Losartan-N Canon, 12.5mg+50 mg 30 pcs

Pharmacotherapeutic group:

Hypotensive drug combined (angiotensin II receptor antagonist + diuretic)

HYPATH code: C09DA01

Indications

Active ingredient

Composition

1 film-coated tablet contains:

active ingredients:

hydrochlorothiazide 12.5 mg,

losartan potassium 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:

Opadray yellow 5 mg, including:

hypromellose (hydroxypropyl methylcellulose) 1.7 mg,

hyprolose (hydroxypropyl cellulose) 1.75 mg,

p> titanium dioxide 1.342 mg,

iron oxide yellow 0.207 mg,

aluminum sunset yellow dye varnish 0.001 mg.

How to take, the dosage

Overly, regardless of meals. The tablets are swallowed without chewing and with water. Lozartan-N Canon can be combined with other hypotensive drugs.

Hypertension

The starting and maintenance dose is 1 tablet of Lozartan-N Canon (12.5/50 mg) once daily. In the absence of 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 is 1 tablet of Lozartan-N Canon (25/100 mg).

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

Lower risk of cardiovascular morbidity and mortality 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 on losartan 50 mg/day should select therapy by combining losartan with low-dose hydrochlorothiazide (12.5 mg) and, if necessary, it is necessary to increase the dose of losartan to 100 mg in combination with hydrochlorothiazide at a dose of 12.5 mg/day, and further to increase to 100 mg of losartan and 25 mg of hydrochlorothiazide once daily (1 tablet of the drug Losartan-N Canon 25/100 mg).

Interaction

Lozartan

May be used concomitantly with other hypotensive agents.

No clinically significant drug interactions of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin have been reported. Rifampicin and fluconazole have been reported to decrease plasma concentrations of the active metabolite. The clinical significance of these interactions is not yet known.

As with other agents that block angiotensin II formation and its 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.

Hypotensive agents may increase the antihypertensive effect of losartan.

Tricyclic antidepressants, neuroleptics, baclofen, and amifostine may also increase the antihypertensive effects of losartan as a primary or side effect and may increase the risk of arterial hypotension.
Concomitant use of angiotensin II receptor antagonists and nonsteroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 inhibitors, acetylsalicylic acid as an anti-inflammatory agent) may reduce the antihypertensive effects of losartan. 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 with ACE inhibitors a reversible increase in serum lithium concentration and development of toxicity has been reported; in very rare cases this has been observed with angiotensin II receptor antagonists. Caution should be exercised when using lithium concomitantly with losartan. If this combination is necessary, it is recommended that serum lithium concentrations be monitored.

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

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

Hydrochlorothiazide

With thiazide diuretics, drugs such as ethanol, barbiturates, and narcotics may potentiate the risk of orthostatic hypotension.

Hypoglycemic agents (oral and insulin) – Dose adjustments of hypoglycemic agents may be required. Metformin should be used with caution because of the risk of lactate acidosis due to possible renal failure associated with taking hydrochlorothiazide.

Other hypotensive agents – possible additive effect.

Corticosteroids, ACTH (adrenocorticotropic hormone) – pronounced decrease of electrolytes, in particular hypokalemia.
Pressor amines (e.g., epinephrine, norepinephrine) – reduction in the severity of the response to pressor amines.

Myorelaxants of the non-depolarizing type of action (e.g., tubocurarin) – enhancement of myorelaxant action.

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

NSAIDs (including cyclooxygenase-2 inhibitors) – may decrease diuretic, natriuretic and antihypertensive effects of diuretics.
Probenecid, sulfinpyrazone, allopurinol – co-administration with drugs for the treatment of gout may require dose adjustment of these drugs, since hydrochlorothiazide can increase the concentration of uric acid in the blood serum: increasing 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 decreased gastrointestinal motility and gastric emptying rate.

Cytotoxic drugs (cyclophosphamide, methotrexate) – Thiazides may decrease renal excretion of cytotoxic drugs and stimulate their myelotoxic effect.

Salicylates – when taking high doses of salicylates, hydrochlorothiazide may increase their toxic effects on the central nervous system.

Methyldopa – cases of hemolytic anemia have been reported separately when hydrochlorothiazide and methyldopa are used together.
Cyclosporine – coadministration with cyclosporine may increase the risk of hyperuricemia and gout-like complications.
Cardiac glycosides – thiazide-stimulated hypokalemia or hypomagnesemia may contribute to cardiac rhythm disturbances when used together with cardiac glycosides.

