Losartan-NAN

Losartan

Film-coated tablets

White, round biconvex, film-coated tablets.

Each tablet contains:
Active substance: losartan potassium 100 mg;
Excipients: lactose monohydrate, pregelatinized corn starch, magnesium stearate, microcrystalline cellulose;
Shell composition: polyvinyl alcohol, macrogol 3350, talc, titanium dioxide.

Agents acting on the renin–angiotensin system. Angiotensin II Receptor Antagonists.

C09CA01

Losartan is an antihypertensive medicinal product that is a specific angiotensin II receptor antagonist (type AT1). Losartan reduces total peripheral vascular resistance (vascular resistance to blood flow), reduces afterload (blood pressure in the aorta by reducing peripheral vascular resistance to blood flow), and lowers blood pressure (BP). Losartan reduces pressure in the small (pulmonary) circulation, prevents sodium and water retention in the body. Losartan increases exercise tolerance in patients with heart failure.

After a single dose, the hypotensive effect reaches its maximum after 6 hours and then gradually decreases within 24 hours. A stable decrease in blood pressure in most patients is observed between the 2nd and the 6th week of the treatment course.

• Treatment of essential hypertension in adults and children (adolescents) aged 6-18 years;
• Treatment of renal failure in adult patients with hypertension and type 2 diabetes mellitus with proteinuria ≥ 0.5 g/day as part of antihypertensive therapy;
• Treatment of chronic heart failure in adult patients, when treatment with angiotensin-converting enzyme (ACE) inhibitors is unacceptable due to drug intolerance, especially due to cough or contraindications. If a patient with heart failure has stabilized with an ACE inhibitor, the patient should not be switched to losartan. Patients should have a left ventricular ejection fraction ≤ 40% and be clinically stable with an established chronic heart failure treatment regimen;
• Reduced risk of stroke in patients with arterial hypertension and left ventricular hypertrophy documented by ECG results.

Arterial hypertension
The standard initial and maintenance dose for most patients is 50 mg once daily. The maximum hypotensive effect is achieved after 3-6 weeks from the start of therapy. In some patients, to achieve a greater effect, the dose may be increased to 100 mg 1 time per day (in the morning). Losartan may be taken with other antihypertensive agents, including diuretics (hydrochlorothiazide).

Hypertensive patients with type II diabetes with proteinuria ≥ 0.5 g/day
The standard initial dose of the drug is 50 mg 1 time per day. The dose may be increased to 100 mg once daily based on blood pressure control results after the first month of therapy. Losartan may be used in combination with other antihypertensive drugs (eg, diuretics, calcium channel blockers, alpha- or beta-blockers, and centrally acting drugs), as well as with insulin and other commonly used hypoglycemic drugs (eg, sulfonylureas, glitazones, and glucosidase inhibitors).

Heart failure
Initial dose of losartan for patients with heart failure is 12.5 mg once daily. The dose may be increased at weekly intervals (i.e. 12.5 mg once daily for the first week, 25 mg once daily for the second week, 50 mg once daily for the third week, 100 mg once daily for the fourth weeks until the maximum dose of 150 mg once daily is reached) according to patient tolerance.

Reduced risk of stroke in patients with left ventricular hypertrophy documented by ECG.
The initial dose of losartan is 50 mg once daily. In the future, low-dose hydrochlorothiazide may be added and / or the dose of losartan may be increased to 100 mg per day in one dose, based on the results of blood pressure control.

Special populations

Use in patients with circulating blood volume deficiency
In patients with a deficiency in circulating blood volume (including patients taking diuretics in high doses), the initial dose of losartan is 25 mg 1 time per day.

Use in patients with renal insufficiency and patients on hemodialysis
It is not required to adjust the initial dose in patients with renal insufficiency and patients on hemodialysis.

Use in patients with hepatic impairment
A lower dose should be given to patients with a history of hepatic impairment. There is no therapeutic experience in patients with severe hepatic impairment, therefore losartan is contraindicated for this group of patients.

Use in children and adolescents

Children from 6 months to 6 years
Safety and efficacy in children aged 6 months – 6 years have not been established. There are limited data, but use cannot be recommended.

Children from 6 years old to 18 years old
For patients weighing 20 to 50 kg who are able to swallow tablets, the recommended dose is 25 mg once daily. In exceptional cases, the dose may be increased to a maximum dose of 50 mg once daily. The dosage should be adjusted according to changes in blood pressure.

