Lozarel 50 mg, 30 pcs.

Lozarel is an AT₁ receptor blocker, antihypertensive.

Pharmacodynamics

. Angiotensin II selectively binds to AT1 receptors located in many tissues (vascular smooth muscle tissues, adrenal glands, kidneys and heart) and causes vasoconstriction and release of aldosterone and proliferation of smooth muscle.

In vitro and in vivo studies have proven that losartan and its pharmacologically active metabolite block all physiologically important effects of angiotensin II, regardless of its source or synthesis pathway.

Lozartan decreases RPS, blood aldosterone concentration, BP, small circulatory pressure; reduces post-load, has a diuretic effect. Prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure (CHF). After a single oral administration, the hypotensive effect (decreases arterial pressure and arterial pressure) reaches its maximum after 6 hours, and then gradually decreases during 24 hours. The maximum hypotensive effect develops after 3-6 weeks after regular drug administration. It does not inhibit ACE and therefore does not prevent bradykinin degradation, therefore there are no bradykinin-mediated side effects with losartan (e.g. angioedema).

In patients with arterial hypertension without concomitant diabetes mellitus with proteinuria (>2 g/day), use of the drug significantly reduces proteinuria, albumin and immunoglobulin G excretion.

Stabilizes plasma urea levels. It does not affect vegetative reflexes and has no long-term effect on plasma norepinephrine levels.

In dose up to 150 mg once daily, it does not affect serum levels of triglycerides, total cholesterol and HDL cholesterol in patients with arterial hypertension. In the same dose losartan has no effect on fasting blood glucose levels.

Pharmacokinetics

Intake

. When administered orally, losartan is well absorbed and is metabolized on first passage through the liver by carboxylation with the participation of cytochrome P450 2C9 isoenzyme to form the active metabolite. Systemic bioavailability of losartan is about 33%. C_max of losartan and its active metabolite are reached in serum approximately 1 h and 3-4 h 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 to albumin. The V_d of losartan is 34L. Losartan practically does not penetrate through the HEB.

Metabolism

Approximately 14% of losartan administered to a patient by IV or ingestion is converted to an active metabolite.

The plasma clearance of losartan is 600 mL/min and that of the active metabolite is 50 mL/min. Renal clearance of losartan and its active metabolite is 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 as an 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 T_1/2 of losartan about 2 h and of the active metabolite about 6-9 h. At a dose of 100 mg/day, neither losartan nor the active metabolite significantly cumulates in plasma.

Lozartan and its metabolites are eliminated from the body through the intestine and the kidneys.

Pharmacokinetics in special patient groups

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

When creatinine Cl is above 10 ml/min, plasma concentrations of losartan do not differ from those of normal renal function. In patients who require hemodialysis, theAUC 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. 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 do not differ between men and women. This pharmacokinetic difference is not clinically significant.

Indications

Active ingredient

Composition

Active substance:

Potassium losartan 50 mg;

Ancillary substances:

MCC;

Lactose monohydrate;

Pregelatinized starch;

How to take, the dosage

Overly, once daily, regardless of meals.

Hypertension

In most cases, the initial and maintenance dose is 50 mg once daily. If necessary, the dose of the drug can be increased to 100 mg/day (1 or 2 doses).

When taking high doses of diuretics, it is recommended to start therapy with Lozarel 25 mg (1/2 tablet of 50 mg) daily in a single dose.

The initial dose is 12.5 mg/day with a subsequent weekly doubling to 50 mg/day, depending on drug tolerance.

Diabetes mellitus type 2 with proteinuria (reducing the risk of hypercreatininemia and proteinuria)

The initial dose is 50 mg once daily in 1 dose. During treatment, depending on BP values, the daily dose of the drug may be increased to 100 mg in 1 or 2 doses.

Lozarel decreases the risk of cardiovascular events and mortality in patients with arterial hypertension and left ventricular hypertrophy

The starting dose is 50 mg of Lozarel once daily; the dose of Lozarel may be increased to 100 mg/day, if necessary.

Patients with impaired renal function (creatinine Cl less than 20 ml/min), a history of liver disease, dehydration, dialysis therapy, or who are 75 or older may use a lower starting dose of 25 mg (1/2 tablet 50 mg) once daily.

Contraindications

With caution:

Side effects

Systemic diseases: sometimes – orthostatic hypotension (dose-dependent), nasal bleeding, palpitation, tachycardia, bradycardia, arrhythmia, angina pectoris, myocardial infarction, vasculitis.

Gastrointestinal tract: frequently – nausea, diarrhea, dyspeptic phenomena, abdominal pain; sometimes – anorexia, taste disorder, dry mouth, toothache, vomiting, flatulence, gastritis, constipation, hepatitis, liver function disorder.

The skin: sometimes – dry skin, erythema, subcutaneous hemorrhages, photosensitization, increased sweating, alopecia.

Allergic reactions: sometimes – hives, skin rash, itching, angioedema.

Blood and hemopoietic system: sometimes – anemia, thrombocytopenia, eosinophilia, Schoenlein-Henoch purpura.

Musculoskeletal system: often – cramps, myalgia, pain in the back, chest, legs; sometimes – arthralgia, arthritis, fibromyalgia; rarely – rhabdomyolysis.

CNS and sense organs: frequently – dizziness, asthenia, headache, fatigue, insomnia; sometimes – anxiety, sleep disturbance, somnolence, memory disturbances, peripheral neuropathy, paresthesia, hypoesthesia, tremor, ataxia, depression, syncope, tinnitus, visual disturbances, conjunctivitis, migraine.

Respiratory system disorders: often – nasal congestion, cough, upper respiratory tract infections, pharyngitis, dyspnea, bronchitis, nasal mucous membrane edema.

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

Laboratory measures: often – hyperkalemia (plasma potassium level over 5.5 mmol/l); sometimes – increasing of urate and residual nitrogen or creatinine level in blood serum; very rarely – moderate increase of liver transaminases AST and ALT activity, hyperbilirubinemia.

Others: gout.

Overdose

Symptoms: marked BP decrease and tachycardia; bradycardia may develop as a result of parasympathetic (vagus) stimulation.

Treatment: forced diuresis, symptomatic therapy. Hemodialysis is ineffective because losartan and its active metabolite are not eliminated from the body by hemodialysis.

Similarities