Losarel tabs 50mg #30

Losarel instruction

You can buy Losarel here

Composition

1 tablet film coated contains: tablet core: losartan potassium 50,000 mg, microcrystalline cellulose 60,000 mg, lactose monohydrate 28.520 mg, pregelatinized starch 20,000 mg, silicon dioxide colloidal anhydrous 0.480 mg magnesium stearate 1,000 mg; film cover: hypromellose 1,984 mg, hyprose of 0.496 mg, macrogol 400 0.400 mg, titanium dioxide (E 171) 0.920 mg, talc 0.200 mg.

Description

Round biconvex tablets of white or white with a yellowish shade of color, film-coated, with a risk on one side.

Pharmacotherapeutic group

Angiotensin II receptor antagonist
ATC code: C09CA01

Pharmacodynamics

Losartan is a specific antagonist of angiotensin II (type AT1) receptors.
Angiotensin II binds selectively to the AT1 receptors found in many tissues (in smooth muscle tissues of the blood vessels, adrenal glands, kidneys and heart) and causes vasoconstriction and release of aldosterone, smooth muscle proliferation.
In vitro and in vivo studies have shown that losartan and its pharmacologically active metabolite block all the physiologically important effects of angiotensin II, regardless of the source or the path of its synthesis. Does not suppress kinase II - an enzyme that destroys bradykinin.
Reduces total peripheral vascular resistance (OPSS), aldosterone blood levels, blood pressure (BP), pressure in the "small" circulation; reduces afterload, has a diuretic effect.
Interferes with the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure (CHF).
After a single oral administration, the hypotensive effect (the systolic and diastolic blood pressure decreases) reaches a maximum after 6 hours, then gradually decreases within 24 hours. The maximum hypotensive effect develops 3-6 weeks after regular use of Lirta.
Does not inhibit angiotensin-converting enzyme (ACE) and, accordingly, does not prevent the destruction of bradykinin, so losartan does not have side effects indirectly associated with bradykinin (for example, angioedema).
In patients with arterial hypertension without concomitant diabetes mellitus with proteinuria (more than 2 g / day), the use of Lirta reliably reduces proteinuria, excretion of albumin and immunoglobulins G.
Stabilizes the level of urea in the blood plasma. Does not affect vegetative reflexes, and does not have a long-term effect on the level of norepinephrine in the blood plasma.
At a dose of up to 150 mg once a day, it does not affect the level of triglycerides, total cholesterol and high density lipoprotein cholesterol (HDL) in the blood serum of patients with arterial hypertension. At the same dose, losartan does not affect fasting blood glucose levels.

Pharmacokinetics

Suction

When ingested, losartan is well absorbed, systemic bioavailability of losartan is about 33%. The maximum concentration of losartan and its active metabolite in the blood plasma is reached in approximately 1 hour and 3-4 hours after oral administration, respectively. Eating does not affect the bioavailability of losartan.

Distribution

More than 99% of losartan and its active metabolite binds to plasma proteins, mainly albumin. The volume of distribution is 34 liters. Losartan practically does not penetrate the blood-brain barrier.

Metabolism

Losartan undergoes metabolism during “primary passage” through the liver by carboxylation, with the participation of predominantly cytochrome P450 isoenzymes CYP2С9 and CYP3А4 with the formation of a pharmacologically active carboxylated metabolite and inactive metabolites.
About 14% of losartan when used intravenously or orally is converted into its active metabolite. In addition to the active metabolite, biologically inactive metabolites are formed, including two major metabolites, resulting from the hydroxylation of the butyl side chain, and one minor, N-2-tetrazol glucuronide.

Removal

Plasma clearance of losartan is 600 ml / min, its active metabolite is 50 ml / min. The renal clearance of losartan and its active metabolite is 74 ml / min and 26 ml / min, respectively. Approximately 4% of the accepted dose of Lirta is excreted by the kidneys unchanged, about 6% as an active metabolite. Losartan and its active metabolite have linear pharmacokinetics when used orally in doses up to 200 mg.
After oral administration, plasma concentrations of losartan and its active metabolite are reduced polyexponentially with a final half-life of losartan about 2 hours, and the active metabolite decreases about 6-9 hours. blood plasma.
Losartan and its metabolites are excreted in the bile through the intestines (58%) and the kidneys (35%).

Pharmacokinetics in Special Patient Groups

Elderly patients

The concentrations of losartan and its active metabolite in the blood plasma in elderly patients with arterial hypertension do not differ significantly from the values ​​of these parameters in young men with arterial hypertension.

Floor

The values ​​of plasma concentrations of losartan in women with arterial hypertension are 2 times higher than the corresponding values ​​in men with arterial hypertension. Concentrations of the active metabolite in men and women do not differ. This pharmacokinetic difference has no clinical significance.

