Lozartan-N Canon - instructions for use, dose, side effects, contraindications

active substances: hydrochlorothiazide 12.5 mg, potassium losartan 50 mg; Excipients: corn starch 30 mg, croscarmellose sodium 6.8 mg, mannitol 36 mg, magnesium stearate 1.2 mg, povidone 4 mg, microcrystalline cellulose 29.5 mg;

film sheath: Fill yellow 5 mg, including: hypromellose (hydroxypropylmethylcellulose) 1.7 mg, giprolose (hydroxypropylcellulose) 1.75 mg, titanium dioxide 1.342 mg, iron oxide yellow 0.207 mg, aluminum dye-based dye sunset yellow 0.001 mg .

Dosage of 25 mg + 100 mg

1 tablet, film-coated, contains: active substances: hydrochlorothiazide 25 mg, losartan potassium 100 mg; Excipients: corn starch 60 mg, croscarmellose sodium 13.6 mg, mannitol 72 mg, magnesium stearate 2.4 mg, povidone 8 mg, microcrystalline cellulose 59 mg; film sheath: Fill yellow 10 mg, including: hypromellose (hydroxypropylmethylcellulose) 3.4 mg, giprolose (hydroxypropylcellulose) 3.5 mg, titanium dioxide 2.685 mg, iron oxide yellow 0.413 mg, aluminum dye-based dye sunset yellow 0.002 mg .

Description:Round, biconvex tablets, covered with a film coating of yellow color. On the cross-section - almost white.

Pharmacotherapeutic group:hypotensive combined agent (angiotensin II receptor antagonist [ARA II] + diuretic).

ATX: & nbsp

C.09.D.A.01 Losartan in combination with diuretics

Pharmacodynamics:

Lozartan-N Kanon is a combined preparation that provides

antihypertensive effect.

Losartan

Angiotensin II is a potent vasoconstrictor, the main active hormone of the renin-angiotensin-aldosterone system (RAAS), and decisive pathophysiological link in the development of arterial hypertension. Losartan highly effective at ingestion selective

antagonist of angiotensin II receptors (type AT1). Angiotensin II selectively communicates with AT1-receptors found in many tissues (in the smooth-muscle tissues of blood vessels, in the adrenal gland, kidneys and heart) and performs several important biological functions, including

vasoconstrictor function and aldosterone release. Besides, angiotensin II stimulates proliferation of smooth muscle cells. Losartan and its pharmacologically active metabolite (E-3174), as in vitro and in vivo block all the physiological effects of angiotensin II, independently from the source or pathway of synthesis.Unlike some peptide

angiotensin II receptor antagonists, losartan does not have the effects of an agonist. Losartan selectively communicates with AT1receptors, does not bind or block receptors of other hormones and ion channels, which play an important role in regulating the function of the cardiovascular system. Besides, losartan does not inhibit the angiotensin-converting enzyme (ACE) responsible for the destruction of bradykinin. Consequently, effects that are not directly related to the blockade AT1-receptors, including bradykinin-mediated effects and the development of peripheral edema (losartan 1.7%, placebo 1.9%), are not related to the action of losartan. Reduces the overall peripheral resistance of blood vessels (OPSS), the concentration in the blood of norepinephrine and aldosterone, blood pressure (BP), pressure in the "small" circle of the circulation; reduces afterload, has a diuretic effect. Prevents development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure (CHF). When taking losartan, the plasma activity of renin (PAR) increases, which leads to an increase in angiotensin II in the blood plasma.After a single dose of antihypertensive effect (decreases systolic and diastolic blood pressure) reaches a maximum after 6 hours, then within 24 hours gradually decreases. In the course of treatment, antihypertensive activity and decrease in plasma aldosterone concentration were manifested after 2 and 6 weeks of therapy, which indicates effective blockade of angiotensin II receptors. However, after the abolition of losartan, the plasma renin activity and angiotensin II level decreased to the baseline values observed after the drug was administered 3 days later. AND losartan and its active metabolite have a higher affinity for receptors of the type AT1, than to AT2 type receptors. The active metabolite is 10-40 times more active than losartan.

