RIZORTA HD 100/12.5 [Losartan + Hydrochlorothiazide] 100 + 12.5 mg Film-coated tablets
RIZORTA HD 100/12.5
RIZORTA HD 100/25
instructions for medical use of the medicinal product
Tradename
Rizorta HD 100/12.5;
Rizorta HD 100/25;
International non-proprietary name
Losartan + Hydrochlorothiazide, Losartan + Hydrochlorothiazide
Composition
Risorta HD 100/12.5
Each film-coated tablet contains:
active substances: losartan (as l ozartan potassium) 100 mg, hydrochlorothiazide 12.5 mg
excipients: corn starch, dextrin, microcrystalline cellulose, CMS - Na , hypromellose, silicon dioxide, magnesium stearate, talc
Risorta HD 100/25
Each film-coated tablet contains:
active substances: losartan (as l ozartan potassium) 100 mg, hydrochlorothiazide 25 mg
excipients: corn starch, dextrin, microcrystalline cellulose, CMS - Na , hypromellose, silicon dioxide, magnesium stearate, talc
Dosage form
Tablets.
Pharmacotherapeutic group
Antihypertensive combined agent (angiotensin II receptor antagonist + diuretic).
Pharmacological properties
The combined drug 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.
The combination of losartan + hydrochlorothiazide effectively reduces blood pressure in any degree of arterial hypertension (AH). 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).
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 ( T 1 / 2) is from 5.6 to 14.8 hours (mean 6.4 hours).
Indications for use
• arterial hypertension (patients who are indicated for combination therapy);
• reduction in 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
Taken orally, regardless of the meal. Tablets are swallowed whole, without chewing, drinking plenty of water.
The combination of losartan and hydrochlorothiazide is not intended for initial therapy: the use is recommended in cases of lack of adequate control of blood pressure with losartan and hydrochlorothiazide used separately. Dose titration by components (losartan and hydrochlorothiazide) is recommended. When clinically necessary, it is advisable to consider switching from monotherapy to the use of a fixed combination.
The usual initial and maintenance dose is 1 tablet at a dosage of 50 mg / 12.5 mg 1 time per day. With insufficient therapeutic response, the dose may be increased to 1 tablet at a dosage of 100 mg / 12.5 mg 1 time per day or up to 1 tablet at a dosage of 100 mg / 25 mg 1 time per day.
The maximum dose is 1 tablet at a dosage of 100 mg / 25 mg per day.
The antihypertensive effect is achieved within 3-4 weeks after the start of therapy.
Can be used with other antihypertensive drugs.
It is recommended to follow the regimen prescribed by the doctor for taking the drug. If you miss a daily dose, you should simply continue taking it as usual. Do not take a double dose to make up for a forgotten one.
The tablets are indivisible and cannot be used to obtain a lower dosage. If necessary, the use of the drug in a dose of less than 50 mg/12.5 mg, it is recommended to consider the possibility of using drugs containing losartan and hydrochlorothiazide in the appropriate dosage.
Use in impaired renal function and in patients on hemodialysis
Patients with moderate renal insufficiency (creatinine clearance 30-50 ml / min) dose adjustment is not required. It is not recommended to start this combination in severe renal impairment (creatinine clearance <30 ml / min) and in patients on hemodialysis.
Conditions accompanied by depletion of intravascular volume
Before using the combination of losartan / hydrochlorothiazide, correction of intravascular volume deficit and / or sodium deficiency is required.
Use in liver failure
Use is contraindicated in patients with severe hepatic impairment.
Elderly patients
Dose adjustment in elderly patients is usually not required.
Special instructions and precautions
- 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 and during breastfeeding
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 RAAS blockade (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 edema of the larynx and tongue, causing airway obstruction and / or swelling of the face, lips, pharynx), urticarial rash.
From 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: often - orthostatic hypotension (dose-dependent), palpitations, tachycardia; infrequently - AV blockade of the II degree, chest pain, myocardial infarction, arrhythmias; rarely - vasculitis.
From the respiratory system: often - cough, infections of the upper respiratory tract, sinusitis, swelling of the nasal mucosa, nasal congestion; infrequently - pharyngitis, laryngitis, rhinitis, dyspnea, bronchitis, epistaxis.
From the digestive system: often - diarrhea, dyspepsia, nausea, vomiting, abdominal pain; rarely - hepatitis, liver dysfunction.
From the urinary system: infrequently - urinary tract infections, frequent urination, nocturia, glucosuria.
From the reproductive system: infrequently - weakening of libido, decreased potency.
From the sense organs: infrequently - blurred vision, burning sensation in the eyes, conjunctivitis.
From the side of the skin: often - alopecia, dry skin, erythema, photosensitivity, increased sweating; infrequently - urticaria, pruritus.
From the musculoskeletal system: often - myalgia, back pain; infrequently - arthralgia.
Others: often - asthenia, weakness, peripheral edema; infrequently - anorexia, exacerbation of the course of gout.
From the side of laboratory indicators: often - hyperkalemia, a slight decrease in the concentration of hemoglobin and hematocrit; infrequently - a moderate increase in the concentration of urea and creatinine in the blood plasma, hyperglycemia, hyperuricemia, disturbances in the water and electrolyte balance; rarely - increased activity of ALT; very rarely - an increase in ACT activity and bilirubin concentration.
If any of the side effects listed in the instructions get worse, or if you notice any other side effects not listed in the instructions, tell your doctor.
Overdose
There are no data on the specific treatment of overdose with the combination of losartan + hydrochlorothiazide. The drug should be discontinued and the patient should be monitored. In case of overdose, symptomatic therapy is indicated: gastric lavage if the drug has been taken recently, as well as the elimination of dehydration, water and electrolyte disorders and lowering blood pressure by standard methods (restoration of circulating blood volume and water and electrolyte balance).
Storage conditions
Store in a cool and dry place, at a temperature not exceeding 30º C.
Keep out of the reach of children.
Best before date
3 years. Do not use after the expiry date stated on the package.
Holiday conditions
Released by prescription.
Release form
Risorta HD 100/12.5
10 tablets in an aluminum foil blister. 3 blisters with instructions for use in a cardboard box.
Risorta HD 100/25
10 tablets in an aluminum foil blister. 3 blisters with instructions for use in a cardboard box.