Losartan-N Canon pills 25mg+100mg, 30pcs

Composition

1 film-coated tablet contains: Active ingredients: 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 coated: Opadray yellow 10 mg, including: hypromellose (hydroxypropylmethylcellulose) 3.4 mg, hyprolose (hydroxypropylcellulose) 3.5 mg, titanium dioxide 2.685 mg, iron oxide yellow 0.413 mg, aluminum paint based on the dye sunny sunset yellow 0.002 mg

Pharmacological action

Losartan-N Canon is a combined drug that has an antihypertensive effect.

Losartan is a highly effective oral selective angiotensin II receptor antagonist (type AT1). Angiotensin II is a powerful vasoconstrictor, the main active hormone of RAAS, and also a crucial pathophysiological link in the development of arterial hypertension. Angiotensin II selectively binds to AT1 receptors found in many tissues (vascular smooth muscle cells, adrenal glands, kidneys, and heart) and performs several important biological functions, including vasoconstrictor function and aldosterone release. In addition, angiotensin II stimulates the proliferation of smooth muscle cells.

Losartan and its pharmacologically active metabolite (E-3174), both in vitro and in vivo, block all physiological effects of angiotensin II, regardless of the source or route of synthesis. Unlike some peptide angiotensin II receptor antagonists, losartan does not have agonist effects. Losartan selectively binds to AT-1 receptors, does not bind or block the receptors of other hormones and ion channels that play an important role in regulating the function of the cardiovascular system. In addition, losartan does not inhibit ACE, which is responsible for the breakdown of bradykinin. Therefore, effects not directly related to AT1-receptor blockade, including bradykinin-mediated effects and the development of peripheral edema (losartan 1.7%, placebo 1.9%), are not related to the effect of losartan.

Reduces OPSS, blood pressure, norepinephrine and aldosterone concentrations in the blood, pressure in the small circulatory circle; reduces afterload, has a diuretic effect. Prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure (CHF). When losartan is taken orally, the plasma activity of renin (PAR) increases, which leads to an increase in the content of angiotensin II in blood plasma.

After a single dose, the antihypertensive effect (systolic and diastolic blood pressure decreases) reaches a maximum in 6 hours, then gradually decreases within 24 hours. During treatment, antihypertensive activity and a decrease in plasma aldosterone concentrations were observed after 2 and 6 weeks of therapy, which indicates an effective blockade of angiotensin II receptors. However, after losartan was discontinued, plasma renin activity and angiotensin II levels decreased after 3 days to the initial values observed before starting the drug.

Both losartan and its active metabolite have a higher affinity for AT1 receptors than for AT2 receptors. The active metabolite is 10-40 times more active than losartan.

Hydrochlorothiazide is a thiazide diuretic whose diuretic effect is associated with impaired reabsorption of sodium, chlorine, potassium, magnesium, and water ions in the distal nephron; it delays the excretion of calcium and uric acid ions. It has an antihypertensive effect, which develops due to the expansion of arterioles. It has virtually no effect on normal blood pressure.

The diuretic effect occurs in 1-2 hours, reaches a maximum in 4 hours and lasts 6-12 hours. The antihypertensive effect occurs in 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect.

Indications

-arterial hypertension (patients who are indicated for combination therapy);

– reduction of the risk of developing cardiovascular diseases and mortality in patients with arterial hypertension and left ventricular hypertrophy.

Use during pregnancy and lactation

Losartan-N Canon is contraindicated during pregnancy. At the same time, the degree of risk for the fetus in the first trimester is lower compared to the second and third trimesters, since renal perfusion in the fetus, depending on RAAS, appears in the second trimester.

In the first trimester, Losartan-N Canon is not recommended. However, in those extremely rare cases (less than one woman in a thousand), when the use of all other antihypertensive drugs is impossible, the drug can be prescribed under the careful supervision of a doctor, including weekly ultrasound of the fetus. If signs of oligohydramnion are detected, treatment with an angiotensin II receptor antagonist should be discontinued.

The use of angiotensin II receptor antagonists in the second or third trimesters of pregnancy has a toxic effect on the fetus (decreased renal function, development of oligohydramnios, slowing of cranial ossification) and the newborn (renal failure, hypotension, hyperkalemia).

