Expiration date: 06/2025
Composition
Dosage of 12.5 mg + 50 mg
1 tablet, film-coated, contains:
active substances: 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, 4 mg povidone, microcrystalline cellulose was 29.5 mg;
film cover: Opadry yellow 5 mg, including: hypromellose (hydroxypropyl methylcellulose) 1.7 mg, hyprolose (hydroxypropyl-cellulose) 1.75 mg, titanium dioxide 1,342 mg, iron oxide yellow 0,207 mg, aluminum lacquer dye sunset yellow 0,001 mg.
Description
Round, biconvex tablets, film-coated yellow color. In the cross-section – almost white.
Pharmacotherapeutic group:
Combined antihypertensive (angiotensin II receptor antagonist + diuretic)
Pharmacological action
Pharmacodynamics
Losartan-H Canon – combined drug having antihypertensive effect.
Losartan
Angiotensin II is a potent vasoconstrictor, the main active hormone of the renin-angiotensin-aldosterone system (RAAS), as well as a crucial pathophysiological role in the development of hypertension. Losartan is highly effective administered selective antagonist of the angiotensin II receptor (type AT1). Angiotensin II selectively binds to AT1-receptors in many tissues (smooth muscle tissue of blood vessels, in adrenal glands, kidney and heart) and performs several important biological functions, including vasoconstrictor function and the release of aldosterone. In addition, angiotensin II stimulates proliferation of smooth muscle cells. Losartan and its pharmacologically active metabolite (E-3174) as in vitro and in vivo block all physiological effects of angiotensin II, regardless of the source or route of synthesis. In contrast to some peptide antagonists of receptors of angiotensin II, losartan has no agonist effects. Losartan selectively binds to AT1-receptors, do not bind or block other hormone receptors and ion channels, playing an important role in the regulation of the function of the cardiovascular system. In addition, losartan does not inhibit angiotensin converting enzyme (ACE) responsible for the destruction of bradykinin. Consequently, effects not directly associated with the blockade of AT1-receptors, including bradykininogen effects and the development of peripheral edema (losartan 1.7 %, the placebo to 1.9 %), are not related to the action of losartan. Reduces the total peripheral vascular resistance (OPSS), the blood concentration of norepinephrine and aldosterone, blood pressure (BP), the pressure in the "small" circle of blood circulation; reduces afterload, has a diuretic effect. Prevents the development of myocardial hypertrophy, increases tolerance to physical load in patients with chronic heart failure (CHF). While taking losartan increased plasma renin activity (RPA), which leads to an increase in angiotensin II in plasma. After receiving a single antihypertensive effect (reduced systolic and diastolic BP) reaches a maximum after 6 hours, then for 24 hours gradually decreases. In the treatment of antihypertensive activity and a decrease in the concentration of aldosterone in the blood plasma was shown after 2 and 6 weeks of treatment, indicating effective blockade of the angiotensin II receptor. However, after the cancellation of losartan, the renin activity of blood plasma and angiotensin II levels after 3 days decreased to baseline values observed before the start of treatment. And losartan and its active metabolite have a higher affinity for the receptors of type AT1 than for the AT2 receptor type. The active metabolite is 10-40 times more active than losartan.
Hydrochlorothiazide
Thiazide diuretic, the diuretic effect of which is associated with impaired reabsorption of sodium ions, chlorine, potassium, magnesium, water in the distal nefrona; delaying the removal of calcium ions, uric acid. Has antihypertensive properties antihypertensive effect develops due to the expansion of the arterioles. Almost no effect on normal blood pressure (BP). The diuretic effect occurs in 1-2 hours, reaches its maximum after 4 hours and lasts 6-12 hours. Antihypertensive activity occurs within 3-4 day, but to achieve optimal therapeutic effect may be required 3-4 of the week.
Pharmacokinetics
The pharmacokinetics of losartan and gidrohlorotiazida while receiving no different from that in their separate appointment.
