Presartan® - 100

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PRESARTAN® - 100 (PRESARTAN® - 100)

Composition:

Active substance: losartan potassium;

One film-coated tablet contains 100 mg of losartan potassium;

Excipients: maize starch, microcrystalline cellulose, colloidal anhydrous silicon dioxide, sodium starch glycolate (type A), magnesium stearate, talc;

Film coating: hydroxypropylmethylcellulose, titanium dioxide (E 171), talc, polyethylene glycol.

Pharmaceutical form. Film-coated tablets.

Main physico-chemical properties: oval, biconvex, film-coated tablets of white or almost white color, with "100" embossed on one side and "BL" on the other.

Pharmacotherapeutic group.
Simple preparations of angiotensin II receptor antagonists. ATC code C09C A01.

Pharmacological Properties.

Pharmacodynamics.

Losartan is a synthetic angiotensin II receptor antagonist (type AT₁) for oral administration. Angiotensin II is a potent vasoconstrictor and the primary active hormone of the renin-angiotensin system, playing a key role in the pathophysiology of arterial hypertension. Angiotensin II binds to the AT₁ receptor, found in many tissues (e.g., vascular smooth muscle, adrenal glands, kidneys, and heart), mediating several important biological effects, including vasoconstriction and aldosterone release. Angiotensin II also stimulates smooth muscle cell proliferation. Losartan selectively binds to the AT₁ receptor. In vitro and in vivo, losartan and its pharmacologically active metabolite, the carboxylic acid (E-3174), block all physiologically significant effects of angiotensin II, regardless of its source or pathway of synthesis. Losartan has no agonist activity and does not block other hormone receptors or ion channels important in cardiovascular regulation. Moreover, losartan does not inhibit ACE (kininase II), the enzyme responsible for bradykinin degradation. As a result, there is no potentiation of bradykinin-mediated adverse effects.

During losartan administration, the removal of angiotensin II's negative feedback on renin secretion leads to increased plasma renin activity (PRA). This increase in renin activity results in elevated plasma angiotensin II levels. Despite this rise, antihypertensive activity and suppression of plasma aldosterone concentration are maintained, indicating effective blockade of angiotensin II receptors. After discontinuation of losartan, plasma renin activity and angiotensin II levels return to baseline values within 3 days.

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

Once-daily administration of losartan to patients with mild to moderate essential hypertension results in statistically significant reductions in systolic and diastolic blood pressure. Blood pressure measurements taken 24 hours after dosing compared to 5–6 hours after dosing demonstrated sustained blood pressure reduction over 24 hours; the natural circadian rhythm was preserved. Blood pressure reduction at the end of the dosing interval was 70–80% of the effect observed 5–6 hours after dosing.

Discontinuation of losartan in patients with arterial hypertension did not lead to a sudden increase in blood pressure (rebound phenomenon). Despite significant blood pressure reduction, losartan had no clinically relevant effect on heart rate.

Losartan demonstrates equivalent efficacy in men and women, as well as in younger (under 65 years) and older patients with arterial hypertension.

Pharmacokinetics.

Absorption

After oral administration, losartan is well absorbed and undergoes first-pass metabolism, forming 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 at approximately 1 hour and 3–4 hours, respectively.

Distribution

Losartan and its active metabolite are approximately 99% bound to plasma proteins, primarily albumin. The volume of distribution of losartan is 34 L.

Biological Transformation

Approximately 14% of losartan, following intravenous administration or oral intake, is converted into the active metabolite. After intravenous or oral administration of radiolabeled ¹⁴C-losartan potassium, radioactivity in circulating plasma is generally represented by losartan and its metabolites. Minimal conversion of losartan to its active metabolite was observed in approximately 1% of cases. In addition to the active metabolite, inactive metabolites are also formed.

Elimination

Plasma clearance of losartan and its active metabolite is 600 mL/min and 50 mL/min, respectively. Renal clearance of losartan and its active metabolite is approximately 74 mL/min and 26 mL/min, respectively. After oral administration, approximately 4% of the dose is excreted unchanged in urine, and approximately 6% is excreted in urine as the active metabolite. The pharmacokinetic properties of losartan and its active metabolite are linear following 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. After oral administration of ¹⁴C-labeled losartan, approximately 35% of radioactivity is recovered in urine and 58% in feces.