Since drugs acting on the RAAS in the second and third trimesters of pregnancy can lead to impaired development and/or death of the fetus, when determining the fact of pregnancy, Losartan-N Canon should be stopped immediately.

For newborns and children who have been exposed to an angiotensin II receptor antagonist in utero, it is recommended to conduct careful monitoring for the timely detection of a 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, as this increases the risk of developing adverse events such as fetal jaundice and neonatal jaundice, and in the mother – thrombocytopenia.

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

Contraindications

— arterial hypotension;

— anuria;

— severe renal dysfunction (CC less than 30 ml/min);

— hyperkalemia;

refractory hypokalemia;

— dehydration (including on the background of the use of diuretics in high doses);

— severe violations of the liver (more than 9 points on a scale child-Pugh);

— Addison’s disease;

— simultaneous use with aliskiren in patients with diabetes and patients with renal insufficiency (CC less than 60 ml/min);

— pregnancy;

— the period of breastfeeding;

— age under 18 years (effectiveness and safety not established);

— hypersensitivity to the drug and other sulfonamide derivatives.

With care

, violations of water-electrolyte balance (hyponatremia, gipohloremichesky alkalosis, hypomagnesemia, hypokalemia, hyperkalemia, hypercalcemia);

— reduced BCC (including on the background of the use of diuretics in high doses);

— liver failure (less than 9 points on a scale child-Pugh);

— disorders of renal function (QC more than 30 ml/min);

— condition after kidney transplantation (no experience);

— bilateral renal artery stenosis or stenosis of the artery to a solitary kidney;

— ischemic heart disease;

— the aortic and mitral stenosis;

hypertrophic obstructive cardiomyopathy;

heart failure with concomitant renal insufficiency, severe;

— chronic heart failure severe (IV functional class NYHA classification);

— heart failure with life-threatening arrhythmias;

— cerebrovascular disease;

diabetes mellitus;

symptomatic hyperuricemia and/or worsening of gout;

— allergic history (some patients develop angioedema previously, the use of other drugs, including ACE inhibitors);

— bronchial asthma;

systemic connective tissue diseases (including systemic lupus erythematosus);

— acute myopia;

— secondary angle-closure glaucoma;

— simultaneous use of NSAIDs, including COX-2 inhibitors;

— concomitant use of cardiac glycosides;

the old age.

Side effects

WHO classification of side effects: very common – ≥1/10 prescriptions (>10%); common – ≥1/100 to ><1/10 prescriptions (>1% and <1/10 prescriptions (><10%); uncommon – ≥1/1000 to <1/100 prescriptions (>0.1% and <1/100 prescriptions (><1%); rare – ≥1/10 000 to <1/1000 prescriptions (>0.01% and <1/1000 prescriptions (><0.1%); very rare – <1/10,000 appointments (

Losartan

From the hematopoietic system:  infrequently-thrombocytopenia, anemia.

Allergic reactions:  infrequently-pruritus, rash, urticaria, vasculitis, including Schonlein-Heinoch purpura; rarely – anaphylactic reactions, angioedema, including laryngeal and vocal cord edema with the development of airway obstruction and/or swelling of the face, lips, pharynx and / or tongue. Some of these patients have previously experienced angioedema with other medications, including ACE inhibitors.

Nervous system disorders: often – sleep disorders, insomnia, headache, dizziness; infrequently-anxiety, drowsiness, memory disorders, peripheral neuropathy, paresthesia, hypesthesia, tremor, migraine, ataxia, depression, panic states, anxiety, loss of consciousness, acute cerebrovascular accident.

From the side of the visual organ: infrequently-visual acuity disorder, conjunctivitis.

From the side of the hearing organ: infrequently-ringing in the ears.

From the cardiovascular system: infrequently – bradycardia, atrial fibrillation, atrial and ventricular fibrillation, tachycardia, ventricular tachycardia, angina pectoris, myocardial infarction, orthostatic hypotension, cerebrovascular disorders, syncope.

Respiratory system disorders: often – nasal congestion, sinusitis, sinusitis, cough; infrequently-upper respiratory tract infections, rhinitis, pharyngitis, laryngitis, dyspnoea, bronchitis, nosebleeds.

From the digestive system: often – diarrhea, dyspepsia, cramps, abdominal pain, nausea; infrequently-taste disorders, dry mouth, constipation, flatulence, gastritis, vomiting, anorexia, liver function disorders; rarely-hepatitis.