Losartan
Suction
If ingestion losartan is well absorbed from the gastrointestinal tract (GIT) and metabolizmu with "primary pass" through the liver by carboxylation with the participation of isoenzyme CYP2C9 with the formation of active metabolite.
The systemic bioavailability of losartan is approximately 33 %. Maximal concentration of losartan and its active metabolite are achieved in the serum after about 1 hour and in 3-4 hours after ingestion, respectively. Eating does not affect the bioavailability of losartan.
Distribution
Losartan and its active metabolite are associated with blood plasma proteins (mostly albumin) is more than 99 %. The volume is 34 l. Raspredelitelnaya Losartan almost does not penetrate the blood-brain barrier.
Metabolism
About 14% the dose losartan, injected intravenously or by mouth, is converted into its active metabolite. After oral or intravenous administration of radioactive labelled 14C losartan, circulating plasma radioactivity of blood due to the presence of losartan and its active metabolite. In addition to the active metabolite are biologically inactive metabolites, including two major, formed by hydroxylation of butyl side chain, and one secondary – N-2-tetrazole-glucuronide.
Excretion
Plasma clearance of losartan and its active metabolite is about 600 ml/min and 50 ml/min, respectively. Renal clearance of losartan and its active metabolite is about 74 ml/min and 26 ml/min, respectively. While taking losartan inside about 4 % dose is excreted unchanged by the kidneys, and about 6 % of the dose is excreted by the kidneys as an active metabolite. Losartan and its active metabolite exhibit linear pharmacokinetics when administered in doses up to 200 mg. Once inside the plasma concentrations of losartan and its active metabolite polyexponential decline with a finite half-life (T1/2) of approximately 2 and 6-9 hours, respectively. When drug dosing regimen 100 mg once a day, there is no significant accumulation in plasma, neither losartan nor its active metabolite. Elimination of losartan and its metabolites occurs through the intestine with the bile and kidneys. After intake of labeled radioactive carbon 14C losartan, about 35% of radioactivity found in the urine and 58% in the feces. After intravenous injection labeled with radioactive 14C losartan for approximately 43 % of the radioactivity detected in the urine and 50% in the feces.
Pharmacokinetics in special patient groups
Elderly patients: concentrations of losartan and its active metabolite in blood plasma in elderly male patients with hypertension do not differ significantly from the values of these parameters in the male patients of younger age with hypertension.
Gender: values of plasma concentrations of losartan in women with hypertension in 2 times higher than the corresponding values in men with hypertension. Concentrations of the active metabolite of men and women do not differ. This apparent pharmacokinetic difference, however, has no clinical significance.
Patients with hepatic impairment: while taking losartan patients with easy and moderate alcoholic cirrhosis of the liver, concentrationary 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: the plasma concentrations of losartan in patients with creatinine clearance (CC) above 10 ml/min did not differ from those patients with unchanged renal function. When comparing the area under the curve "concentration–time" (AUC) in patients with normal renal function, the AUC of losartan in patients, on hemodialysis, was approximately 2 times more. Plasma concentrations of the active metabolite is not changed in patients with impaired renal function or hemodialysis. Losartan and its active metabolite are excreted through kidney dialysis.
Hydrochlorothiazide
After oral absorption and bioavailability of hydrochlorothiazide is 70 %. Relationship with blood plasma proteins – 60-80 %. The ingestion of 12.5 mg hydrochlorothiazide maximum plasma concentrations are reached within 1.5-4 hours and is 70 ng/ml, and when administered 25 mg of hydrochlorothiazide maximum plasma concentrations are reached within 2-5 hours and is 142 ng/ml In the therapeutic dose range average AUC increases with the increase in dose, the appointment, 1 time per day accumulation is negligible. Gematoplatzentarnyi penetrates through the barrier and into breast milk. T1/2 is 5-15 hours Hydrochlorothiazide is slightly metabolized in the liver. Excreted almost completely (over 95 %) by the kidneys in unchanged form. 50-70% of an oral dose is excreted within 24 hours.
Indications for use
- Arterial hypertension (in patients, which shows the combined therapy).
