Composition, form of production and packaging
The tablets covered with a film cover of orange color, capsular, biconcave, with the squeezed out inscription "25" on the one hand and risk from another side.
Losartan potassium 25 mg
Excipients: starch 45.5 mg, lactose 38.0 mg, povidone (K-30) 2.0 mg, microcrystalline cellulose 13.0 mg, magnesium stearate 1.00 mg.
Film Sheath :
hypromellose 1.5 mg, talc 0.45 mg, titanium dioxide 0.40 mg, propylene glycol 0.15 mg, diethyl phthalate 0.30 mg, dye sunset yellow (sanset yellow) 0.05 mg.
10 pieces. - blisters of PVC / aluminum foil (5) - packs of cardboard.
The tablets covered with a film membrane of green color, capsular, biconcave, with the squeezed out inscription "50" on the one hand and risk on the other hand.
Losartan potassium 50 mg
Excipients: starch 33.0 mg, lactose 25.0 mg, povidone (K-30) 2.0 mg, microcrystalline cellulose 13.0 mg, magnesium stearate 1.05 mg.
Film Sheath :
hypromellose 1.5 mg, talc 0.45 mg, titanium dioxide 0.40 mg, propylene glycol 0.15 mg, diethyl phthalate 0.30 mg, dye green (dye Green Pe) 0.05 mg.
10 pieces. - blisters of PVC / aluminum foil (5) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
Losartan is a specific antagonist of angiotensin II receptors (subtype AT1) for oral administration. Angiotensin II selectively binds to AT1 receptors found in many tissues (in the smooth muscle tissues of the vessels, adrenal glands, kidneys and heart) and performs several important biological functions, including vasoconstriction and aldosterone release. Angiotensin II also stimulates proliferation of smooth muscle cells.
Losartan and its pharmacologically active metabolite (e 3174) both in vitro and in vivo block all the physiological effects of angiotensin II, regardless of the source or pathway of synthesis. Losartan selectively binds to AT1 receptors and does not bind or block receptors of other hormones and ion channels that play an important role in
regulation of cardiovascular function. In addition, losartan does not inhibit ACE-kinase II and, accordingly, does not interfere with the destruction of bradykinin, therefore side effects mediated by bradykinin (eg, angioedema) are rare.
When using losartan, the absence of negative feedback influence on renin secretion leads to an increase in renin plasma activity. Increased renin activity leads to an increase in the concentration of angiotensin II in blood plasma.
However, the antihypertensive activity and decrease in the plasma aldosterone concentration are preserved, which indicates an effective blockade of the angiotensin II receptors.
Losartan and its active metabolite have a greater affinity for angiotensin I receptors than for angiotensin II receptors. The active metabolite is 10-40 times more active than losartan.
After a single oral intake, the antihypertensive effect (systolic and diastolic blood pressure decreases) reaches a maximum after 6 hours, then gradually decreases within 24 hours.
The maximum antihypertensive effect develops in 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), the use of the drug significantly reduces proteinuria, albumin and immunoglobulin excretion. Stabilizes the urea content in the blood plasma. Does not affect vegetative reflexes and does not have a long-term effect on the concentration of norepinephrine in the blood plasma.
Losartan in a dose of 150 mg / day does not affect the concentration of triglycerides, total cholesterol and high-density lipoprotein cholesterol (HDL) in the blood serum in patients with arterial hypertension. At the same dose, losartan does not affect the concentration of glucose in the blood on an empty stomach.
When administered orally, losartan is well absorbed from the digestive tract and at the same time is metabolized by "primary passage" through the liver by carboxylation with the participation of the isoenzyme CYP2S9 to form an active
metabolite. Systemic bioavailability of losartan is approximately 33%. C max losartan and its active metabolite are reached in the blood serum approximately 1 hour and 3-4 hours after ingestion, respectively. Eating does not affect the bioavailability of losartan.
More than 99% of losartan and its active metabolite bind to plasma proteins, mainly albumin. V d losartan - 34 liters. Losartan practically does not penetrate the blood-brain barrier.
Approximately 14% of losartan administered to a patient intravenously or inwardly becomes an active metabolite.
