Losartan pills 100mg, 30pcs

Composition

Active ingredient:

losartan potassium-100,000 mg;

excipients:

lactose monohydrate-115,000 mg,

microcrystalline cellulose-40,000 mg,

croscarmellose sodium-11,200 mg,

povidone (polyvinylpyrrolidone low molecular weight) – 9,000 mg,

colloidal silicon dioxide -2,000 mg,

magnesium stearate-2,800 mg;

film coating:

[hypromellose − 4,800 mg, talc − 1,600 mg, titanium dioxide -0,826 mg, macrogol 4000 (polyethylene glycol 4000) − 0,720 mg, iron oxide yellow (iron oxide) – 0,054 mg] or [dry mix for film coating containing hypromellose (60%), talc (20%), titanium dioxide (10,33%), macrogol 4000 (polyethylene glycol 4000) (9%), iron oxide yellow (iron oxide) (0,67%)]- 8,000 mg

Pharmacological action

Pharmacotherapy group

Angiotensin II receptor antagonist.

ATX code

C09CA01

Pharmacological properties

Pharmacodynamics

Losartan is a specific oral angiotensin II (AT1 type) receptor antagonist. 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 smooth muscle cell proliferation.

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; it does not bind or block the 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 the angiotensin-converting enzyme (ACE), which contributes to the degradation of bradykinin, so side effects indirectly associated with bradykinin (for example, angioedema) are quite rare.

When losartan is used, the absence of negative feedback 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 blood plasma. However, antihypertensive activity and a decrease in plasma aldosterone concentration remain, which indicates an effective blockade of angiotensin II receptors. After discontinuation of losartan, plasma renin activity and angiotensin II concentration decreased for 3 days to the initial values observed before starting the drug. Losartan and its active metabolite have a high affinity for angiotensin II (AT1 type) receptors.

The plasma concentrations of losartan and its active metabolite, as well as the antihypertensive effect of losartan, increase with increasing dose. The maximum antihypertensive effect develops in 3-6 weeks after the start of taking the drug.

In patients with arterial hypertension, proteinuria (more than 2 g per day), without diabetes mellitus, the use of the drug significantly reduces proteinuria, albumin and immunoglobulin G (IgG) excretion.

In postmenopausal women with arterial hypertension who took losartan at a dose of 50 mg / day for 4 weeks, there was no effect of therapy on renal and systemic prostaglandin levels.

Losartan has no effect on autonomic reflexes and does not have a long-term effect on the level of norepinephrine in blood plasma.

In patients with arterial hypertension, losartan at doses up to 150 mg per day does not cause clinically significant changes in the concentration of triglycerides, total cholesterol and high-density lipoprotein cholesterol. In the same doses, losartan does not affect the concentration of glucose in the fasting blood. Losartan caused a decrease in the serum uric acid concentration (usually less than 0.4 mg / dl), which persisted during long-term therapy. In controlled clinical trials involving patients with arterial hypertension, there were no cases of drug withdrawal due to an increase in serum creatinine or potassium.

Pharmacokinetics

Suction

When taken orally, losartan is well absorbed from the gastrointestinal tract. The systemic bioavailability of losartan is approximately 33%, and food intake does not affect the bioavailability of losartan. The average maximum concentrations of losartan and its active metabolite are reached after 1 h and after 3-4 h, respectively.

Distribution

Losartan and its active metabolite bind to plasma proteins (mainly albumin) by more than 99%. The volume of distribution of losartan is 34 l. Losartan practically does not penetrate the blood-brain barrier.

Metabolism

Losartan undergoes the effect of “primary passage” through the liver, is metabolized with the participation of the cytochrome P450 CYP2 C9 isoenzyme. Approximately 14% of the dose of losartan administered intravenously or orally is converted to its active metabolite (EXP3174) with a carboxyl group. Biologically inactive metabolites are also formed: two main ones (as a result of hydroxylation of the butyl side chain) and a less significant one-N-2-tetrazole-glucuronide.

Deduction

The plasma clearance of losartan and its active metabolite is 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 taking losartan orally, about 4% of the dose is excreted unchanged by the kidneys and within 6% of the dose is excreted by the kidneys as an active metabolite. Losartan and its active metabolite have linear pharmacokinetics when taking losartan orally at doses up to 200 mg. After oral use, plasma concentrations of losartan and its active metabolite decrease polyexponentially with final half-lives of T1/2 of approximately 2 and 6-9 hours, respectively.