- Reducing the risk of cardiovascular disease and mortality in patients with hypertension and left ventricular hypertrophy.
Contraindications
- Hypersensitivity to the drug and other derivative of sulfonamide.
- Hypotension.
- Anuria, severe violations of kidney function (KK less 30 ml/min).
- Hyperkalemia.
- Refractory hypokalemia.
- Dehydration (including in patients receiving high doses of diuretics).
- Severe violations of the liver (more 9 points on a scale child-Pugh).
- Addison's Disease.
- Concurrent use with aliskiren in patients with diabetes mellitus and patients with renal insufficiency (creatinine clearance less than 60 ml/min).
- Pregnancy and breast-feeding.
- The age of 18 years (efficacy and safety not established).
With caution
Violations vodno-elektrolitnogo balance (hyponatremia, gipohloremichesky alkalosis, hypomagnesemia, hypokalemia, hyperkalemia, hypercalcemia).
Bilateral renal artery stenosis or stenosis of artery only kidneys, violations of the kidney (QC over 30 ml/min).
Liver failure (less than 9 points on a scale child-Pugh).
Diabetes.
Symptomatic hyperuricemia and/or worsening of gout.
Allergic history (some patients angioedema developed earlier when taking other drugs, including ACE inhibitors) and asthma.
Systemic connective tissue diseases (including systemic lupus erythematosus).
Reduced volume of circulating blood (BCC) (including on the background of high doses of diuretics).
Co-administration of nonsteroidal anti-inflammatory drugs (NSAIDs), including inhibitors of cyclooxygenase-II (COX-2 inhibitors), cardiac glycosides, elderly patients, coronary heart disease.
Condition after kidney transplantation (no experience).
Aortic and mitral stenosis, hypertrophic obstructive cardiomyopathy, heart failure with concomitant severe renal insufficiency, severe chronic heart failure (IV functional class NYHA classification), heart failure with life threatening arrhythmias.
Cerebrovascular disease.
Acute myopia and secondary angle-closure glaucoma.
Use during pregnancy and breastfeeding
The drug Losartan, N Canon contraindicated in pregnancy. The degree of risk to the fetus in the first trimester is lower in comparison with the II-III trimesters, since renal perfusion in the fetus, independent from the renin-angiotensin-aldosterone system (RAAS), appears in the II trimester.
In the first trimester the medication Losartan-N Canon is not recommended. However, in those extremely rare cases (less than one woman out of thousands) when all other hypotensive drugs cannot allowed the drug under close medical supervision, including weekly ultrasound examination of the fetus. In case of detection of signs of oligogidroamniona treatment with antagonist of angiotensin II receptor should be discontinued.
The use of receptor antagonists of angiotensin II in II or III trimester of pregnancy has a toxic effect on the fetus (reduction of renal function, development of oligohydramnion, slow ossification of the skull) and newborn (renal failure, hypotension, hyperkalemia).
Because drugs acting on the RAAS, in II-III trimesters of pregnancy can cause developmental disorder and/or fetal death, in establishing the fact of pregnancy the drug Losartan, N Canon should cease immediately.
For newborns and infants who in utero was exposed to the antagonist receptor of angiotensin II, we recommend that you maintain thorough surveillance for early detection of expressed lower AD, oliguria, hyperkalemia.
Thiazides cross the placental barrier and are found in the blood of the umbilical cord. The use of diuretics in pregnant women is not recommended because it increases the risk of fetal adverse events such as fetal jaundice and neonatal jaundice, and the mother – thrombocytopenia.
Unknown, selects whether losartan in breast milk, however it is known that thiazides are excreted in breast milk. In connection with risk of development of adverse events in infants the medication Losartan-N Canon is contraindicated during breast-feeding. If necessary, taking the drug, breastfeeding should be discontinued.
Method of application and doses
Inside, regardless of meals. Pills proglatyvayut not liquid, squeezed water. The drug Losartan, N Canon can be combined with other antihypertensives.