Medicines that can cause pirouette-type arrhythmias. Caution is required when using Lozartan-N Canon concomitantly with the following drugs, which may cause pirouette tachycardia due to the risk of hypokalemia: Antiarrhythmic drugs (e.g., quinidine, hydroquinidine, disopyramide, amiodarone, sotalol) some antipsychotics (e.g., thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopyride, amisulpiride, thiapride, pimozide, haloperidol, droperidol) Others (e.g., bepridil, cisapride, difemanil, IV erythromycin, halofantrine, misolastine, pentamidine, terfenadine, IV vincamycin, saprofloxacin, moxifloxacin, astemizole).

Calcium salts – 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.

Impact on laboratory test results – due to the effect on calcium excretion, thiazides can distort the results of parathyroid gland function tests.

Carbamazepine – increases the risk of symptomatic hyponatremia. Serum sodium content should be monitored.
Iodine contrast agents – in dehydration caused by diuretics administration the risk of acute renal failure increases, especially when administering high doses of iodine-containing drugs. The patient should be rehydrated before administering such agents.

Amphotericin B, corticosteroids, adrenocorticotropic hormone, and laxatives: when used together, hydrochlorothiazide may aggravate electrolyte imbalances, particularly causing hypokalemia.

Special Instructions

Patients with decreased RBC (e.g., those receiving high doses of diuretics) may have symptomatic arterial hypotension, so prior to treatment, RBC replenishment or lower dose treatment with Losartan-N Canon should be initiated.

Phase plasma potassium and creatinine clearance should be monitored regularly during treatment, especially in elderly patients and those with impaired renal function. The drugs affecting renin-angiotensin-aldosterone system can increase blood urea and serum creatinine concentrations in patients with bilateral renal stenosis or arterial stenosis of the sole kidney.

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

In patients with cirrhosis, plasma concentrations of losartan are significantly increased, so it should be prescribed in lower doses if there is a history of liver disease.

There is no need for a specific 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 single 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, or obstructive hypertrophic cardiomyopathy.

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

There is insufficient experience with the use of 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 the drug
Lozartan-N Canon should be used with beta-adrenoblockers with caution.

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

Patients with primary hyperaldosteronism usually do not respond to hypotensive agents acting through inhibition of the renin-angiotensin system. Therefore, the use of Lozartan-N Canon is not recommended for the treatment of such patients.

Hydrochlorothiazide

Hydrochlorothiazide may exacerbate 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 administration 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 taking thiazide diuretics may lead to hyperuricemia and/or exacerbation 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. Untreated, an acute attack of closed-angle glaucoma may result in permanent loss of vision. Treatment:Stop hydrochlorthiazide as soon as possible. If intraocular pressure remains uncontrolled, emergency medication or surgery may be necessary. 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 for allergy or bronchial asthma in the anamnesis. There are reports of exacerbation or progression of systemic lupus erythematosus with thiazide diuretics.

Impact on the ability to drive vehicles and mechanisms

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

Contraindications

With caution

Side effects

World Health Organization Classification of the frequency of side effects:
very frequently ≥1/10 appointments (>10%)
frequently ≥1/100 to < 1/10 appointments (>1% < 10%)
infrequently ≥1/1000 to < 1/100 appointments (>0.1 % and < 1 %)
rarely from ≥1/10000 to < 1/1000 appointments (>0.01 % and < 0.1 %)
very rarely < 1/10000 appointments (< 0.01 %)
frequency is unknown on the available data it is impossible to determine the incidence.

Lozartan
Blood and lymphatic system disorders:
Infrequent: thrombocytopenia, anemia.

Immune system disorders:
Infrequent: vasculitis, including Schoenlein-Henoch purpura;
Rare: anaphylactic reactions, angioedema, including laryngeal and vocal cord edema with development of airway obstruction and/or edema of the face, lips, pharynx and/or tongue. Some of these patients have previously had angioedema when using other medications, including ACE inhibitors.

Nervous system disorders:
Often: sleep disturbance, insomnia, headache, dizziness.
Infrequent: restlessness, somnolence, memory disorders, peripheral neuropathy, paresthesia, hypoesthesia, tremor, migraine, ataxia, depression, panic states, anxiety, loss of consciousness, acute cerebral circulation disorder.

