Composition, form of production and packaging
The tablets covered with a film coat of brownish-yellow color, round, biconcave, with engraving "C23" on one side.
1 tab.
Losartan potassium 50 mg
hydrochlorothiazide 12.5 mg
Excipients: magnesium stearate - 3.25 mg, lactose monohydrate - 63 mg, pregelatinized starch - 25 mg, microcrystalline cellulose - 96.25 mg.
The composition of the film shell: opadray orange code: 85F23426 (polyvinyl alcohol - 4 mg, titanium dioxide - 2.2783 mg, macrogol - 2.02 mg, talc - 1.48 mg, iron oxide, yellow - 0.166 mg, dye sunset yellow (E110) - 0.05 mg , ferric oxide black oxide - 0.0057 mg).
10 pieces. - blisters (3) - packs of cardboard.
The tablets covered with a film cover of yellow color, oval, biconcave, with engraving "РЎ25" on one side; the other side without engraving.
1 tab.
Losartan Potassium 100 mg
hydrochlorothiazide 12.5 mg
Excipients: magnesium stearate - 6.5 mg, lactose monohydrate - 126 mg, pregelatinized starch - 50 mg, microcrystalline cellulose - 205 mg.
The composition of the film shell: opadray II yellow code: 85F27044 (polyvinyl alcohol - 8 mg, titanium dioxide - 4.578 mg, macrogol - 4.04 mg, talc - 2.96 mg, iron oxide, yellow 0.4 mg, dye sunset yellow (E110) - 0.2 mg, ferric oxide black oxide - 0.002 mg).
10 pieces. - blisters (3) - packs of cardboard.
The tablets covered with a film coat of brownish-yellow color, oval, biconcave, with engraving "C24" on one side.
1 tab.
Losartan Potassium 100 mg
hydrochlorothiazide 25 mg
Excipients: magnesium stearate - 6.5 mg, lactose monohydrate - 126 mg, pregelatinized starch - 50 mg, microcrystalline cellulose - 192.5 mg.
The composition of the film shell: opadray orange code: 85F23426 (polyvinyl alcohol - 8 mg, titanium dioxide - 4.5566 mg, macrogol - 4.04 mg, talc - 2.96 mg, iron oxide oxide yellow - 0.332 mg, dye sunset yellow (E110) 0.1 mg , ferric oxide black oxide - 0.0114 mg).
10 pieces. - blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
The combined drug has an antihypertensive effect. Contains potassium losartan - angiotensin II receptor antagonist (type AT 1 ) and hydrochlorothiazide - diuretic.
Losartan is a specific antagonist of angiotensin II receptors (type AT 1 ). Does not inhibit kinase II - an enzyme that destroys bradykinin. Reduces OPSS, the concentration in the blood of norepinephrine and aldosterone, blood pressure, pressure in a small circle of circulation; reduces afterload, has a diuretic effect. Prevents development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure (CHF).
Hydrochlorothiazide is a thiazide diuretic. Reduces the reabsorption of sodium ions, increases the release of kidney ions of potassium, bicarbonate and phosphate.Reduces blood pressure by reducing bcc, changing the reactivity of the vascular wall, reducing the pressor effect of vasoconstrictors.
PHARMACOKINETICS
Losartan
Suction and distribution
Losartan is rapidly absorbed from the digestive tract. Bioavailability is about 33%. C max losartan in the blood plasma after ingestion is achieved after 1 hour, C max ofits active metabolite - 3-4 hours after ingestion.
Binding to blood plasma proteins - 99%. V d is 34 liters.
Metabolism and excretion
It is subjected to the effect of "first passage" through the liver, is metabolized by carboxylation with the formation of an active metabolite. Approximately 14% of the dose of losartan is converted to an active metabolite.