Hydrochlorothiazide

A thiazide diuretic whose diuretic effect is associated with a disruption of the reabsorption of sodium, chlorine, potassium, magnesium, water in the distal nephron; delays the excretion of calcium ions, uric acid. Has antihypertensive properties; antihypertensive effect develops due to the expansion of arterioles. Virtually no effect on normal blood pressure (BP). Diuretic effect occurs in 1-2 hours, reaches a maximum after 4 hours and lasts 6-12 hours.Antihypertensive effect occurs in 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect.

Pharmacokinetics:

The pharmacokinetics of losartan and hydrochlorothiazide with simultaneous administration does not differ from that for their separate administration.

Losartan

Suction

Ingestion losartan is well absorbed from the gastrointestinal tract (GIT) and at the same time is metabolized by "primary passage" through the liver by carboxylation with the participation of isoenzyme CYP2C9 with the formation of an active metabolite. Systemic bioavailability of losartan is approximately 33%. The maximum concentration of losartan and its active metabolite is reached in the blood serum approximately after 1 hour and 3-4 hours after ingestion, respectively. Eating does not affect the bioavailability of losartan.

Distribution

Lozartan and its active metabolite bind to plasma proteins (mainly albumins) by more than 99%. The volume of distribution of losartan is 34 liters. Losartan practically does not penetrate the blood-brain barrier.

Metabolism

Approximately 14% of the dose of losartan administered intravenously orally,

turns into its active metabolite. After ingestion or

intravenous radiolabelled ¹⁴With losartan, the radioactivity of circulating blood plasma is due to the presence of losartan and its active metabolite. In addition to the active metabolite, biologically inactive metabolites are formed, including two basic metabolites formed as a result of hydroxylation of the butyl side chain, and one secondary - N-2-tetrazole-glucuronide.

Excretion

The plasma clearance of losartan and its active metabolite is about 600 ml / min and 50 ml / min, respectively. The renal clearance of losartan and its active metabolite is approximately 74 ml / min and 26 ml / min, respectively. When taking losartan, about 4% of the dose is excreted unchanged by the kidneys and about 6% of the dose is excreted by the kidneys in the form of an active metabolite. Losartan and its active metabolite demonstrate linear pharmacokinetics when ingested at doses up to 200 mg. After oral administration, the plasma concentrations of losartan and its active metabolite decrease polyexponentially with a finite half-life (T_1/2) approximately 2 and 6-9 hours, respectively.With the dosing regimen of 100 mg once a day, there is no significant cumulation in the plasma of either losartan or its active metabolite.

The excretion of losartan and its metabolites occurs through the intestine with bile and kidneys. After ingestion with radioactive carbon labeled ¹⁴With losartan, about 35% of radioactivity is found in urine and 58% in feces. After intravenous administration of radioactive carbon labeled ¹⁴With losartan, approximately 43% of radioactivity is detected in urine and 50% in feces.

Pharmacokinetics in specific patient groups

Elderly patients: the concentration of losartan and its active metabolite in blood plasma in elderly male patients with arterial hypertension do not differ significantly from the values of these parameters in male patients of younger age with arterial hypertension.

Floor: values of plasma concentrations of losartan in women with arterial hypertension were 2 times higher than the corresponding values in men with arterial hypertension. The concentrations of active metabolite in men and women did not differ. This apparent pharmacokinetic difference, however, has no clinical significance.

Patients with impaired hepatic function: when losartan was administered orally to patients with mild and moderate alcoholic liver cirrhosis, the concentrations of losartan and its active metabolite in blood plasma were respectively 5 and 1.7 times higher than in young healthy male volunteers.

Patients with impaired renal function: plasma concentrations of losartan in patients with creatinine clearance (CC) above 10 ml / min did not differ from those in patients with unchanged renal function. When comparing the area under the curve "concentration-time" (AUC) in patients with normal renal function AUC losartan in patients on hemodialysis, was approximately 2 times more. Plasma concentrations of the active metabolite did not change in patients with impaired renal function or on hemodialysis. Losartan and its active metabolite are not excreted by hemodialysis.