Skin and subcutaneous tissue disorders: infrequently – alopecia, dermatitis, dry skin, hyperemia of the skin, photosensitization, increased sweating.

Musculoskeletal disorders: often – cramps in the muscles of the lower extremities, myalgia, back pain, chest pain, leg pain; infrequently-arthralgia, arthritis, pain in the hands, knee pain, shoulder pain, hip pain, muscle rigidity, fibromyalgia, rhabdomyolysis.

From the urinary system: infrequently – urgent urge to urinate, urinary tract infections, impaired renal function, acute renal failure.

From the genitals and breast: infrequently-decreased libido, impotence.

From the side of laboratory parameters: often-hyperkalemia; infrequently-moderate increase in the concentration of urea and creatinine in the blood serum, hypoglycemia, hyponatremia, hyperuricemia; very rarely-increased activity of liver enzymes, hyperbilirubinemia.

Other services: often-asthenia, increased fatigue.

Hydrochlorothiazide

From the hematopoietic system: infrequently-thrombocytopenia, aplastic anemia, hemolytic anemia, leukopenia, agranulocytosis.

Allergic reactions: infrequently-pruritus, rash, urticaria; rarely-anaphylactic reactions.

Nervous system disorders: often – headache, dizziness; infrequently-sleep disorders, paresthesia, depression.

From the side of the visual organ: infrequently – visual acuity disorders, conjunctivitis, xanthopsia.

From the cardiovascular system: infrequently – pain behind the sternum, bradycardia, AV block II degree, angina pectoris, orthostatic hypotension, vasculitis.

Respiratory system disorders: infrequently – respiratory distress syndrome (including pneumonitis and pulmonary edema).

From the digestive system: infrequently-constipation, diarrhea, pancreatitis, salivary gland inflammation, decreased appetite, anorexia, intrahepatic cholestasis; rarely-hepatitis.

Skin and subcutaneous tissue disorders: infrequently – alopecia, hyperemia of the skin, photosensitization, increased sweating.

Musculoskeletal disorders: infrequently – cramps in the muscles of the lower extremities, muscle weakness, arthralgia.

From the urinary system: infrequently-nocturia, interstitial nephritis.

From the genitals and breast: infrequently-impotence.

From the side of laboratory parameters: often-hyperkalemia; infrequently-hypokalemia, hypomagnesemia, hypercalcemia, hypochloremic alkalosis, moderate increase in serum urea and creatinine concentrations, hyponatremia, hyperuricemia, glucosuria; very rarely-increased activity of liver enzymes, hyperbilirubinemia.

Other services: infrequently-fever.

Hydrochlorothiazide/losartan combination

Nervous system disorders: often – dizziness.

From the digestive system: rarely-hepatitis.

From the side of laboratory parameters: rarely – hyperglycemia, increased activity of liver enzymes.

Interaction

Losartan

It can be used simultaneously with other antihypertensive agents.

There were no clinically significant drug interactions between losartan and hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole, and erythromycin.

Rifampicin and fluconazole have been reported to reduce plasma concentrations of the active metabolite. The clinical significance of this interaction is still unknown.

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

Antihypertensive agents may enhance the antihypertensive effect of losartan.

The hypotensive effect of losartan may also be enhanced by tricyclic antidepressants, neuroleptics, baclofen, amifostine, which reduce blood pressure as a main or side effect and increase the risk of hypotension.

Concomitant use of angiotensin II receptor antagonists and NSAIDs (including selective COX-2 inhibitors, acetylsalicylic acid as an anti-inflammatory agent) may reduce the hypotensive effect of losartan. In patients with impaired renal function, concomitant use of angiotensin II receptor antagonists or diuretics and NSAIDs may cause further deterioration of renal function, including acute renal failure and increased serum potassium. This combination should be used with caution, especially in elderly patients.

When lithium preparations were co-administered with ACE inhibitors, a reversible increase in serum lithium concentrations and toxicity was reported; in very rare cases, this was observed with the use of angiotensin II receptor antagonists. Caution should be exercised when lithium preparations are co-administered with losartan. 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.

Dual blockade of the 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 hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared to the use of a single-component RAAS blockade. The use of double blockade of the RAAS should be decided in each case individually and with careful monitoring of blood pressure, blood water-electrolyte balance and kidney function.