The elimination of losartan and its metabolites occurs in the bile and kidneys. After oral use of losartan labeled with 14C, about 35% of the radioactive label is detected in the urine and 58% in the feces.

Pharmacokinetics in special patient groups

The plasma concentrations of losartan and its active metabolite in elderly male patients with arterial hypertension do not significantly differ from those in younger male patients with arterial hypertension.

Plasma concentrations of losartan were 2 times higher in women with arterial hypertension compared to men with arterial hypertension. Concentrations of the active metabolite did not differ between men and women. This apparent pharmacokinetic difference is not clinically relevant.

When taking losartan orally in patients with alcoholic cirrhosis of mild and moderate severity, the concentrations of losartan and its active metabolite in blood plasma were 5 and 1.7 times higher (respectively) than in young healthy male volunteers.

Plasma concentrations of losartan in patients with creatinine clearance above 10 ml / min did not differ from those in patients with normal renal function. In patients requiring hemodialysis, the area under the concentration-time curve (AUC) is approximately 2 times larger than in patients with normal renal function. Plasma concentrations of the active metabolite do not change in patients with impaired renal function or in patients undergoing hemodialysis. Losartan and its active metabolite are not removed from the bloodstream by hemodialysis.

Indications

• hypertension;

• reduce the risk of associated cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy, manifested by a reduction in the overall frequency of cardiovascular mortality, stroke and myocardial infarction;

• to protect the kidneys in patients with diabetes type 2 diabetes with proteinuria and slowing down the progression of renal failure, manifested by a decrease in the frequency of hypercreatininemia, the incidence of end-stage chronic renal disease (ESRD) requiring hemodialysis or kidney transplantation, mortality, and the reduction of proteinuria;

• chronic heart failure with failure of treatment with ACE inhibitors.

Contraindications

• hypersensitivity to any component of the drug;

• pregnancy and lactation;

• the age of 18;

• refractory hyperkalemia;

• lactose intolerance, lactase deficiency syndrome glucose-galactose malabsorption;

• dehydration;

• severe liver failure (no experience);

• concurrent use with aliskiren in patients with diabetes mellitus and/or impaired renal function (glomerular filtration rate less than 60 ml/min).

With caution

Liver failure (less than 9 Child-Pugh score), hypotension, reduced circulating blood volume (BCC), impaired water-electrolyte balance, hyperkalemia, bilateral renal artery stenosis or single kidney artery stenosis, renal failure, post-kidney transplant conditions, aortic and mitral stenosis, obstructive hypertrophic cardiomyopathy, history of angioedema, severe heart failure heart failure(NYHA Functional Class IV), coronary heart disease, heart failure with life-threatening arrhythmias, cerebrovascular diseases, primary aldosteronism, heart failure with concomitant severe renal failure.

Side effects

In most cases, losartan is well tolerated, side effects are mild and transient and do not require discontinuation of the drug.

Side effects observed when taking the drug are classified into categories depending on the frequency of their occurrence: very often ≥ 1/10 (10%); often > 1/100(1%) ≤ 1/10 (10%); sometimes ≥ 1/1000 (0,1%), ≤ 1/100 (1%); rarely ≥1/10000 (0,01%), ≤ 1/1000 (0,1%); very rarely ≤ 1/10000 (0.01%), including individual events.

Side effects occurring with a frequency of more than 1%

General disorders: asthenia, weakness, fatigue, chest pain, peripheral edema.

From the cardiovascular system: palpitation, tachycardia.

From the digestive system: abdominal pain, diarrhea, dyspepsia, nausea.

Musculoskeletal system disorders: back pain, leg pain, muscle cramps.

From the central nervous system (CNS): dizziness, headache, insomnia.

Respiratory system disorders: cough, bronchitis, swelling of the nasal mucosa, pharyngitis, sinusitis, upper respiratory tract infections.

Side effects occurring with a frequency of less than 1%

From the cardiovascular system: angina pectoris, symptomatic arterial hypotension (especially in patients with intravascular dehydration, for example, patients with severe heart failure or taking high-dose diuretics), dose-dependent orthostatic hypotension, bradycardia, arrhythmias, myocardial infarction, vasculitis.

From the digestive system: anorexia, dryness of the oral mucosa, toothache, flatulence, gastritis, constipation, hepatitis, liver function disorders, vomiting.

From the skin: dry skin, ecchymosis, erythema, photosensitization, increased sweating, alopecia.

Allergic reactions: urticaria, pruritus, skin rash, angioedema (including swelling of the larynx, vocal fold, causing airway obstruction, and/or swelling of the face, lips, pharynx, and / or tongue).

