Index of drugs

Treatment of essential hypertension. It is indicated for use in adult patients whose blood pressure is not adequately controlled with Amlodipine or valsartan.

1 tabl contains a combination of amlodipine (as amlodipine besilate) and valsartan, respectively: 5 mg + 80 mg, 5 mg + 160 mg or 10 mg + 160 mg.

Antihypertensive preparation containing 2 antihypertensive components with complementary mechanisms of action: Calcium channel antagonist (amlodipine) and angiotensin II receptor antagonist (valsartan). The combination of these substances has an additional antihypertensive effect, lowering blood pressure to a greater extent than either component alone. Amlodipine is an inhibitor of the influx of calcium ions into cells, it inhibits the transmembrane influx of calcium ions into the interior of the heart muscle cells and the smooth muscle of blood vessels. The mechanism of antihypertensive effect of amlodipine is direct diastolic action on the smooth muscle of blood vessels, leading to a reduction in peripheral vascular resistance and reduction of blood pressure. Valsartan is a specific angiotensin II receptor antagonist. It acts selectively on the AT receptor subtype₁by blocking the effects of angiotensin II. It has no agonist activity towards the AT receptor₁it does not bind or block other hormone receptors or ion channels important for regulation in the circulatory system. It is not an ACE inhibitor (kinase II), so it does not increase the effects of bradykinin-dependent effects. The rate and extent of absorption of the preparation are equivalent to the bioavailability of amlodipine and valsartan administered in separate tablets. The bioavailability of amlodipine after oral administration is approximately 64-80%, C_max reaches 6-12 h after administration. About 97.5% is bound to plasma proteins. It is extensively (approximately 90%) metabolised in the liver to inactive metabolites. The elimination of amlodipine is biphasic; T_0,5 in the final stage it is 30-50 h. 10% of amlodipine and 60% of amlodipine metabolites are excreted in the urine. The bioavailability of valsartan after oral administration is approximately 23%, C_max it reaches 2-4 h after administration. In 94-97% it is bound to plasma proteins. To a small extent (about 20%) it is metabolized to pharmacologically inactive hydroxymetabolite. It is excreted mainly in unchanged form with faeces (83%) and urine (13%). T_0,5 is 6 hours.

Hypersensitivity to active substances, dihydropyridines or to any of the excipients. Severe liver dysfunction, liver biliary cirrhosis or cholestasis. Severe renal impairment (GFR <30 ml / min / 1.73 m²) and dialysis patients. Concomitant use of angiotensin receptor antagonists (including valsartan) or ACE inhibitors with aliskiren in patients with diabetes or impaired renal function (GFR <60 ml / min / 1.73 m²). Severe hypotension. Shock (including cardiogenic shock). Narrowing of the left ventricle outflow pathway (eg, hypertrophic cardiomyopathy with left ventricular outflow narrowing, high aortic stenosis). Haemodynamically unstable heart failure after having acute myocardial infarction. II and III trimester of pregnancy.

The safety and efficacy of the medicine in children <18 years have not been established. It is not recommended for patients with primary hyperaldosteronism, as they do not respond to drugs acting through the inhibition of the renin-agiotensin-aldosterone system (RAA). As with other vasodilators, particular caution is recommended in patients with mitral stenosis or significant aortic stenosis, which is not high. Especially caution should be used in patients with mild to moderate hepatic impairment or biliary obstruction. In patients ≥65 years of age, use caution when increasing the dose.Because of the risk of hypotension, use with caution in patients with sodium deficiency or dehydrated; before starting treatment, hyponatraemia and / or volume of circulating blood should be compensated or the patient should be closely monitored at the beginning of treatment. In patients at risk of hyperkalemia (eg using potassium supplements, potassium sparing diuretics, potassium-containing salt substitutes or other medications that may increase potassium levels, i.e. heparin), potassium levels in the blood should often be monitored. Caution should be exercised in patients with unilateral or bilateral renal artery stenosis or stenosis of the artery supplying the sole kidney, as these patients may increase urea and creatinine in the blood. There are no data on the use of the preparation in patients after recent kidney transplantation. In patients with moderate renal impairment, monitoring of potassium and creatinine levels in the blood is recommended. In patients with severe heart failure whose renal function depends on RAA activity, treatment with ACE inhibitors and angiotensin receptor antagonists has been associated with oliguria and / or progressive azotemia and (rarely) with acute renal failure and / or death; evaluation of patients with heart failure or after myocardial infarction should always include assessment of renal function. Due to the risk of hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure), dual RAA blocking is not recommended (eg, by the combined use of an angiotensin II receptor antagonist with an ACE inhibitor or aliskiren); if the use of the RAA double block is absolutely necessary, it should only be carried out under the supervision of a specialist. At the same time, angiotensin II receptor antagonists and ACE inhibitors should not be used in patients with diabetic nephropathy. In patients with non-ischemic non-ischemic heart failure NYHA class III or IV, there is an increased risk of pulmonary edema following administration of amlodipine. In patients with congestive heart failure, amlodipine should be used with caution as it may increase the risk of cardiovascular events and death. The safety and efficacy of amlodipine at hypertensive crisis has not been studied. In patients who develop angioneurotic edema, the preparation should be discontinued immediately and should not be administered again. The concomitant use of angiotensin receptor antagonists, including valsartan, with other agents acting on the renin-angiotensin-aldosterone system (RAA) is associated with an increase in the incidence of hypotension, hyperkalaemia and changes in renal function compared with monotherapy. It is recommended to monitor blood pressure, renal function and electrolyte concentration in patients using the product and other agents acting on the RAA system. Caution should be exercised when concomitant use of angiotensin receptor antagonists, including valsartan, with other RAA blocking agents, such as ACE inhibitors or aliskiren.