Hydrochlorothiazide

After ingestion, the absorption and bioavailability of hydrochlorothiazide are about 70%. Connection with blood plasma proteins - 60-80%. When ingestion 12.5 mg hydrochlorothiazide maximum plasma concentration is achieved after 1.5-4 hours and is 70 ng / ml, and when ingestion 25 mg hydrochlorothiazide maximum plasma the concentration is reached after 2-5 hours and is 142 ng / ml. AT therapeutic range of doses average value AUC grows straight

in proportion to the increase in dose, with the appointment of once a day, cumulation is insignificant. Penetrates through the hematoplacental barrier and into breast milk. T_1/2 is 5-15 hours. Hydrochlorothiazide slightly metabolized in the liver. It is excreted almost completely (more than 95%) by the kidneys in unchanged form. 50-70% of the dose taken internally is excreted within 24 hours.

Indications:

- Arterial hypertension (patients who are shown combined therapy).

- Reducing the risk of developing cardiovascular disease and mortality in patients with hypertension and left ventricular hypertrophy.

Contraindications:

- Hypersensitivity to the components of the drug and to other derivatives of sulfonamide.

- Arterial hypotension.

- Anuria, severe renal dysfunction (CK less than 30 ml / min).

- Hyperkalemia.

- Refractory hypokalemia.

- Dehydration (including on the background of taking high doses of diuretics).

- Severe violations of the liver (more than 9 points on the scale Child-Pugh).

- Addison's disease.

- Simultaneous use with aliskiren in patients with diabetes mellitus and patients with renal insufficiency (creatinine clearance less than 60 ml / min).

- Pregnancy and lactation.

- Age to 18 years (effectiveness and safety not established).

Carefully:

- Violations of the water-electrolyte balance of blood (hyponatremia, hypochloraemic alkalosis, hypomagnesemia, hypokalemia, hyperkalemia, hypercalcemia).

- Two-sided stenosis of the renal arteries or stenosis of the artery of a single kidney, a violation of kidney function (QC more than 30 ml / min.).

- Hepatic failure (less than 9 on the Child-Pugh scale).

- Diabetes.

- Symptomatic hyperuricemia and / or exacerbation of gout.

- Weighed allergic anamnesis (in some patients angioedema has developed earlier with the intake of other medicinal substances, including ACE inhibitors) and bronchial asthma.

- Systemic diseases of connective tissue (including systemic lupus erythematosus).

- Reduced volume of circulating blood (BCC) (including against a background of high doses of diuretics).

- Simultaneous administration of non-steroidal anti-inflammatory drugs (NSAIDs)including cyclooxygenase-P (COX-2 inhibitors) inhibitors, cardiac glycosides, elderly age, ischemic heart disease.

- Condition after kidney transplantation (no experience of application).

- Aortic and mitral stenosis, hypertrophic obstructive cardiomyopathy, heart failure with concomitant severe renal insufficiency, severe chronic heart failure (NYHA functional class IV), heart failure with life-threatening arrhythmias.

- Cerebrovascular diseases.

- Acute myopia and secondary closed angle glaucoma.

Pregnancy and lactation:

The drug Losartan-N Canon is contraindicated in pregnancy. At the same time, the risk for the fetus in the first trimester is lower than in the II-III trimesters, since renal perfusion in the fetus, depending on the renin-angiotensin-aldosterone system (RAAS), appears in the second trimester. In the first trimester, the drug Losantan-N Canon is not recommended. However, in those extremely rare cases (less than one in a thousand women), when the use of all other antihypertensive drugs is not possible, the drug may be administered under close medical supervision, including a weekly ultrasound examination of the fetus.In case of signs of oligohydramnion, treatment with an angiotensin II receptor antagonist should be discontinued. The use of angiotensin II receptor antagonists in the II or III trimesters of pregnancy has a toxic effect on the fetus (decreased kidney function, development of oligohydramnion, slowing ossification of the skull) and newborn (renal failure, arterial hypotension, hyperkalemia).