T 1/2 losartan - 1.5-2 h, active metabolite - 3-4 h. The plasma clearance of losartan and its active metabolite is 600 ml / min and 50 ml / min, respectively. The renal clearance of losartan and active metabolite is 74 ml / min and 26 ml / min, respectively. About 35% of the dose is excreted by the kidneys, about 60% by the intestine.
Hydrochlorothiazide
Suction and distribution
Hydrochlorothiazide is rapidly absorbed from the digestive tract. Penetrates through the placental barrier.
Metabolism and excretion
It is not metabolized in the liver.
T 1/2 is 5.8-14.8 hours. About 61% is excreted by the kidneys unchanged.
INDICATIONS
- treatment of arterial hypertension in patients who are shown combined therapy;
- reduced risk of cardiovascular disease and mortality in patients with hypertension and left ventricular hypertrophy.
DOSING MODE
The drug is taken orally, regardless of food intake, with a sufficient amount of liquid.
Typically, the initial and maintenance dose of Lozartan-N Richter is 50 mg losartan + 12.5 mg hydrochlorothiazide or 100 mg losartan + 12.5 mg hydrochlorothiazide. For patients who do not manage to achieve adequate blood pressure control at this dosage, the dose can be increased to a maximum of 2 tablets 50 mg / 12.5 mg or 1 tablet 100 mg / 25 mg 1 time / day.
In general, the maximum antihypertensive effect is achieved within 3 weeks of regular intake of the drug.
Reduction of bcc and hyponatremia should be adjusted before starting Lozartan-N Richter.
There is no need for a special selection of an initial dose for elderly patients .
In patients with moderate renal dysfunction (CK 30-50 ml / min), correction of the initial dose is not required. It is not recommended to use Losartan-N Richter inpatients on hemodialysis . In patients with severe renal dysfunction (CK less than 30 ml / min), the use of the drug is contraindicated.
The use of the drug is contraindicated in patients with severe impairment of liver function .
SIDE EFFECT
Side effects are limited to those observed with losartan and / or hydrochlorothiazide.
Side effects observed with the use of the drug are classified into categories according to the frequency of their occurrence: very often (? 1/10); often (? 1/100, <1/10);infrequently (? 1/1000, <1/100); rarely (? 1/10 000, <1/1000); very rarely (<1/10 000), is unknown (it is impossible to estimate based on available data).
The most common side effects in the treatment of essential hypertension include dizziness.
Allergic reactions: infrequently, when taking losartan, there were manifestations of vasculitis, including Shenlen-Henoch disease; infrequently when taking hydrochlorothiazide - toxic epidermal necrolysis; rarely anaphylactic reactions, angioedema, including laryngeal and / or tongue edema, resulting in airway obstruction, and / or swelling of the face, lips, pharynx and / or tongue occasionally noted with losartan. Some of these patients had angioedema earlier when other drugs were used, including ACE inhibitors.
From the side of the cardiovascular system: infrequent - a pronounced decrease in blood pressure, orthostatic hypotension, chest pain, bradycardia, atrial fibrillation, atrial fibrillation and ventricles, tachycardia, ventricular tachycardia, arrhythmias, AV blockade II degree, angina pectoris, syncope, cerebrovascular disorders, myocardial infarction, vasculitis.
From the digestive system: often - pain in the abdomen, nausea, diarrhea, indigestion; infrequent - constipation, toothache, dry mouth, flatulence, gastritis, pancreatitis, vomiting, salivary gland inflammation, decreased appetite, anorexia, infrequently - jaundice (intrahepatic cholestasis); rarely - cases of hepatitis have been reported with losartan; unknown - a violation of the liver.
On the part of the respiratory system: often - nasal congestion, sinusitis, sinusitis, with the use of losartan - cough, infrequently - rhinitis, pharyngitis, laryngitis, dyspnoea, bronchitis, epistaxis, pneumonitis, pulmonary edema.
On the part of the skin: infrequent - alopecia, dermatitis, dry skin, skin hyperemia, photosensitivity, itching, rash, urticaria, increased sweating.