VIight organ disorders:
Infrequent: impaired visual acuity, conjunctivitis.

Hearing organ disorders and labyrinth disorders:
Infrequent: tinnitus.

Taste organ disorder:
Infrequent: taste disorder.

Heart disorders:
Infrequent: bradycardia, atrial fibrillation, tachycardia, ventricular tachycardia, angina pectoris, myocardial infarction.

Vascular disorders:
Infrequent: orthostatic hypotension, cerebrovascular disorders, fainting.

Respiratory system, thoracic organs, mediastinum:
Often: nasal congestion, sinusitis, maxillary sinusitis, cough.
Infrequent: upper respiratory tract infections, rhinitis, pharyngitis, laryngitis, dyspnea, bronchitis, nasal bleeding.

Gastrointestinal tract:
Often: diarrhea, dyspepsia, cramps, abdominal pain, nausea.
Infrequent: constipation, dry mouth, flatulence, gastritis, vomiting, anorexia.

Hepatobiliary system disorders:
Infrequent: impaired liver function.
Rare: hepatitis.

Skin and subcutaneous fat:
Infrequent: alopecia, dermatitis, dry skin, skin hyperemia, photosensitization, itching, rash, urticaria, increased sweating.

Skeletal-muscular system and connective tissue:
Often: muscle cramps in the lower extremities, myalgia, back pain, chest pain, pain in the legs.
Infrequent: arthralgia, arthritis, hand pain, knee pain, shoulder pain, hip pain, muscle stiffness, fibromyalgia, rhabdomyolysis.

Renal and urinary tract disorders:
Infrequent: imperative urge to urinate, urinary tract infections, impaired renal function, acute renal failure.

Gender and mammary gland disorders:
Infrequent: decreased libido, impotence.
General disorders:
Often: asthenia, increased fatigue.

Laboratory indices:
Often: hyperkalemia.
Infrequent: moderate increase of urea and creatinine level in blood serum, hypoglycemia, hyponatremia, hyperuricemia.
Very rarely: increase of liver enzymes activity, hyperbilirubinemia.

Hydrochlorothiazide

Blood and lymphatic system disorders:
Infrequent: thrombocytopenia, aplastic anemia, hemolytic anemia, leukopenia, agranulocytosis.

Immune system disorders:
Rarely: anaphylactic reactions.

Nervous system disorders:
Often: headache, dizziness.
Infrequent: sleep disturbance, paresthesia, depression.

Visually:
Infrequent: visual acuity impairment, conjunctivitis, xanthopsia.

Cardiac disorders: Infrequent: chest pain, bradycardia, atrioventricular (AV) block of degree II, angina pectoris.

Vascular disorders: Infrequent: orthostatic hypotension, vasculitis.

Respiratory system, thoracic organs, mediastinum:
Infrequent: respiratory distress syndrome (including pneumonitis and pulmonary edema).

Gastrointestinal tract:
Infrequent: constipation, diarrhea, pancreatitis, salivary gland inflammation, decreased appetite, anorexia.

Hepatobiliary system disorders:
Infrequent: intrahepatic cholestasis.
Rarely: hepatitis.

Skin and subcutaneous fat:
Infrequent: alopecia, skin hyperemia, photosensitization, itching, rash, urticaria, increased sweating.

Skeletal-muscular system and connective tissue:
Infrequent: muscle cramps of the lower extremities, muscle weakness, arthralgia.

Renal and urinary tract:
Infrequent: nycturia, interstitial nephritis.

Genital and mammary tract disorders:
Infrequent: impotence.

Laboratory indices:
Often: hyperkalemia.
Infrequent: hypokalemia, hypomagnesemia, hypercalcemia, hypochloremic alkalosis, moderate increase in serum urea and creatinine, hyponatremia, hyperuricemia, glucosuria.
Very rarely: increase of liver enzymes activity, hyperbilirubinemia.

General disorders:
Infrequent: fever.
There are reports of adverse reactions reported while using the hydrochlorothiazide/lozartan combination:

Nervous system disorders:
Often: dizziness.

Hepatobiliary system disorders:
Rarely: hepatitis.

Laboratory indices:
Rarely: hyperglycemia, increased activity of “liver” enzymes.

Overdose

Lozartan

Symptoms: marked 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 administration of cardiac glycosides, hypokalemia may aggravate the course of arrhythmias.

Treatment: symptomatic.

Similarities