Instructions for Losartan Sandoz tablets 50 mg No. 28
Composition
active ingredient: losartan potassium;
1 film-coated tablet contains 50 mg or 100 mg of losartan potassium;
excipients: microcrystalline cellulose, povidone, sodium starch glycolate (type A), colloidal anhydrous silicon dioxide, magnesium stearate;
Opadry white shell (OY-L-28900): lactose monohydrate, hypromellose, titanium dioxide (E 171), polyethylene glycol 4000.
Dosage form
Film-coated tablets.
Main physicochemical properties: 50 mg tablets: white oval tablets with one score on each side and imprinted with 3 on one side; 100 mg tablets: white oblong tablets with three scores on each side and imprinted with 5 on one side.
Pharmacotherapeutic group
Simple angiotensin II receptor antagonists. ATC code C09C A01.
Pharmacological properties
Pharmacodynamics
Losartan is a synthetic angiotensin II (type AT1) receptor antagonist for oral administration. Angiotensin II, a potent vasoconstrictor, is the active hormone of the renin-angiotensin system and one of the most important factors in the pathophysiology of arterial hypertension. Angiotensin II binds to the AT1 receptor, which is found in many tissues (e.g., vascular smooth muscle, adrenal glands, kidneys, and heart), determining a number of important biological effects, including vasoconstriction and aldosterone release. Angiotensin II also provokes the proliferation of smooth muscle cells.
Losartan binds selectively to the AT1 receptor. In vitro and in vivo, losartan and its pharmacologically active metabolite, the carboxylic acid (E 3174), block all physiologically relevant effects of angiotensin II, regardless of the source or route of synthesis. Losartan does not bind to or block other hormone receptors or ion channels important for cardiovascular regulation. Losartan does not inhibit angiotensin-converting enzyme (ACE) (kinase II), the enzyme that catalyzes the degradation of bradykinin. Therefore, there is no potentiation of bradykinin-mediated adverse effects.
When losartan is used, the elimination of the negative feedback loop of angiotensin II on renin secretion increases plasma renin activity (PRA). This increase in PRA leads to an increase in plasma angiotensin II concentration. Despite this increase, antihypertensive activity and suppression of plasma aldosterone concentration are maintained, indicating effective blockade of angiotensin II receptors. After discontinuation of losartan treatment, PRA and angiotensin II levels return to baseline within 3 days.
Both losartan and its major metabolite have a higher affinity for AT1 receptors than for AT2 receptors. The active metabolite is 10-40 times more active than losartan.
In clinical studies, administration of losartan (once daily) to patients with mild to moderate essential hypertension resulted in statistically significant reductions in systolic and diastolic blood pressure. The antihypertensive effect was maintained for up to one year. Discontinuation of losartan in hypertensive patients did not result in a sharp increase in blood pressure (reversal reaction). Despite the marked reduction in blood pressure, losartan had no clinically significant effect on heart rate.
In patients with hypertension and proteinuria but without diabetes, administration of losartan potassium reduces proteinuria, fractional excretion of albumin, and IgG. Losartan maintains glomerular filtration rate and reduces filtration fraction. Losartan causes a slight decrease in serum uric acid levels, including during chronic therapy.
In patients with left ventricular dysfunction, doses of losartan 25 mg and 50 mg produced positive hemodynamic and neurohormonal effects characterized by an increase in cardiac index and a decrease in pulmonary capillary wedge pressure, systemic vascular resistance, mean arterial pressure, and heart rate, as well as a decrease in circulating levels of aldosterone and norepinephrine, respectively. In these patients with heart failure, the occurrence of arterial hypotension was dose-dependent.
Losartan is equally effective in both men and women, in young patients (under 65 years of age) and in elderly patients (over 65 years of age) with arterial hypertension. Although losartan has antihypertensive effects in patients of all races, black hypertensive patients had a lower mean response to losartan monotherapy than Caucasian hypertensive patients, as with all other drugs that affect the renin-angiotensin system.
Treatment with losartan reduced the risk of stroke by 25% compared with atenolol. The incidence of cardiovascular death and myocardial infarction did not differ significantly between treatment groups. Patients receiving losartan had a significantly greater reduction in left ventricular hypertrophy on ECG compared with patients receiving atenolol.