In patients weighing more than 50 kg, the daily dose is 50 mg once a day. In exceptional cases, the dose may be adjusted up to a maximum dose of 100 mg once daily. Doses above 1.4 mg/kg (or more than 100 mg) per day have not been studied in this group of patients.

Losartan is not recommended for use in children under the age of 6 years, there are only limited data in these groups of patients.

Losartan is not recommended for use in children with a glomerular filtration rate < 30 ml/min/1.73 m² due to lack of data. Losartan is not recommended for children with hepatic impairment.

Elderly patients
Losartan therapy should be started using a dosage of 25 mg in patients over 75 years of age. As a rule, dose adjustment in elderly patients is not required.

Administration
Losartan-NAN should be swallowed with a glass of water. Administration of Losartan-NAN is carried out regardless of the meal every day at the same time.

If you forget to take Losartan-NAN, you should not make up for the missed dose by taking a double dose, just take the usual dose of Losartan-NAN.

In general, losartan is well tolerated, side effects are mild and transient and do not require discontinuation of Losartan-NAN. During treatment with losartan potassium, undesirable effects may develop, which are divided according to the frequency of occurrence as follows:

Very common (≥ 1/10);
Common (≥ 1/100, < 1/10);
Uncommon (≥ 1/1000, < 1/100);
Rare (≥ 1 /10000, < 1/1000);
Very rare (< 1/10000);
Not known (frequency cannot be estimated from the available data).

The frequency of undesirable effects from various organs and systems:

Arterial hypertension

Nervous system disorders
Common: dizziness;
Uncommon: drowsiness, headache, sleep disturbances.

Ear and labyrinth disorders
Common: vertigo.

Heart disorders
Uncommon: palpitation, angina pectoris.

Vascular disorders
Uncommon: symptomatic hypotension (especially in patients with reduced circulating blood volume, for example, patients with severe heart failure or when treated with diuretics in high doses), dose-dependent orthostatic effect.

Gastrointestinal disorders
Uncommon: abdominal pain, constipation.

Skin and subcutaneous tissue disorders
Uncommon: rash.

General disorders and disorders at the injection site
Uncommon: asthenia, fatigue, edema.

Influence on the results of laboratory and instrumental studies
Common: hyperkalemia;
Rare: an increase in the activity of alanine aminotransferase (ALAT), usually reversible after discontinuation of Losartan-NAN.

Patients with arterial hypertension and left ventricular hypertrophy

General disorders and disorders at the injection site
Common: asthenia, fatigue.

Nervous system disorders
Common: dizziness.

Ear and labyrinth disorders
Common: vertigo.

Chronic heart failure

Blood and lymphatic system disorders
Common: anemia.

Nervous system disorders
Common: dizziness;
Uncommon: headache;
Rare: paresthesia.

Cardiac disorders
Rare: syncope, atrial fibrillation, stroke.

Vascular disorders
Common: hypotension, including orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders
Uncommon: dyspnea, cough.

Gastrointestinal disorders
Uncommon: diarrhea, nausea, vomiting.

Skin and subcutaneous tissue disorders
Uncommon: urticaria, itching, rash.

Renal and urinary tract disorders
Common: impaired renal function, renal failure.

General disorders and disorders at the injection site
Uncommon: asthenia, fatigue.

Influence on the results of laboratory and instrumental studies
Common: an increase in the concentration of urea in the blood, creatinine and potassium in the blood serum;
Uncommon: hyperkalemia (common – in patients who received losartan at a dose of 150 mg instead of 50 mg).

Arterial hypertension and type II diabetes mellitus in combination with kidney disease

Nervous system disorders
Common: dizziness.

Vascular disorders
Common: hypotension.

General disorders and disorders at the injection site
Common: asthenia, fatigue.

Influence on the results of laboratory and instrumental studies
Common: hypoglycemia, hyperkalemia (in a clinical study performed in patients with type 2 diabetes with nephropathy, 9.9% of patients taking losartan and 3.4% of patients taking placebo developed hyperkalemia > 5.5 mmol/l).

Post-marketing experience

Blood and lymphatic system disorders
Frequency not known: anemia, thrombocytopenia.

Immune system disorders
Rare: hypersensitivity reactions, anaphylactic reactions, angioedema (including swelling of the larynx, glottis, tongue, face, lips, pharynx and / or tongue, causing airway obstruction) and vasculitis (Schönlein-Genoch purpura).

Respiratory, thoracic and mediastinal disorders
Frequency not known: cough.

Gastrointestinal disorders
Frequency not known: diarrhea.

