Index of drugs

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

1 tabl powl. contains 50 mg of potassium losartan and 12.5 mg of hydrochlorothiazide or 100 mg of losartan potassium and 25 mg of hydrochlorothiazide. The tablets contain lactose.

The preparation is a combination of losartan - an angiotensin II receptor antagonist and a hydrochlorothiazide - diuretic. 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. The maximum blood concentration of losartan is reached 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. Hydrochlorothiazide is a thiazide diuretic. It affects the reabsorption of electrolytes in the kidney tubules, increasing the excretion of sodium and chloride in almost equal amounts. After oral administration, the diuretic effect starts within 2 h with a maximum intensity of about 4 h and lasts for 6-12 h, the antihypertensive effect lasts up to 24 h. Hydrochlorothiazide is not metabolised in the body, it is excreted in the urine. T_0,5 it is 5.6-14.8 h.

Hypersensitivity to losartan, sulfonamide derivatives (such as hydrochlorothiazide) or to any of the excipients. Resistant to the treatment of potassium deficiency in the blood or excess of Calcium in the blood. Severe liver dysfunction; stagnation of bile and disorders obstructing bile ducts. Sodium deficient in blood. Symptomatic excessive levels of uric acid in the blood / gout. Severe renal impairment (ie creatinine clearance <30 ml / min). Anuria. II and III trimester of pregnancy.

Patients with a history of angioneurotic edema (swelling of the face, throat and / or tongue) should be closely monitored. In patients with circulating and / or sodium depleted blood volume due to intensive diuretic therapy, dietary salt restriction, diarrhea or vomiting, symptomatic hypotension may occur, particularly after the first dose. Such deficiencies should be corrected before administration of the preparation. In patients with renal dysfunction with or without diabetes, electrolyte imbalance often needs to be compensated. Therefore, potassium levels and creatinine clearance should be carefully monitored, particularly in patients with heart failure and creatinine clearance from 30 to 50 ml / min. The concomitant use of potassium-sparing diuretics, potassium supplements and potassium-containing salt substitutes is not recommended. Use with caution in patients with mild or moderate hepatic impairment. No experience in patients with severe hepatic impairment. As a consequence of renin-angiotensin-aldosterone system inhibition, renal dysfunction with renal insufficiency has been observed (especially in patients whose renal function depends on the activity of the renin-angiotensin-aldosterone system, such as those with severe heart failure or pre-existing renal dysfunction ).Increased blood urea and creatinine levels have been observed in patients with bilateral renal artery stenosis or stenosis of the artery to a single kidney; these changes may disappear after treatment. The preparation should be used with caution in patients with bilateral renal artery stenosis or stenosis of the artery to the only kidney. There are no experiences in patients after a recent kidney transplantation. Patients with primary hyperaldosteronism generally do not respond to antihypertensive drugs that act by inhibiting the activity of the renin-angiotensin system - the use is not recommended in this group of patients. Excessive reduction in blood pressure in patients with ischemic heart disease and cerebrovascular disease may result in myocardial infarction or stroke. In patients with heart failure with or without coexisting kidney function, there is 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. Patients using hydrochlorothiazide should be monitored for symptoms associated with water-electrolyte imbalance, such as decreased circulating volume, hyponatremia, hypochloraemia, hypomagnesaemia or hypokalemia, which may develop during simultaneous diarrhea or vomiting. Serum electrolytes should be monitored regularly in these patients. Patients with edema may experience hyponatremia from dilution in hot weather. The use of thiazides may impair Glucose tolerance and therefore dosage adjustment of antidiabetic agents, including insulin, may be necessary. Latent diabetes can occur during treatment with thiazide. Thiazides may reduce the excretion of calcium in the urine, resulting in a small and transient hypercalcemia. Significant hypercalcemia may occur in patients with latent hyperparathyroidism. The use of thiazide diuretics may be associated with an increase in cholesterol and triglyceride levels as well as hyperuricemia and (or) gout attacks. Because losartan reduces the levels of uric acid in the blood, the use of losartan in combination with hydrochlorothiazide reduces the diuretic-induced hyperuricemia. In patients with impaired hepatic function or progressive liver disease, thiazides should be used with caution as they may cause intrahepatic cholestasis and slight changes in the balance of fluids and electrolytes - hepatic coma. In patients taking thiazides, hypersensitivity reactions may occur, both in the case of a positive or negative history of allergy or bronchial asthma. Cases of the disclosure or exacerbation of systemic lupus erythematosus have been observed. Due to the lactose content, the preparation should not be used in patients with galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose. No experience in the use of the preparation in children and adolescents - should not be used.