Since drugs acting on RAAS in the II-III trimesters of pregnancy can lead to disruption in the development and / or death of the fetus, when establishing the fact of pregnancy, the drug Lozartan-N Canon should be stopped immediately.

For newborns and infants who have been in utero exposed to the angiotensin II receptor antagonist, careful monitoring is recommended for the timely detection of a marked decrease in blood pressure, oliguria, and hyperkalemia.

Thiazides penetrate the placental barrier and are detected in the blood of the umbilical cord. The use of diuretics in pregnant women is not recommended. this increases the risk of developing fetal adverse events such as fetal jaundice and jaundice of newborns, and the mother-thrombocytopenia.

It is not known whether losartan with breast milk, but it is known that thiazides are excreted in breast milk. In connection with the risk of adverse events in infants, the drug Losartan-N Canon is contraindicated during breastfeeding. If necessary, breast-feeding should be discontinued.

Dosing and Administration:

Inside, regardless of food intake. Tablets are swallowed, not liquid, squeezed with water. The drug Losartan-N Canon can be combined with other antihypertensive drugs.

Arterial hypertension

The initial and maintenance dose is 1 tablet of the drug Losartan-N Canon (12.5 / 50 mg) once a day. In the absence of an adequate therapeutic effect, the dose of Lozartan-N canon is increased to 25/100 mg. The maximum antihypertensive effect is achieved within three weeks of therapy. The maximum daily dose - 1 tablet formulation Losartan-H Canon (25/100 mg).

Older patients and patients with moderate renal impairment (creatinine clearance of 30-50 ml / min) is required initial dose adjustment.

Reducing the risk of cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy.

The standard initial dose of losartan is 50 mg once a day. Patients who failed to achieve target BP levels when taking losartan 50 mg / day require treatment with a combination of losartan with low doses of hydrochlorothiazide (12.5 mg) and, if necessary, a dose of losartan to 100 mg in combination with hydrochlorothiazide at a dose of 12.5 mg / day, further increase to 100 mg of losartan and 25 mg of hydrochlorothiazide per day once (1 tablet of the drug Lozartan-N Canon 25/100 mg).

Side effects:Classification of the World Health Organization frequency of development of side effects:

Often - >1/10 appointments (> 10%)

often from >1/100 to <1/10 of appointments (> 1% and <10%)

infrequently - from >1/1000 to <1/100 of prescriptions (> 0.1% and <1%)

rarely from> 1/10000 to <1/1000 appointments (> 0.01% and <0.1%)

very rarely - <1/10000 prescriptions (<0.01%)

frequency is unknown-it is not possible to establish the frequency of occurrence on the available data.

Losartan

From the side of the blood and lymphatic system:

Infrequently: thrombocytopenia, anemia.

From the immune system:

Infrequently: vasculitis, including purple Shenlen Genoch; Rarely: anaphylactic reactions, angioedema, including swelling of the larynx and vocal cords with the development of airway obstruction and / or swelling of the face, lips, pharynx and / or tongue.Some of these patients had angioedema earlier with other drugs, including ACE inhibitors.

From the nervous system: Often: sleep disturbance, insomnia, headache, dizziness. Infrequently: anxiety, drowsiness, memory disorders, peripheral neuropathy, paresthesia, hypoesthesia, tremor, migraine, ataxia, depression, panic conditions, anxiety, loss of consciousness, acute disturbance of cerebral circulation.

From the side of the organ of vision: Infrequently: visual acuity, conjunctivitis.

Violation of the hearing organ and labyrinthine disturbances: Infrequently: tinnitus.

Impaired organ of taste: Infrequently: a taste disorder.

From the heart: Infrequently: bradycardia, atrial fibrillation, atrial and ventricular fibrillation, tachycardia, ventricular tachycardia, angina pectoris, myocardial infarction.