Pharmacokinetics
After oral administration, losartan is well absorbed and undergoes first-pass metabolism to form the active carboxylic acid metabolite and inactive metabolites. The systemic bioavailability of losartan tablets is approximately 33%. Mean peak concentrations of losartan and its active metabolite are reached after 1 hour and 3-4 hours, respectively. There is no clinically significant effect on the plasma concentrations of losartan when the drug is administered with a standard meal.
Distribution
More than 99% of losartan and its active metabolite are bound to plasma proteins, primarily albumin. The volume of distribution of losartan is 34 liters.
Biotransformation
About 14% of losartan is converted to the active metabolite after intravenous or oral administration. In vitro studies indicate that cytochrome P450 2C9 and 3A4 are involved in the metabolism of losartan. Following intravenous and oral administration of 14C-labeled losartan potassium, the radioactivity in circulating plasma is generally associated with losartan and its metabolite. Minimal conversion of losartan to its active metabolite has been observed in approximately 1% of cases due to a genetic defect in enzyme formation. In addition to the active metabolite, inactive metabolites are formed, including two major metabolites formed by hydroxylation of the butyl chain and a minor metabolite, the N-2 tetrazole glucuronide.
Breeding
The plasma clearance of losartan and its active metabolite is 600 ml/min and 50 ml/min, respectively. The renal clearance of losartan and its active metabolite is approximately 74 ml/min and 26 ml/min, respectively. When losartan is administered orally, approximately 4% of the dose is excreted unchanged in the urine and approximately 6% of the dose is excreted in the urine as the active metabolite. The pharmacokinetics of losartan and its active metabolite are linear over oral doses of losartan potassium up to 200 mg.
After oral administration, plasma concentrations of losartan and its active metabolite decline polyexponentially with terminal half-lives of approximately 2 hours and 6-9 hours, respectively. At a dose of 100 mg once daily, losartan and its active metabolite do not accumulate significantly in plasma.
Losartan and its metabolites are excreted in both bile and urine. After oral/intravenous administration of 14C-labeled losartan, approximately 35%/43% of the radiolabeled drug was recovered in urine and 58%/50% in feces.
Certain patient groups
Elderly patients
Plasma concentrations of losartan and its active metabolite in elderly hypertensive patients do not differ significantly from those in young hypertensive patients.
Sex
Plasma concentrations of losartan were 2-fold higher in hypertensive women compared to men, while plasma concentrations of the active metabolite were not significantly different between men and women.
Liver and kidney dysfunction
After oral administration in patients with mild to moderate alcoholic cirrhosis, plasma concentrations of losartan and its active metabolite were 5 and 1.7 times higher, respectively, than in young male volunteers.
Plasma concentrations of losartan in patients with creatinine clearance above 10 ml/min did not differ from those in subjects with normal renal function. The area under the concentration-time curve (AUC) of losartan in patients with normal renal function was approximately 2 times higher than in patients on hemodialysis.
Plasma concentrations of the active metabolite are not altered in patients with renal impairment and patients undergoing hemodialysis.
Losartan and its active metabolite cannot be removed by hemodialysis.
Indication
Treatment of essential hypertension in adults.
Treatment of kidney disease in adult patients with hypertension and type 2 diabetes mellitus with elevated serum creatinine and proteinuria (urine albumin/creatinine ratio ≥ 300 mg/g).
Treatment of mild to moderate heart failure in adults, usually in combination with diuretics and digitalis, when the use of angiotensin-converting enzyme (ACE) inhibitors is considered impossible due to incompatibility, especially in the case of cough, or is contraindicated. Adverse events due to ACE inhibitor therapy resulting from a general effect on the renin-angiotensin-aldosterone system (e.g. progressive renal failure, hyperkalemia) are not an indication for the use of losartan.
Reduction in the risk of stroke in adult patients with arterial hypertension and left ventricular hypertrophy, documented by ECG.
Contraindication
Hypersensitivity to the active substance or any of the excipients.
Hereditary angioedema or development of angioedema during previous treatment with an ACE inhibitor or angiotensin II receptor antagonists. Pregnancy or planning pregnancy (see section "Use during pregnancy and lactation").