Pharmacokinetics in Specific Patient Populations

Elderly Patients

Plasma concentrations of losartan and its active metabolite in elderly patients with arterial hypertension do not significantly differ from those in younger patients with arterial hypertension.

Gender

Plasma concentrations of losartan were twice as high in women with arterial hypertension compared to men. Plasma concentrations of the active metabolite did not differ between men and women.

Hepatic and Renal Impairment

Following oral administration in patients with mild to moderate alcoholic cirrhosis of the liver, plasma concentrations of losartan and its active metabolite were 1.7–5 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 individuals with normal renal function. The area under the concentration-time curve (AUC) of losartan was approximately twice as high in patients with normal renal function compared to patients undergoing hemodialysis.

Plasma concentrations of the active metabolite do not change in patients with renal impairment or in patients undergoing hemodialysis. Losartan and its active metabolite cannot be removed by hemodialysis.

Pharmacokinetics in Children

Pharmacokinetics of losartan have been studied in 50 children with arterial hypertension aged 1 month to 16 years who received once-daily oral doses ranging from 0.54 to 0.77 mg/kg (mean doses).

Results showed that the active metabolite of losartan is formed in patients across all age groups. Findings indicate approximately similar pharmacokinetic parameters of losartan after oral administration in neonates, preschool, and school-aged children. Pharmacokinetic parameters of the metabolite varied more depending on age group. Statistically significant differences were observed when comparing preschool children and adolescents. Exposure in neonates/infants was relatively high.

Clinical characteristics.

Indications.

• Treatment of essential arterial hypertension in adults, as well as children aged 6 years and older.

• Treatment of kidney disease in adult patients with arterial hypertension and type 2 diabetes mellitus with proteinuria ≥ 0.5 g/day as part of antihypertensive therapy.

• Treatment of chronic heart failure (in patients aged 60 years and older) when the use of angiotensin-converting enzyme (ACE) inhibitors is considered impossible due to intolerance, particularly cough, or is contraindicated. Patients with heart failure whose condition has been stabilized on ACE inhibitor therapy should not be switched to losartan. The patient must have a left ventricular ejection fraction ≤ 40%, a clinically stable condition, and should be on established treatment for chronic heart failure.

• Reduction of the risk of stroke in adult patients with arterial hypertension and left ventricular hypertrophy confirmed by ECG.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients contained in the medicinal product (see section "Composition");

• Pregnancy or planned pregnancy (see sections "Special precautions", "Use during pregnancy or breastfeeding");

• Severe hepatic impairment;

• Concomitant use with aliskiren-containing medicinal products is contraindicated in patients with diabetes mellitus or renal impairment (glomerular filtration rate < 60 ml/min/1.73 m²) (see sections "Interaction with other medicinal products and other forms of interaction" and "Special precautions").

Interaction with other medicinal products and other forms of interaction.

Other antihypertensive agents may enhance the hypotensive effect of losartan. Concomitant use with other medicinal products that may induce hypotension (e.g., tricyclic antidepressants, antipsychotics, baclofen, and amifostine) may increase the risk of arterial hypotension. Losartan is primarily metabolized via the cytochrome P450 (CYP) 2C9 system to its active carboxylic acid metabolite. Clinical studies have shown that fluconazole (a CYP2C9 inhibitor) reduces exposure to the active metabolite by approximately 50%. Concomitant treatment with rifampicin (an enzyme inducer) has been shown to reduce plasma concentrations of the active metabolite by 40%. The clinical significance of this effect is unknown. There is no difference in exposure when losartan is used concomitantly with fluvastatin (a weak CYP2C9 inhibitor). As with other medicinal products that block angiotensin II or its effects, concomitant use of potassium-sparing agents (e.g., potassium-sparing diuretics such as spironolactone, triamterene, amiloride), agents that may increase potassium levels (such as heparin), potassium-containing supplements, or potassium-containing salt substitutes may lead to increased serum potassium levels. Concomitant use of such agents is not recommended.

Reversible increases in serum lithium concentrations, as well as lithium toxicity, have been reported with concomitant use of lithium and ACE inhibitors. Concomitant use of lithium and losartan should be performed with caution. If such combination therapy is considered necessary, monitoring of serum lithium concentrations during combination therapy is recommended.