From the side of the vessels: Infrequently: orthostatic hypotension, cerebrovascular disorders, fainting.

From the respiratory, thoracic, mediastinal: Often: nasal congestion, sinusitis, sinusitis, cough. Infrequently: upper respiratory tract infections, rhinitis, pharyngitis, laryngitis, dyspnoea, bronchitis, nosebleeds.

From the gastrointestinal tract: Often: diarrhea, indigestion, spasms, abdominal pain, nausea. Infrequently: constipation, dry mouth, flatulence, gastritis, vomiting, anorexia.

From the hepatobiliary system: Infrequently: a violation of the liver. Rarely: hepatitis.

From the skin and subcutaneous fat: Infrequently: alopecia, dermatitis, dry skin, skin hyperemia, photosensitization, pruritus, rash, urticaria, increased sweating.

From the musculoskeletal system and connective tissue: Often: cramps in the muscles of the lower extremities, myalgia, pain in the back, chest, leg pain. Infrequently: arthralgia, arthritis, pain in the hands, pain in the knee, shoulder pain, hip pain, muscle rigidity, fibromyalgia, rhabdomyolysis.

From the side of the kidneys and urinary tract: Infrequently: mandatory urges for urination, urinary tract infections, impaired renal function, acute renal failure.

From the genitals and the breast: Infrequently: decreased libido, impotence.

Common violations: Often: asthenia, increased fatigue.

Laboratory indicators: Often: hyperkalemia. Infrequently: a moderate increase in serum urea and creatinine, hypoglycemia, hyponatremia, hyperuricemia. Rarely: increased activity of "hepatic" enzymes, hyperbilirubinemia.

Hydrochlorothiazide

From the side of the blood and lymphatic system: Infrequently: thrombocytopenia, aplastic anemia, hemolytic anemia, leukopenia, agranulocytosis.

From the immune system: Rarely: anaphylactic reactions.

From the nervous system: Often: headache, dizziness. Infrequently: sleep disturbance, paresthesia, depression.

From the side of the organ of vision: Infrequently: violation of visual acuity, conjunctivitis, xantopsy.

From the heart: Infrequently: pain behind the sternum, bradycardia, atrioventricular (AV) blockade of the II degree, angina pectoris.

From the side of the vessels: Infrequently: orthostatic hypotension, vasculitis.

From the respiratory, thoracic, mediastinal: Infrequently: Respiratory distress syndrome (including pneumonitis and pulmonary edema).

From the gastrointestinal tract: Infrequently: constipation, diarrhea, pancreatitis, inflammation of salivary glands, decreased appetite, anorexia.

From the hepatobiliary system: Infrequently: intrahepatic cholestasis. Rarely: hepatitis.

From the skin and subcutaneous fat: Infrequently: alopecia, skin hyperemia, photosensitivity, itching, rash, urticaria, increased sweating.

From the musculoskeletal system and connective tissue: Infrequently: cramps in the muscles of the lower extremities, muscle weakness, arthralgia.

From the side of the kidneys and urinary tract: Infrequently: nocturia, interstitial nephritis.

From the genitals and the breast: Infrequently: impotence.

Laboratory indicators: Often: hyperkalemia. Infrequently: hypokalemia, hypomagnesemia, hypercalcemia, hypochloraemic alkalosis, moderate increase in urea and serum creatinine, hyponatremia, hyperuricemia, glucosuria. Rarely: increased activity of "hepatic" enzymes, hyperbilirubinemia.

Common violations: Infrequently: fever.

There are reports of adverse reactions reported during the use of a combination of hydrochlorothiazide / losartan:

From the nervous system: Often: dizziness.

From the hepatobiliary system: Rarely: hepatitis.

Laboratory indicators: Rarely: hyperglycemia, increased activity

"hepatic" enzymes.

Overdose:

Losartan

Symptoms: marked decrease in blood pressure, tachycardia. Bradycardia can occur due to parasympathetic (vagal) stimulation.