The preparation is not recommended during the first trimester of pregnancy (there is a risk of teratogenic effects). In the second and third trimester, the use of the preparation is contraindicated. Administration of the preparation during the second and third trimester of pregnancy results in toxic effects on the fetus (deterioration of fetal renal function, oligohydramnios, delayed ossification of the skull) and the newborn (renal failure, hypotension, hyperkalemia). If the exposure to angiotensin II receptor antagonists has occurred since the second trimester of pregnancy, ultrasound examination of the kidneys and the skull is recommended. Infants whose mothers took the preparation should be observed for hypotension. Hydrochlorothiazide crosses the placenta. Used in the second and third trimester of pregnancy may weaken fetal-placental perfusion and cause such effects in the fetus and newborn, such as electrolyte abnormalities, jaundice, and thrombocytopenia. Hydrochlorothiazide should not be used for gestational edema, gestational hypertension or preeclampsia due to the risk of decreased plasma volume and hypoperfusion of the placenta without a beneficial effect on the course of the disease.Hydrochlorothiazide should not be used in pregnant women with essential hypertension, except in rare situations where alternative treatment is not possible. The administration of losartan during breastfeeding is not recommended. Hydrochlorothiazide is excreted in breast milk in small amounts. High doses of thiazide diuretics, causing intense diuresis, may inhibit milk production. The use is not recommended during breastfeeding, however, if it is used during this period, the lowest dose should be taken.

In clinical trials for the treatment of primary hypertension, dizziness was the only adverse drug reaction associated with a frequency greater than the placebo group in at least 1% of patients. In addition, hepatitis, hyperkalemia and ALT increased seldom during post-marketing experience. Adverse reactions observed after using one of the active substances may be potential side effects for a combination drug.losartan. Common: insomnia, hyperkalemia, slight decrease in hematocrit and hemoglobin, headache and dizziness, cough, upper respiratory tract infection, nasal congestion, sinus disease (including sinusitis), abdominal pain, nausea, diarrhea, indigestion , muscle cramps, back pain, lower limb pain, muscle aches, weakness, fatigue, chest pain. Uncommon: anemia, Henoch-Schönleel purpura, ecchymosis, hemolysis, anxiety, anxious disorder, panic attacks (panic disorder), confusion, depression, unusual dreams, sleep disturbances, drowsiness, memory problems, slight increase in urea and serum creatinine, hypotension, orthostatic hypotension, retrosternal pain, angina pectoris, AV block II., cerebrovascular incident, myocardial infarction, palpitations, arrhythmia (atrial fibrillation, sinus tachycardia, tachycardia, ventricular tachycardia, ventricular fibrillation), nervousness, paresthesia, peripheral neuropathy , tremor, migraine, fainting, blurred vision, burning / stinging in the eye, conjunctivitis, reduced visual acuity, diarrheal vertigo, tinnitus, vasculitis, discomfort in the throat, pharyngitis, laryngitis, dyspnoea, bronchitis , nosebleeds, runny nose, respiratory congestion, zap arcia, toothache, dry mouth, bloating, gastritis, vomiting, bedwetting, frequent urination, urinary tract infection, alopecia, dermatitis, dry skin, erythema, hot flush with redness, hypersensitivity to light, pruritus, rash, urticaria, sweating, shoulder pain, swollen joints, knee pain, musculoskeletal pain, shoulder pain, stiffness, joint pain, arthritis, hip pain, muscle fiber pain, muscle weakness, anorexia, gout, decreased sex drive, impotence, swelling of the face, fever. Rare: anaphylactic reactions, angioneurotic edema, urticaria. Very rare: increased liver enzymes and bilirubin. Not known: liver dysfunction, rhabdomyolysis.hydrochlorothiazide. Common: headache. Uncommon: agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, purpura, thrombocytopenia, transient blurred vision, yellow vision, necrosis causing necrosis (vasculitis, vasculitis), acute respiratory distress syndrome (including pneumonia and pulmonary edema) ), salivary gland inflammation, stomach cramps, nausea, vomiting, diarrhea, constipation, glycosuria, interstitial nephritis, renal dysfunction, renal failure, photosensitivity, urticaria, toxic epidermal necrolysis, muscle spasms, anorexia, hyperglycemia, hyperuricemia , hypokalemia, hyponatremia, fever, dizziness, jaundice (intrahepatic cholestasis), pancreatitis, insomnia. Rarely: anaphylactic reactions.

Orally. The preparation can be used simultaneously with other antihypertensive drugs. It should not be used as initial therapy, but for those who have not had blood pressure checked by either losartan alone or hydrochlorothiazide alone.It is recommended to gradually increase the dose of individual components. In appropriate clinical cases, a direct change in monotherapy for combination therapy may be considered in patients whose blood pressure is not adequately controlled. Usually, the maintenance dose is 1 tablet. 50 mg + 12.5 mg once a day. In patients who do not get an adequate response, the dose can be increased to 1 tablet. 100 mg + 25 mg once a day. The maximum dose is 1 tablet. 100 mg + 25 mg once a day. The antihypertensive effect is obtained within 3-4 weeks from the beginning of treatment. The 100 mg / 12.5 mg formulation is used in those patients who have been increased in the dose of losartan to 100 mg and who require additional blood pressure control.
No dose adjustment is necessary in patients with moderate renal impairment (ie, creatinine clearance 30-50 ml / min) and usually in elderly patients. The preparation is not recommended in hemodialyzed patients.
The tablets can be taken with or without water.