Index of drugs

Treatment of primary hypertension in patients whose blood pressure is not adequately controlled during treatment with either Losartan or hydrochlorothiazide only.

1 tabl powl. contains 50 mg of losartan potassium and 12.5 mg of hydrochlorothiazide.

Antihypertensive preparation containing two antihypertensive agents with complementary mechanisms of action: angiotensin II receptor antagonist (losartan) and thiazide diuretic (hydrochlorothiazide). Losartan selectively binds to the AT receptor₁ 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. Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the reabsorption of electrolytes in the renal tubules, directly increasing the excretion of sodium and chlorides. The diuretic action of hydrochlorothiazide reduces plasma volume, increases plasma renin activity, increases aldosterone secretion, increases urinary potassium and bicarbonate loss, decreases in potassium in the blood. The concomitant administration of losartan causes the blockade of the renin-angiotensin-aldosterone system to stop the potassium loss associated with the action of diuretics. Co-administration of losartan and hydrochlorothiazide does not affect the pharmacokinetics of any of these active substances. Losartan is well absorbed from the gastrointestinal tract and undergoes a first-pass effect, resulting in the active metabolite - carboxylic acid and other inactive metabolites. The bioavailability of losartan is approximately 33%. The mean maximum concentrations of losartan and its active metabolite occur respectively after 1 hour and 3-4 hours. Losartan and its active metabolite are approximately 99% bound to plasma proteins. About 14% of the losartan dose is converted to the active metabolite. Losartan and its metabolites are excreted in the bile and in the urine. T_0,5 is about 2 h for losartan and 6-9 h for the active metabolite. Hydrochlorothiazide is not metabolised, it is almost completely excreted unchanged in the urine. T_0,5 it is 5.6-14.8 h.

Hypersensitivity to Losartan, hydrochlorothiazide or other sulfonamide derivatives or other ingredients of the preparation. Treatment-resistant hypokalemia, hyponatremia or hypercalcaemia. Symptomatic hyperuricemia (gout). Severe liver dysfunction, cholestasis, obstruction of the bile ducts. Severe renal impairment (creatinine clearance <30 ml / min), anuria. II and III trimester of pregnancy. Concomitant use with aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (glomerular filtration rate, GFR <60 ml / min / 1.73 m²).

Patients with angioedema in an interview should remain under close observation. In patients with circulating and / or sodium-depleted blood volume reduction due to intensive diuretic therapy, dietary salt restriction, diarrhea or vomiting, symptomatic hypotension may occur, particularly after the first dose and during dose escalation - these deficiencies should be corrected before administration or use a lower starting dose. In patients with renal dysfunction with or without diabetes, electrolyte imbalance often needs to be compensated. Use with caution in patients with mild and moderate hepatic impairment. As a consequence of inhibition of the renin-angiotensin-aldosterone system (RAA), renal dysfunction with renal insufficiency has been observed (especially in patients whose renal function depends on RAA activity, such as those with severe heart failure or pre-existing renal dysfunction) .Caution should be used in patients with bilateral renal artery stenosis or stenosis of the artery that supplies blood to the only kidney. 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. There is no experience regarding patients who have recently had a kidney transplant. Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs acting by inhibiting the activity of the renin-angiotensin system - the use of the preparation in this group of patients is not recommended. In patients with ischemic heart disease and cerebrovascular disease, excessive hypotension may result in myocardial infarction or stroke. In patients with heart failure with or without renal impairment, there is - as with other agents acting on the renin-angiotensin system - a risk of severe hypotension and (often acute) renal failure. Particularly cautiously use in patients with aortic or mitral stenosis or hypertrophic cardiomyopathy with narrowing of the outflow pathway. Angiotensin II receptor antagonists are less effective in the treatment of hypertension in the black population. Caution in patients with diabetes, as thiazide therapy may impair Glucose tolerance - you may need to adjust your insulin dose or oral antidiabetic medicines. Thiazides may accelerate the onset of diabetes in patients with latent diabetes; they can cause hyperuricemia and trigger a gout attack; may cause or exacerbate the symptoms of systemic lupus erythematosus; may cause slight and transient hypercalcaemia - significant hypercalcemia may indicate an unrecognized hyperparathyroidism; they can cause higher cholesterol and triglycerides in the blood and electrolyte imbalance. Hypersensitivity reactions to hydrochlorothiazide can occur in patients with or without allergy or bronchial asthma. Concomitant use of potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes is not recommended. No experience in the treatment of children and adolescents - do not use. Due to the cochineal red content, the preparation may cause allergic reactions.