Hypertension
The initial and maintenance dose is 1 tablet of the drug Losartan-N Kanon (12,5/50 mg) 1 times a day. In the absence of adequate therapeutic effect, the dose of the drug Losartan-N Canon increased to 25/100 mg. the Maximal antihypertensive effect is attained within three weeks of therapy. The maximum daily dose – 1 tablet of the drug Losartan-N Kanon (25/100 mg).
Elderly patients and patients with moderate renal insufficiency (QC 30-50 ml/min) is not required correction initial dose.
Reducing the risk of cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy.
The standard starting dose of losartan is 50 mg 1 time a day. Patients who have failed to achieve target BP levels on the background piemerosana 50 mg/day, requires selection of the therapy by combination of losartan with low dose of hydrochlorothiazide (12.5 mg), and, if necessary, increase the dose losartan to 100 mg in combination with hydrochlorothiazide dose 12.5 mg/day, later increased to 100 mg losartan and 25 mg hydrochlorothiazide once a day (1 tablet of the drug Losartan-N Canon 25/100 mg).
Side effects
The classification of the world Health Organization, the incidence of side effects:
very often ?1/10 appointments (>10 %)
often from ?1/100 to < 1/10 appointments (>1 % and <10 %)
from uncommon ?1/1000 to <1/100 appointments (>0.1 % and <1 %)
from rare ?1/10000 to <1/1000 appointments (>0.01 % and <0.1 %)
very rare <1/10000 assignments (<0.01 %)
frequency is unknown according to the available data set the frequency of occurrence is not possible.
Losartan
The blood and lymphatic system:
Infrequent: thrombocytopenia, anemia.
The immune system:
Uncommon: vasculitis, including purpura, Shenleyn-Schonlein purpura;
Rare: 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 language. Some of these patients previously had angioedema while taking other medicines, including ACE inhibitors.
From the nervous system:
Frequent: sleep disturbances, insomnia, headache, dizziness.
Uncommon: anxiety, drowsiness, memory disorders, peripheral neuropathy, paresthesia, hypoesthesia, tremor, migraine, ataxia, depression, panic, anxiety, loss of consciousness, acute violation of cerebral circulation.
Side of body:
Infrequent: impaired visual acuity, conjunctivitis.
Violation on the part of the organ of hearing and labyrinth disorders:
Uncommon: ringing in the ears.
Breach by the authority of taste:
Uncommon: taste disturbance.
Heart:
Infrequent: bradycardia, atrial fibrillation, atrial fibrillation and ventricular tachycardia, ventricular tachycardia, angina, myocardial infarction.
From vessels:
Uncommon: orthostatic hypotension, cerebrovascular disorders, fainting.
The respiratory system of the chest, mediastinum:
Frequent: nasal congestion, sinusitis, sinusitis, cough.
Uncommon: infections of the upper respiratory tract, rhinitis, pharyngitis, laryngitis, dyspnoea, bronchitis, epistaxis.
The gastro-intestinal tract.
Frequent: diarrhea, dyspepsia, cramping, abdominal pain, nausea.
Uncommon: constipation, dry mouth, flatulence, gastritis, vomiting, anorexia.
Hepatobiliary system:
Infrequent: abnormal liver function.
Rarely: hepatitis.
On the part of the skin and subcutaneous fat:
Uncommon: alopecia, dermatitis, dry skin, skin flushing, photosensitivity, pruritus, rash, urticaria, sweating.
On the part of the musculoskeletal system and connective tissue:
Often cramps in the muscles of the lower extremities, myalgia, back pain, chest, pain in the legs.
Infrequent: arthralgia, arthritis, pain in hands, knee pain, shoulder pain, pain in the hip, muscle stiffness, fibromyalgia, rhabdomyolysis.
The kidneys and urinary tract:
Uncommon: an imperative urge to urinate, urinary tract infections, impaired renal function, acute renal failure.
From the genital organs and breast cancer:
Uncommon: decreased libido, impotence.
General disorders:
Frequent: asthenia, fatigue.
Laboratory findings:
Common: hyperkalemia.
Uncommon: moderate rise in the level of urea and creatinine in the serum, hypoglycemia, hyponatremia, hyperuricemia.
