Lozartan-Teva, 25 mg 30 pcs.

Lozartan is an oral specific angiotensin II receptor antagonist (AT1 subtype). Angiotensin II selectively binds to AT1 receptors located in many tissues (vascular smooth muscle tissues, adrenal glands, kidneys, and heart) and performs several important biological functions including vasoconstriction and aldosterone release. Angiotensin II also stimulates smooth muscle cell overgrowth.

Lozartan and its pharmacologically active metabolite (E 3174) both in vitro and in vivo block all physiological effects of angiotensin II, regardless of the source or synthesis route. Losartan selectively binds to AT1 receptors and does not bind to or block receptors for other hormones and ion channels that play an important role in the regulation of cardiovascular function. In addition, losartan does not inhibit angiotensin-converting enzyme (ACE)-kininase II and therefore does not interfere with bradykinin degradation, so bradykinin-mediated side effects (such as angioedema) are quite rare.

When using losartan, the lack of negative feedback effects on renin secretion results in increased plasma renin activity. Increased renin activity results in increased plasma angiotensin II concentrations. However, antihypertensive activity and decreased blood plasma aldosterone concentration remain, indicating effective blockade of angiotensin P receptors. losartan and its active metabolite have greater affinity for angiotensin I receptors than angiotensin I receptors. the active metabolite is 10-40 times more active than losartan.

After a single oral administration, the hypotensive effect (decreases systolic and diastolic blood pressure) reaches a maximum after 6 hours, then gradually decreases over 24 hours. The maximum hypotensive effect develops 3-6 weeks after the start of the drug.

In patients with arterial hypertension without concomitant diabetes mellitus with proteinuria (more than 2 g/day), application of the drug significantly decreases proteinuria, albumin and immunoglobulin G excretion. Stabilizes the content of urea in blood plasma. It does not affect vegetative reflexes and has no long-term effect on plasma concentration of norepinephrine.

Lozartan at a dose of 150 mg daily has no effect on serum triglyceride, total cholesterol and high-density lipoprotein cholesterol (HDL-C) concentrations in patients with arterial hypertension. At the same dose, losartan has no effect on fasting blood glucose concentration.

Pharmacokinetics

Intake

. When ingested, losartan is well absorbed from the gastrointestinal tract (GIT) and is metabolized on “first pass” through the liver by carboxylation with the participation of CYP2C9 isoenzyme to form the active metabolite.
Systemic bioavailability of losartan is approximately 33% g Maximum concentration of losartan and its active metabolite are reached in serum approximately 1 hour and 3-4 hours after oral administration, respectively. Food intake does not affect the bioavailability of losartan.

Distribution

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

Metabolism

About 14% of losartan administered to a patient intravenously or orally is converted to an active metabolite.

The plasma clearance of losartan and its active metabolite is approximately 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. When administered orally, approximately 4% of the dose taken is excreted unchanged by the kidneys and approximately 6% is excreted by the kidneys in the form of the active metabolite. Lozartan and its active metabolite have linear pharmacokinetics at oral doses up to 200 mg.

After oral administration, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a final elimination half-life of losartan about 2 hours and of the active metabolite about 6-9 hours. When administered at a dose of 100 mg per day, neither losartan nor its active metabolite significantly cumulate in plasma.
Losartan and its metabolites are eliminated from the body through the intestine and the kidneys.

In healthy volunteers, after ingestion of the C14-labeled isotope losartan, about 35% of the radioactive label is detected in the urine and 59% in the feces.

Pharmacokinetics in special patient groups

In patients with mild to moderate alcoholic cirrhosis, the concentration of losartan was 5 times and the active metabolite 1.7 times higher than in healthy male volunteers.

In creatinine clearance (CK) above 10 mL/min, plasma concentrations of losartan are not different from those of normal renal function.

In patients requiring hemodialysis, the area under the concentration-time curve (AUC) is approximately 2 times higher than in patients with normal renal function.

Neither losartan nor its active metabolite is eliminated from the body by hemodialysis.

Plasma concentrations of losartan and its active metabolite in older men with arterial hypertension are not significantly different from those in younger men with arterial hypertension.
Values of plasma concentrations of losartan in women with arterial hypertension are 2 times higher than corresponding values in men with arterial hypertension. Concentrations of the active metabolite in men and women do not differ.

Indications

arterial hypertension;
chronic heart failure (as part of combination therapy, with intolerance or ineffectiveness of therapy with ACE inhibitors);
reducing the risk of developing cardiovascular diseases (including stroke) and mortality in patients with arterial hypertension and left ventricular hypertrophy;
diabetic nephropathy or hypercreatininemia and proteinuria (the ratio of urine albumin to creatinine more than 300 mg/day) in patients with type 2 diabetes mellitus and concomitant arterial hypertension (reducing the progression of diabetic nephropathy to end-stage chronic renal failure).

Pharmacological effect

Losartan is a specific angiotensin II receptor antagonist (AT1 subtype) for oral administration. Angiotensin II selectively binds to AT1 receptors found in many tissues (vascular smooth muscle, adrenal glands, kidneys and heart) and performs several important biological functions, including vasoconstriction and aldosterone release. Angiotensin II also stimulates the proliferation of smooth muscle cells.

Losartan and its pharmacologically active metabolite (E 3174) both in vitro and in vivo block all physiological effects of angiotensin II, regardless of the source or route of synthesis. Losartan selectively binds to AT1 receptors and does not bind to or block receptors of other hormones and ion channels that play an important role in regulating the function of the cardiovascular system. In addition, losartan does not inhibit angiotensin-converting enzyme (ACE) kininase II, and, accordingly, does not interfere with the destruction of bradykinin, so side effects indirectly associated with bradykinin (for example, angioedema) occur quite rarely.