Treatment: forced diuresis, symptomatic therapy. Hemodialysis is not effective.

Hydrochlorothiazide

Symptoms: the most frequent symptoms are a consequence of a deficiency of electrolytes (hypokalemia, hypochloraemia, hyponatremia) and dehydration due to excessive diuresis. With the simultaneous administration of cardiac glycosides, hypokalemia can aggravate the course of arrhythmias. Treatment: symptomatic.

Interaction:

Losartan

Can be used concomitantly with other antihypertensive agents.

No clinically significant drug

interactions of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin. Reportedly rifampicin and fluconazole reduce the concentration of the active metabolite in the blood plasma.The clinical significance of these interactions is still unknown.

As with the use of other agents that block the formation of angiotensin II and its effects, the concomitant use of potassium-sparing diuretics (spironolactone and eplerenone, triamterene, amiloride), potassium supplements and potassium-containing salts can lead to an increase in the potassium ion content in the serum.

Hypotensive drugs can increase the antihypertensive effect of losartan.

Also increase the antihypertensive effect of losartan may tricyclic antidepressants, antipsychotics, baclofen, amifostine, which reduce blood pressure as a major or side effect and may increase the risk of developing hypotension.

With simultaneous use of angiotensin II receptor antagonists and

non-steroidal anti-inflammatory drugs (NSAIDs) (including

selective inhibitors of cyclooxygenase-2, acetylsalicylic acid in

as an anti-inflammatory agent) may decrease

antihypertensive effect of losartan. In patients with impaired function

kidney concurrent use of angiotensin II receptor antagonists

or diuretics and NSAIDs may cause further deterioration

kidney function, including acute renal failure and an increase

the content of potassium in the blood serum. This combination should

use with caution, especially in elderly patients.

With simultaneous use of lithium with ACE inhibitors,

registered a reversible increase in serum lithium concentration

blood and toxicity; In very rare cases, this was observed

when angiotensin II receptor antagonists are used. When Care should be taken when using lithium with losartan concomitantly. If this combination is necessary, it is recommended to monitor the concentration of lithium in the blood serum.

Mutually enhances the effect of beta-blockers and sympatholytics; the combined use of losartan with diuretics causes an additive effect.

Double blockade of RAAS (for example, by combining an angiotensin II receptor antagonist with ACE inhibitors or aliskiren) in patients with an established diagnosis of atherosclerosis, heart failure, or diabetes mellitus with target organ damage is associated with a higher incidence of arterial hypotension, fainting,hyperkalemia and renal dysfunction (including the development of acute renal failure) compared with the use of a one-component blockade of the RAAS. The question of using the double blockade of RAAS should be solved in each case individually and with careful monitoring of blood pressure, water-electrolyte balance of blood and kidney function.

Hydrochlorothiazide

With thiazide diuretics, such medicines as ethanol, barbiturates and narcotics, can potentiate the risk of developing orthostatic hypotension.

Hypoglycemic agents (for oral administration and insulin) - dosage correction of hypoglycemic agents may be required. Metformin should be used with caution because of the risk of lactic acidosis due to possible kidney failure associated with taking hydrochlorothiazide.

Other antihypertensives - additive effect is possible. Corticosteroids, ACTH (adrenocorticotropic hormone) - a marked decrease in the content of electrolytes, in particular hypokalemia.

Pressor amines (e.g., epinephrine, norepinephrine) - a decrease in the severity of response to the reception of pressor amines.

Muscle relaxants of nondepolarizing action type (eg, tubocurarine) - Strengthening of muscle relaxants.

Lithium - diuretics reduce renal clearance of lithium and increase the risk of toxic action of lithium; simultaneous use is not recommended.

NSAIDs (including cyclooxygenase-2 inhibitors) - can reduce the diuretic, natriuretic and antihypertensive effect of diuretics.

Probenecid, sulphinpyrazone, allopurinol - joint admission with medicines for the treatment of gout may require correction of the dose of these drugs, since hydrochlorothiazide can increase the concentration of uric acid in the blood serum: an increase in the dose of probenecid or sulfinpyrazone. Joint administration of thiazide diuretics may increase the incidence of hypersensitivity to allopurinol.

