Index of drugs

Spontaneous hypertension in patients whose blood pressure is not adequately controlled with Losartan or hydrochlorothiazide alone.

1 tabl powl. contains 50 mg of potassium losartan and 12.5 mg of hydrochlorothiazide or 100 mg of potassium losartan 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 about 33%), undergoes a first pass effect, about 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 at> 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. 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, sulphonamide derivatives (such as hydrochlorothiazide) and the other ingredients. Resistance to hypokalemia or hypercalcemia. Severe hepatic dysfunction, cholestasis and disorders that reduce the patency of bile ducts. Hyponatremia-resistant treatment. Symptomatic hyperuricemia / gout. Severe renal impairment (ie creatinine clearance <30 ml / min). Anuria. II and III trimester of pregnancy. Breastfeeding period.

Patients with a history of angioedema should be closely monitored. In patients with reduced intravascular volume and / or sodium depletion due to intensive diuretic therapy, dietary sodium 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 mellitus, electrolyte imbalance is common. 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 adult patients with mild or moderate hepatic impairment. No experience in patients with severe hepatic impairment. As a consequence of the suppression of the renin-angiotensin-aldosterone system, renal dysfunction with renal failure has been observed (including in patients 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 are usually reversible 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 fluid and electrolyte imbalance, for example, reduced volume of endoluminal fluid, hyponatremia, hypochloraemia, hypomagnesaemia or hypokalaemia that may develop during simultaneous diarrhea or vomiting. Serum electrolytes should be monitored regularly in these patients. In patients with swelling in hot weather, hyponatraemia may occur with dilution of fluids. 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, causing moderate and transient hypercalcaemia. Significant hypercalcemia may indicate the presence of asymptomatic hyperparathyroidism. The use of thiazide diuretics may increase cholesterol and triglyceride levels and accelerate the onset of hyperuricaemia and / or gout. 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 minor changes in the balance of fluids and electrolytes may precipitate the onset of hepatic coma. A hypersensitivity reaction may occur in patients who are taking thiazide, both with or without a history of allergy or bronchiectasis asthma. Cases of activation or increase in systemic lupus erythematosus have been reported. 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.

It is not recommended during the first trimester of pregnancy. In the II and III trimester of pregnancy and during breastfeeding, 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 placental barrier and into breast milk of women. It may cause a decrease in plasma volume and blood flow through the uterus and placenta, electrolyte imbalance in the fetus, and other reactions observed in adults, as well as jaundice in fetuses and infants and thrombocytopenia in newborns.

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: hyperkalemia, slight decrease in hematocrit and hemoglobin, central 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 ache, asthenia, fatigue, chest pain, insomnia. Uncommon: slight elevation of urea and serum creatinine, hypotension, orthostatic hypotension, retrosternal pain, angina pectoris, atrio-ventricular block IIst., Cerebrovascular accident, myocardial infarction, palpitations, arrhythmia (atrial fibrillation, sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation), anemia, Henoch-Schonlein purpura, ecchymosis, haemolysis, nervousness, paresthesia, peripheral neuropathy, tremor, migraine, fainting, burning / eye prickness, conjunctivitis, reduced visual acuity, peripheral vertigo, noise ear, throat discomfort, pharyngitis, laryngitis, dyspnoea, bronchitis, epistaxis, rhinitis, airway congestion, constipation, toothache, dry mouth, bloating, gastritis, vomiting, bedwetting, frequent donation urine, urinary tract infection, alopecia, dermatitis, dryness dermatitis, erythema, flushing, hypersensitivity to light, pruritus, rash, urticaria, hyperhidrosis, shoulder pain, swollen joints, knee pain, musculoskeletal pain, shoulder pain, stiffness, pain and arthritis, hip pain, fibromyalgia, muscle weakness, anorexia, gout, vasculitis, face edema, fever, decreased libido, impotence, anxiety, anxiety disorders, panic attacks, confusion, depression, abnormal dreams, sleep disorders, drowsiness, memory disorders. Rare: anaphylactic reactions, angioneurotic edema, urticaria. Very rare: increased liver enzymes and bilirubin. Frequency unknown: liver dysfunction.hydrochlorothiazide. Common: headache. Uncommon: agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, purpura, thrombocytopenia, transient blurred vision, yellow vision, acute respiratory distress syndrome (including pneumonia and pulmonary edema), salivary gland inflammation, spasms, stomach irritation, nausea, vomiting, diarrhea, constipation, glycosuria, interstitial nephritis, renal dysfunction, renal failure, photosensitivity, urticaria, toxic epidermal necrolysis, muscle spasms, anorexia, hyperglycemia, hyperuricemia, hypokalaemia, hyponatremia, necrotizing vasculitis (vasculitis, vasculitis), fever, dizziness, jaundice (intrahepatic cholestasis), pancreatitis, insomnia. Rarely: anaphylactic reactions.

Orally. The preparation can be used simultaneously with other antihypertensive drugs. It must not be used during initial treatment, but in patients whose blood pressure is not adequately controlled with either potassium or hydrochlorothiazide monotherapy.
It is recommended to gradually increase the dose of individual components. In patients whose blood pressure is not adequately controlled, a direct switch from monotherapy to the use of a combined preparation may be considered, if clinically appropriate. 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 occurs 3-4 weeks after the start of treatment.
There is no need to adjust the starting dose in patients with moderate renal impairment (ie, creatinine clearance 30-50 ml / min). No dose adjustment is necessary in elderly patients. The preparation is not recommended in patients undergoing dialysis.
The tablets can be taken with or without a meal, with a glass of water.