Very rare: increased activity of "liver" enzymes, hyperbilirubinemia.
hydrochlorothiazid
The blood and lymphatic system:
Uncommon: thrombocytopenia, aplastic anemia, hemolytic anemia, leukopenia, agranulocytosis.
The immune system:
Rarely: anaphylactic reactions.
From the nervous system:
Often: headache, dizziness.
Uncommon: sleep disturbance, paresthesia, depression.
Side of body:
Infrequent: impaired visual acuity, conjunctivitis, xanthopsia.
Heart: Uncommon: chest pain, bradycardia, atrioventricular (AV) blockade of the II degree, angina.
From vessels: Uncommon: orthostatic hypotension, vasculitis.
The respiratory system of the chest, mediastinum:
Uncommon: respiratory distress (including pneumonitis and pulmonary edema).
The gastro-intestinal tract.
Uncommon: constipation, diarrhea, pancreatitis, inflammation of the salivary glands, loss of appetite, anorexia.
Hepatobiliary system:
Rare: intrahepatic cholestasis.
Rarely: hepatitis.
On the part of the skin and subcutaneous fat:
Uncommon: alopecia, skin flushing, photosensitivity, pruritus, rash, urticaria, sweating.
On the part of the musculoskeletal system and connective tissue:
Uncommon: cramps in the muscles of the lower extremities, muscular weakness, arthralgia.
The kidneys and urinary tract:
Uncommon: nocturia, interstitial nephritis.
From the genital organs and breast cancer:
Uncommon: impotence.
Laboratory findings:
Common: hyperkalemia.
Uncommon: hypokalemia, hypomagnesemia, hypercalcemia, gipohloremichesky alkalosis, a moderate increase in the level of urea and creatinine in the serum, hyponatremia, hyperuricemia, glucosuria.
Very rare: increased activity of "liver" enzymes, hyperbilirubinemia.
General disorders:
Uncommon: fever.
There is information on adverse reactions reported in the process of applying the combination of hydrochlorothiazide/losartan:
From the nervous system:
Often: dizziness.
Hepatobiliary system:
Rarely: hepatitis.
Laboratory findings:
Rarely: hyperglycemia, increased activity of "liver" enzymes.
Overdose
Losartan
Symptoms: expressed lower AD, 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 a consequence of the lack of electrolytes (hypokalemia, gipohloremia, hyponatremia) and dehydration due to excessive diuresis. While receiving cardiac glycosides gipokaliemia may worsen arrhythmias.
Treatment: symptomatic.
Interaction with other drugs
Losartan
Can be used in conjunction with other antihypertensives.
There were no clinically significant drug interactions with losartan hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin. According to reports rifampicin fluconazole and reduce the concentration of the active metabolite in plasma. The clinical significance of these interactions is still unknown.
As the use of other means of blocking the formation of angiotensin II and its effects, concomitant appointment kalisberegath dioretikov (spironolactone and eplerenone, triamterene, amiloride), potassium supplements and salts containing potassium, may lead to increased content of potassium ions in the blood serum.
Antihypertensives may increase the antihypertensive effect of losartan.
Also to enhance the antihypertensive effect of losartan may tricyclic antidepressants, antipsychotics, baclofen, amifostine, which can reduce blood pressure as a primary or side effect and can increase the risk of hypotension.
While the use of antagonists of angiotensin II receptor and non-steroidal anti-inflammatory drugs (NSAIDs) (including a selective cyclooxygenase-2 inhibitors, acetylsalicylic acid as anti-inflammatory agents), may decrease the antihypertensive effect of losartan. In patients with impaired renal function concomitant use of antagonists of angiotensin II receptors blockers or diuretics and NSAIDs may cause a further deterioration of renal function, including acute renal failure and an increase in the potassium content in the blood serum. This combination should be used with caution, especially in elderly patients.
