Lozartan-Richter, 100 mg 30 pcs

A specific angiotensin II receptor antagonist (type AT1). Angiotensin II selectively binds to AT1receptors located in many tissues (vascular smooth muscle tissues, adrenal glands, kidneys and heart) and causes important biological effects, including vasoconstriction and aldosterone release and 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. 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 (more than 2 g/day) without concomitant diabetes mellitus, use of the drug significantly reduces proteinuria, albumin and immunoglobulin G excretion.

Indications

– arterial hypertension;

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

– reducing the risk of cardiovascular disease and mortality in patients with arterial hypertension and left ventricular hypertrophy.

Active ingredient

Composition

Associates:

colloidal silicon dioxide – 1.5 mg,

magnesium stearate – 3 mg,

croscarmellose sodium – 6 mg,

pregelatinized starch – 40.4 mg,

Microcrystalline cellulose – 149.1 mg.

Composition of the film coating:

Opadray 33G28523 white (triacetin – 0.6 mg, macrogol – 0.8 mg, lactose monohydrate – 2.1 mg, titanium dioxide (C.I.77891, E171) – 2.5 mg, hypromellose – 4 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 3-6 weeks after the start of the drug. 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 25 mg/day (1/2 tablet of 50 mg) in 1 dose.

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

Chronic heart failure (with ineffective therapy with ACE inhibitors)

Kidney protection in patients with type 2 diabetes mellitus with proteinuria

The initial dose is 50 mg once daily. During treatment, the daily dose can be increased to 100 mg/day in 1 or 2 doses, depending on the blood pressure.

Chronic heart failure

To treat chronic heart failure, the starting dose is 12.5 mg once daily (alternate dosage form of 12.5 mg tablets can be used).

In order to reach the usual maintenance dose of 50 mg/day, doses should be increased gradually at 1 week intervals (e.g., 12.5 mg, 25 mg, 50 mg once daily). 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:

Week 1: Days 1 through 7, 1 tablet 12.5 mg once daily.

Week 2: Day 8 to 14: 1/2 tablet 50 mg once daily.

Week 3: From day 15 to day 21, 1 tablet 50 mg once daily.

Week 4: From day 22 to day 28, 1 tablet 50 mg once daily.

Interaction

No pharmacokinetic interactions of Losartan-Richter with hydrochlorthiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin have been noted.

Rifampicin and fluconazole have been reported to decrease plasma levels of the active metabolite. The clinical significance of these interactions is not yet known.

As with other agents that inhibit angiotensin II or its effects, co-administration of Losartan-Richter with potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium preparations, and salts containing potassium increases the risk of hyperkalemia.

Coadministration of angiotensin II receptor antagonists and lithium preparations may increase plasma lithium concentrations. Co-administration of Lozartan-Richter and lithium salts is possible only when the expected benefit exceeds the potential risk. If they are used together, plasma lithium levels should be monitored regularly.

The co-administration of Lozartan-Richter with diuretics has an additive effect. It enhances (mutually) the effect of other hypotensive agents (diuretics, β-adrenoblockers, sympatholytics).

Special Instructions

Hypersensitivity reactions

Possible angioedema.

Hypotension and electrolyte balance disorders

Symptomatic arterial hypotension may occur in the presence of hypovolemia (e.g., when treated with high doses of diuretics). This condition should be corrected before starting therapy with Lozartan-Richter or therapy should be started at a lower dose.

In kidney disease with or without diabetes mellitus, water-electrolyte imbalances are common and should be corrected. In clinical studies in patients with type 2 diabetes mellitus with proteinuria, the incidence of hyperkalemia was increased with Lozartan-Richter compared to placebo. However, the level of hyperkalemia only required discontinuation in a small number of cases.

Hepatic impairment

According to pharmacokinetic studies, plasma concentrations of losartan are significantly increased in cirrhosis, so patients with a history of hepatic impairment should be given the drug at a lower dose.

Renin function impairment

The drug may impair renal function due to suppression of the renin-angiotensin system, especially in patients whose renal function is highly dependent on the renin-angiotensin-aldosterone system, such as those with severe CHF or pre-existing renal dysfunction.

Drugs affecting the renin-angiotensin-aldosterone system may increase plasma levels of residual nitrogen or creatinine in patients with bilateral renal artery stenosis or artery stenosis of the single kidney.

These changes in renal function may disappear after discontinuation of therapy with the drug.

When treating with Lozartan-Richter, special attention should be paid to patients with significant renal impairment and to patients after renal transplantation, since anemia has been noted in these patients.

Hyperkalemia and electrolyte imbalance

Serum potassium levels should be monitored during treatment with Lozartan-Richter, especially in elderly patients.

Lactose intolerance

In case of lactose intolerance, note that Lozartan-Richter 50 mg tablet contains 1.050 mg lactose and 100 mg tablet contains 2.10 mg lactose.