Hydrochlorothiazide

When used concomitantly with thiazide diuretics, medications such as ethanol, barbiturates, and narcotic drugs may potentiate the risk of orthostatic hypotension.

Concomitant use of hydrochlorothiazide with hypoglycemic agents (for oral use and insulin) may require dose adjustment of the latter. Metformin should be used with caution because of the risk of lactic acidosis due to possible renal failure associated with taking hydrochlorothiazide.

When used with other antihypertensive agents, an additive effect is possible.

Corticosteroids, ACTH, when used concomitantly with hydrochlorothiazide can cause an excessive decrease in the content of electrolytes, in particular, hypokalemia.

When used concomitantly with hydrochlorothiazide, it is possible to reduce the severity of the response to taking pressor amines (for example, epinephrine, norepinephrine).

Hydrochlorothiazide enhances the effect of non-depolarizing muscle relaxants (for example, tubocurarin).

Diuretics reduce the renal clearance of lithium and increase the risk of lithium toxicity; concomitant use is not recommended.

NSAIDs (including COX-2 inhibitors) may reduce the diuretic, natriuretic, and antihypertensive effects of diuretics.

Concomitant use with medications for the treatment of gout (probenecid, sulfinpyrazone, allopurinol) may require dose adjustment of these drugs, since hydrochlorothiazide can increase the concentration of uric acid in the blood serum, it may be necessary to increase the dose of probenecid or sulfinpyrazone. Co-use of thiazide diuretics may increase the incidence of hypersensitivity to allopurinol.

Anticholinergic agents (atropine, biperiden) increase the bioavailability of thiazide diuretics due to a decrease in gastrointestinal motility and gastric emptying rate.

Thiazides can reduce the renal excretion of cytotoxic drugs (cyclophosphamide, methotrexate) and stimulate their myelotoxic effect.

When salicylates are used in high doses, hydrochlorothiazide may increase their toxic effect on the central nervous system.

Cases of hemolytic anemia have been reported separately with the combined use of hydrochlorothiazide and methyldopa.

Concomitant use with cyclosporine may increase the risk of hyperuricemia and gout-like complications.

Hypokalemia or hypomagnesemia caused by the use of thiazide diuretics may contribute to the development of cardiac arrhythmias when combined with cardiac glycosides.

Due to the risk of hypokalemia, caution is required when using Losartan-N Canon concomitantly with the following drugs that can cause pirouette-type tachycardia: antiarrhythmic agents (for example, quinidine, hydroquinidine, disopyramide, amiodarone, sotalol); some antipsychotic drugs (for example, thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride sultopiride, amisulpiride, tiapride, pimozide, haloperidol, droperidol); others (for example, bepridil, cisapride, difemanil, erythromycin iv, halofantrin, mizolastine, pentamidine, terfenadine, vincamycin iv, sparofloxacin, moxifloxacin, astemizole).

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

Vitamin D increases the risk of hypercalcemia.

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

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

Dehydration caused by diuretics increases the risk of acute renal failure, especially when high doses of iodine-containing drugs are administered. Rehydration should be performed before the introduction of such drugs.

Concomitant use of hydrochlorothiazide with amphotericin B, corticosteroids, ACTH, and laxatives may worsen electrolyte disturbances, especially hypokalemia.

How to take, course of use and dosage

The drug is taken orally, regardless of food intake. Tablets are swallowed without chewing, washed down with water.

Losartan-N Canon can be combined with other antihypertensive agents.

Arterial hypertension

The initial and maintenance dose is 1 tab. (12.5 / 50 mg) 1 time/day. In the absence of an adequate therapeutic effect, the dose of Losartan-N Canon is increased to 25/100 mg. The maximum antihypertensive effect is achieved within 3 weeks of therapy. The maximum daily dose is 1 tablet (25/100 mg).

In elderly patients and patients with moderate renal insufficiency (creatinine clearance 30-50 ml / min) no adjustment of the initial dose is required.

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

The standard initial dose of losartan is 50 mg once a day. Patients who failed to achieve the target blood pressure levels during the use of losartan at a dose of 50 mg/day need to select therapy by combining losartan with hydrochlorothiazide at a low dose (12.5 mg); if necessary, increase the dose of losartan to 100 mg in combination with hydrochlorothiazide at a dose of 12.5 mg/day, then – 100 mg of losartan and 25 mg of hydrochlorothiazide 1 time/day (1 table 25/100 mg).

