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

Losartan-N Canon is a combination drug with an antihypertensive effect.

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

Lozartan 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 synthesis pathway. Unlike some peptide angiotensin II receptor antagonists, losartan has no agonist effects. Losartan selectively binds to AT1 receptors and does not bind to or block receptors of other hormones and ion channels that play an important role in the regulation of cardiovascular function. In addition, losartan does not inhibit ACE, which is responsible for bradykinin degradation. Consequently, 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 relevant to the action of losartan.

Decreases RPS, BP, norepinephrine and aldosterone blood concentrations, small circulatory pressure; decreases post-load, has diuretic effect. Prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure (CHF). Oral administration of losartan increases plasma renin activity (PAR), which leads to an increase in plasma angiotensin II.

After a single dose, the antihypertensive effect (decreases systolic and diastolic BP) reaches a maximum after 6 h, then gradually decreases within 24 h. During treatment, antihypertensive activity and decreased blood plasma aldosterone concentration were manifested after 2 and 6 weeks of therapy, indicating effective blockade of angiotensin II receptors. However, after discontinuation of losartan, plasma renin activity and angiotensin II levels decreased after 3 days to baseline values observed before initiation of therapy.

Both losartan and its active metabolite have 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, the diuretic effect of which is associated with disruption of reabsorption of sodium, chloride, potassium, magnesium, water ions in the distal nephron; it delays the excretion of calcium ions, uric acid. It has an antihypertensive effect, which develops due to the expansion of the arterioles. It has practically no effect on normal blood pressure.

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

Indications

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

– reducing the risk of cardiovascular disease and mortality in patients with arterial hypertension and left ventricular hypertrophy.

Active ingredient

How to take, the dosage

The drug is taken orally, regardless of meals. The tablets are swallowed without chewing and with water.

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

Arterial hypertension

The starting and maintenance dose is 1 tablet (12.5/50 mg) once daily. If there is no adequate therapeutic effect, the dose of Lozartan-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 (CKR 30-50 ml/min) no adjustment of the initial dose is required.

Recrease cardiovascular morbidity and mortality risk in patients with arterial hypertension and left ventricular hypertrophy

The standard starting dose of losartan is 50 mg once daily. Patients who have failed to achieve target BP levels with losartan 50 mg/day require selection of therapy by combining losartan with hydrochlorothiazide at a low dose (12.5 mg); if necessary, the dose of losartan should be increased to 100 mg combined with hydrochlorothiazide at 12.5 mg/day, thereafter 100 mg of losartan and 25 mg of hydrochlorothiazide once daily (1 tablet 25/100 mg).

Interaction

Lozartan

May be used concomitantly with other antihypertensive agents.

There have been no clinically significant drug interactions of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin.

Rifampicin and fluconazole have been reported to decrease plasma concentrations of the active metabolite. The clinical significance of this interaction is not yet known.

As with other agents that block angiotensin II formation and effects, concomitant administration of potassium-saving diuretics (spironolactone and eplerenone, triamterene, amiloride), potassium supplements and salts containing potassium may result in increased serum potassium ions.

Antihypertensive agents may increase the hypotensive effect of losartan.

The hypotensive effects of losartan may also be enhanced by tricyclic antidepressants, neuroleptics, baclofen, and amifostine, which decrease BP as a primary or side effect and increase the risk of arterial hypotension.

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

When concomitant use of lithium preparations with ACE inhibitors a reversible increase in serum lithium concentration and development of toxicity has been registered; in very rare cases this has been observed with angiotensin II receptor antagonists. Caution should be exercised when lithium preparations are used concomitantly with losartan. If this combination is necessary, it is recommended to monitor serum lithium concentration.

Mutually enhances the effect of beta-adrenoblockers and sympatholytics; coadministration of losartan with diuretics causes an additive effect.

Double blockade of the RAAS (e.g., by combining an angiotensin II receptor antagonist with ACE inhibitors or aliskiren) in patients diagnosed with atherosclerosis, heart failure or diabetes with target organ damage is associated with a higher incidence of arterial hypotension, syncope, hyperkalemia and impaired renal function (including development of acute renal failure).development of acute renal failure) compared to the use of single-component blockade of the RAAS. Double RAAS blockade should be performed individually in each case with careful monitoring of BP, blood water-electrolyte balance and renal function.

Hydrochlorothiazide

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

In concomitant use of hydrochlorothiazide with hypoglycemic agents (oral and insulin) a dose adjustment of the latter may be required. Metformin should be used with caution due to the risk of lactacidosis because of possible renal failure associated with the use of hydrochlorothiazide.