Influence on driving and other machinery

There are no data on the effect of Lozartan-Richter on driving and other machinery.

In impaired renal function

Patients with renal impairment (including bilateral renal artery stenosis or artery stenosis of the sole renal artery) are indicated with caution.

When CK is greater than 10 ml/min, plasma concentrations of losartan do not differ from those in 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.

The drug may impair renal function due to suppression of the renin-angiotensin system, particularly in patients whose renal function is highly dependent on the renin-angiotensin-aldosterone system, such as those with severe CHF or pre-existing renal dysfunction.

The drugs affecting the renin-angiotensin-aldosterone system may increase plasma levels of residual nitrogen or creatinine in patients with bilateral renal artery stenosis or artery stenosis of the single kidney.

These changes in renal function may disappear after discontinuation of therapy with the drug.

Patients with significant renal impairment and patients after renal transplantation require special attention during treatment with Lozartan-Richter because anemia has been noted in these patients

In liver function disorders

Patients with hepatic impairment are indicated with caution.

In patients with mild to moderate alcoholic cirrhosis, the concentration of losartan was 5-fold higher and the active metabolite was 1.7-fold higher than in healthy male volunteers. Therefore, patients with a history of hepatic pathology should be prescribed the drug in a lower dose.

Application in Elderly

The plasma concentrations of losartan and its active metabolite in elderly men with arterial hypertension are not significantly different from those in younger men with arterial hypertension. There is no need to adjust the dose in elderly patients.

Serum potassium levels should be monitored during treatment with Lozartan-Richter, especially in elderly patients.

Paediatric use

Paediatric use is contraindicated in children less than 18 years of age (there are insufficient data on efficacy and safety).

Features

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 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.

Contraindications

– pregnancy and breastfeeding period;

– age under 18 years (effectiveness and safety not established);

– lactose intolerance;

– galactosemia;

– impaired glucose/galactose absorption syndrome;

– hypersensitivity to the components of the drug.

With caution: arterial hypotension, disorder of the 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

Lozartan-Richter side effects are usually transient and do not require withdrawal.

When using the drug to treat essential hypertension in controlled trials, among side effects only the incidence of dizziness differed from placebo by more than 1% (4.1% vs. 2.4%).

The dose-dependent orthostatic effects typical of antihypertensive agents were seen in less than 1% of patients with Lozartan-Richter.

The side effects observed with the drug are classified into categories according to their frequency of occurrence: very often ≥1/10, often > 1/100 or ≤ 1/10, sometimes ≥1/1000 or ≤ 1/100, rarely ≥1/10000 or ≤ 1/1000, very rarely ≤ 1/10000, including individual reports.

Side effects occurring with an incidence greater than 1%:

Lozartan (n=2085)Placebo (n=535)General symptoms

asthenia/fatigue3.83.9 chest pain1.12.6peripheral edema1.71.9Cardiovascular

palpitations1.00.4 tachycardia1.00.7Gastrointestinal system

abdominal pain1.71.7diarrhea1.91.9dyspeptic phenomena1.11.5 nausea1.82.8Muscular system

back pain1.61.1 muscle spasm1.01.1Nervous system/CNS

Dizziness4.12.4 headache14.117.2 insomnia1.10.7 Respiratory system

cough3.12.6 nasal congestion1.31.1 pharyngitis1.52.6 sinusitis1.01.3 upper respiratory tract infections6.55.6

Some side effects occurring with a frequency of less than 1%

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

Digestive system disorders: decreased appetite, dry mouth, toothache, vomiting, flatulence, gastritis, constipation, hepatitis, liver function disorders, very rare – moderate increase in “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 g% and 0.09 vol% respectively, rarely clinically significant), thrombocytopenia, eosinophilia, Schönlein-Henoch purpura.

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

CNS and sense organs: anxiety, sleep disturbance, somnolence, memory disorders, peripheral neuropathy, paraesthesia, hypoesthesia, tremor, ataxia, depression, syncopal states, tinnitus, taste disturbance, visual disturbance, conjunctivitis, migraine.

In the respiratory system: dyspnea, bronchitis, nasal mucosal edema.

Injuries to the urinary system: imperative urge to urinate, urinary tract infections, renal dysfunction.

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

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

Others: gout, decreased libido, decreased potency.

Overdose

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

Treatment: symptomatic therapy, forced diuresis.

Hemodialysis is ineffective.

Pregnancy use

There are no data on the use of losartan in pregnancy. Fetal renal perfusion, which depends on renin-angiotensin activity, begins to function in the third trimester of pregnancy. The risk to the fetus increases when losartan is taken in the second and third trimesters of pregnancy. If pregnancy is established, therapy with losartan should be discontinued immediately.

There are no data on excretion of losartan with breast milk. Therefore, the prescription of therapy with losartan should consider discontinuation of breastfeeding.

Similarities