RIZORTA HD 50/12.5 [Losartan + Hydrochlorothiazide] 50 + 12.5 mg Film-coated tablets
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RIZORTA HD 50/12.5
instructions for medical use of the medicinal product
Tradename
Rizorta HD 50/12.5,
grouping name
Losartan + Hydrochlorothiazide, Losartan + Hydrochlorothiazide
Composition
Each film-coated tablet contains:
Active Ingredients: L Osartan Potassium USP 50 mg, hydrochlorothiazide USP 12.5 mg
excipients: pregelatinized starch, sugar powder, microcrystalline cellulose, hypromellose , CCNa, CMS-Na, magnesium stearate.
Dosage form
Tablets.
Pharmacotherapeutic group
Antihypertensive combined agent (angiotensin II receptor antagonist + diuretic).
Pharmacological properties
Risorta HD 50/12.5 is a combination drug that has an antihypertensive effect. Contains losartan, an angiotensin II receptor antagonist, and hydrochlorothiazide, a thiazide diuretic.
Pharmacodynamics
Losartan and hydrochlorothiazide demonstrate a synergistic antihypertensive effect, lowering blood pressure (BP) to a greater extent than either of the components separately. It is assumed that this effect is the result of the additive action of both components. In addition, as a result of the diuretic action, hydrochlorothiazide increases the activity of renin in the blood plasma, the secretion of aldosterone, reduces the concentration of potassium in the blood plasma and increases the content of angiotensin II. The use of losartan blocks all physiologically significant actions of angiotensin II and reduces the loss of potassium associated with the use of a diuretic, through inhibition of aldosterone. Losartan has a mild and short-term uricosuric effect. Hydrochlorothiazide leads to a moderate increase in plasma uric acid. The combination of losartan and hydrochlorothiazide helps to reduce diuretic-induced hyperuricemia. The antihypertensive effect of hydrochlorothiazide + losartan persists for 24 hours. In clinical studies lasting at least one year, the antihypertensive effect persisted during ongoing therapy.
Despite a significant decrease in blood pressure, taking the combination of losartan + hydrochlorothiazide losartan does not have a significant clinical effect on heart rate (HR). Clinical studies have shown that after 12 weeks of therapy with losartan 50 mg / hydrochlorothiazide 12.5 mg, the minimum diastolic blood pressure (measured in the sitting position) decreased by an average of 13.2 mm Hg. Art.
The combination of losartan + hydrochlorothiazide effectively reduces blood pressure in any degree of arterial hypertension (AH).
Pharmacokinetics
Losartan
After oral administration, losartan is rapidly absorbed from the gastrointestinal tract. Bioavailability is about 33%. It is metabolized during the "first pass" through the liver with the formation of a carboxyl metabolite, which has a more pronounced pharmacological activity than losartan, and a number of inactive metabolites. C max in blood plasma of losartan and the active metabolite is reached after 1 hour and 3-4 hours, respectively. Plasma protein binding of losartan and the active metabolite is high - more than 98%.
T 1/2 of losartan and the active metabolite in the final phase is about 1.5-2.5 hours and 3-9 hours, respectively. Losartan is excreted in the urine and feces (with bile) unchanged and as metabolites. About 35% is excreted in the urine and about 60% in the feces.
Hydrochlorothiazide
Hydrochlorothiazide is incompletely but rapidly absorbed from the gastrointestinal tract (GIT). After oral administration at a dose of 100 mg, the maximum concentration (Cmax) of hydrochlorothiazide in plasma is reached after 1.5-2.5 hours. At the maximum diuretic activity (approximately 4 hours after ingestion), the concentration of hydrochlorothiazide in blood plasma is 2 μg / ml. Communication with blood plasma proteins is 40%.
Hydrochlorothiazide is not metabolized in the human body.
The primary route of excretion is through the kidneys (filtration and secretion) unchanged. Approximately 61% of the ingested dose is excreted within 24 hours. In patients with normal renal function, the half-life (T1 / 2) is from 5.6 to 14.8 hours (average 6.4 hours).
Indications for use
• Arterial hypertension (for patients who are indicated for combination therapy).
• Reducing the risk of associated cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy, manifested by a cumulative reduction in the incidence of cardiovascular mortality, stroke and myocardial infarction.