Additive effect is possible when used with other hypotensive agents.

The corticosteroids, ACTH when used concomitantly with hydrochlorothiazide may cause excessive reduction of electrolytes, particularly hypokalemia.

Concomitant use with hydrochlorothiazide may decrease the severity of response to pressor amines (e.g., epinephrine, norepinephrine).

Hydrochlorothiazide increases the effect of myorelaxants of non-depolarizing type of action (e.g., tubocurarin).

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

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

Co-use with medicinal products 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-administration of thiazide diuretics may increase the incidence of hypersensitivity to allopurinol.

The anticholinergic agents (atropine, biperiden) increase bioavailability of thiazide diuretics due to reduction of GI motility and gastric emptying rate.

The thiazides may decrease renal excretion of cytotoxic drugs (cyclophosphamide, methotrexate) and stimulate their myelotoxic effect.

When using salicylates at high doses, hydrochlorothiazide may increase their toxic effects on the CNS.

Cases of hemolytic anemia have been reported separately when hydrochlorothiazide and methyldopa are coadministered.

Co-administration with cyclosporine may increase the risk of hyperuricemia and gout-like complications.

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

Because of the risk of hypokalemia, caution is required when using Lozartan-N Canon concomitantly with the following drugs that may cause pirouette tachycardia: Antiarrhythmic drugs (e.g., quinidine, hydroquinidine, disopyramide, amiodarone, sotalol); certain antipsychotics (e.g., thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopiride, amisulpiride, thiapride, pimozide, haloperidol, droperidol) Others (e.g., bepridil, cisapride, difemanil, erythromycin IV, halofantrine, misolastine, pentamidine, terfenadine, vincamycin IV, sparofloxacin, moxifloxacin, astemisol).

Thiazide diuretics may increase serum calcium content due to decreased calcium excretion. If it is necessary to use calcium preparations, the dose should be adjusted under control of serum calcium content.

Vitamin D increases the risk of hypercalcemia.

Because of the effect on calcium excretion, thiazides may distort the results of parathyroid function tests.

Carbamazepine increases the risk of symptomatic hyponatremia. Serum sodium levels should be monitored.

In dehydration caused by taking diuretics, the risk of acute renal failure increases, especially when administering iodine-containing drugs in high doses. Rehydration should be performed before administering such drugs.

The co-administration of hydrochlorothiazide with amphotericin B, corticosteroids, ACTH and laxatives may aggravate electrolyte imbalances, particularly hypokalemia.

Special Instructions

Lozartan

Patients with decreased RBC (e.g., those receiving high-dose diuretics) may experience symptomatic arterial hypotension, so replete the RBC or start treatment with Lozartan-N Canon at a lower dose before starting treatment.

Phase plasma potassium and CK levels should be monitored regularly during treatment, especially in elderly patients and patients with impaired renal function. Agents affecting the RAAS may increase serum urea and creatinine concentrations in patients with bilateral renal artery stenosis or stenosis of the artery of the sole kidney.

Patients with a history of allergy (including patients who have developed angioedema when using other medications, including ACE inhibitors) and patients with bronchial asthma should be cautioned when prescribing Lozartan-N Canon.

Patients with cirrhosis have significantly increased plasma concentrations of losartan, so the drug should be prescribed in lower doses if there is a history of liver disease.

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

The drug may increase plasma urea and creatinine concentrations in patients with bilateral renal artery stenosis or renal artery stenosis of the sole kidney.

There is no experience with losartan in patients after renal transplantation.

As with all drugs with vasodilatory effects, Losartan-N Canon should be administered with caution in patients with aortic or mitral stenosis, obstructive hypertrophic cardiomyopathy.

In patients with severe chronic heart failure, the use of drugs affecting the RAAS may lead to severe arterial hypotension and acute renal failure. There are separate reports about the development of oliguria and/or increasing azotemia and acute renal failure, including mortality.

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, caution should be exercised when using Lozartan-N Canon with beta-adrenoblockers.

In patients with cerebrovascular disease of ischemic nature, excessive lowering of BP may lead to stroke. Physician supervision is recommended when titrating the dose.

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

Hydrochlorothiazide

Hydrochlorothiazide may increase arterial hypotension and water-electrolyte balance disorders (decreased RBC, hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), impair glucose tolerance, decrease urinary calcium excretion and cause transient, slight excess of plasma calcium concentration. Severe hypercalcemia may indicate occult hyperparathyroidism. Due to the effect of thiazides on calcium metabolism, their use may distort the results of parathyroid gland function study, so the thiazide diuretic should be discontinued before parathyroid function study.