From the urinary system: infrequently - nocturia, mandatory urination, urinary tract infections, interstitial nephritis, impaired renal function, renal failure.
On the part of the reproductive system: infrequently - weakening of the libido, a decrease in potency.
From the musculoskeletal system: often - cramps in the muscles of the lower limbs, back pain, leg pain, myalgia; infrequently - pain in the hands, swelling of the joints, pain in the knee, fibromyalgia, shoulder pain, muscle stiffness, arthralgia, arthritis, hip pain, muscle weakness.
From the nervous system: often - insomnia, headache, dizziness; infrequently - anxiety, sleep disorders, drowsiness, memory disorders, peripheral neuropathy, paresthesia, hypesthesia, tremor, migraine, ataxia, depression, panic conditions, increased anxiety, loss of consciousness.
From the hemopoietic system: infrequently - anemia, ecchymosis, agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, thrombocytopenic purpura, thrombocytopenia.
From the senses: infrequent - ringing in the ears, a violation of taste, a change and decrease in visual acuity, conjunctivitis, xantopsy.
On the part of laboratory indicators: often - hyperkalemia, a slight decrease in hematocrit and hemoglobin; infrequent - a slight increase in the concentration of urea and serum creatinine, hyperglycemia, hyperuricemia, hypokalemia, hyponatremia, glucosuria; very rarely - hyperbilirubinemia, increased activity of hepatic enzymes.
Other: often - asthenia, increased fatigue; infrequently, fever.
CONTRAINDICATIONS
anuria;
- severe renal dysfunction (CC less than 30 ml / min);
- pronounced violations of the liver function;
- Cholestasis, bile duct obstruction;
- severe arterial hypotension;
- Hypovolemia (including against a background of high doses of diuretics);
- uncontrollable hypokalemia or hypercalcemia, refractory hyponatremia;
- symptomatic hyperuricemia / gout;
- Pregnancy;
- the period of breastfeeding;
- age under 18 years (effectiveness and safety not established);
- Hypersensitivity to the components of the drug and to other derivatives of sulfonamides.
The drug contains lactose, therefore, patients with rare hereditary lactose intolerance, lactase deficiency or impaired glucose / galactose absorption should not take Lozartan-N Richter.
Caution should be given to the drug with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney; hypovolemic conditions (including diarrhea, vomiting); hyponatremia (increased risk of developing hypotension in patients on low-salinity and salt-free diets), hypochloraemic alkalosis, hypomagnesemia, hypokalemia; violations of the liver and / or kidneys of mild and moderate; primary hyperaldosteronism; IHD; cerebrovascular insufficiency; stenosis of aortic, mitral valves, obstructive hypertrophic cardiomyopathy; diseases of connective tissue (including systemic lupus erythematosus); diabetes mellitus; bronchial asthma;aggravated allergic anamnesis; hypercalcemia; simultaneous application with NSAIDs, incl. with COX-2 inhibitors.
PREGNANCY AND LACTATION
The use of the drug Losartan-N Richter is contraindicated in pregnancy, and when establishing pregnancy during treatment should immediately stop taking the drug.
Patients taking Lozartan-N Richter and planning a pregnancy should be transferred to an alternative method of drugs that have confirmed safety data for use in pregnancy. It is known that therapy with losartan and hydrochlorothiazide in the II and III trimesters of pregnancy has a toxic effect on the fetus (renal dysfunction, hydramnios, delay in the formation of the skull bones) and the newborn baby (renal failure, arterial hypotension, hypokalemia). If therapy with the drug Lozartan-N Richter was started from the second trimester of pregnancy, ultrasound is recommended for kidney function and skull structure. For newborns whose mothers have taken Losartan-N Richter, one should observe for timely detection and correction of arterial hypotension.