Contraindications
• hypersensitivity to any of the components of the drug;
• severe liver dysfunction;
• severe renal dysfunction (CC less than 30 ml / min);
• refractory hyponatremia;
• refractory hypokalemia or hypercalcemia;
• simultaneous use with drugs containing aliskiren in patients with diabetes mellitus and patients with moderate and severe renal insufficiency (GFR less than 60 ml / min / 1.73 m2 of body surface area);
• pregnancy and breastfeeding period;
• children's and adolescence up to 18.
Dosage and administration
Inside, regardless of the meal. The tablets are swallowed whole, without chewing, with water.
The drug can be taken in combination with other antihypertensive drugs.
Arterial hypertension
Usually the initial and maintenance dose is 1 tablet of the drug 1 time per day.
In patients without an adequate therapeutic response to taking 1 tablet of the drug (contains 50 mg of losartan + 12.5 mg of hydrochlorothiazide) 1 time per day for 2-4 weeks, the dose of the drug can be increased to 2 tablets of the drug 1 time per day. The maximum dose is 2 tablets of the drug (50 mg + 12.5 mg) 1 time per day.
As a rule, the antihypertensive effect is achieved within 3 weeks after the start of therapy.
Reducing the risk of cardiovascular morbidity in patients with arterial hypertension and left ventricular hypertrophy
The usual starting dose of losartan is 50 mg once daily. Patients who fail to achieve target blood pressure levels while taking losartan 50 mg per day require selection of therapy by combining losartan with low doses of hydrochlorothiazide (12.5 mg). If necessary, increase the dose of losartan to 100 mg per day in combination with hydrochlorothiazide at a dose of 12.5 mg per day (1 tablet of the drug 1 time per day), then increase the dose to 2 tablets of the drug (50 mg + 12.5 mg) (total 100 mg of losartan and 25 mg of hydrochlorothiazide) 1 time per day.
Use in patients with impaired renal function or in patients on hemodialysis
Selection of the initial dose of the drug for patients with impaired renal function of moderate severity (CC 30-50 ml / min) is not required. The drug is not recommended for patients on hemodialysis. The drug should not be used in patients with severely impaired renal function (CC less than 30 ml / min).
Use in patients with reduced circulating blood volume
Before starting therapy with the drug, it is necessary to restore the volume of circulating blood and / or sodium content in the blood.
Use in patients with impaired liver function
The drug is contraindicated in patients with severe hepatic impairment.
Use in elderly patients
Selection of the initial dose of the drug for elderly patients is not required .
Special instructions and precautions
Apply with caution:
- bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney;
− hyperkalemia;
- conditions after kidney transplantation;
- aortic or mitral stenosis;
− hypertrophic obstructive cardiomyopathy;
- chronic heart failure with concomitant severe renal impairment;
− severe heart failure (functional class IV according to NYHA classification);
- chronic heart failure with life-threatening arrhythmias, coronary heart disease;
− cerebrovascular diseases;
- primary hyperaldosteronism;
- angioedema in history;
- arterial hypotension;
- violations of liver function;
- impaired renal function, impaired water and electrolyte balance;
- patients with a reduced volume of circulating blood (for example, treated with high doses of diuretics) due to the possibility of symptomatic arterial hypotension;
− hypokalemia;
− hyponatremia;
− hypercalcemia;
- an increase in the QT interval on the ECG;
- simultaneous use of drugs that can cause polymorphic ventricular tachycardia of the "pirouette" type or increase the duration of the QT interval on the ECG;
- simultaneous use of drugs that can cause hypokalemia, cardiac glycosides;
- allergic reactions to penicillin in history;
− hyperparathyroidism;
- hyperuricemia, gout.
Influence on the ability to drive vehicles and mechanisms
It should be borne in mind that against the background of treatment with antihypertensive drugs when driving or working with mechanisms, dizziness or drowsiness may occur, especially at the beginning of treatment or when the dosage of the drug is increased.
Use during pregnancy or lactation
Use during pregnancy and during breastfeeding is contraindicated. If you need to take the drug during lactation, then breastfeeding should be stopped.
