
SPECIAL INSTRUCTIONS

Care must be taken when assigning Exforge patients with liver disease (especially in obstructive disorders of the biliary tract). Valsartan is derived mostly unchanged in the bile, whereas amlodipine is extensively metabolized in the liver.
Patients with initial and moderate renal impairment (creatinine clearance of 30-50 ml / min) Exforge correction dose is not required. Caution must be exercised when administering the drug to patients with severe renal impairment (creatinine clearance <10 mL / min), because data on safety of the drug in such cases is not obtained.
As well as the application of other vasodilators, special caution should be observed when administering the drug to patients with mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy.
If necessary, cancel the beta-blocker therapy before Exforge dose of beta-blockers should be reduced gradually. As amlodipine is not a beta-blocker, application Exforge preparation does not prevent the development of withdrawal syndrome that occurs when a dramatic treatment of beta-blockers.
In placebo-controlled trials in patients with uncomplicated hypertension in 0.4% of cases there was marked hypotension. Patients with RAAS activated (e.g., when deficiency BCC and / or sodium in patients receiving high doses of diuretics), upon receipt of ARBs may develop symptomatic hypotension. Before treatment Exforge should conduct correction of sodium in the body and / or BCC or begin therapy under careful medical supervision.
In the case of hypotension patients should be laid with a raised feet, if necessary, to carry out on / in infusion of physiological saline. After stabilization of blood pressure Exforge treatment may be continued.
With the simultaneous application of the drug with the biologically active additives containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or other drugs that may cause increased potassium concentrations in the blood (e.g., heparin), care should be taken to carry out regular monitoring of the concentration of potassium in the blood .
Impact on the ability to drive vehicles and manage mechanisms

There are no data on the effect of the drug on the ability to drive vehicles and to work with mechanisms. Due to the possible occurrence of vertigo or fatigue caution when driving or operating machinery.
OVERDOSE

Data on cases of overdosing on currently available.
In case of overdose can be expected to develop valsartan pronounced reduction in blood pressure and dizziness. Amlodipine Overdosing can lead to excessive peripheral vasodilatation and possible reflex tachycardia. It was also reported the occurrence of severe and prolonged systemic hypotension up to the development of shock with a fatal outcome.
Treatment:Accidental overdose, induce vomiting (if the drug was recently adopted) or to gastric lavage, activated charcoal designate. The use of activated carbon in healthy volunteers immediately or within 2 h after administration of amlodipine significantly reduces its absorption. If symptomatic hypotension caused Exforge should put the patient with elevated legs, to take proactive measures to support the cardiovascular system, including frequent monitoring of cardiac function and respiratory system, bcc, and urine output. In the absence of contraindications, to restore vascular tone and blood pressure can be applied (with caution) vasoconstrictor. B / in a calcium gluconate may be effective for removal of blockade of calcium channels.Withdrawal of valsartan and amlodipine during hemodialysis is unlikely.
DRUG INTERACTION

Amlodipine

Inhibitors of CYP3A4 isoenzyme. When applied together with amlodipine diltiazem in elderly patients amlodipine marked slowing metabolism, probably by inhibiting the isozyme CYP3A4, which leads to an increase in the plasma concentration of amlodipine of about 50% and increased clinical effect. In the application of amlodipine together with potent inhibitors of CYP3A4 (e.g., ketoconazole and ritonavir itrakonashl) optionally amlodipine pronounced increase in systemic exposure.
Inducers of CYP3A4 isoenzyme. Since the use of amlodipine together with isoenzyme inducers
CYP3A4 (e.g., carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone, rifampicin, grapefruit juice, vegetable preparations containing St. John's wort), can lead to a marked decrease in its concentration in blood plasma; the appointment of amlodipine with inducers of CYP3A4, should be monitored its clinical effect.
In monotherapy with amlodipine is not observed clinically significant interaction with thiazide diuretics, beta-blockers, ACE inhibitors, long-acting nitrates, nitroglycerin sublingual application, digoxin, warfarin, atorvastatin, sildenafil, Maalox (aluminum hydroxide gel, magnesium hydroxide, simethicone), cimetidine, NSAIDs, antibiotics and oral hypoglycemic drugs.
valsartan
It is found that when monotherapy valsartan no clinically significant interaction with the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.
Preparations and substances affecting the content of potassium in blood serum: while the appointment with biologically active additives containing potassium, potassium-sparing diuretics, potassium-containing salt substitutes, or with other drugs which may cause an increase of potassium in the blood (e.g., heparin) should be careful and conduct frequent monitoring of potassium in the blood.
NSAIDs, including selective inhibitors of COX-2:assignment angnotenzina II receptor antagonists in conjunction with NSAID may weaken hypotensive effect. In older patients, patients with deficiency of bcc (including receiving therapy with diuretic drugs) or impaired renal simultaneous application angiotenziia II receptor antagonists and NSAIDs function may lead to increased risk of deterioration of renal function. When starting or changing the mode of application patients angiotensin II receptor antagonist with NSAID recommended regular monitoring of renal function.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

The drug should be kept out of the reach of children, dry place at a temperature not higher than 30 ° C.
Shelf life - 3 years.
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