Hydrochlorothiazide can reduce both the volume of blood plasma and blood flow in the uterus and placenta. Thiazide diuretics are able to penetrate the placental barrier and are found in the blood of the umbilical cord. They can cause violations of the electrolyte blood composition in the fetus, as well as lead to the possible development of reactions observed in adults. There have been reported cases of thrombocytopenia in a newborn and in a fetus or jaundice in a fetus after the mother has used thiazide diuretics.
There are no data on the isolation of the drug with breast milk. If you need to use the drug during breastfeeding, you should decide whether to abort breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindications for patients with severe renal dysfunction (CC less than 30 ml / min), anuria.
With caution: bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, impaired renal function of mild and moderate degree.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in patients with severe impaired liver function, with cholestasis, bile duct obstruction.
With caution should prescribe the drug for violations of liver function of light and medium degree.
APPLICATION FOR CHILDREN
Contraindicated use for children under the age of 18 (efficacy and safety not established).
APPLICATION IN ELDERLY PATIENTS
There is no need for a special selection of an initial dose for elderly patients.
SPECIAL INSTRUCTIONS
Losartan-N Richter can be prescribed with other antihypertensive agents.
Hypersensitivity / Angioedema
Patients who have had a history of angioedema, swelling of the face, lips, tongue, epiglottis and larynx should be carefully monitored.
Symptomatic arterial hypotension
Most often, excessive BP decrease, especially after taking the first dose of the drug, occurs with a decrease in bcc caused by diuretic therapy, a reduction in the amount of salt in the food, dialysis, diarrhea, or vomiting. Prior to the start of treatment, if possible, the sodium content should be normalized and / or replace the lost volume of the liquid, carefully monitor the effect of the initial dose of the drug on the patient.
Violation of the water-electrolyte balance
Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, the use of potassium drugs or drugs that cause an increase in potassium in the blood (eg, heparin), especially in patients with impaired renal function. Thus, it is necessary to monitor the potassium content in the blood plasma and the QC values, as well as to monitor patients with heart failure and CC 30-50 ml / min.
Additional use of potassium-sparing diuretics, potassium-containing food additives and potassium-containing salt substitutes in combination with the combination of losartan / hydrochlorothiazide is not recommended.
Dysfunction of the liver
In patients with cirrhosis of the liver, a significant increase in the concentration of losartan in the blood plasma. In this regard, Losartan-N Richter should be used with caution in patients with mild to moderate liver function impairment. Experience with losartan in patients with severe liver dysfunction is absent. Therefore, the drug is contraindicated in this category of patients. Thiazide diuretics should be used with caution in patients with impaired hepatic function or progressive liver disease. their use can lead to intrahepatic cholestasis, and violations of water-electrolyte balance and hypovolemia can contribute to the development of hepatic coma.
Impaired renal function
As a result of inhibition of RAAS, administration of the drug may lead to further impairment of renal function (especially in patients whose kidney function depends on RAAS activity, for example, patients with severe heart failure or patients with existing renal dysfunction). Cases of acute renal failure are noted. In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney, there was an increase in the concentration of urea and creatinine in the blood serum, usually reversible after discontinuation of treatment. It was more common in patients with renal insufficiency.
Kidney Transplantation
The experience of using the drug in patients who have recently undergone kidney transplantation is absent.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism usually do not respond to therapy with antihypertensive drugs that act through inhibition of RAAS, so the use of Losartan-Richter is not recommended.
IHD and cerebrovascular insufficiency
In such patients, treatment should be started under the strict supervision of a physician, since A sharp decrease in blood pressure can lead to myocardial infarction or stroke.
Chronic heart failure
In patients with chronic heart failure and concomitant with or without renal insufficiency, excessive BP reduction and acute renal dysfunction are possible.
Stenosis of aortic and mitral valves, obstructive hypertrophic cardiomyopathy
Like other vasodilators, Lozartan-N Richter should be used with caution in patients suffering from stenosis of the aortic and mitral valves or obstructive hypertrophic cardiomyopathy.