The use of valsartan in the first trimester of pregnancy is not recommended (there is a risk of teratogenic effects). Use in the second and third trimester of pregnancy is contraindicated. Valsartan used in the second and third trimester of pregnancy is toxic to fetal development (deterioration of renal function, oligohydramnios, delayed ossification of the skull) and the newborn (renal failure, hypotension, hyperkalemia) - in the case when exposure to the drug occurred from the second trimester of pregnancy, it is recommended an ultrasound examination of the fetus skull and kidneys; children whose mothers took the drug during pregnancy should be closely monitored for hypotension. The safety of amlodipine during pregnancy has not been established. It is not recommended to use the product during breastfeeding.

Side effects with a combined drug (amlodipine + valsartan) - often: pharyngitis, flu, hypokalemia, headache, weakness, fatigue, swelling, pressure-forming edema, facial edema, peripheral edema, paroxysmal redness of the face; uncommon: lack of appetite, hypercalcemia, hyperlipidemia, hyperuricemia, hyponatremia, impaired coordination of movements, dizziness, dizziness related to the position of the body, paresthesia, drowsiness, worsening of vision,dizziness, palpitations, tachycardia, orthostatic hypotension, cough, sore throat and larynx, abdominal discomfort, epigastric pain, constipation, diarrhea, dry mouth, nausea, erythema, rash, joint pain, pain backache, swelling of the joints; rare: hypersensitivity reactions, anxiety, visual disturbances, tinnitus, syncope, hypotension, exanthema, hyperhidrosis, pruritus, muscle spasm, heaviness, pollakiuria, polyuria, erectile dysfunction. In addition, in addition to the above adverse reactions, side effects may occur with individual components of the combined preparation. Amlodipine - often: swollen ankles; uncommon: depression, sleep disorders (including insomnia), mood changes, taste disturbances, fainting, tremor, hypoaesthesia, dyspnea, rhinitis, change of bowel rhythm, reduced appetite, vomiting, dyspepsia, alopecia, photosensitivity reaction, purpura, skin discoloration, muscle pain, micturition disorders, nocturia, impotence, gynecomastia, anxiety, malaise, chest pain not related to the heart, pain, increase or decrease in body weight; rarely: confusion; very rare: leukopenia, thrombocytopenia (sometimes with purpura), hyperglycemia, increased tension, peripheral neuropathy, neuropathy, arrhythmia (including bradycardia, ventricular tachycardia, atrial fibrillation), myocardial infarction, vasculitis, gastritis, gingival hypertrophy, pancreatitis, increased liver enzymes, increased bilirubin in the blood, hepatitis, intrahepatic cholestasis, jaundice, angioneurotic edema, erythema multiforme, urticaria and other forms of rash, exfoliative dermatitis, Stevens-Johnson syndrome, Quincq's edema; frequency unknown: extrapyramidal syndrome. Valsartan - frequency unknown: decrease in hemoglobin and hematocrit, neutropenia, thrombocytopenia (sometimes with purpura), vasculitis, elevation of liver enzymes, increase in bilirubin in the blood, angioneurotic edema, muscle pain, increase in blood creatinine, renal failure, kidney problems, hyperkalemia, serum sickness.

Orally. Adults: 1 tabl. per day. The 5 mg / 80 mg formulation can be given to patients whose blood pressure is not adequately controlled with either amlodipine 5 mg or valsartan 80 mg monotherapy. The 5 mg / 160 mg formulation can be given to patients whose blood pressure is not adequately controlled with either amlodipine 5 mg or 160 mg valsartan as monotherapy. The 10 mg / 160 mg formulation can be given to patients whose blood pressure is not adequately controlled with amlodipine 10 mg or 160 mg valsartan alone or with a 5 mg / 160 mg formulation. Before changing to a fixed-dose medication, individual adjustment of the dose of amlodipine and valsartan is recommended.Special groups of patients. Patients with mild to moderate renal impairment - no dosage adjustment is necessary; patients with severely impaired renal function - do not use. Patients with mild to moderate hepatic impairment without cholestasis - no dosage schedule has been established, do not exceed the 80 mg dose of valsartan per day; patients with severe hepatic impairment - do not use.
The drug can be taken with or without food, and with water.