When angiotensin II antagonists are used concomitantly with non-steroidal anti-inflammatory drugs (NSAIDs) (such as selective cyclooxygenase-2 (COX-2) inhibitors, acetylsalicylic acid at anti-inflammatory doses, non-selective NSAIDs), the antihypertensive effect may be attenuated. Concomitant use of angiotensin II antagonists or diuretics with NSAIDs may lead to an increased risk of worsening renal function, including possible development of acute renal failure, as well as increased serum potassium levels, particularly in patients with pre-existing renal impairment. Such combinations should be used with caution, especially in elderly patients. Adequate hydration should be ensured, and monitoring of renal function should be considered upon initiation of concomitant therapy and periodically thereafter. Dual blockade of the renin-angiotensin-aldosterone system (RAAS) by combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is associated with a higher incidence of adverse reactions such as arterial hypotension, hyperkalemia, and worsening renal function (including acute renal failure) compared to monotherapy affecting the RAAS (see sections "Contraindications" and "Special precautions").

Special precautions for use.

Hypersensitivity

Angioedema

Patients with a history of angioedema (facial, lip, throat and/or tongue swelling) should be monitored frequently.

Arterial hypotension and fluid-electrolyte imbalance

Symptomatic arterial hypotension, particularly after administration of the first dose or after dose escalation, may occur in patients with reduced intravascular volume or sodium deficiency caused by treatment with potent diuretics, dietary salt restriction, diarrhoea, or vomiting. Such conditions should be corrected prior to initiating treatment with Presartan® - 100 or the initial dose of the drug should be reduced (see "Dosage and administration"). The same recommendations apply to children aged 6 to 18 years.

Electrolyte imbalance

Electrolyte imbalance is frequently observed in patients with impaired renal function (with or without diabetes mellitus) and should be taken into account. In a clinical trial involving patients with type II diabetes mellitus and nephropathy, the incidence of hyperkalaemia was higher with Presartan® - 100 treatment compared to placebo (see section "Adverse reactions"). Therefore, plasma potassium concentrations and creatinine clearance should be monitored frequently, especially in patients with heart failure and creatinine clearance of 30–50 ml/min.

Concomitant use of Presartan® - 100 with potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

Hepatic impairment

Based on pharmacokinetic data indicating a marked increase in plasma concentrations of losartan in patients with hepatic cirrhosis, dose reduction should be considered in patients with a history of hepatic dysfunction. There is no experience with the use of the drug in patients with severe hepatic impairment; therefore, losartan is contraindicated in such patients (see section "Contraindications"). Presartan® is not recommended for use in children with hepatic impairment (see section "Dosage and administration").

Renal impairment

Changes in renal function, including renal failure, have been reported and associated with inhibition of the renin-angiotensin system (particularly in patients whose renal function depends on the renin-angiotensin-aldosterone system, i.e., in cases of severe heart failure or existing renal impairment). Medicinal products affecting the renin-angiotensin-aldosterone system (RAAS) may cause increases in blood urea nitrogen and serum creatinine levels in patients with bilateral renal artery stenosis or stenosis of the artery of a solitary kidney. These changes in renal function may be reversible upon discontinuation of therapy. Presartan® - 100 should be used with caution in patients with bilateral renal artery stenosis or stenosis of the artery of a solitary kidney.

Use in children with renal impairment.

The drug is not recommended for use in children with a glomerular filtration rate < 30 ml/min/1.73 m² due to lack of relevant data (see section "Dosage and administration").

Renal function should be monitored regularly during treatment with Presartan® - 100, as deterioration is possible. This is particularly relevant in situations where losartan is used in the presence of other pathological conditions (e.g., fever, dehydration) that may affect renal function.

Concomitant use of losartan and ACE inhibitors may worsen renal function; therefore, this combination is not recommended.

Kidney transplantation.

There is no experience regarding the safety of the drug in patients who have recently undergone kidney transplantation.

Primary hyperaldosteronism.

Patients with primary hyperaldosteronism generally do not respond to medicinal products acting via inhibition of the renin-angiotensin system (RAAS). Therefore, Presartan® - 100 is not recommended for this patient group.

Coronary artery disease and cerebrovascular disease.

As with other antihypertensive agents, excessive reduction in blood pressure in patients with ischemic coronary artery disease or cerebrovascular disease may lead to the development of myocardial infarction or stroke.