Anticholinergics (atropine, biperidene) - increase the bioavailability of thiazide diuretics due to a decrease in the motility of the gastrointestinal tract and the rate of gastric emptying.

Cytotoxic agents (cyclophosphamide, methotrexate) - Thiazides may reduce renal excretion of cytotoxic drugsand stimulate their myelotoxic effect.

Salicylates - when taking high doses of salicylates hydrochlorothiazide can enhance their toxic effect on the central nervous system.

Methyldopa - separately reported cases of hemolytic anemia with the combined use of hydrochlorothiazide and methyldopa.

Cyclosporine - sharing with cyclosporine may increase the risk of hyperuricemia and similar gout complications.

Cardiac glycosides - Thiazide-stimulated hypokalemia or hypomagnesemia can contribute to the development of cardiac arrhythmias when combined with cardiac glycosides.

Medications that can cause arrhythmia of the "pirouette" type. Because of the risk of developing hypokalemia, caution is required when using Lozartan-N Canon simultaneously with the following drugs that can cause tachycardia such as pirouettes: antiarrhythmics (for example, quinidine, hydroquinidine, disopyramide, amiodarone, sotalol), some antipsychotics (for example, thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopyride, amisulpiride, tiapride, pimozide, haloperidol, droperidol); other (for example, bepridil, cisapride, difemanyl, erythromycin intravenous, halofantrine, misolastine, pentamidine, terfenadine, vincamycin intravenously, saprofloxacin, moxifloxacin, astemizole).

Salts of calcium - Thiazide diuretics can increase the calcium content in the serum due to a decrease in its excretion. If it is necessary to use calcium preparations, the dose is selected under the control of the calcium content in the blood serum.

Vitamin D - increases the risk of hypercalcemia.

Impact on laboratory results - Due to the effect on calcium excretion, thiazides can distort the results of studies of the function of parathyroid glands.

Carbamazepine - increases the risk of symptomatic hyponatremia. It is necessary to control the sodium content in the blood serum.

Iodine-contrast agents - with dehydration caused by taking diuretics, the risk of acute renal failure increases, especially when high doses of iodine-containing drugs are administered. Before the introduction of such funds, the patient should be rehydrated.

Amphotericin In, corticosteroids, adrenocorticotropic hormone and laxatives - when combined hydrochlorothiazide can exacerbate abnormalities of electrolyte balance, in particular, cause the development of hypokalemia.

Special instructions:

Losartan

In patients with reduced BCC (for example, receiving high doses of diuretics) symptomatic arterial hypotension may occur, so before the start of treatment, it is necessary to replenish BCC or begin treatment with Lozartan-N Canon at a lower dose.

During the treatment should be regularly monitored potassium in the blood plasma and creatinine clearance, especially in elderly patients and with impaired renal function. Drugs that affect the renin-angiotensin-aldosterone system can increase the concentration of urea in the blood and serum creatinine in patients with bilateral renal stenosis or stenosis of the artery of a single kidney.

Caution should be used when prescribing the drug Lozartan-N Canon for patients with a history of allergic history (including patients whose angioedema has developed earlier with other medications, including ACE inhibitors), as well as patients with bronchial asthma.

In patients with cirrhosis of the liver, the concentration of losartan in the blood plasma is significantly increased, in connection with which, in the presence of liver diseases in an anamnesis, it should be prescribed in lower doses.

There is no need for a special selection of an initial dose for elderly patients. The drug can increase the concentration of urea and creatinine in the blood plasma in patients with bilateral stenosis of the renal arteries or stenosis of the renal artery of a single kidney. The experience of losartan in patients after kidney transplantation is not.

Like all drugs that have a vasodilating effect, the drug Losartan-N Canon should be administered with caution to patients with aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.

