Lozartan-Richter, 50 mg 30 pcs

Lozartan Richter is a specific angiotensin II receptor antagonist (type AT1). Angiotensin II selectively binds to AT1 receptors located in many tissues (vascular smooth muscle tissues, adrenal, kidney and heart) and causes important biological effects including vasoconstriction and aldosterone release as well as smooth muscle cell proliferation.

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

Does not inhibit kinase II, an enzyme that degrades bradykinin. Reduces total peripheral vascular resistance (TPR), blood concentrations of norepinephrine and aldosterone, blood pressure (BP), pressure in the small circle of the circulation; reduces post-load, has a diuretic effect. Prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure (CHF).

The hypotensive effect (decrease in systolic and diastolic BP) reaches its maximum after 6 hours after single oral administration and then gradually decreases during 24 hours.

The maximum hypotensive effect develops 3-6 weeks after starting regular use of the drug.

Lozartan does not inhibit angiotensin converting enzyme (ACE) and therefore does not interfere with bradykinin degradation, so bradykinin-mediated side effects (e.g., angioedema) are not associated with losartan.

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

Lozartan stabilizes plasma urea levels. It does not affect autonomic reflexes. Losartan in dose up to 150 mg/ has no effect on serum levels of triglycerides, total cholesterol and high-density lipoprotein cholesterol (HDL) in patients with arterial hypertension. At the same dose, losartan has no effect on fasting blood glucose levels.

Pharmacokinetics

Intake

. When administered orally, losartan is well absorbed and is metabolized during “first pass” through the liver by carboxylation with the participation of cytochrome P450 isoenzyme CYP2C9 to form a 10-40 times more active metabolite. Systemic bioavailability of losartan is about 33%. Cmax of losartan in blood plasma after oral administration is reached after 1-1.5 hours, Cmax of its active metabolite – after 3-4 hours. Food intake does not affect the bioavailability of losartan.

Distribution

92% of losartan and 99% of its active metabolite are bound to plasma proteins, mainly to albumin. The Vd of losartan is 34 l. Losartan practically does not penetrate through the blood-brain barrier.

Metabolism

Approximately 14% of patient ingested losartan is converted to an active metabolite. In a small number of patients (approximately 1%), a minimal amount of the active metabolite is formed from losartan.

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. Losartan and its active metabolite have linear pharmacokinetics at oral doses up to 200 mg.

Lozartan and its metabolites are eliminated from the body through the intestine and the kidneys. The kidneys excrete 35% (of which 4% unchanged and 6% as an active metabolite), the rest (60%) – through the intestines.

In healthy volunteers, after ingestion of 14C isotope-labeled losartan, the radioactive label was detected in urine at about 35% and in feces at about 58%.

Pharmacokinetics in Special Patient Groups

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

When CK is greater than 10 mL/min, plasma concentrations of losartan do not differ from those of normal renal function. In patients who require hemodialysis, the 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.

The values of plasma concentrations of losartan in women with arterial hypertension are twice as high as in men with arterial hypertension. This pharmacokinetic difference has no clinical significance. Concentrations of the active metabolite do not differ in men and women.

Indications

Active ingredient

Composition

Active substance:

lozartan potassium 50 mg;

Associates:

Silica colloidal – 0.75 mg;

Magnesium stearate – 1.5 mg;

Croscarmellose sodium – 3 mg;

Pregelatinized starch – 20.2 mg;

MCC – 74.55 mg;

Filmed film sheath:

Opadry 33G28523 white (triacetin – 0.3 mg, macrogol – 0.4 mg, lactose monohydrate – 1.05 mg, titanium dioxide (E171 – C.I.77891) – 1.25 mg, hypromellose – 2 mg) – 5 mg

How to take, the dosage

Overly, once daily, regardless of meals.

Arterial hypertension

In most cases, the initial and maintenance dose is 50 mg once daily. The maximum antihypertensive effect is reached after 3-6 weeks of taking the drug. If necessary, the drug dose can be increased to 100 mg/day (in 1-2 doses).

When taking high doses of diuretics, it is recommended to start therapy with Lozartan-Richter 25 mg (1/2 tablet of 50 mg) daily in one dose.

There is no need to adjust the dose in elderly patients or patients with impaired renal function, including patients on hemodialysis.

Patients with impaired liver function should be prescribed lower doses of the drug.

Chronic heart failure (if ACE inhibitor therapy is ineffective)

The starting dose of Lozartan-Richter is 50 mg once daily in a single dose. Subsequently, hydrochlorothiazide may be added in low doses and/or the dose of Lozartan-Richter may be increased to 100 mg per day.

Renal protection in patients with type 2 diabetes mellitus with proteinuria

The initial dose of Lozartan-Richter is 50 mg once daily in a single dose. During treatment, depending on the blood pressure, the daily dose may be increased to 100 mg in 1 or 2 doses.

Chronic heart failure

To treat chronic heart failure, the starting dose of the drug is 12.5 mg (alternate dosage form of losartan, 12.5 mg tablets, may be used) at a single dose.

In order to reach the usual maintenance dose of 50 mg/day, the dose of Lozartan-Richter should be increased gradually at 1 week intervals (e.g., 12.5, 25, 50 mg at a single daily dose). Lozartan-Richter is usually prescribed in combination with diuretics and cardiac glycosides.

The dose of the drug should be increased according to the following pattern:

Contraindications

With caution: arterial hypotension, impaired water-electrolyte balance, decreased volume of circulating blood, hepatic and/or renal insufficiency (including bilateral renal artery stenosis or stenosis of the artery of the sole kidney).

Side effects

Cardiovascular system disorders: orthostatic hypotension (dose-dependent), nasal bleeding, palpitations, tachycardia and bradycardia, arrhythmias, angina pectoris, vasculitis.

Digestive system disorders: decreased appetite, dry mouth, toothache, vomiting, flatulence, gastritis, constipation, hepatitis, liver function disorders, very rarely – moderate increase of “liver” transaminases activity, hyperbilirubinemia.

Dermatological reactions: dry skin, erythema, photosensitization, increased sweating, alopecia.

Allergic reactions: urticaria, rash, pruritus, angioedema (including laryngeal and tongue edema, causing airway obstruction and/or swelling of the face, lips, throat). Some patients have a history of angioedema when taking other drugs, including ACE inhibitors.

Hematopoietic system: anemia (slight decrease of hemoglobin and hematocrit concentration, on average 0.11% and 0.09% respectively, rarely clinically significant), thrombocytopenia, eosinophilia, Schönlein-Henoch purpura.

Muscular system disorders: arthralgia, arthritis, pain in the shoulder, knee joint pain, fibromyalgia.

CNS and sensory system disorders: anxiety, sleep disturbance, somnolence, memory disorders, peripheral neuropathy, paresthesia, hypoesthesia, tremor, ataxia, depression, syncopal states, tinnitus, taste disorders, vision disorders, conjunctivitis, migraine.

Respiratory system: dyspnea, bronchitis, nasal mucosal edema.

Urinary system disorders: imperative urge to urinate, urinary tract infections, impaired renal function.

Water-electrolyte balance: often – hyperkalemia (plasma level of potassium over 5.5 mmol/l).

Metabolism disorders: infrequent – increase of serum levels of urea and residual nitrogen or creatinine.

Others: gout, decreased libido, decreased potency.

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