When using losartan, the lack of negative feedback influence on renin secretion leads to an increase in plasma renin activity. An increase in renin activity leads to an increase in the concentration of angiotensin II in the blood plasma. However, antihypertensive activity and a decrease in plasma aldosterone concentrations persist, indicating an effective blockade of angiotensin P receptors. Losartan and its active metabolite have a greater affinity for angiotensin I receptors than for angiotensin I receptors. The active metabolite is 10-40 times more active than losartan.

After a single oral dose, the hypotensive effect (systolic and diastolic blood pressure decreases) reaches a maximum after 6 hours, then gradually decreases over 24 hours. The maximum hypotensive effect develops 3-6 weeks after starting the drug.

In patients with arterial hypertension without concomitant diabetes mellitus with proteinuria (more than 2 g/day), the use of the drug significantly reduces proteinuria, excretion of albumin and immunoglobulin G. Stabilizes the urea content in the blood plasma. Does not affect autonomic reflexes, and does not have a long-term effect on the concentration of norepinephrine in the blood plasma.

Losartan at a dose of 150 mg per day does not affect the concentration 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 concentrations.

Pharmacokinetics

Suction

When taken orally, losartan is well absorbed from the gastrointestinal tract (GIT) and undergoes first-pass metabolism through the liver by carboxylation with the participation of the CYP2C9 isoenzyme to form an active metabolite.
The systemic bioavailability of losartan is approximately 33%. The maximum concentration of losartan and its active metabolite is achieved in the blood serum approximately 1 hour and 3-4 hours after oral administration, respectively. Food intake does not affect the bioavailability of losartan.

Distribution

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

Metabolism

Approximately 14% of losartan administered intravenously or orally to a patient is converted into an active metabolite.

Removal

Plasma clearance of losartan and its active metabolite is approximately 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 taken orally, approximately 4% of the dose taken is excreted unchanged by the kidneys and about 6% is excreted by the kidneys in the form of an active metabolite. Losartan and its active metabolite exhibit linear pharmacokinetics when taken orally in doses up to 200 mg.

After oral administration, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a terminal half-life of about 2 hours for losartan and about 6-9 hours for the active metabolite. When taking the drug at a dose of 100 mg per day, neither losartan nor its active metabolite accumulates significantly in the blood plasma.
Losartan and its metabolites are excreted from the body through the intestines and kidneys.

In healthy volunteers, after ingestion of losartan labeled with the C14 isotope, about 35% of the radioactive label is found in the urine and 59% in the feces.

Pharmacokinetics in special groups of patients

In patients with mild to moderate alcoholic cirrhosis, the concentration of losartan was 5 times higher, and the active metabolite was 1.7 times higher than in healthy male volunteers.

When creatinine clearance (CC) is above 10 ml/min. the concentration of losartan in the blood plasma does not differ from that with normal renal function.

In patients requiring hemodialysis, the area under the concentration-time curve (AUC) is approximately 2 times higher than in patients with normal renal function.

Neither losartan nor its active metabolite is removed from the body by hemodialysis.

Plasma concentrations of losartan and its active metabolite in elderly men with arterial hypertension do not differ significantly from the values ​​of these parameters in young men with arterial hypertension.
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 do not differ between men and women.

Active ingredient

Losartan

Composition

Active ingredient:

losartan potassium;

Excipients:

lactose monohydrate;

microcrystalline cellulose;

pregelatinized starch;

magnesium stearate;

Shell Opadrv II85F18422 white:

polyvinyl alcohol (partially hydrolyzed); titanium dioxide (E 171);
macrogol; talc

Contraindications

hypersensitivity to the components of the drug;
severe liver failure (more than 9 points on the Child-Pugh scale);
age under 18 years;
hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome;
pregnancy and lactation period.

With caution: arterial hypotension, reduced circulating blood volume (CBV), water-electrolyte imbalance, bilateral renal artery stenosis or stenosis of the artery of a single kidney, renal failure, liver failure (less than 9 points on the Child-Pugh scale).

Side Effects

From the nervous system and sensory organs: dizziness, asthenia/fatigue, headache, insomnia; anxiety, sleep disturbance, drowsiness, memory disorders, peripheral neuropathies, paresthesia, hypoesthesia, migraine, tremor, ataxia, depression, syncope, tinnitus, taste disturbance, vision changes, conjunctivitis.

From the respiratory system: nasal congestion, cough, upper respiratory tract infections (fever, sore throat, etc.), sinusopathy, sinusitis, pharyngitis; dyspnea, bronchitis, rhinitis.

From the gastrointestinal tract: nausea, diarrhea, dyspeptic symptoms, abdominal pain; anorexia, dry mouth, toothache, vomiting, flatulence, gastritis, constipation.

From the musculoskeletal system: convulsions, myalgia, pain in the back, chest, legs; arthralgia, shoulder pain, knee pain, arthritis, fibromyalgia.

From the cardiovascular system and blood (hematopoiesis, hemostasis): orthostatic reactions (dose-dependent), hypotension, palpitations, tachy- or bradycardia, arrhythmias, angina pectoris, anemia.

From the genitourinary system: imperative urge to urinate, urinary tract infections, impaired renal function, weakened libido, impotence.

From the skin: dry skin, erythema, flushing, photosensitivity, increased sweating, alopecia.

Allergic reactions: urticaria, rash, itching, angioedema, incl. face, lips, pharynx and/or tongue.

Other: hyperkalemia; fever, gout, increased levels of liver transaminases and bilirubin in the blood.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25 °C

Shelf life

2 years

Manufacturer

Teva Pharma, S.L.U., Spain