Concomitant use of losartan with aliskiren-containing medicinal products is contraindicated in patients with diabetes mellitus or renal insufficiency (glomerular filtration rate (GFR) < 60 ml/min/1.73 m2).
Breastfeeding period.
Interaction with other medicinal products and other types of interactions
Known enzyme inducers and inhibitors affect the metabolism of losartan.
In clinical pharmacokinetic studies, no clinically significant interactions were observed with substances such as hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole, and erythromycin.
Other antihypertensive drugs may enhance the hypotensive effect of losartan. Drugs that may cause hypotension include tricyclic antidepressants, antipsychotics, baclofen, amifostine. Concomitant use of these drugs with antihypertensive drugs increases the risk of developing hypotension. Losartan is metabolized primarily by the cytochrome P450 (CYP) 2C9 system to form the active carboxylic acid metabolite.
Fluconazole (a CYP2C9 inhibitor) has been reported to reduce the exposure of the active metabolite by approximately 50%. Concomitant administration of losartan and rifampicin (an inducer of metabolic enzymes) has been shown to result in a 40% decrease in plasma concentrations of the active metabolite. The clinical significance of this effect is unknown. There is no difference in exposure when losartan is coadministered with fluvastatin (a weak CYP2C9 inhibitor).
As with other drugs that block angiotensin II or its effects, concomitant use of drugs that retain potassium in the body (e.g. potassium-sparing diuretics: spironolactone, triamterene, amiloride) or may increase potassium levels (e.g. heparin), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium. Concomitant use of such drugs is not recommended.
Reversible increases in serum lithium concentrations and toxic effects have been reported with concomitant use of lithium with ACE inhibitors. Very rarely, such effects have also been reported with angiotensin II receptor antagonists. Concomitant treatment with lithium and losartan should be undertaken with caution. If the combination is considered necessary, it is recommended that serum lithium levels be monitored during concomitant treatment.
Phenobarbital, an enzyme inducer, caused a 20% decrease in the AUC of losartan and its active metabolite. Cimetidine, an enzyme inhibitor, caused an 18% increase in the AUC of losartan, but not its active metabolite. These effects were not considered clinically significant.
The potential interaction of Losartan Sandoz with the oral anticoagulants acenocoumarol and phenprocoumon has not been studied.
With the simultaneous use of angiotensin II receptor antagonists and non-steroidal anti-inflammatory drugs (NSAIDs) (e.g. selective cyclooxygenase-2 (COX-2) inhibitors, acetylsalicylic acid at anti-inflammatory doses, non-selective NSAIDs) the antihypertensive effect may be reduced. The simultaneous use of angiotensin II antagonists or diuretics with NSAIDs increases the risk of worsening of renal function, including the development of acute renal failure, as well as an increase in serum potassium, especially in patients with pre-existing impaired renal function. Such a combination should be prescribed with caution, especially in elderly patients. Patients should be adequately hydrated, and it may also be advisable to monitor renal function after the start of concomitant use of the drugs, as well as periodically during treatment.
In the case of dual blockade with drugs (e.g. addition of an ACE inhibitor to angiotensin II receptor antagonists), renal function should be closely monitored and concomitant medication should be limited if necessary. ACE inhibitors and angiotensin II receptor antagonists should not be used concomitantly in patients with diabetic nephropathy.
Clinical trial data have shown that dual blockade of the renin-angiotensin-aldosterone system (RAAS) through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher incidence of adverse events, such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure), compared with the use of a single RAAS agent. Therefore, dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended. If dual blockade therapy is considered absolutely necessary, it should only be carried out under specialist supervision and with frequent close monitoring of renal function, electrolytes and blood pressure.
Application features
Increased sensitivity
Patients with a history of angioedema (swelling of the face, lips, throat and/or tongue) should be particularly monitored.
Symptomatic hypotension, especially after the first dose or after dose increases, may occur in patients with volume or sodium depletion caused by potent diuretics, dietary salt restriction, diarrhea, or vomiting. Such conditions should be corrected before initiating treatment with losartan or the initial dose should be reduced.
Electrolyte imbalance
Electrolyte imbalance is common in patients with renal impairment (with or without diabetes mellitus) and should be considered. In patients with type 2 diabetes mellitus and nephropathy, hyperkalemia has been reported to occur more frequently with losartan than with placebo. Therefore, plasma potassium and creatinine clearance should be monitored frequently, especially in patients with heart failure and creatinine clearance of 30-50 ml/min.