In patients with severe chronic heart failure, drugs that affect RAAS can lead to severe arterial hypotension and acute renal failure. There are some reports of the development of oliguria and / or increasing azotemia and acute renal failure, including fatal.There is insufficient experience with losartan in patients with heart failure with concomitant severe renal failure, in patients with severe chronic heart failure (NYHA functional class IV), in patients with heart failure with life-threatening arrhythmias. In these groups with caution should be used drug Lozartan-N Canon with beta-adrenoblockers.

In patients with cerebrovascular diseases of ischemic nature, an excessive decrease in blood pressure can lead to a stroke. It is recommended that the doctor check the titration dose. Patients with primary hyperaldosteronism usually do not respond to antihypertensive agents acting through inhibition of the renin-angiotensin system. Therefore, it is not recommended to use the drug Losartan-N Canon for the treatment of such patients.

Hydrochlorothiazide

Hydrochlorothiazide can increase arterial hypotension and disturbances of water-electrolyte balance (decrease in BCC, hyponatremia, hypochloraemic alkalosis, hypomagnesemia, hypokalemia), impair glucose tolerance, reduce calcium excretion in urine and cause transient,a slight excess of calcium in the blood plasma. Expressed hypercalcemia may indicate latent hyperparathyroidism. Due to the influence of thiazides on calcium metabolism, their administration can distort the results of the investigation of parathyroid gland function, therefore, before the investigation of parathyroid gland functions, the thiazide diuretic should be discarded.

Increasing the concentration of cholesterol and triglycerides of blood can also be associated with therapy with thiazide diuretics.

In some patients, the use of thiazide diuretics can lead to hyperuricemia and / or exacerbation of gout.

Hydrochlorothiazide can cause an idiosyncratic reaction, leading to the development of acute transient myopia and an acute attack of closed-angle glaucoma. Symptoms include a sudden drop in visual acuity or eye pain, which usually appears within a few hours or weeks of initiating hydrochlorothiazide therapy. In the absence of treatment, an acute attack of angle-closure glaucoma can lead to persistent loss of vision. Treatment: as soon as possible stop taking hydrochlorothiazide.If intraocular pressure remains uncontrolled, immediate medical treatment or surgery may be required. Risk factors for the development of an acute attack of closed-angle glaucoma are: allergic reactions to sulfonamide derivatives and penicillins in history.

In patients receiving thiazides, hypersensitivity reactions can occur even if there is no indication of a history of allergy or bronchial asthma. There are reports of the development of exacerbation or progression of systemic lupus erythematosus on the background of thiazide diuretics.

Effect on the ability to drive transp. cf. and fur:

Studies of the impact on the possibility of driving and using technology were not conducted. Nevertheless, care must be taken when driving a vehicle or using machinery.

Form release / dosage:Tablets, film-coated 12.5 mg + 50 mg, 25 mg + 100 mg.

Packaging:Dosage of 12.5 mg + 50 mg: 7, 10, 28 or 30 tablets per contour cell pack of a PVC film or PVC / PVHD film or PVC / PCTFE film and aluminum-lacquered aluminum foil.According to 1, 2 contour cell packs of 7 tablets or 1, 2, 3, 9 contour cell packs of 10 tablets or 1, 2 contourcell packs of 28 tablets or 1, 3 contour packs of 30 tablets together with the instructions for use are placed in a pack of cardboard. Dosage of 25 mg + 100 mg: 7, 10, 14 or 15 tablets per contour cell pack of a PVC film or PVC / PVDC film or PVC / PCTFE film and aluminum foil printed lacquer. 1, 2 contour packs of cells with 7 tablets or 1, 2, 3, 6 contour packs of 10 tablets or 1, 2 contour packs of 14 tablets or 2, 4 circuit packs of 15 tablets together with instructions for application is placed in a pack of cardboard.

Storage conditions:In a dry, protected from light place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002409

Date of registration:21.03.2014

Date of cancellation:2019-03-21

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Information update date: & nbsp19.12.2015

Illustrated instructions

Instructions

Losartan-N Canon (Losartan-H Canon)