Heart failure.

As with other agents affecting the RAAS, patients with heart failure, with or without renal impairment, are at risk of developing severe arterial hypotension and (often acute) deterioration in renal function.

There is insufficient therapeutic experience with the use of losartan in patients with heart failure and concomitant severe renal impairment, in patients with severe heart failure (NYHA class IV), and in patients with heart failure and symptomatic life-threatening cardiac arrhythmias. Therefore, losartan should be used with caution in these patient groups. Concomitant use of losartan and β-blockers should be approached with caution.

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy.

As with other vasodilators, Presartan® should be prescribed with particular caution in patients with aortic or mitral valve stenosis or obstructive hypertrophic cardiomyopathy.

Pregnancy

Initiation of losartan therapy during pregnancy is not recommended. Unless continuation of therapy is considered necessary, alternative antihypertensive therapy with an established safety profile in pregnancy should be prescribed to women planning pregnancy. If pregnancy is diagnosed, losartan treatment should be discontinued immediately and, if necessary, alternative therapy initiated (see sections "Contraindications" and "Use in pregnancy or breastfeeding").

Other warnings and precautions.

As established for angiotensin-converting enzyme (ACE) inhibitors, losartan and other angiotensin II antagonists are less effective in reducing blood pressure in patients of black racial origin compared to other patients, possibly due to low renin activity in this group of black patients with arterial hypertension.

Dual blockade of the RAAS

It is known that concomitant use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of arterial hypotension, hyperkalaemia, and worsening renal function (including acute renal failure). Due to dual blockade of the RAAS, concomitant use of aliskiren with angiotensin II receptor antagonists or ACE inhibitors is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

If dual blockade is considered absolutely necessary, it should be performed only under specialist supervision with frequent and careful monitoring of renal function, electrolytes, and blood pressure.

ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

Use during pregnancy or breastfeeding.

Pregnancy. The use of losartan is not recommended during the first trimester of pregnancy and is contraindicated during the second and third trimesters.

Epidemiological data on the teratogenic risk associated with the use of ACE inhibitors during the first trimester of pregnancy are inconclusive; however, a small increased risk cannot be excluded. As there are no controlled epidemiological data on the risk of angiotensin II receptor antagonists (ARBs), similar risks may exist for this class of drugs. Unless continuation of ARB therapy is considered necessary, alternative antihypertensive therapy with an established safety profile in pregnancy should be prescribed to women planning pregnancy. If pregnancy is diagnosed, ARB therapy should be discontinued immediately and, if necessary, alternative therapy initiated.

It is known that ARB use during the second and third trimesters induces fetotoxicity (impaired renal function, oligohydramnios, delayed skull ossification) and neonatal toxicity (renal failure, arterial hypotension, hyperkalaemia). If ARBs were used during the second trimester of pregnancy, ultrasound examination is recommended to assess renal function and skull ossification. Newborns of mothers who received ARBs should be monitored frequently for the development of arterial hypotension.

Breastfeeding. As there is no information on the use of losartan during breastfeeding, the drug is not recommended for administration to breastfeeding women. Alternative therapy with medicinal products with a better-established safety profile during breastfeeding should be considered, especially during the neonatal period or if the infant is premature.

Ability to affect the speed of reactions when driving vehicles or operating machinery.

Studies on the effect of the drug on the ability to drive vehicles or operate machinery have not been conducted. However, the possibility of adverse reactions such as dizziness and somnolence, particularly at the beginning of treatment and during dose escalation, should be considered.

Method of Administration and Dosage.

Presartan®-100 tablets can be taken regardless of food intake, with a glass of water.

Essential arterial hypertension

The usual initial and maintenance dose for most patients is 50 mg of the drug once daily (1 tablet of Presartan® 50 mg). The maximum antihypertensive effect is achieved within 3–6 weeks after starting treatment with Presartan®. For some patients, increasing the dose to 100 mg once daily (in the morning) may be beneficial. The drug may be used in combination with other antihypertensive agents, particularly diuretics (e.g., hydrochlorothiazide).