The concomitant use of losartan and potassium-sparing diuretics, potassium supplements, and potassium-containing salt substitutes is not recommended.
Liver dysfunction
Since pharmacokinetic data indicate a significant increase in plasma concentrations of losartan in patients with cirrhosis, a dose reduction should be considered in patients with a history of hepatic impairment. There is no therapeutic experience with losartan in patients with severe hepatic impairment, and losartan should not be used in such patients.
Kidney dysfunction
Changes in renal function, including renal failure, have been reported, which have been associated with inhibition of the renin-angiotensin system (particularly in patients whose renal function is dependent on the renin-angiotensin-aldosterone system, i.e. patients with severe heart failure or pre-existing renal impairment). These changes in renal function may be reversible upon discontinuation of treatment.
In renal artery stenosis, the drug may cause severe hypotension. In severe renal failure (creatinine clearance <10 ml/min), losartan should be used with caution in patients with signs of hypovolemia who have received high doses of diuretics.
The starting dose should be reduced
Drugs that affect the renin-angiotensin-aldosterone system may cause increases in blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. These changes in renal function may be reversible upon discontinuation of therapy. Losartan should be used with caution in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney.
Renal function should be monitored regularly during treatment with losartan, as it may deteriorate. This is especially true when losartan is used in the presence of other pathological conditions (fever, dehydration) that may affect renal function.
Concomitant use of losartan and ACE inhibitors worsens kidney function, so this combination is not recommended.
Kidney transplantation
There are no data on the safety of the drug in patients who have recently undergone a kidney transplant.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism generally do not respond to antihypertensive drugs that act by inhibiting the renin-angiotensin system. Therefore, losartan is not recommended in this group of patients.
Coronary artery disease and cerebrovascular disease
As with other antihypertensive drugs, excessive reduction in blood pressure in patients with ischemic coronary artery disease and cerebrovascular disease may lead to the development of myocardial infarction or stroke.
Heart failure
As with other drugs that affect the renin-angiotensin-aldosterone system, there is a risk of severe hypotension and renal impairment (often acute) in patients with heart failure with or without renal impairment.
There is insufficient therapeutic experience with losartan in patients with heart failure and concomitant severe renal impairment, in patients with severe heart failure (NYHA class IV), or in patients with heart failure and symptomatic, life-threatening cardiac arrhythmias. Therefore, losartan should be used with caution in such patients. Caution should be exercised when combining losartan with β-blockers.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy
As with other vasodilators, the drug should be administered with extreme caution to patients with aortic or mitral valve stenosis and obstructive hypertrophic cardiomyopathy.
There is evidence that the concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure). Therefore, dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended.
In cases where dual blockade is considered absolutely necessary, it should be carried out only under specialist supervision, with close monitoring of renal function, fluid and electrolyte balance and blood pressure. ACE inhibitors and angiotensin II receptor blockers should not be administered concomitantly in patients with diabetic nephropathy.
Pregnancy
Losartan should not be used in pregnant women or in women planning to become pregnant. Unless therapy with losartan is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with losartan should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.4).
Other caveats
Losartan and other angiotensin antagonists are less effective in lowering blood pressure in black patients than in non-black patients, possibly because of lower renin activity in black patients with hypertension.
This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use during pregnancy or breastfeeding
Pregnancy
Use is contraindicated in pregnant women and women planning to become pregnant.
Patients planning pregnancy should be changed to alternative antihypertensive treatments with an established safety profile for use in pregnancy. When pregnancy is confirmed, treatment with losartan should be stopped and, if appropriate, alternative therapy should be started.
In the rare case where a suitable alternative to losartan is not available for the patient, the mother should be informed of the potential risks to the fetus. Regular ultrasound examinations should be performed to assess the intra-amniotic environment. If oligohydramnios develops, losartan should be discontinued unless treatment is considered essential for the mother. Depending on the gestational age, fetal studies may be indicated. The patient and physician should be aware that the fetus may have already suffered permanent irreversible damage before oligohydramnios develops.
It has been established that the use of ARAII during the II and III trimesters of pregnancy induces fetotoxicity (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and neonatal toxicity (renal failure, arterial hypotension, hyperkalemia) and lethal outcome in humans.