Liver dysfunction

In patients with mild and moderate alcoholic liver cirrhosis, losartan concentration is 5 times, and the active metabolite is 1.7 times higher than in healthy male volunteers. In patients with hepatic insufficiency, plasma clearance of losartan was 50% lower, and bioavailability when administered orally - 2 times higher compared with healthy volunteers.

Renal impairment

In patients with mild (creatinine clearance (CK) 50-74 ml / min) and moderate (CK 30-49 ml / min) the degree of renal dysfunction, plasma concentration and area under the concentration-time curve of losartan and its active metabolite is increased by 50-90%. Neither losartan nor its active metabolite is removed from the body by hemodialysis. In renal insufficiency, dose adjustment is not required (except in cases of dehydrated patients).

Indications for Losarel

• Arterial hypertension;
• Chronic heart failure (with the failure of treatment with ACE inhibitors);
• Nephropathy in diabetes mellitus type 2 (reducing the risk of hypercreatininemia and proteinuria);
• Reducing the risk of cardiovascular complications and mortality in patients with arterial hypertension and left ventricular hypertrophy.

Contraindications

• hypersensitivity to the components of Lirta, as well as to other drugs, which are derivatives of sulfonamide;
• hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
• severe liver failure (more than 9 points on the Child-Pugh scale);
• simultaneous use with aliskiren in patients with type 2 diabetes mellitus and renal failure (Glomerular filtration rate (GFR) less than 60 ml / min / 1.73 m²) (see the section "Interaction with other drugs");
• pregnancy, breastfeeding period;
• age up to 18 years (efficacy and safety have not been established).

Carefully

Patients with moderate hepatic and / or renal insufficiency; after kidney transplantation (there is no experience of use); conditions accompanied by a decrease in the volume of circulating blood (BCC, including diarrhea, vomiting, use in patients on hemodialysis); violations of water and electrolyte balance; diet restriction of salt intake; bilateral renal artery stenosis or renal artery stenosis of a single kidney; cerebrovascular diseases; chronic heart failure (NYHA functional class IV); a combination of heart failure with concomitant severe renal failure, and life-threatening arrhythmias; coronary heart disease; stenosis of aortic and mitral valves, hypertrophic obstructive cardiomyopathy; history of angioedema; primary hyper aldosteronism, diabetes mellitus (increased risk of hyperkalemia); combined use with beta-blockers, inhibitors of angiotensin-converting enzyme (ACE), potassium preparations.

Use during pregnancy and during breastfeeding

Use of the drug Losarel during pregnancy is contraindicated.
Use of the drug Losarel during pregnancy can lead to malnutrition, intrauterine growth retardation, premature birth, fetal death, as well as an increased risk of developing a newborn, arterial hypotension, anuria, reversible or irreversible renal failure, hypoplasia of the skull bones, contractures of the extremities, and bone deformities skull, pulmonary hypoplasia.
If during pregnancy a drug Losarel is necessary for health reasons, it is necessary to conduct careful ultrasound monitoring of fetal development. In identifying anomalies (especially low water), you must stop using the drug.
It is not known whether losartan penetrates into breast milk, so it is necessary to stop breastfeeding during the period of drug treatment.

Dosage and administration

Inside, 1 time per day, regardless of the meal.

Arterial hypertension

Standard initial and maintenance doses are 50 mg 1 time per day.
If necessary, the dose can be increased to a maximum daily dose of 100 mg.
In patients with reduced BCC (for example, against the background of the use of large doses of diuretics), it is recommended to start therapy with Losarel with 25 mg (1/2 tablets of 50 mg) 1 time per day.

Chronic heart failure

The standard initial dose is 12.5 mg / day, followed by a weekly increase in 2 times (ie, 12.5 mg / day, 25 mg / day, 50 mg / day, 100 mg / day, 150 mg / day) , depending on the individual tolerance of the drug.
The maximum daily dose of 150 mg (only for this indication).
To start therapy with Losarel in a reduced dosage (12.5 mg), it is recommended to use dosage forms with a lower content of the active substance (25 mg tablets with a risk).
Nephropathy in diabetes mellitus type 2 (reducing the risk of hypercreatininemia and proteinuria)
The standard initial dose is 50 mg 1 time per day. During treatment, depending on the indicators of blood pressure, it is possible to increase the daily dose of the drug to 100 mg 1 time per day.
The maximum daily dose is 100 mg.
The drug Losarel can be used in combination with other antihypertensive drugs (diuretics, blockers of “slow” calcium channels, alpha and beta-blockers, antihypertensive drugs of central action), insulin and other hypoglycemic drugs (sulfonylurea derivatives, glytazones and glucosidase inhibitors inhibitors
Reducing the risk of cardiovascular complications and mortality in patients with arterial hypertension and left ventricular hypertrophy
The standard initial dose of Losarel is 50 mg 1 time per day; if necessary, it is possible to increase the daily dose of Losarel to 100 mg, taking into account the degree of blood pressure reduction or the addition of low doses of hydrochlorothiazide to therapy.
The maximum daily dose is 100 mg.
Patients with impaired renal function (severe or moderate severity - creatinine clearance (CC) less than 20 ml / min), with a history of liver disease, dehydration, during the dialysis procedure, as well as patients older than 75 years, a lower initial dose is recommended - 25 mg (1/2 tablets of 50 mg) 1 time per day.