The use of losartan in the first trimester of pregnancy is not recommended (there is a risk of teratogenicity). The use of losartan in the second and third trimester of pregnancy is contraindicated. Losartan 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 newborn (renal failure, hypotension, hyperkalemia) - when exposure to the drug occurred from the second trimester of pregnancy, it is recommended ultrasound examination of fetal skull and kidneys; children whose mothers took the drug during pregnancy should be closely monitored for hypotension. Hydrochlorothiazide crosses the placental barrier. Used in the second and third trimester of pregnancy may reduce the blood flow through the placenta and may cause such effects in the fetus and newborn, such as electrolyte abnormalities, jaundice, and thrombocytopenia. The drug should not be used to treat oedemas in pregnant women, gestational hypertension and preeclampsia. Hydrochlorothiazide should not be used in pregnant women with severe hypertension, except in rare cases when alternative treatment is not possible. The preparation is not recommended during breast-feeding.

In controlled clinical trials for the treatment of primary hypertension, dizziness was the only adverse drug reaction associated with a higher incidence than in the placebo group in at least 1% of patients.In addition to this action, post-marketing experience has been reported - rarely: hepatitis, hyperkalemia, increased ALT. Additional side effects that have been observed for one of the ingredients.losartan - often: insomnia, headache and dizziness, cough, upper respiratory tract infection, nasal congestion, sinusitis, sinus disorder, abdominal pain, nausea, diarrhea, indigestion, muscle spasms, back pain, leg pain, muscle pain , renal impairment, renal failure, weakness, fatigue, chest pain, hyperkalemia, slight hematocrit reduction and hemoglobin concentration, hypoglycaemia; uncommon: anemia, Schönlein-Henoch purpura, ecchymosis, hemolysis, anorexia, gout, anxiety, anxiety disorders, panic disorder, confusion, depression, unusual dreams, sleep disorders, drowsiness, memory disorders, nervousness, paresthesia, peripheral neuropathy, tremor, migraine, fainting, blurred vision, burning or prickling in the eye, conjunctivitis, reduced visual acuity, labyrinthine dizziness, tinnitus, hypotension, orthostatic hypotension, retrosternal pain, angina pectoris, AV blockade II, cerebrovascular accident, myocardial infarction myocardial infarction, palpitations, arrhythmia (atrial fibrillation, sinus contraction, tachycardia, ventricular tachycardia, ventricular fibrillation), vasculitis, throat discomfort, pharyngitis, laryngitis, dyspnoea, bronchitis, epistaxis, runny nose, respiratory congestion, constipation, toothache, dry mouth, bloating, zap gastritis, vomiting, alopecia, dermatitis, dry skin, erythema, hot flush with redness, allergic reaction to light, pruritus, rash, urticaria, sweating, shoulder pain, swollen joints, knee pain, musculoskeletal pain, shoulder pain, stiffness, joint pain, arthritis, hip pain, fibromyalgia, muscle weakness, bedwetting, frequent urination, urinary tract infection, decreased sex drive, erectile dysfunction / impotence, facial edema, fever, slightly increased urea and creatinine in the blood; rare: hypersensitivity, anaphylactic reactions, angioneurotic edema, including laryngeal and glottal edema causing airway obstruction and / or swelling of the face, lips, throat and / or tongue; some patients have experienced angioneurotic edema in the past due to other medicines, including ACE inhibitors; very rare: increase in liver enzymes and bilirubin; unknown frequency: thrombocytopenia, pancreatitis, liver dysfunction, rhabdomyolysis, flu-like symptoms, malaise, hyponatraemia.hydrochlorothiazide - often: headache; uncommon: agranulocytosis, aplastic anemia, hemolytic anemia, decrease in white blood cell count, purpura, thrombocytopenia, anorexia, hyperglycemia, hyperuricaemia, hypokalemia, hyponatremia, insomnia, transient blurred vision, yellow vision, angiitis causing necrosis (vasculitis, vasculitis), acute respiratory distress syndrome (including pneumonia and pulmonary edema), salivary gland inflammation, spasms, stomach irritation, nausea, vomiting, diarrhea, constipation, jaundice (intrahepatic cholestasis), pancreatitis, photosensitivity, urticaria, toxic epidermal necrolysis, muscle spasms, glycosuria, interstitial nephritis, renal dysfunction, renal failure, fever, dizziness; rare: anaphylactic reactions.

Orally. Adults: 1 tabl. once a day. In patients in whom the response to treatment is not satisfactory, the dose can be increased to 2 tablets. once a day (maximum daily dose). The antihypertensive effect is obtained within 3-4 weeks from the beginning of treatment. A dose adjustment of each component of the preparation is recommended before using a fixed dose of the combined preparation. It is recommended to gradually increase the dose of individual components (losartan and hydrochlorothiazide). The drug can be used simultaneously with other antihypertensive agents.Special groups of patients. Adaptation of the initial dosage in patients with moderate renal impairment (creatinine clearance 30-50 ml / min) is not necessary.There is no need to modify the dosage in elderly patients.
The preparation can be taken regardless of meals. The tablets should be swallowed with a glass of water.