If there have been cases of use of losartan from the second trimester of pregnancy, it is recommended to perform an ultrasound examination of renal function and the condition of the skull bones.
These adverse events are usually associated with use in the second and third trimesters. Most epidemiological studies investigating fetal malformations following first-trimester antihypertensive therapy have not found differences between antihypertensive agents that act on the renin-angiotensin system and other antihypertensive agents. Appropriate treatment of maternal hypertension is important during pregnancy to optimize outcomes for both the mother and the fetus.
Infants whose mothers have taken losartan during pregnancy should be observed for signs of hypotension, oliguria, and hyperkalemia. Subsequent oligohydramnios may be associated with pulmonary hypoplasia or skeletal deformities in the fetus. Potential adverse effects in the newborn include skull hypoplasia, anuria, hypotension, renal failure, and death. If oliguria or hypotension occurs, priority should be given to maintaining blood pressure and renal perfusion. Exchange transfusion or dialysis may be necessary to correct hypotension and/or renal dysfunction.
Breast-feeding
Losartan should not be used during breastfeeding. Alternative treatments with better established safety profiles during breastfeeding should be used during lactation.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies have been conducted on the effect of the drug on the ability to drive and use machines. However, it should be borne in mind that side effects such as dizziness and drowsiness may occur, especially at the beginning of treatment and when the dose of the drug is increased. Given the possible side effects, caution should be exercised when driving or using machines.
Method of administration and doses
Losartan tablets should be taken with 1 glass of water. Take the drug regardless of meals.
The usual initial and maintenance dose for most patients is 50 mg once daily. The maximum antihypertensive effect is achieved within 3-6 weeks of treatment. Some patients may benefit from increasing the dose to 100 mg once daily (in the morning).
Losartan can be used in combination with other antihypertensive drugs, especially diuretics (e.g. hydrochlorothiazide).
Patients with hypertension and type 2 diabetes mellitus with elevated serum creatinine and proteinuria.
An initial dose of 50 mg once daily is recommended. The dose may be increased to 100 mg once daily depending on blood pressure response 1 month after initiation of treatment. Losartan may be used with other antihypertensive agents (e.g. diuretics, calcium channel blockers, α- or β-receptor blockers and centrally acting agents), as well as with insulin and other hypoglycaemic agents (e.g. sulphonylureas, glitazones and glucosidase inhibitors).
Heart failure
For patients with heart failure, a starting dose of 12.5 mg losartan once daily is recommended. The dose is usually titrated at weekly intervals (i.e. 12.5 mg daily, 25 mg daily, 50 mg daily, 100 mg once daily to a maximum dose of 150 mg once daily), depending on individual tolerability.
Reduction in the risk of stroke in patients with arterial hypertension and left ventricular hypertrophy, documented by ECG
The recommended starting dose is 50 mg losartan once daily. Depending on the response to treatment, low-dose hydrochlorothiazide should be added and/or the dose of losartan should be increased to 100 mg once daily.
Use in patients with reduced circulating blood volume
Patients with reduced circulating blood volume (e.g., as a result of treatment with high doses of diuretics) should begin therapy with a dose of 25 mg of losartan once daily.
Use in patients with renal impairment and patients undergoing hemodialysis sessions
When prescribing losartan to patients with impaired renal function and patients undergoing hemodialysis, no initial dose adjustment is required. Use in patients with impaired hepatic function In patients with a history of impaired hepatic function, a lower dose should be considered. There is no experience in treating patients with severe hepatic impairment, therefore losartan is contraindicated in such patients.
Use in elderly patients
As a rule, there is no need to adjust the initial dose for elderly patients, although it is possible to prescribe losartan at an initial dose of 25 mg for patients over 75 years of age.
Children
Losartan is used only in adult patients due to lack of experience in children.
Overdose
Symptoms
Oral administration resulted in significant lethality in mice at 1000 mg/kg (3000 mg/m2) and rats at 2000 mg/kg (11800 mg/m2), which is 500/1000 times the recommended daily human dose, respectively (based on a patient weighing (50 kg). Data on overdose with losartan in humans are limited. Depending on the degree of intoxication, symptoms such as arterial hypotension, tachycardia, bradycardia, which may occur due to parasympathetic (vagal) stimulation, may occur.