During concomitant administration of lithium with ACE inhibitors was was a reversible increase of lithium concentration in blood serum and the development of toxicity; in very rare cases is observed in the application of antagonists of angiotensin II receptors. While the use of lithium and losartan should be used with caution. 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 simpatolitikov; concomitant use of losartan with diuretics causing an additive effect.
Dual blockade of the RAAS (e.g., by combining the antagonist receptor of angiotensin II with ACE inhibitors or aliskiren) in patients with an established diagnosis of atherosclerosis, heart failure, or diabetes with damage to target organs associated with a higher frequency of hypotension, syncope, hyperkalemia and impaired renal function (including acute renal failure) compared with use of single RAAS blockade. The question of the use of dual RAAS blockade should be decided in each case individually and with careful monitoring of blood pressure, fluid and electrolyte balance of the blood 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) may require dosage adjustment of hypoglycemic agents. Metformin should be used with caution because of the risk of lactate acidosis due to possible renal failure associated with ingestion of hydrochlorothiazide.
Other antihypertensive drugs – additive effect possible.
Corticosteroids, ACTH (adrenocorticotropic hormone) – marked reduction of electrolytes, particularly hypokalemia.
Pressor amines (e.g. epinephrine, norepinephrine) – lower the intensity of the response to the reception of Pressor amines.
Muscle relaxants non-depolarizing type of action (e.g., tubokurarin) – potentiation of muscle relaxants.
Lithium – diuretics reduce kidney klirens lithium and increase the risk of lithium toxic effects; concurrent use is not recommended.
NSAIDs (including cyclooxygenase-2 inhibitors) may reduce the diuretic, natriuretic, and antihypertensive effect of diuretics.
Probenecid, sulfinpirazon, allopurinol – co-administration with drugs for treatment of gout may require dose adjustment of these drugs, as hydrochlorothiazide is able to increase the concentration of uric acid in serum: increased doses of probenecid or sulfinpirazon. The co-administration of thiazide diuretics may increase the incidence of cases of hypersensitivity to allopurinol.
Anticholinergics (atropine, biperiden) increase the bioavailability of thiazide diuretics as a result of reduced motility of the gastrointestinal tract and speed the stomach emptying.
Cytotoxic agents (cyclophosphamide, methotrexate) – thiazides may reduce renal excretion of cytotoxic medicinal products and to encourage their myelotoxic effects.
Salicylates – in high doses of salicylates hydrochlorothiazide may enhance their toxic effects on the Central nervous system.
Methyldopa – separately reported cases of hemolytic anemia when used together hydrochlorothiazide and methyldopa.
Cyclosporine: co-administration with cyclosporine may increase the risk of developing hyperuricemia and gout-like complications.
Cardiac glycosides – thiazid-induced hypokalemia or hypomagnesemia may contribute to the development of heart rhythm disturbances combined with cardiac glycosides.
Drugs, can cause arrhythmia type "pirouette". Because of the risk of development of hypokalemia, care should be taken when concomitant use of the drug Losartan-N the Canon with the following drugs that can cause tachycardia type "pirouette": antiarrhythmic agents (e.g. quinidine, hydrogenizing, disopyramide, amiodarone, sotalol) some antipsychotics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultoprid, amisulpiride, tiapride, pimozide, haloperidol, droperidol); others (e.g. bepridil, cisapride, diphemanil, erythromycin intravenously, halofantrine, mizolastine, pentamidine, terfenadine, vancomycin intravenous, ciprofloxacin, moxifloxacin, astemizole).
Calcium – thiazide diuretics can increase the calcium content in blood serum by reducing its excretion. If necessary, the use of calcium, the dose is selected under the control of the calcium content in blood serum.
Vitamin D increases the risk of hypercalcaemia.
Effect on laboratory results is due to the effect on calcium excretion, thiazides may distort the results of studies of the function of the parathyroid glands.
Carbamazepine increases the risk of symptomatic hyponatremia. It is necessary to control the sodium content in the blood serum.
Iodine contrast – to dehydration caused by diuretics, increased risk of acute renal failure, especially with the introduction of high doses of iodine-containing drugs. Before the introduction of such tools, the patient should be conducted rehydration.