Racial differences
According to studies, losartan and other antagonists of angiotensin II receptors less effectively reduce blood pressure in representatives of the Negroid race. Perhaps this is due to the fact that among the patients of the Negroid race, suffering from hypertension, persons with a reduced content of renin predominate.
Metabolic and endocrine effects
Thiazide diuretics can influence glucose tolerance, so you need to adjust the dose of hypoglycemic agents for oral administration.
Thiazide diuretics can reduce the secretion of calcium by the kidneys and cause hypercalcemia. Expressed hypercalcemia may be a symptom of latent hyperparathyroidism. It is recommended to stop treatment with thiazide diuretics before the parathyroid gland function test.
During the period of treatment with the drug, regular monitoring of the concentration in the blood plasma of potassium, glucose, urea, lipids is required.
An increase in the concentration of cholesterol and triglycerides can be associated with therapy with thiazide diuretics.
Thiazide diuretics can provoke the appearance of hyperuricemia and / or gout.
Against the background of the use of thiazide diuretics reported cases of exacerbation of systemic lupus erythematosus.
During the period of treatment it is not recommended to drink alcoholic beverages. Ethanol enhances the antihypertensive effect of the drug.
Care should be taken when performing physical exercises, hot weather (the risk of dehydration and excessive blood pressure lowering due to a decrease in BCC).
Losartan-H Richter comprises sunset yellow dye, which can cause allergic reactions.
Impact on the ability to drive vehicles and manage mechanisms
Studies of the effect on the ability to drive vehicles and use machinery have not been conducted. However, it is necessary to take into consideration that when receiving antihypertensive drugs can occur dizziness or drowsiness, especially at the initial stage of treatment with increasing doses or while driving a vehicle or using machinery.
OVERDOSE
Symptoms
Losartan - marked reduction of blood pressure, tachycardia; as a result of parasympathetic (vagal) stimulation may develop bradycardia. Hydrochlorothiazide - loss of electrolytes (hypokalemia, hypochloremia, hyponatremia), as well as dehydration that occurs due to excessive diuresis.
Treatment: symptomatic supportive therapy. If the drug has recently adopted, it should wash out the stomach, carry out the correction of water and electrolyte imbalance, if necessary. Losartan and its active metabolite are not removed by hemodialysis.
DRUG INTERACTION
Losartan
Enhances the effect of other antihypertensive agents. There were no clinically significant interaction with hydrochlorothiazide, digoxin, indirect anticoagulants, cimetidine, phenobarbital, ketoconazole, erythromycin. According to rifampicin and fluconazole reduced kontsentraitsiyu active metabolite in the blood plasma. The clinical significance of these interactions is not yet known.
As with other agents that inhibit angiotensin II or its effects, co-administration of potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium salt substitutes or medications containing potassium, increases the risk of hyperkalemia. The combined use is not recommended.
Losartan has an effect on the excretion of sodium and lithium can reduce excretion. In connection with what is necessary to control serum lithium concentration when combined with the use of angiotensin II receptor antagonists.
NSAIDs, including selective inhibitors of COX-2 may reduce the effectiveness of diuretics or other antihypertensives. The combined use of angiotensin II receptor antagonists with NSAIDs, including selective COX-2 inhibitors may increase the risk for renal dysfunction (including a possible risk of kidney failure), as well as lead to increase of potassium in blood serum, especially in patients existing impaired renal function. In some patients with impaired renal function, treated with NSAIDs (including COX-2 inhibitors), angiotensin II antagonists treatment receptors can cause a further deterioration of renal function, including acute renal failure, which is usually reversible. Combination of drugs should be used with caution, especially in elderly patients.It should be adequate to maintain the bcc and monitor renal function.
The hypotensive effect of losartan, like other antihypertensive agents, can be weakened when receiving indomethacin.
Co-administration with tricyclic antidepressants, antipsychotics, baclofen, amifostine may increase the risk of hypotension.