Liver and biliary tract disorders
Rare: hepatitis;
Frequency not known: pancreatitis impaired liver function.

Skin and subcutaneous tissue disorders
Frequency not known: urticaria, pruritus, rash, photosensitivity.

Musculoskeletal and connective tissue disorders
Frequency not known: myalgia, arthralgia, rhabdomyolysis.

Reproductive system and breast disorders
Frequency is unknown: erectile dysfunction / impotence.

General disorders and disorders at the injection site
Frequency not known: malaise.

Mental disorders
Frequency not known: depression.

Nervous system disorders
Frequency not known: migraine, dysgeusia.

Hearing disorders and labyrinth disorders
Frequency not known: ringing in the ears.

Influence on the results of laboratory and instrumental studies
Frequency not known: hyponatremia.

The following adverse reactions occurred more frequently in patients receiving losartan than in patients receiving placebo (frequency not known): back pain, urinary tract infections, flu-like symptoms.

Renal and urinary tract disorders
Due to inhibition of the renin-angiotensin-aldosterone system, changes in renal function, including renal failure, have been reported in patients at risk; these changes in renal function may be reversible after discontinuation of therapy.

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

Losartan-NAN, coated tablets, 100 mg contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, you should consult your doctor before taking this medicine.

• Hypersensitivity to losartan or to any of the excipients;
• 2nd and 3rd trimesters of pregnancy (see Sections Warnings and precautions, and Pregnancy and breast-feeding);
• Severe liver failure;
• Simultaneous use of losartan with aliskiren-containing medicinal products in patients with diabetes mellitus or moderate / severe renal insufficiency (glomerular filtration rate (GFR) < 60 ml/min / 1.73 m²).

When taking more than prescribed immediately contact a healthcare provider to provide timely medical assistance!

Symptoms: there is not enough data on cases of Losartan-NAN overdose. The most likely manifestations of an overdose may be arterial hypotension and tachycardia. Bradycardia may occur due to parasympathetic (vagal) stimulation.

Treatment: if arterial hypotension occurs, supportive treatment should be carried out.

Treatment depends on the length of time after taking Losartan-NAN, as well as the nature and severity of the symptoms. The priority measure should be stabilization of the cardiovascular system. After oral administration of Losartan-NAN, the use of activated charcoal in the appropriate dose is indicated. Later, the main vital signs of the body should be monitored and adjusted if necessary.

Losartan and the active metabolite are not excreted from the body by hemodialysis.

Other antihypertensive medicinal products may enhance the hypotensive effect of losartan.

Simultaneous use with other medicinal products that can induce the occurrence of arterial hypotension as an adverse reaction (tricyclic antidepressants, antipsychotics, baclofen and amifostine) may increase the risk of hypotension.

Losartan is metabolized mainly with the participation of the cytochrome P450 (CYP) 2C9 system to the active carboxylic acid metabolite. In a clinical study, fluconazole (a CYP2C9 inhibitor) was found to reduce the exposure of the active metabolite by approximately 50%. It has been established that simultaneous treatment with losartan and rifampicin (an inducer of metabolic enzymes) leads to a 40% decrease in the concentration of the active metabolite in plasma. The clinical significance of this effect is unknown. There is no difference in exposure when losartan and fluvastatin (a weak inhibitor of CYP2C9) are co-administered.

As with other drugs that block angiotensin II or its effects, concomitant use of drugs that retain potassium in the body (eg, potassium-sparing diuretics: spironolactone, triamterene, amiloride) or may increase potassium levels (eg, heparin), and as well as potassium supplements or potassium-containing salt substitutes, may lead to an increase in the content of potassium in the blood serum. Simultaneous adminidtration of such agents is not recommended.

A reversible increase in serum lithium concentrations, as well as its toxicity, has been reported with the simultaneous use of lithium with ACE inhibitors. This adverse reaction has also been very rarely reported with angiotensin II receptor antagonists (ARAII). Simultaneous treatment with lithium and losartan should be carried out with caution. If the use of such a combination is considered necessary, it is recommended to check the levels of lithium in the blood serum during the co-administration.

With the simultaneous use of ARAII and non-steroidal anti-inflammatory drugs (for example, selective inhibitors of cyclooxygenase-2 (COX-2), acetylsalicylic acid in doses that have an anti-inflammatory effect, non-selective NSAIDs), the antihypertensive effect may be weakened. The simultaneous use of angiotensin II antagonists or diuretics with NSAIDs may lead to an increased risk of worsening renal function, including the possibility of developing acute renal failure, as well as an increase in serum potassium levels, especially in patients with existing impaired renal function. This combination should be used with caution, especially in elderly patients. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of appropriate therapy, and periodically thereafter.

