Index of drugs

Treatment of primary hypertension. The preparation is indicated for the substitution treatment of patients whose blood pressure is adequately controlled during the concomitant use of Losartan and Amlodipine at the same doses as in the co-administered drug.

1 tabl powl. contains 50 mg of potassium losartan and 5 mg of amlodipine (as besilate) or 50 mg of losartan potassium and 10 mg of amlodipine or 100 mg of losartan potassium and 5 mg of amlodipine or 100 mg of losartan potassium and 10 mg of amlodipine. The tablets contain lactose.

The preparation is a combination of losartan - an angiotensin II receptor antagonist and amlodipine - a Calcium antagonist. Losartan and its active metabolite (carboxylic acid) selectively bind to the AT receptor₁by blocking the effects of the action of angiotensin II without affecting the source and route of its synthesis; they do not bind or block other hormone receptors or ion channels important for regulation in the circulatory system. Potassium losartan is not an inhibitor of kininase II (an enzyme that breaks down bradykinin), so it does not increase the effects of bradykinin-dependent effects. It is well absorbed after oral administration (bioavailability approximately 33%), undergoes a first pass effect, approximately 14% of the administered dose is converted into the active metabolite. C_max in blood, losartan reaches after about 1 hour (the active metabolite after about 3-4 hours). Losartan and its active metabolite bind to plasma proteins ≥ 99%. Losartan and its metabolites are excreted in urine (35%) and faeces (58%). T_0,5 is about 2 h for Losartan, about 6-9 h for the active metabolite. Amlodipine is a calcium antagonist from the group of dihydropyridine derivatives. It inhibits the influx of calcium ions across the cell membrane into the smooth muscle cells of blood vessels and cardiac muscle cells. It has antihypertensive effects by direct relaxation effect on the smooth muscle of the vessels. In angina, it has bi-directional effects: it expands the peripheral arterioles, which results in a reduction in peripheral resistance and post-traumatic stress and extends the main arteries and coronary arterioles. Amlodipine is well absorbed from the gastrointestinal tract, reaching C_max within 6-12 h after administration. Bioavailability is 64-80%. Food does not affect the bioavailability of amlodipine. It is 97.5% bound to plasma proteins. It is extensively metabolised in the liver to inactive metabolites. It is excreted in the urine in the form of metabolites (60%) and unchanged form (10%). It is not removed from the body during dialysis. T_0,5 Amlodipine is 35-50 h and allows dosing once a day

Hypersensitivity to active substances, dihydropyridines or to any of the excipients. Severe liver dysfunction. Severe hypotension. Shock (including cardiogenic shock). Narrowing the outflow path from the left ventricle (eg aortic valve stenosis). Haemodynamically unstable heart failure after having acute myocardial infarction. II and III trimester of pregnancy. Concomitant use with aliskiren-containing products in patients with diabetes mellitus or renal impairment (glomerular filtration rate, GFR <60 ml / min / 1.73 m²).

Patients with a history of angioneurotic edema (swelling of the face, lips, throat and / or tongue) should be carefully monitored. In patients with water-electrolyte disorders, symptomatic hypotension may occur as a result of intense diuretic therapy, low salt diet, diarrhea or vomiting, especially after the first dose or after increasing the dose. These disorders should be corrected before administration of the preparation or a lower starting dose. Electrolyte abnormalities are common in patients with impaired renal function, with or without diabetes, and should be compensated. Therefore, serum potassium and creatinine should be monitored, especially in patients with heart failure and creatinine clearance 30-50 ml / min. Co-administration of losartan with potassium-sparing diuretics, potassium supplements and potassium-containing potassium replacers is not recommended.There is no experience regarding the use of the preparation in patients after recent kidney transplantation. It is not recommended for use in patients with primary hyperaldosteronism. Use with caution in patients with ischemic heart disease or cerebrovascular disease (risk of myocardial infarction or stroke). In patients with heart failure, with or without renal impairment, there is a risk of severe hypotension and (often acute) renal failure. Insufficient therapeutic experience in the use of losartan in patients with heart failure and severely impaired renal function, in patients with severe heart failure (NYHA stage IV), as well as in patients with heart failure and symptomatic life-threatening cardiac arrhythmia - caution should be exercised when losartan is used in these patient groups. The combination of losartan and β-blockers should be used with caution. Caution should be exercised when using calcium antagonists in patients with congestive heart failure because they may increase the risk of future cardiovascular events and death. In the study of patients with severe heart failure (NYHA class III and IV), more cases of pulmonary edema were reported in the amlodipine group than in the placebo group. Use with caution in patients with mild to moderate or impaired hepatic function or a history of liver dysfunction. As a consequence of the renin-angiotensin system inhibition, renal dysfunction with renal failure has been observed (especially in patients whose renal function depends on the activity of the renin-angiotensin-aldosterone system, such as patients with severe heart failure or pre-existing renal dysfunction). Increased serum urea and creatinine levels have been observed in patients with bilateral renal artery stenosis or stenosis of the artery to the sole active kidney. Losartan should be used with caution in patients with bilateral renal artery stenosis or stenosis of the artery to the sole active kidney. Caution should be exercised in elderly patients. Particularly cautiously used in patients with aortic stenosis or mitral valve or hypertrophic cardiomyopathy with narrowing of the outflow pathway. Angiotensin antagonists are less effective in lowering blood pressure in black patients than in non-black patients. The concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalaemia and renal dysfunction (including acute renal failure) - therefore, dual blocking of the RAA system is not recommended by concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren. If the use of a dual RAA blockade is absolutely necessary, it should only be carried out under the supervision of a specialist, and the vital parameters of the patient, such as kidney function, electrolyte concentration and blood pressure should be closely monitored. In patients with diabetic nephropathy, ACE inhibitors and angiotensin II receptor antagonists should not be used concurrently. Due to the lack of data on safety and efficacy, it is not recommended for use in children under 18 years of age. Due to the lactose content, patients with rare hereditary galactose intolerance, lactase deficiency (Lapp type) or malabsorption of glucose-galactose should not be used.