Interaction with other drugs
Simultaneous use with potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), potassium preparations or potassium-containing salt substitutes, as well as the use of other drugs that increase the concentration of potassium in the blood plasma, increase the risk of developing hyperkalemia.
NSAIDs, incl. selective COX-2 inhibitors may reduce the effect of diuretics and other antihypertensive drugs, including losartan.
The antihypertensive effect of losartan, like other antihypertensive drugs, may be reduced when using indomethacin.
Double blockade of the RAAS, i.e. adding an ACE inhibitor to an angiotensin II receptor antagonist therapy is possible only in selected cases under close monitoring of renal function.
In patients with atherosclerosis, heart failure, or diabetes mellitus with target organ damage, dual blockade of the RAAS (with concomitant use of angiotensin II receptor antagonists, ACE inhibitors, or aliskiren) is accompanied by an increased incidence of arterial hypotension, syncope, hyperkalemia, and renal dysfunction (including acute renal insufficiency) in comparison with the use of the drug of one of the listed groups.
Possible decrease in the excretion of lithium ions. Therefore, with the simultaneous use of angiotensin II receptor antagonists with lithium salts, serum lithium concentrations should be carefully monitored.
When used simultaneously with thiazide diuretics, drugs such as ethanol, barbiturates and opioid analgesics may potentiate the risk of developing orthostatic hypotension.
With simultaneous use, it is possible to increase the hypoglycemic effect of oral hypoglycemic agents (sulfonylurea derivatives) and / or insulin in patients with diabetes mellitus. With such combinations, an increase in glucose tolerance is possible, which may require dose adjustment of hypoglycemic agents for oral administration and / or insulin.
With simultaneous use with other antihypertensive drugs - an additive effect.
The absorption of hydrochlorothiazide is impaired in the presence of cholestyramine and colestipol.
With simultaneous use with GCS, ACTH, there is a pronounced decrease in the content of electrolytes, in particular hypokalemia.
There is a decrease in the severity of the therapeutic effect of hydrochlorothiazide against the background of the use of pressor amines (for example, epinephrine (adrenaline), norepinephrine (norepinephrine)).
Hydrochlorothiazide enhances the effect of muscle relaxants of a non-depolarizing type of action (for example, tubocurarine chloride).
Diuretics reduce the renal clearance of lithium and increase the risk of lithium toxicity. Simultaneous use is not recommended.
With simultaneous use with barbiturates, narcotic analgesics, antidepressants, ethanol, the risk of developing orthostatic hypotension increases.
Drugs used to treat gout (probenecid, sulfinpyrazone and allopurinol): hydrochlorothiazide can increase the serum concentration of uric acid, so dose adjustment of uricosuric drugs may be required - an increase in the dose of probenecid or sulfinpyrazone. The simultaneous use of thiazide diuretics may increase the frequency of hypersensitivity reactions to allopurinol.
Simultaneous use with cyclosporine may increase the risk of developing hyperuricemia and exacerbate the course of gout.
Anticholinergics (eg, atropine, biperiden) increase the bioavailability of thiazide diuretics by reducing gastrointestinal motility and gastric emptying rate.
Thiazide diuretics can reduce the renal excretion of cytotoxic drugs (cyclophosphamide, methotrexate) and enhance their myelosuppressive effect.
In the case of the use of salicylates in high doses, hydrochlorothiazide may increase their toxic effects on the central nervous system.
There are limited data on the development of hemolytic anemia with the simultaneous use of hydrochlorothiazide and methyldopa.
Caused by thiazide diuretics, hypokalemia or hypomagnesemia can lead to the development of arrhythmias against the background of the use of cardiac glycosides.
Side effect
From the immune system: rarely - anaphylactic reactions, angioedema (including swelling of the larynx and tongue, causing airway obstruction and / or swelling of the face, lips, pharynx), urticarial rash.
On the part of the hematopoietic system: infrequently - anemia, Shenlein-Genoch purpura, ecchymosis, hemolysis, agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, thrombocytopenia.
From the nervous system: often - headache, dizziness, insomnia, increased fatigue; infrequently - migraine, anxiety, confusion, depression, sleep disturbances, memory impairment, drowsiness, nervousness, paresthesia, tremor, fainting.
From the side of the cardiovascular system: &a