From the hematopoietic system: anemia, thrombocytopenia, eosinophilia, Schonlein-Henoch purpura.

From the nervous system and sensory organs: restlessness, sleep disorders, drowsiness, memory disorders, peripheral neuropathy, paresthesia, hyposthesia, tremor, ataxia, depression, fainting, tinnitus, taste disorders, visual disturbances, conjunctivitis, migraine.

Musculoskeletal disorders: arthralgia, arthritis, shoulder and knee pain, fibromyalgia.

From the urinary system: urgent urge to urinate, urinary tract infections, impaired renal function.

From the side of the reproductive system: decreased libido, impotence.

Other: exacerbation of gout, nosebleeds.

From the side of laboratory parameters:

often-hyperkalemia (potassium content more than 5.5 mmol / l);

infrequently-increased concentration of urea, residual nitrogen, creatinine in the blood serum;

very rarely-moderate increase in the activity of transaminases (aspartate-aminotransferase, alanine aminotransferase), hyperbilirubinemia.

Attention! If any of the side effects listed in the instructions get worse or you notice any other side effects not listed in the instructions, tell your doctor.

Interaction

It can be prescribed with other antihypertensive agents.

There was no clinically significant interaction of losartan with drugs such as hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital, ketoconazole and erythromycin.

Rifampicin and fluconazole reduce the level of the active metabolite. The clinical significance of these interactions has not been established.

As with other agents that block the formation of angiotensin II and its effects, the simultaneous use of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride, eplerenone) or agents that increase the potassium content (for example, heparin), potassium supplements and salts containing potassium may lead to an increase in serum potassium.

As with other agents that affect the excretion of sodium, losartan treatment may be accompanied by a decrease in sodium excretion and an increase in the serum concentration of lithium, so when treating lithium concomitantly, its serum concentration should be monitored.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors, may reduce the effect of diuretics and other antihypertensive agents. Therefore, the antihypertensive effect of angiotensin II receptor antagonists or ACE inhibitors may be weakened by concomitant use with NSAIDs, including selective COX-2 inhibitors.

In some patients with impaired renal function who have been treated with NSAIDs, concomitant use of angiotensin II antagonists may cause further deterioration of renal function. This effect is usually reversible.

Other antihypertensive agents may increase the antihypertensive effect of losartan. Concomitant use of medications (for example, tricyclic antidepressants, antipsychotics, baclofen, amifostine) that reduce blood pressure as a main or side effect may increase the risk of hypotension.

Dual blockade of the RAAS with angiotensin II receptor antagonists, ACE inhibitors, or aliskiren is associated with an increased risk of hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared to monotherapy. Blood pressure, renal function, and water-electrolyte balance should be carefully monitored in patients taking losartan and other medications that affect the RAAS. Losartan should not be used concomitantly with aliskiren in patients with diabetes mellitus. Concomitant use of Losartan and aliskiren should be avoided in patients with renal insufficiency (glomerular filtration rate less than 60 ml / min).

When used concomitantly with fluvastatin (a weak inhibitor of the CYP 2C9 isoenzyme), there was no difference in exposure.

If you have been prescribed losartan and are taking other medications, please consult your doctor.

How to take, course of use and dosage

Inside, regardless of the meal.

The drug can be taken either as monotherapy or in combination with other antihypertensive drugs.

Arterial hypertension

The standard initial and maintenance dose for most patients is 50 mg once daily. The maximum antihypertensive effect is achieved after 3-6 weeks from the start of therapy.

In some patients, to achieve a greater effect, the dose may be increased to a maximum daily dose of 100 mg once a day.

In patients with reduced circulating blood volume (for example, when taking diuretics in large doses), the initial dose of the drug should be reduced to 25 mg once a day (see the section “Special instructions”).

There is no need to adjust the initial dose in elderly patients and in patients with renal insufficiency, including patients on dialysis.

Patients with hepatic insufficiency (less than 9 points on the Child-Pugh scale) during the hemodialysis procedure, as well as patients over 75 years of age, are recommended to prescribe the drug at a lower initial dose of 25 mg once a day.

Reducing the risk of associated cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy

The standard initial dose of the drug is 50 mg once a day. In the future, it is recommended to add hydrochlorothiazide or increase the dose of Losartan to 100 mg (taking into account the degree of reduction in blood pressure (BP)) in one or two doses.