Amphotericin b, corticosteroids, adrenocorticotropic hormone and laxatives – when used together hydrochlorothiazide may intensify electrolyte imbalance, particularly condition the development of hypokalemia.
Special instructions
In patients with reduced BCC (for example, receiving high doses of diuretics) may experience symptomatic hypotension, so before treatment it is necessary to fill the BCC or start treatment with the drug Losartan, N Canon at a lower dose.
During treatment should regularly monitor the content of potassium in the blood plasma and creatinine clearance, especially in elderly patients with impaired renal function. Drugs that affect the renin-angiotensin-aldosterone system, can increase the concentration of blood urea and serum creatinine in patients with bilateral renal stenosis or stenosis of the artery to a solitary kidney.
Care should be taken when administering the drug Losartan-N the Canon of the patients with allergic history (including patients in whom angioedema developed earlier when taking other drugs, including ACE inhibitors), patients with bronchial asthma.
In patients with cirrhosis concentration of losartan in blood plasma increases considerably and, therefore, in the presence of liver diseases in anamnesis and should be administered in lower doses.
No need for special selection of the initial dose in elderly patients. The drug may increase the concentration of urea and creatinine in blood plasma in patients with bilateral renal artery stenosis or renal artery stenosis to a solitary kidney.
Experience in the use of losartan in patients after kidney transplantation not.
Like all drugs, have vazodilatiruushimi effects, 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 affecting the RAAS can lead to severe arterial hypotension and acute renal failure. There are separate reports on the development of oliguria and/or increasing azotemia and acute renal failure, including fatalities.
There is insufficient experience with the use of losartan in patients with heart failure with concomitant severe renal impairment, in patients with severe chronic heart failure
(IV functional class NYHA classification) in patients with heart failure with life threatening arrhythmias. In these groups with caution should use the drug
Losartan-N Canon with beta-blockers.
In patients with cerebrovascular diseases of ischemic nature of the excessive decrease in blood pressure can lead to stroke. Recommended medical monitoring for dose titration.
Patients with primary hyperaldosteronism do not generally react on antihypertensive drugs acting through inhibition of the renin-angiotensin system. Therefore, it is not recommended to use the drug Losartan no Canon to treat such patients.
Hydrochlorothiazide
Hydrochlorothiazide may increase hypotension and violations vodno-elektrolitnogo balance (reduction of BCC, hyponatremia, gipohloremichesky alkalosis, hypomagnesemia, hypokalemia), break tolerance to glucose, to reduce the excretion of calcium in the urine and cause transient, slight excess of the calcium concentration in the blood plasma. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. In connection with the effect of thiazides on calcium metabolism, and it may distort the results of research of function of the parathyroid glands, therefore, before the study of the functions of the parathyroid glands thiazide diuretics should be discontinued.
Increasing the concentration of cholesterol and blood triglycerides may also be associated with tiazidnami dioretikami therapy.
Some patients receiving thiazide diuretics can cause hyperuricemia and/or worsening of gout.
Gidrokhlorisiazit may cause idiosyncratic reaction, resulting in the development of acute transient myopia and acute attack zakratougolna glaucoma. Symptoms include: sudden decrease in vision or eye pain that appear, usually within a few hours or weeks from the start of therapy gidrohlortiazidom. If untreated, an acute attack of angle-closure glaucoma can lead to permanent loss of vision. Treatment: as soon as possible to stop taking hydrochlorothiazide. If the intraocular pressure remains uncontrolled, it may require emergency medical treatment or surgery. Risk factors for developing acute angle-closure glaucoma attack are: an allergic reaction to sulfonamide derivatives and penicillins in history.
In patients receiving thiazides, hypersensitivity reactions may occur even in the absence of indications of Allergy or bronchial asthma in history. There are reports of the development of an exacerbation or progression of systemic lupus erythematosus in patients receiving a thiazide diuretic.
Effects on ability to drive vehicles and mechanisms
Study of the effect on driving ability and use of technology was conducted. However, when driving a vehicle or using machinery be careful.