Double blockade of the renin-angiotensin-aldosterone system.

Data from clinical studies have shown that dual blockade of the renin-angiotensin-aldosterone system (RAAS) due to concomitant use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is associated with an increased incidence of hypotension, hyperkalemia, and impaired renal function (including acute renal failure), in compared with monotherapy with a drug that affects the RAAS.

Your healthcare provider must be informed about all medicines you are taking. Talk to your healthcare provider before you start taking any medicine while you are taking Losartan-NAN.

Hypersensitivity
Perhaps the manifestation of such a symptom of hypersensitivity as angioedema. Patients with a history of angioedema (swelling of the face, lips, throat, and/or tongue) should be closely monitored.

Arterial hypotension, and water and electrolyte imbalance
Symptomatic arterial hypotension, especially after taking the first dose of the drug or after increasing the dose, may occur in patients with reduced intravascular volume and / or sodium deficiency due to high-dose diuretic therapy, a salt-restricted diet, diarrhea or vomiting. These conditions should be corrected before the appointment of losartan or use a lower initial dose of the drug. The same recommendations apply to the use of the drug in children from 6 to 18 years.

Electrolyte imbalance
Electrolyte imbalance is common in patients with renal insufficiency with or without diabetes mellitus, so these patients should pay special attention. In clinical studies involving patients with type 2 diabetes mellitus with nephropathy, the incidence of hyperkalemia was higher in the group treated with losartan than in the group treated with placebo. Thus, it is necessary to carefully monitor the concentration of potassium in the blood plasma, as well as the values ​​of creatinine clearance, especially in patients with heart failure and creatinine clearance of 30-50 ml / min. The concomitant use of potassium-sparing diuretics, potassium supplements, and potassium-containing salt substitutes with losartan is not recommended.

Impaired liver function
Based on pharmacokinetic data, which indicate a significant increase in the concentration of losartan in blood plasma in patients with liver cirrhosis, a lower dose of the drug should be used in case of impaired liver function. There is no therapeutic experience with losartan in patients with severe hepatic impairment, therefore losartan should not be used in patients with severe hepatic impairment.

Losartan is not recommended for the treatment of children with hepatic impairment.

Impaired kidney function
Due to inhibition of the renin-angiotensin system, changes in renal function, including renal failure, have been observed in some patients (in particular, in patients whose kidney function is dependent on the renin-angiotensin-aldosterone system, for example, in patients with severe heart failure or patients with existing impairment kidney function). As with the use of other drugs that affect the renin-angiotensin-aldosterone system, an increase in blood urea and serum creatinine has been reported in patients with bilateral renal artery stenosis or stenosis of the artery to a single 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 single kidney.

Use in children with impaired renal function
It is not recommended to use Losartan-NAN for treatment of children with a glomerular filtration rate < 30 ml / min / 1.73 m², since there are no data on the experience of use in this group of patients.

During treatment with losartan, kidney function should be monitored regularly, as it may worsen. In particular, this applies to those cases when losartan is used against the background of other conditions (fever, dehydration) that can impair kidney function.

It has been proven that the use of losartan in combination with an ACE inhibitor worsens kidney function. For this reason, the combined use of these medicines is not recommended.

Kidney transplant
There is no experience with the use of losartan for the treatment of patients who have recently undergone kidney transplantation.

Primary hypoaldosteronism
Patients with primary aldosteronism generally do not respond to antihypertensive drugs that act by inhibiting the renin-angiotensin system. Therefore, the use of losartan is not recommended.

Ischemic heart disease and cerebrovascular disease
As with the use of other antihypertensive drugs, excessive lowering of blood pressure in patients with coronary heart disease and cerebrovascular disease can lead to the development of myocardial infarction or stroke.

Heart failure
As with other drugs that affect the renin-angiotensin system, in patients with heart failure with or without impaired renal function, there is a risk of severe hypotension and renal dysfunction (often acute).

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), as well as in patients with heart failure and symptomatic, life-threatening cardiac arrhythmia. Therefore, losartan should be used with caution in this group of patients. Losartan should be used with caution in combination with beta-blockers.

Stenosis of the aortic and mitral valves, obstructive hypertrophic cardiomyopathy
As with the use of other vasodilators, the drug is prescribed with particular caution to patients with stenosis of the aortic and mitral valves or obstructive hypertrophic cardiomyopathy.