Side effects of Losarel

In general, losartan is well tolerated by patients with hypertension, adverse events are mild and transient and do not require discontinuation of the drug. The overall incidence of side effects of losartan is comparable to that of placebo.
In clinical trials, dizziness was the most common adverse event with losartan.
According to the World Health Organization (WHO), adverse effects are classified according to their frequency of development as follows: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, < 1/100), rarely (> 1/10000, <1/1000) and very rarely (<1/10000), including individual messages, the frequency is unknown (impossible to calculate from the available data).
From the blood system and lymphatic system
often: anemia;
rarely: thrombocytopenia;
frequency is unknown: eosinophilia, Shenlein's purpura - Genokh.
Metabolism and nutrition
frequency is unknown: loss of appetite, weight gain.
Since the cardiovascular system
often: marked reduction in blood pressure, orthostatic hypotension (in patients with CHF);
infrequently: feeling of palpitations, arrhythmias (including sinus tachy- and bradycardia, ventricular tachycardia, atrial fibrillation), angina pectoris;
frequency is unknown: nasal bleeding, myocardial infarction, cerebrovascular accident, atrioventricular block II degree.
From the digestive system
infrequently: nausea, vomiting, diarrhea, constipation, dyspepsia, abdominal pain;
rarely: abnormal liver function, hepatitis, pancreatitis;
frequency is unknown: anorexia, dryness of the oral mucosa, toothache, flatulence, gastritis.
On the part of the skin
infrequently: skin rash, itching of the skin, urticaria;
frequency is unknown: dry skin, subcutaneous hemorrhage, photosensitivity, alopecia, cellulitis.
From the musculoskeletal system
frequency is unknown: convulsions, myalgia, arthralgia, "swelling" of the joints, rhabdomyolysis, pain in the gluteus muscle, back pain, in the chest.
The nervous system
often: dizziness, asthenia;
infrequently: drowsiness, headache, sleep disturbance (including insomnia), depression, anxiety, memory disorders, peripheral neuropathy, hypoesthesia, tremor, ataxia, impaired motor coordination, confusion;
rarely: paresthesia;
frequency unknown: migraine.
From the senses
infrequently: taste disturbance (dysgeusia);
frequency is unknown: "ringing" in the ears, conjunctivitis, pain / burning sensation in the eye, visual impairment.
On the part of the respiratory system
often: dry non-productive cough, swelling of the mucous membrane of the nasal cavity;
infrequently: dyspnea;
frequency is unknown: nasal congestion, infections of the upper respiratory tract, pharyngitis, sinusitis, bronchitis.
From the genitourinary system
often: acute renal failure, renal failure;
frequency unknown: urgency to urinate, urinary tract infections, decreased libido, erectile dysfunction / impotence.
Allergic reactions
rarely: angioedema (including laryngeal and tongue edema, causing airway obstruction and / or swelling of the face, lips, pharynx), vasculitis.
Laboratory values
often: hyperkalemia (the content of potassium in the blood plasma is more than 5.5 mmol / l), hypoglycemia;
rarely: an increase in the concentration of urea and residual nitrogen or creatinine in the blood plasma; moderate increase in liver transaminase activity. hyperbilirubinemia;
frequency is unknown: hyponatremia.
General disorders and disorders at the site of administration
often: weakness, fatigue.

Overdose

Symptoms: marked reduction in blood pressure and tachycardia; As a result of parasympathetic (vagal) stimulation, bradycardia can develop.
Treatment: forced diuresis, symptomatic therapy. Hemodialysis is not effective, because Losartan and its active metabolite are not excreted through hemodialysis.