Treatment
Treatment depends on the time elapsed since ingestion, the nature and severity of the symptoms. In the event of symptomatic hypotension, supportive therapy should be given. The priority should be to stabilize cardiovascular function. After oral overdose, activated charcoal is indicated in an appropriate dose. Induction of emesis and gastric lavage are recommended. Vital signs should be monitored and adjusted as necessary. Losartan and its active metabolites are not removed by hemodialysis.
Adverse reactions
Adverse reactions are classified by system organ class and listed in order of decreasing frequency: very common (≥ 1/10), common (≥ 1/100 - < 1/10), uncommon (≥ 1/1,000 - < 1/100), rare (< 1/10,000, including isolated case reports). The most common adverse reaction with losartan was dizziness.
Infections and infestations
Common: upper respiratory tract infections.
On the part of the immune system
Hypersensitivity reactions, anaphylactic reactions, angioedema*.
From the psyche
Common: insomnia.
Rare: depression.
From the nervous system
Very common: headache.
Common: dizziness.
Rare: drowsiness, sleep disorders, paresthesia, migraine, dysgeusia.
Hearing and balance disorders
Common: vertigo.
Rare: ringing in the ears.
Cardiovascular system
Common: palpitations, tachycardia, orthostatic hypotension**.
Uncommon: dose-dependent orthostatic effects.
Rare: vasculitis, including Henoch-Schönlein disease.
Rare: angina pectoris, syncope, atrial fibrillation, acute cerebrovascular accident.
Respiratory, thoracic and mediastinal disorders
Common: cough, pharyngitis, nasal congestion, sinus dysfunction.
Rare: shortness of breath.
Common: abdominal pain, diarrhea, nausea, dyspepsia, vomiting.
Rare: intestinal obstruction.
Skin and subcutaneous tissue disorders
Uncommon: rash.
Rare: urticaria, pruritus, erythroderma, photosensitivity.
Musculoskeletal and connective tissue disorders
Common: back pain, muscle cramps.
Rare: myalgia, arthralgia, rhabdomyolysis.
General disorders and administration site conditions
Common: asthenia, fatigue, edema, chest pain, malaise.
Research results
Common: hyperkalemia, proteinuria, increased alanine aminotransferase (ALT)§.
Rare: increased blood urea, serum creatinine and serum potassium, hyponatremia. hypoglycemia.
From the circulatory and lymphatic system
Rare: anemia, megaloblastic anemia, thrombocytopenia.
Reproductive system and breast disorders
Erectile dysfunction/impotence.
Hepatobiliary disorders
Uncommon: hepatitis.
Rare: pancreatitis, liver dysfunction.
Renal and urinary disorders
Rare: renal dysfunction, renal failure.
*Including swelling of the larynx, glottis, face, lips, pharynx and/or tongue (causing airway obstruction); a history of angioedema associated with other medicinal products, including ACE inhibitors, has been reported in some of these patients.
**Hypotension is not a common side effect in patients with hypertension, but is common in patients with heart failure and in patients with type 2 diabetes who have kidney disease and hypertension. "Especially in patients with reduced circulating blood volume, including patients with severe heart failure or those receiving high doses of diuretics.
§ Usually disappears after discontinuation of treatment.
The following additional adverse reactions occurred more frequently in patients taking losartan than in patients taking placebo: back pain, urinary tract infections, and flu-like symptoms.
Renal and urinary disorders: As a result of inhibition of the renin-angiotensin-aldosterone system, changes in renal function have been observed in patients at high risk. These changes may be reversible and disappear after discontinuation of therapy.
Use in pediatrics
The adverse reaction profile observed in children and adolescents is similar to that observed in adults. Data on the use of the drug in pediatrics are limited.
Expiration date
48 months.
Storage conditions
Store at room temperature (15-25°C) in the original packaging to protect from light.
Keep out of reach of children.
Packaging
14 film-coated tablets in a blister: 2 or 7 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Lek Pharmaceutical Company Ltd.
Location of the manufacturer and address of its place of business
Verovškova 57, Ljubljana 1526, Slovenia.
Trimlini, 2D, 9220 Lendava, Slovenia.