The use of angiotensin II receptor antagonists (AIIRAs) in the first trimester of pregnancy is not recommended (there is a risk of teratogenic effects). The use of AIIRA is contraindicated in the second and third trimester of pregnancy. The use of AIIRA during the second and third trimester of pregnancy has a toxic effect on fetal development (deterioration of renal function, oligohydramnios, delayed ossification of the skull) and the newborn (renal failure, hypotension, hyperkalemia). If the exposure to AIIRA took place from the second trimester of pregnancy, it is recommended that the ultrasound of the skull and renal function of the fetus are performed. Children whose mothers have taken AIIRA should be closely monitored for possible hypotension. The safety of amlodipine during pregnancy in humans has not been established.The preparation is not recommended in women who are breastfeeding because there is no data on the use of losartan and amlodipine during this period

losartan. Common: dizziness of central origin, dizziness, hyperkalemia. Uncommon: drowsiness, headache, sleep disturbances, palpitations, angina pectoris, orthostatic hypotension (including dose-dependent orthostatic symptoms, particularly in patients with decreased intravascular volume, e.g. with severe heart failure or those treated with high diuretics) , abdominal pain, constipation, rash, fatigue, edema, asthenia. Rare: anaphylactic reactions, angioneurotic edema (including swelling of the larynx, glottis, lips, throat and / or tongue), inflammation of blood vessels (including Schonlein-Henoch purpura), hypersensitivity reactions, hepatitis, ALT increase. Frequency unknown: respiratory tract infections, thrombocytopenia, anemia, depression, taste disorders, migraine, tinnitus, cough, diarrhea, pancreatitis, liver dysfunction, pruritus, urticaria, photosensitivity, muscle pain, arthralgia, rhabdomyolysis, back pain , erectile dysfunction / impotence, malaise, flu-like symptoms, hyponatremia. In addition, fainting, atrial fibrillation, cerebrovascular accident, dyspnoea, nausea, kidney disease, renal failure, increased urea and creatinine in the blood, hyperkalaemia, hypoglycaemia were observed during treatment with losartan.amlodipine. Common: dizziness, drowsiness, headache, palpitations, sudden redness of the skin (especially of the face), abdominal pain, nausea, swelling of the ankles, fatigue, edema. Uncommon: insomnia, mood changes (including anxiety), depression, paresthesia, hypoesthesia, tremor, disturbed taste, blurred vision (including double vision), tinnitus, hypotension, dyspnoea, rhinitis, vomiting, indigestion change frequency of bowel movements (including diarrhea and constipation), dry mouth, rash, alopecia, purpura, skin discoloration, increased sweating, skin eruption, pruritus, muscle cramps, muscle pain, arthralgia, impaired urination (including urinating at night and frequent urination), erectile dysfunction / impotence, gynecomastia, asthenia, malaise, pain, increase or decrease in body weight. Rare: confusion. Very rare: leukopenia, thrombocytopenia, angioedema (including swelling of the larynx, glottis, lips, throat and / or tongue), hypersensitivity reactions, hyperglycemia, hypertonia, peripheral neuropathy, myocardial infarction, arrhythmias (including bradycardia, tachycardia) ventricular and atrial fibrillation), vasculitis, cough, gastritis, gingival hyperplasia, hepatitis, pancreatitis, jaundice, increased liver enzymes, urticaria, hypersensitivity to light, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome Quincke's swelling.

Orally. The recommended dose is 1 tablet. per day. Do not use a combination medication when starting treatment. Before starting treatment with the combined preparation, the blood pressure must be adequately controlled when concurrently administering fixed doses of individual active substances. The dose of the combined preparation should be determined on the basis of the doses of the individual active substances taken at the time of initiation of the co-administered drug. If for any reason (eg newly diagnosed comorbid illness, change in the patient's condition or interaction with other drugs) it is necessary to change the dose of any active substance of the combined preparation, the individual ingredients should be re-used to determine the dosage. No dose adjustment of losartan is necessary for elderly patients, however caution should be exercised when increasing the dose; consideration should be given to initiating treatment with a 25 mg dose of losartan in patients> 75 years of age. patients with a reduced volume of intravascular (eg high-dose diuretic treatment) should consider starting treatment with 25 mg losartan once a day. In patients with impaired renal function and undergoing hemodialysis therapy, no initial dose adjustment is necessary.For patients with a history of mild to moderate liver dysfunction, a lower dose of losartan should be considered and the treatment should be started with the lowest recommended dose of amlodipine. The tablets can be taken with or without water.