Elevated 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 aggravation of gout.

Hydrochlorthiazide may cause an idiosyncratic reaction leading to the development of acute transient myopia and an acute attack of closed angle glaucoma. Symptoms include a sudden decrease in visual acuity or eye pain that usually occurs within hours or weeks of starting hydrochlorothiazide therapy. If left untreated, an acute attack of closed angle glaucoma may result in permanent loss of vision. Hydrochlorthiazide should be discontinued as soon as possible. If intraocular pressure remains uncontrolled, emergency medication or surgery may be required. Risk factors for an acute attack of closed angle glaucoma include a history of allergic reactions to sulfonamide derivatives and penicillins.

In patients receiving thiazides, hypersensitivity reactions may be observed even if there are no indications of allergy or bronchial asthma in the history.

There have been reports of exacerbation or progression of systemic lupus erythematosus with thiazide diuretics.

Influence on driving and operating machinery

There have been no studies of the effect on the ability to drive vehicles and use machinery. However, caution should be exercised when driving a vehicle or using machinery.

Contraindications

– arterial hypotension;

– anuria;

– severe renal dysfunction (CK less than 30 ml/min);

– hyperkalemia;

– refractory hypokalemia;

– dehydration (includingч.

– severe hepatic impairment (greater than 9 points on the Child-Pugh score);

– Addison’s disease;

– concomitant use with aliskiren in patients with diabetes mellitus and patients with renal impairment (CK less than 60 ml/min);

– pregnancy;

– breastfeeding period;

– age less than 18 years (efficacy and safety not established);

– hypersensitivity to the components of the drug and to other sulfonamide derivatives.

With caution

– disorders of water-electrolyte balance (hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia, hyperkalemia, hypercalcemia);

– decreased BOD (including, in particular, hypothyroidism).ч.

– decreased RBC (including with high-dose diuretics);

– hepatic impairment (less than 9 points in Child-Pugh score);

– Renal dysfunction (CKG greater than 30 ml/min);

– Post kidney transplantation (no experience of use);

– bilateral renal artery stenosis or renal artery stenosis of a single kidney;

– CHD;

– aortic and mitral stenosis;

– hypertrophic obstructive cardiomyopathy;

– heart failure with concomitant severe renal failure;

– severe chronic heart failure (NYHA functional class IV);

– heart failure with life-threatening arrhythmias;

– cerebrovascular disease;

– diabetes mellitus;

– symptomatic hyperuricemia and/or exacerbation of gout;

– a history of allergies (some patients have developed angioedema previously when using other medications, including ACE inhibitors.

– bronchial asthma;

– systemic connective tissue disease (including systemic lupus erythematosus);

– acute myopia;

– secondary closed angle glaucoma;

– concomitant use of NSAIDs, including COPD inhibitors.COX-2 inhibitors;

– concomitant use of cardiac glycosides;

– advanced age.

Side effects

WHO Classification of the incidence of side effects: very frequently, ≥1/10 appointments (>10%); frequently, ≥1/100 to < 1/10 appointments (>1% and < 10%); infrequently, ≥1/1000 to < 1/100 appointments (>01% and < 1%); infrequent – ≥1/10,000 to < 1/1000 appointments (>0.01% and < 0.1%); very rare – < 1/10,000 appointments (< 0.01%); frequency unknown – no data are available to determine the incidence.

Lozartan

Hematopoietic system: infrequent – thrombocytopenia, anemia.

Allergic reactions: infrequent – itching, rash, urticaria, vasculitis, including Schoenlein-Henoch purpura; rarely – anaphylactic reactions, angioedema, including laryngeal and vocal cord edema with development of airway obstruction and/or edema of face, lips, pharynx and/or tongue. Some of these patients have previously had angioedema when using other medications, including ACE inhibitors.

Nervous system disorders: frequently – sleep disturbance, insomnia, headache, dizziness; infrequently – anxiety, somnolence, memory disorders, peripheral neuropathy, paresthesia, hypoesthesia, tremor, migraine, ataxia, depression, panic states, anxiety, loss of consciousness, acute stroke.

VIight: infrequent – visual acuity disorders, conjunctivitis.

Hearing organ: infrequent – tinnitus.

Cardiovascular system: infrequent – bradycardia, atrial fibrillation, tachycardia, ventricular tachycardia, angina pectoris, myocardial infarction, orthostatic hypotension, cerebrovascular disorders, syncope.

