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

Active ingredient

Composition

Active substance:

lozartan potassium;

Associates:

lactose monohydrate;

cellulose microcrystalline;

How to take, the dosage

Lozartan-Teva is taken orally regardless of meals.
Tablets are swallowed without chewing and with water. Frequency of intake is 1 time per day.

Hypertension

In arterial hypertension, the average daily dose is 50 mg 1 time per day. To achieve a greater therapeutic effect, the dose is increased to 100 mg once daily.

Chronic heart failure

The starting dose for patients with chronic heart failure is 12.5 mg once daily. Typically, the dose is increased at weekly intervals (i.e., 12.5 mg/day, 25 mg/day, and 50 mg/day) to an average maintenance dose of 50 mg once daily, depending on patient tolerance.

There is no need to adjust the dose of the drug in elderly patients.

Decrease risk of cardiovascular events (including stroke) and mortality in patients with arterial hypertension and left ventricular hypertrophy

The initial dose of the drug is 50 mg once daily. Subsequently, low-dose hydrochlorothiazide may be added or the dose of Lozartan-Teva may be increased to 100 mg in one or two doses with consideration of decreasing blood pressure (BP).

Patients with concomitant type 2 diabetes mellitus with proteinuria: Lozartan-Teva is indicated in an initial dose of 50 mg once daily with subsequent dose escalation to 100 mg/day (adjusted for BP reduction) in one or two doses.

In patients with decreased RBC (e.g., when taking high-dose diuretics), the recommended starting dose of Lozartan-Teva is 25 mg once daily.

Patients with hepatic impairment (less than 9 points on the Child-Pugh scale), patients undergoing hemodialysis, and patients older than 75 years old are recommended a lower starting dose of 25 mg once daily.

The safety and efficacy of the drug in children under 18 years of age has not been established. There is not enough experience in using the drug in patients with severe hepatic impairment; therefore, the drug is not recommended in this category of patients (see section “Contraindications”).

Contraindications

With caution: arterial hypotension, decreased circulating blood volume (CBC), water-electrolyte balance disorders, bilateral renal artery stenosis or artery stenosis of the sole kidney, renal failure, liver failure (less than 9 points by Child-Pugh scale).

Side effects

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 disorders, vision changes, conjunctivitis.

Respiratory system: nasal congestion, cough, upper respiratory tract infections (high body temperature, sore throat, etc.), sinusopathy, sinusitis, pharyngitis; dyspnea, bronchitis, rhinitis.

Gastrointestinal organs: nausea, diarrhea, dyspeptic phenomena, abdominal pain; anorexia, dry mouth, toothache, vomiting, flatulence, gastritis, constipation.

Musculoskeletal system disorders: cramps, myalgia, pain in the back, chest, legs; arthralgia, pain in the shoulder, knee, arthritis, fibromyalgia.

Cardiovascular and blood (hematopoiesis, hemostasis): orthostatic reactions (dose-dependent), hypotension, palpitations, tachycardia or bradycardia, arrhythmias, angina pectoris, anemia.

Urogenital system disorders: imperative urge to urinate, urinary tract infections, impaired renal function, impaired libido, impotence.

The skin: dry skin, erythema, flushing, photosensitization, increased sweating, alopecia.

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

Others: hyperkalemia; fever, gout, increased liver transaminases and bilirubin in blood.

Similarities