Hydrochlorothiazide
While the use of barbiturates, narcotics, ethanol potentiated antihypertensive effect.
With simultaneous administration with hypoglycemic agents (including oral and insulin) may require adjustment of the dose. Metformin should be used with caution because of the risk of lactic acidosis due to possible renal failure associated with taking hydrochlorothiazide.
When combined with other antihypertensives possible additive effect.
Cholestyramine and colestipol reduce the absorption of hydrochlorothiazide. When a single application cholestyramine or colestipol resins is their binding to hydrochlorothiazide and reducing its absorption from the gastrointestinal tract by 85% and 43%, respectively.
When concomitant administration of corticosteroids and adrenocorticotropic hormone enhanced electrolyte loss, particularly potassium.
In the application of hydrochlorothiazide with pressor amines may be a slight decrease in the last effect without preventing their use.
Hydrochlorothiazide may enhance the effect of non-depolarizing muscle relaxants (e.g., tubocurarine chloride).
Diuretics reduce the renal clearance of lithium and increase the risk of lithium toxicity, therefore their simultaneous use is not recommended.
The combined use of medicines for the treatment of gout (probenecid, sulfinpyrazone and allopurinol) may require dose adjustments of these medications, as hydrochlorothiazide can increase the concentration of uric acid in serum (or increase in dose of probenecid sulfinpirazona). Thiazide diuretics may increase the incidence of cases of hypersensitivity to allopurinol, while the application.
Anticholinergics (e.g., atropine, biperiden) thiazide diuretics enhance bioavailability due to decreased GI motility and gastric emptying rate.
Thiazides may reduce renal excretion of cytotoxic drugs (e.g., cyclophosphamide, methotrexate) and stimulate them myelotoxic effect.
When receiving high doses of salicylates hydrochlorothiazide may enhance their toxic effect on the central nervous system.
Separately reported cases of hemolytic anemia with concomitant use of hydrochlorothiazide and methyldopa.
Co-administration with cyclosporine may increase the risk of hyperuricemia and gout such complications.
Thiazide-stimulated hypokalemia or hypomagnesemia may contribute to the development of cardiac arrhythmias when combined with cardiac glycosides.
Periodic monitoring the potassium content in blood serum and ECG are recommended for the joint use of the drug Losartan-H Richter with drugs that are affected by the change of potassium content in serum (e.g., cardiac glycosides and antiarrhythmic drugs), and with following means (in m . .ch with antiarrhythmic) that cause ventricular tachycardia, with hypokalaemia is a predisposing factor for the development of ventricular tachycardia:
- class 1A antiarrhythmic drugs (for example measures, quinidine, gidrohinidin, disopyramide);
- antiarrhythmic drugs of class III (e.g., amiodarone, sotalol, dofetilide, ibutilide);
- some antipsychotics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, piamemazin, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol);
- Other medicinal agents (e.g., bepridil, cisapride, difemanil methylsulfate, erythromycin w / w, halofantrine, mizolastine, pentamidine, terfenadine, vincamine w / w).
Thiazide diuretics may increase the calcium content in serum due to the reduction of its excretion. If necessary, the use of calcium supplementation dose is selected under the control of calcium in the blood serum.
Due to effects on calcium excretion, thiazide diuretics may distort the results of studies of parathyroid function.
Carbamazepine increases the risk of symptomatic hyponatremia. It is necessary to monitor blood serum sodium content.
When the dehydration caused by diuretics, increased risk of acute renal failure, especially when administered iodinated contrast agents at high doses. Before the introduction of such funds should be held rehydration.
When combined with amphotericin B (parenteral), a corticosteroid, adrenocorticotropic hormone (ACTH) and laxatives hydrochlorothiazide can exacerbate disorders of electrolyte balance, in particular cause the development of hypokalemia.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 30 В° C. Shelf life - 4 years.