Respiratory system disorders: frequently – nasal congestion, sinusitis, maxillary sinusitis, cough; infrequently – upper respiratory tract infections, rhinitis, pharyngitis, laryngitis, dyspnea, bronchitis, nose bleeds.

The digestive system: frequently – 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: infrequent alopecia, dermatitis, dry skin, skin hyperemia, photosensitization, increased sweating.

Muscular system disorders: frequently – cramps in the muscles of the lower extremities, myalgia, backache, chest pain, pain in the legs; infrequently – arthralgia, arthritis, pain in the hands, pain in the knee, pain in the shoulder, pain in the hip joint, muscle stiffness, fibromyalgia, rhabdomyolysis.

Urinary system disorders: infrequent imperative urge to urinate, urinary tract infections, renal dysfunction, acute renal failure.

Gender and mammary system disorders: infrequent – decreased libido, impotence.

Laboratory disorders: frequently – hyperkalemia; infrequent – moderate increase of urea and creatinine concentration in blood serum, hypoglycemia, hyponatremia, hyperuricemia; very rarely – increase of liver enzymes activity, hyperbilirubinemia.

Others: often – asthenia, increased fatigue.

Hydrochlorothiazide

Hematopoietic system: infrequent – thrombocytopenia, aplastic anemia, hemolytic anemia, leukopenia, agranulocytosis.

Allergic reactions: infrequent – itching, rash, urticaria; rarely – anaphylactic reactions.

Nervous system disorders: frequently – headache, dizziness; infrequent – sleep disturbance, paraesthesia, depression.

An organ of vision: infrequent – visual acuity disorders, conjunctivitis, xanthopsia.

Cardiovascular system disorders: infrequent – chest pain, bradycardia, AV blockade of degree II, angina pectoris, orthostatic hypotension, vasculitis.

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

Gastrointestinal system disorders: infrequent – constipation, diarrhea, pancreatitis, salivary gland inflammation, decreased appetite, anorexia, intrahepatic cholestasis; rarely – hepatitis.

Skin and subcutaneous tissue disorders: infrequent alopecia, skin hyperemia, photosensitization, increased sweating.

Muscular system disorders: infrequent cramps in the muscles of the lower extremities, muscle weakness, arthralgia.

Urinary system disorders: infrequent nycturia, interstitial nephritis.

Gender and mammary system disorders: infrequent – impotence.

Laboratory disorders: frequently – hyperkalemia; infrequently – hypokalemia, hypomagnesemia, hypercalcemia, hypochloremic alkalosis, moderate increase of urea and creatinine concentration in serum, hyponatremia, hyperuricemia, glucosuria; very rarely – increase of liver enzymes activity, hyperbilirubinemia.

Others: infrequent – fever.

Hydrochlorothiazide/lozartan combination

Nervous system disorders: often – dizziness.

Gastrointestinal system: rarely – hepatitis.

Laboratory disorders: rarely – hyperglycemia, increased liver enzyme activity.

Overdose

Lozartan

Symptoms: excessive BP decrease, tachycardia. Bradycardia may occur due to parasympathetic (vagus) stimulation.

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

Hydrochlorothiazide

Symptoms: the most common symptoms are a consequence of electrolyte deficiency (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis. When concomitant use of cardiac glycosides, hypokalemia may aggravate the course of arrhythmias.

Treatment: carrying out symptomatic therapy.

Pregnancy use

The drug Lozartan-N Canon is contraindicated in pregnancy. However, the degree of risk to the fetus in the first trimester is lower compared to the second and third trimesters because fetal renal perfusion dependent on RAAS appears in the second trimester.

Lozartan-N Canon is not recommended for administration in the first trimester. However, in those exceptionally rare cases (less than one woman in a thousand) when the use of all other antihypertensive agents is not possible, it is allowed to prescribe the drug under close medical supervision, including weekly fetal ultrasound. If signs of oligohydramnios are found, 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 toxic effects on the fetus (reduced renal function, development of oligohydramnion, delayed cranial ossification) and the newborn (renal failure, arterial hypotension, hyperkalemia).

Because drugs acting on the RAAS in the second and third trimesters of pregnancy may lead to abnormal development and/or fetal death, Lozartan-N Canon should be discontinued immediately if pregnancy is established.

In newborns and infants who have had intrauterine exposure to an angiotensin II receptor antagonist, close monitoring is recommended for the timely detection of decreased BP, oliguria, and hyperkalemia.

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

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

Similarities