Kidney protection in patients with type 2 diabetes mellitus and proteinuria

The standard initial dose of the drug is 50 mg once a day. In the future, it is recommended to increase the dose of Losartan to 100 mg once a day, taking into account the degree of reduction in blood pressure. Losartan can be prescribed together with other antihypertensive drugs (diuretics, slow calcium channel blockers, alpha-and beta-blockers, central-acting antihypertensive drugs), insulin, and other hypoglycemic drugs (sulfonylureas, glitazones, and glucosidase inhibitors).

Chronic heart failure

The initial dose of the drug is 12.5 mg once a day. As a rule, the dose is titrated at weekly intervals (i. e. 12.5 mg once a day,25 mg once a day,50 mg once a day) to the usual maintenance dose of 50 mg once a day, depending on individual tolerance.

Overdose

Information about overdose of the drug is limited.

Most likely symptoms

Marked decrease in blood pressure and tachycardia; bradycardia may occur due to parasympathetic (vagal) stimulation.

Treatment

Forced diuresis, symptomatic therapy.

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

Special instructions

Allergic reactions. Patients taking losartan have rarely experienced anaphylactic reactions, angioedema involving the larynx and pharynx, causing airway obstruction and/or swelling of the face, lips, pharynx and/or tongue.Some of these patients had a history of angioedema when taking other medications, including ACE inhibitors. Therefore, special care should be taken when prescribing the drug to patients with a history of angioedema.

Arterial hypotension and impaired water-electrolyte balance or decreased BCC. Patients with reduced BCC (for example, those treated with high-dose diuretics) may experience symptomatic hypotension. Correction of such conditions should be carried out before prescribing losartan or starting treatment with a lower dose of the drug (see the section “Dosage and use”).

Violation of the water-electrolyte balance is characteristic of patients with renal insufficiency with or without type 2 diabetes mellitus, therefore, when prescribing the drug to this category of patients, special care should be taken due to the risk of hyperkalemia (see the section “Side effects”, subsection “Laboratory parameters”).

During treatment, the blood potassium content should be regularly monitored, especially in elderly patients with impaired renal function. During losartan treatment, patients should not take potassium supplements or salt substitutes containing potassium without prior consultation with their doctor.

Aortic or mitral stenosis, obstructive hypertrophic cardiomyopathy. As with all vasodilating agents, angiotensin II receptor antagonists should be used with caution in patients with aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.

Coronary heart disease and cerebrovascular diseases. As with all vasodilating agents, angiotensin II receptor antagonists should be used with caution in patients with coronary artery disease or cerebrovascular diseases, since excessive lowering of blood pressure in this group of patients can lead to the development of myocardial infarction or stroke.

Chronic heart failure (CHF). As with other drugs that affect the RAAS, patients with CHF and with or without impaired renal function are at risk of developing severe hypotension or acute renal failure.

There is insufficient experience with the use of losartan in patients with heart failure and concomitant severe renal insufficiency, in patients with severe heart failure (NYHA functional class IV), as well as in patients with heart failure and symptomatic life-threatening arrhythmias. Therefore, losartan should be administered with caution to patients in these groups.

Primary hyperaldosteronism. In patients with primary hyperaldosteronism, as a rule, there is no positive response to therapy with antihypertensive agents that act by inhibiting the RAAS, so the use of losartan is not recommended in this group of patients.

Impaired liver function. Data from pharmacokinetic studies indicate that the concentration of losartan in blood plasma in patients with cirrhosis of the liver is significantly increased, so patients with a history of liver disease should use the drug at a lower dose (see the section “Dosage and use”).

Impaired renal function. Due to RAAS inhibition, some predisposed patients experienced changes in renal function, including the development of renal failure. These changes may occur after discontinuation of treatment.

Some drugs that affect the RAAS may increase the concentration of urea in the blood and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney. Changes in renal function may be reversible after therapy. During treatment, it is necessary to regularly monitor the concentration of creatinine in the blood serum at regular intervals.

Elderly patients. Clinical studies have not shown any differences in the safety and efficacy of losartan in elderly patients.

Influence on the ability to drive vehicles and mechanisms

During treatment, caution should be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions (dizziness may occur, especially in patients who have taken diuretic medications and switched to drug therapy).

Form of production

Round biconvex film-coated tablets of white or almost white color (dosages of 12.5 mg and 50 mg) or yellow color (dosages of 25 mg and 100 mg). On a cross-section, the core is white or almost white in color.

Storage conditions

Store in a dry place, protected from light, at a temperature not exceeding 25 °C.

Active ingredient

Losartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Heart failure, Prevention of heart attacks and strokes, Hypertension