Overdose

Losartan

Symptoms: excessive lowering of blood pressure, tachycardia. Bradycardia may occur due to parasympathetic (vagal) stimulation.

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

Hydrochlorothiazide

Symptoms: the most common symptoms are due to electrolyte deficiencies (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis. When cardiac glycosides are used concomitantly, hypokalemia may worsen the course of arrhythmias.

Treatment: conducting symptomatic therapy.

Special instructions

Losartan

Patients with reduced BCC (for example, those receiving high-dose diuretics) may experience symptomatic hypotension, so before starting treatment, it is necessary to replenish the BCC or start treatment with Losartan-N Canon at a lower dose.

During treatment, blood plasma potassium and creatinine clearance should be regularly monitored, especially in elderly patients and patients with impaired renal function. Drugs that affect the RAAS may increase serum urea and creatinine concentrations in patients with bilateral renal stenosis or stenosis of the artery of a single kidney.

Caution should be exercised when prescribing Losartan-N Canon to patients with a burdened allergic history (including patients who have previously developed angioedema 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 increases significantly, and therefore, if there is a history of liver disease, the drug should be prescribed in lower doses.

There is no need for special selection of the initial dose for elderly patients.

The drug may increase the concentration of urea and creatinine in blood plasma in patients with bilateral renal artery stenosis or stenosis of the renal artery of a single kidney.

There is no experience of using losartan in patients after kidney transplantation.

As with all vasodilating agents, Losartan-N Canon should be used with caution in patients with aortic or mitral stenosis or obstructive hypertrophic cardiomyopathy.

In patients with severe chronic heart failure, the use of drugs that affect the RAAS can lead to severe hypotension and acute renal failure. There are isolated reports of the development of oliguria and / or increasing azotemia and acute renal failure, including with a fatal outcome.

There is insufficient experience with the use of losartan in patients with heart failure with concomitant severe renal insufficiency, in patients with severe chronic heart failure (NYHA functional class IV), in patients with heart failure with life-threatening arrhythmias. In these groups, Losartan-N Canon with beta-blockers should be used with caution.

In patients with ischemic cerebrovascular diseases, an excessive decrease in blood pressure can lead to stroke. Medical monitoring is recommended when titrating the dose.

Patients with primary hyperaldosteronism usually do not respond to therapy with antihypertensive agents acting through RAAS inhibition. Therefore, it is not recommended to use Losartan-N Canon for the treatment of such patients.

Hydrochlorothiazide

Hydrochlorothiazide can increase arterial hypotension and water-electrolyte balance disorders (BCC reduction, hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), disrupt glucose tolerance, reduce urinary calcium excretion, and cause a transient, insignificant excess of calcium concentration in blood plasma. Severe hypercalcemia may indicate latent hyperparathyroidism. Due to the effect of thiazides on calcium metabolism, their use may distort the results of studies of parathyroid function, so before studying the functions of the parathyroid glands, a thiazide diuretic should be discontinued.

Increased blood cholesterol and triglyceride concentrations may also be associated with thiazide diuretic therapy.

In some patients, the use of thiazide diuretics may 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 angle-closure glaucoma. Symptoms include: a sudden decrease in visual acuity or pain in the eyes, which usually appear within a few hours or weeks of starting hydrochlorothiazide therapy. If left untreated, an acute attack of angle-closure glaucoma can lead to permanent vision loss. Stop taking hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, urgent medical treatment or surgery may be required. Risk factors for developing an acute attack of angle-closure glaucoma include: a history of allergic reactions to sulfonamide derivatives and penicillins.

Hypersensitivity reactions may occur in patients receiving thiazides even if there is no indication of a history of allergies or bronchial asthma.

There are reports of exacerbation or progression of systemic lupus erythematosus with the use of thiazide diuretics.

Influence on the ability to drive motor vehicles and manage mechanisms

Studies of the effect on the ability to drive vehicles and use equipment have not been conducted. However, care must be taken when driving a vehicle or using machinery.

Form of production

Film-coated tablets are yellow, round, biconvex, and almost white in cross-section.

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 25 °C.

Shelf

life is 2 years.

Active ingredient

Hydrochlorothiazide, Losartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Prevention of heart attacks and strokes, Hypertension