Patients with arterial hypertension and type 2 diabetes mellitus (proteinuria > 0.5 g/day)

The usual initial dose is 50 mg once daily. The dose may be increased to 100 mg once daily depending on blood pressure levels one month after initiation of therapy. Presartan®-100 may be used concomitantly with other antihypertensive agents (e.g., diuretics, calcium channel blockers, α- or β-receptor blockers, centrally acting agents), as well as with insulin and other commonly used hypoglycemic agents (e.g., sulfonylureas, glitazones, and glucosidase inhibitors).

Heart failure

The usual initial dose of losartan in patients with chronic heart failure is 12.5 mg once daily. The dose is typically titrated at weekly intervals (i.e., 12.5 mg daily, 25 mg daily, 50 mg daily, 100 mg daily) up to a maximum dose of 150 mg once daily, based on individual tolerability.

Reduction of stroke risk in adult patients with arterial hypertension and left ventricular hypertrophy confirmed by ECG

The usual initial dose is 50 mg of Presartan® once daily. Depending on blood pressure response, low-dose hydrochlorothiazide should be added and/or the dose of Presartan®-100 increased to 100 mg once daily (see sections "Special precautions for use" and "Interaction with other medicinal products and other forms of interactions").

Special patient groups.

Patients with reduced blood volume

Patients with reduced blood volume (e.g., due to high-dose diuretic therapy) should start treatment at a dose of 25 mg once daily.

Patients with impaired renal function and patients undergoing hemodialysis

No initial dose adjustment is required when prescribing Presartan®-100 to patients with impaired renal function or to patients undergoing hemodialysis.

Patients with impaired liver function

For patients with a history of impaired liver function, consideration should be given to initiating treatment with a lower dose. There is no experience with losartan in patients with severe hepatic impairment; therefore, losartan is contraindicated in this patient group (see sections "Contraindications" and "Special precautions for use").

Children

Data on the efficacy and safety of losartan in children aged 6 years and older for the treatment of arterial hypertension are limited. Pharmacokinetic data in children with arterial hypertension aged 1 month are also limited.

For children who can swallow tablets and whose body weight is more than 20 kg but less than 50 kg, the recommended dose is 25 mg once daily. In exceptional cases, the dose may be increased to 50 mg once daily. The dose should be adjusted based on its effect on blood pressure.

For patients with body weight over 50 kg, the usual dose is 50 mg once daily. In exceptional cases, the dose may be increased to the maximum of 100 mg once daily. Doses exceeding 1.4 mg/kg (or more than 100 mg) per day have not been studied in children.

Losartan is not recommended for use in children under 6 years of age due to insufficient data on its use in this patient group.

The drug is not recommended for use in children with a glomerular filtration rate < 30 mL/min/1.73 m², as there are no adequate data on its use in this patient category (see section "Special precautions for use").

Losartan is also not recommended for use in children with impaired liver function (see section "Special precautions for use").

Elderly patients

Generally, no adjustment of the initial dose is required for elderly patients; however, consideration should be given to initiating treatment at a dose of 25 mg in patients aged 75 years and older.

Children.

The safety and efficacy of Presartan®-100 in children under 6 years of age have not been established. Available data are presented in the section "Pharmacological properties"; however, no dosage recommendations can be provided for children under 6 years of age.

Overdose.

No cases of overdose have been reported.

Symptoms of intoxication.

The most likely symptoms, depending on the severity of overdose, are arterial hypotension and tachycardia. Bradycardia may occur due to parasympathetic (vagal) stimulation.

Treatment of intoxication.

In the event of symptomatic arterial hypotension, supportive therapy should be administered. Treatment depends on the time elapsed since drug ingestion and the nature and severity of symptoms.

The primary measure should be stabilization of cardiovascular function. After oral ingestion, administration of activated charcoal in an appropriate dose is indicated. Vital signs should be monitored frequently thereafter, and adjustments made as necessary. Losartan and its active metabolites are not removed by hemodialysis.

Side effects

The most commonly reported side effect was dizziness.

The frequency of the side effects listed below is defined as follows: very common: >1/10; common: ≥1/100 to <1/10; uncommon: ≥1/1000 to <1/100; rare: ≥1/10000 to <1/1000; very rare: <1/10000; frequency not known (cannot be estimated from the available data).

Frequency of adverse reactions identified in placebo-controlled clinical studies and during the post-marketing period

Table 1.