Excipients
This medicinal product contains lactose. Patients with hereditary galactose intolerance, the lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Pregnancy
Treatment with losartan should not be initiated during pregnancy. Unless treatment with losartan is necessary, patients planning pregnancy should be switched to alternative antihypertensive drugs with confirmed evidence of safety of use during pregnancy. If pregnancy is confirmed, treatment with losartan should be stopped immediately and, if necessary, switched to alternative treatment.

Other warnings and precautions
It has been established that ACE inhibitors, losartan and other angiotensin antagonists are significantly less effective in lowering blood pressure in patients of the black race than in representatives of other races; perhaps this is due to the fact that among patients of the black race suffering from arterial hypertension, persons with a low content of renin predominate.

Double blockade of the renin-angiotensin-aldosterone system
There is evidence that concomitant use of an ACE inhibitor, an angiotensin II receptor blocker, or aliskiren increases the risk of hypotension, hyperkalemia, and decreased renal function (including acute renal failure). In this regard, dual blockade of the RAAS is not recommended with the combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren.

If double blockade is essential, it should only be performed under specialist supervision, with frequent monitoring of renal function, electrolytes, and blood pressure. The combined use of angiotensin II receptor blockers and ACE inhibitors is not indicated in patients with diabetic nephropathy.

If you are pregnant, inform your doctor about it. Losartan-NAN is not recommended for use in the first trimester of pregnancy and is contraindicated for use in the second and third trimesters of pregnancy due to the risk of impaired fetal development.

If you have one of the listed diseases or conditions, be sure to consult your doctor before taking the Losartan-NAN.

Pregnancy
Drugs that act directly on the renin-angiotensin system may cause fetal malformations or death. If pregnancy is diagnosed, Losartan-NAN should be discontinued immediately.

The use of losartan is not recommended during the first trimester of pregnancy and is contraindicated during the second and third trimesters of pregnancy.
Epidemiological data regarding the risk of teratogenicity after the use of ACE inhibitors during the first trimester of pregnancy are not convincing, but a small increase in risk cannot be ruled out. Since there are no controlled epidemiological data on the risk of using angiotensin II receptor antagonists (ARAII), similar risks may exist for this class of drugs. Unless continued ARAII therapy is considered necessary, patients who are planning pregnancy should be given alternative hypertensive therapy with an established safety profile for use during pregnancy. If pregnancy is diagnosed, treatment with losartan should be stopped immediately and, if necessary, alternative treatment should be initiated.

It is known that the use of ARAII during the second and third trimesters of pregnancy induces fetotoxicity (impaired renal function, oligohydramnios, delayed ossification of the skull bones) and neonatal toxicity (renal failure, hypotension, hyperkalemia).

If losartan is used during the second trimester of pregnancy, it is recommended to conduct an ultrasound examination to check the function of the kidneys and the condition of the skull bones.

The condition of newborns whose mothers used losartan should be checked frequently for the occurrence of arterial hypotension.

Breast-feeding
Since there is no information regarding the use of losartan during breast-feeding, it is not recommended to use Losartan-NAN during lactation. Alternative treatment with medicinal products with a better known safety profile during lactation is preferred, especially when feeding newborns and premature babies.

It is not recommended to use losartan for the treatment of children under 6 years of age, since there are limited data on the experience of use in this age group.

It is not recommended to use the drug for the treatment of children with a glomerular filtration rate < 30 ml / min / 1.73 m², since there are no data on the experience of use in this group of patients.

Losartan is also not recommended for use in children with impaired liver function.

Studies on the effect of Losartan-NAN on the ability to drive a car and work with mechanisms have not been conducted. However, when driving a vehicle or working with mechanisms, it must be taken into account that when taking antihypertensive drugs, a sudden onset of dizziness or drowsiness may occur, especially at the beginning of treatment or when the dose is increased.

10 or 15 tablets in a blister pack. 3 blister packs of 10 tablets, or 2 blister packs of 15 tablets with a patient information leaflet in a carton pack.

Protect from light and moisture. Store at a temperature not exceeding 25°C. Keep out of the reach of children.

2 years. Do not use after the expiration date.

State enterprise ACADEMPHARM
220141, 5/3 Kuprevicha Street, Minsk, Belarus
Phone / Fax +375 17 268 63 64
production@academpharm.by
To report adverse reactions use the electronic application form on the manufacturer’s website: https://academpharm.by/en