Interaction with other drugs

Pharmacokinetic interactions of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin, lovastatin were not observed. There are reports that rifampicin and fluconazole (inhibitors of cytochrome P450 2C9 isoenzyme) reduce the content of the active metabolite and increase the concentration of losartan in the blood plasma. The clinical significance of these interactions is not yet known.
It has been shown that patients who do not metabolize losartan to the active metabolite have a very rare and specific defect of the cytochrome P450 2C9 isoenzyme.
Simultaneous use of losartan, as well as other drugs that inhibit the enzyme angiotensin II or its effects, with potassium-saving diuretics (for example, spironolactone, triamterene, amiloride, eplerenone (a derivative of spironolactone)) and potassium preparations (potassium-containing additives) increases the risk of hyperkalemia.
Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors (COX-2), acetylsalicylic acid at a dose of more than 3 grams per day, can reduce the effectiveness of angiotensin II receptor antagonists (APA II), ACE inhibitors, diuretics.
The simultaneous use of ARA II with NSAIDs, including selective COX-2 inhibitors, especially in the presence of reduced kidney function, can lead to impaired renal function, including acute renal failure and an increase in plasma potassium (hyperkalemia). These effects are usually reversible.
With the combined use of APA II and lithium preparations, it is possible to increase the concentration of lithium in the blood plasma. If necessary, their simultaneous use should regularly monitor the plasma concentration of lithium.
The combined use of losartan with diuretics has an additive effect.
Enhances (mutually) the effect of other antihypertensive drugs (diuretics, beta-blockers, sympatholytics).
With the simultaneous use of ACE inhibitors and ARA II, it is necessary to regularly monitor renal function, since there may be an increase in the frequency of side effects, such as a pronounced decrease in blood pressure, hyperkalemia, impaired renal function.
The simultaneous use of ACE inhibitors with other drugs that affect the renin-angiotensin-aldosterone system (RAAS), including the ARA II antagonists and aliskiren, leads to an increase in the incidence of pronounced reduction in blood pressure, fainting states, hyperkalemia, kidney function disorders ( including acute renal failure), especially in patients with confirmed atherosclerosis, heart failure, or diabetes mellitus with target organ damage. The question of the use of a double blockade of the RAAS should be addressed individually in each case. It is necessary to monitor blood pressure indicators, kidney function, as well as the content of electrolytes of blood plasma when using losartan with other drugs that affect the RAAS.
The simultaneous use of ARA II (including losartan) with aliskiren is contraindicated in patients with type 2 diabetes and renal insufficiency (GFR less than 60 ml / min / 1.73 m²).

special instructions

The safety and efficacy of Losarel in children have not been established.
Drugs that affect the RAAS can increase the concentration of urea and creatinine in the blood plasma in patients with bilateral renal artery stenosis or arterial stenosis of a single kidney.
In patients with dehydration (for example, receiving treatment with high doses of diuretics or vomiting, diarrhea on a salt-free diet), symptomatic arterial hypotension may occur at the beginning of treatment with Losarel (Losarel should be corrected ® or start treatment with a lower dose).
Water and electrolyte disorders are characteristic of patients with impaired renal function in combination with diabetes mellitus or without it, and require correction.
In a clinical study involving patients with type 2 diabetes mellitus with nephropathy, the incidence of hyperkalemia in the losartan group was higher than in the placebo group. It is necessary to regularly monitor the content of potassium in the blood plasma, as well as CC, especially in patients with heart failure and CC in the range of 30-50 ml / min.
In patients with hepatic insufficiency, the concentration of losartan in the blood plasma increases, therefore dose adjustment of Losarel is necessary.
Patients with primary hyperaldosteronism usually do not respond to therapy with RAAS inhibitors, therefore the use of Losarel is not recommended.
In patients with ischemic vascular disease of the heart or brain, a pronounced decrease in blood pressure can lead to myocardial infarction or ischemic stroke.
As with the use of other drugs that affect the RAAS, when using Losarel in patients with heart failure (with or without kidney dysfunction) there is a risk of developing severe arterial hypotension and acute renal failure.
There is no experience with the use of losartan in patients with heart failure and associated severe impaired renal function, in patients with severe heart failure (functional class IVHA classification IV), as well as in patients with heart failure and clinically significant life-threatening arrhythmias. Thus, it is necessary to use the drug Losarel in such patients with caution.
At use of the drug Losarel in patients with a hypertrophic obstructive cardiomyopathy or a hemodynamically significant stenosis of the aortic or mitral valve, care should be taken.
Losarel and other angiotensin II receptor antagonists are less effective in patients of the Negroid race, due to the prevalence of patients with arterial hypertension with low renin activity.
There is no need for special precautions when destroying unused drug.

Influence on ability to steer vehicles, mechanisms

During the period of treatment with Losarel, dizziness, drowsiness, headache may occur, so care should be taken when driving and engaging in other activities that require concentration and psychomotor speed.

Release form

Tablets, film coated, 50 mg. On 10 tablets in the blister from Al / Al.
On 3 or 9 blisters together with the application instruction in a cardboard pack.

Storage conditions

List B.
Store at a temperature not higher than 25 ° С.
Keep out of the reach of children.
Shelf life - 3 years.
Do not use the drug after the expiration date.

Terms of sell

You can buy Losarel without a prescription.