Adverse Reactions by organ system classes	Frequency of adverse reactions					Other
	Patients with arterial hypertension		Patients with arterial hypertension and left ventricular hypertrophy	Patients with chronic heart failure	Patients with arterial hypertension and type 2 diabetes mellitus with renal insufficiency	Post-marketing observations
Blood and lymphatic system disorders
anemia				common		frequency unknown
thrombocytopenia						frequency unknown
Immune system disorders
hypersensitivity reactions, anaphylactic reactions, angioedema∗ and vasculitis∗∗						uncommon
Psychiatric disorders
depression						frequency unknown
Nervous system disorders
muscle cramps	common
dizziness	common		common	common	common
drowsiness	uncommon
headache	uncommon			uncommon
sleep disorders (insomnia)	uncommon
paraesthesia				rare
migraine						frequency unknown
dysgeusia						frequency unknown
Ear and labyrinth disorders
vertigo	common		common
tinnitus						frequency unknown
Cardiac disorders
tachycardia	common
palpitations	uncommon
angina pectoris	uncommon
syncope				rare
atrial fibrillation				rare
stroke				rare
Vascular disorders
(orthostatic) hypotension (including dose-dependent orthostatic effect)║	uncommon			common	common
Respiratory, thoracic and mediastinal disorders
dyspnea				uncommon
cough				uncommon		frequency unknown
rhinitis	common
sinusitis	common
pharyngitis	common
upper respiratory tract infection	common
Gastrointestinal disorders
abdominal pain	uncommon
constipation	uncommon
diarrhea				uncommon		frequency unknown
nausea				uncommon
vomiting				uncommon
dyspepsia	common
Hepatobiliary disorders
pancreatitis						frequency unknown
hepatitis						rare
liver function disorders						frequency unknown
Skin and subcutaneous tissue disorders
urticaria				uncommon		frequency unknown
pruritus				uncommon		frequency unknown
rash	uncommon			uncommon		frequency unknown
photosensitivity						frequency unknown
Musculoskeletal and connective tissue disorders
myalgia						frequency unknown
arthralgia						frequency unknown
rhabdomyolysis						frequency unknown
Renal and urinary disorders
renal function disorders				common
renal failure				common
Reproductive system and breast disorders
erectile dysfunction / impotence						frequency unknown
General disorders and administration site conditions
asthenia	uncommon		common	uncommon	common
weakness	uncommon		common	uncommon	common
edema	uncommon
malaise						frequency unknown
Investigations
hyperkalemia	common			uncommon†	common ‡
elevation of alanine aminotransferase (ALT) §	rare
increased blood urea, serum creatinine and serum potassium levels				common
hyponatremia						frequency unknown
hypoglycemia					common

∗Including laryngeal, pharyngeal, facial, lip, glottis, and/or tongue swelling (which may lead to airway obstruction); some patients had a history of angioedema (Quincke's edema) associated with the use of other medicinal products, including ACE inhibitors.

∗∗Including Henoch-Schönlein purpura.

║ Particularly in patients with intravascular volume depletion (e.g., in severe heart failure or patients treated with high-dose diuretics).

† Frequently observed in patients receiving 150 mg losartan instead of 50 mg.

‡ In a clinical trial conducted in patients with type 2 diabetes and nephropathy, hyperkalemia > 5.5 mmol/L was observed in 9.9% of patients receiving losartan tablets and in 3.4% of patients receiving placebo.

§ Usually reversible upon discontinuation of therapy.

The following additional adverse reactions occurred more frequently in patients receiving losartan than placebo (frequency unknown): back pain, urinary tract infections, and influenza-like symptoms.

Renal and urinary disorders: As a consequence of RAAS inhibition, changes in renal function, including renal failure, have been reported in patients at risk; such changes in renal function may be reversible upon discontinuation of treatment (see section "Special precautions").

Children

The adverse reaction profile in children is similar to that in adult patients. Data on adverse reactions in children are limited.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25°C, in a place inaccessible to children.

Packaging.

14 tablets in a blister. 2 blisters in a cardboard pack.

10 tablets in a blister; 3 blisters in a cardboard pack.

Prescription status.

Prescription only.

Manufacturer.

Ipca Laboratories Limited, India.

Manufacturer's address and location of operations.

Plot No. 255/1, Village – Atal, U.T. Dadra and Nagar Haveli, 396230 Silvassa, India.