The plasma clearance of losartan and its active metabolite is about 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 ingested, approximately 4% of the dose taken is excreted by the kidneys unchanged and about 6% is excreted by the kidneys in the form of an active metabolite. Losartan and its active metabolite is characterized by linear pharmacokinetics when administered in doses up to 200 mg. 'After ingestion, the plasma concentrations of losartan and its active metabolite decrease polyexponentially with a finite T 1/2 of losartan for about 2 hours, and the active metabolite is about 6-9 hours. When taking the drug at a dose of 100 mg per day, neither losartan nor its active metabolite not significantly cumulate in plasma
blood. Losartan and its metabolites are excreted through the intestine and the kidneys. In healthy volunteers, after ingestion of a labeled 14 C isotope of losartan, about 35% of the radioactive label is found in urine and 59% in feces.
Pharmacokinetics in specific patient groups
In patients with alcoholic liver cirrhosis of mild and moderate severity, the concentration of losartan was 5 times, and the active metabolite was 1.7 times higher than in healthy male volunteers.
When the creatinine clearance (CK) is above 10 ml / min, the concentration of losartan in the blood plasma does not differ from that with normal kidney function. In patients in need of hemodialysis, the value of AUC is approximately 2 times higher than in patients with normal renal function.
Neither losartan nor its active metabolite is removed from the body by hemodialysis.
The concentrations of losartan and its active metabolite in blood plasma in elderly men with arterial hypertension do not differ significantly from the values вЂ‹вЂ‹of these parameters in young men with arterial hypertension.
Values вЂ‹вЂ‹of plasma concentrations of losartan in women with arterial hypertension are 2 times higher than the corresponding values вЂ‹вЂ‹for men with arterial hypertension. The concentrations of active metabolite in men and women are not different.
- arterial hypertension;
- Chronic heart failure (as part of combination therapy, with intolerance or inefficiency of therapy with ACE inhibitors);
- reduction in the risk of developing cardiovascular diseases (including stroke) and mortality in patients with hypertension and left ventricular hypertrophy;
- diabetic nephropathy or hypercreatininaemia and proteinuria (urine albumin and creatinine ratio more than 300 mg / day) in patients with type 2 diabetes and concomitant arterial hypertension (reduction in progression of diabetic nephropathy to terminal chronic renal failure).
The drug Losartan Macleodz is taken orally regardless of the meal. Tablets are swallowed, not liquid, squeezed with water. Multiplicity of admission - 1 time / day.
With arterial hypertension, the average daily dose is 50 mg 1 time / day. To achieve greater therapeutic effect, the dose is increased to 100 mg / day.
Chronic heart failure
The initial dose for patients with chronic heart failure is 12.5 mg 1 time / day. Typically, the dose increases with a weekly interval (i.e. 12.5 mg / day, 25 mg / day and 50 mg / day) to an average maintenance dose of 50 mg 1 time / day, depending on the patient's tolerability.
No dose adjustment is required in elderly patients .
Reducing the risk of developing cardiovascular diseases (including stroke) and mortality in patients with hypertension and left ventricular hypertrophy
The initial dose of the drug is 50 mg 1 time / day. In the future, hydrochlorothiazide can be added in low doses or the dose of Lozartan Macleodz can be increased to 100 mg in 1 or 2 doses, taking into account the decrease in blood pressure.
Patients with concomitant type 2 diabetes mellitus with proteinuria
The drug is given in an initial dose of 50 mg 1 time / day with a further increase in the dose to 100 mg / day (taking into account the degree of BP reduction) in one or two doses.
In patients with reduced BCC (for example, when taking diuretics in high doses) the recommended initial dose of the drug Losartan Macleodz is 25 mg 1 time / day.
Patients with hepatic insufficiency (less than 9 on the Child-Pugh scale), during the hemodialysis procedure, as well as patients older than 75 years arerecommended a lower initial dose of the drug - 25 mg 1 time / day.
Insufficient experience in the use of the drug in patients with severe hepatic insufficiency , so the drug is not recommended for this category of patients.
The drug does not have the features of the action at the first admission or when it is withdrawn, but it is necessary to control the blood pressure as when taking any antihypertensive drug.
Admission of antihypertensive drugs should be carried out at the same time as prescribed by the doctor to increase the therapeutic effect. If you miss a single dose, you need to take the next dose of the drug at the time closest to the time you took the drug or while remembering that you missed the appointment by moving the time of the next dose. Do not take twice the dose of the drug.
From the nervous system and sensory organs: > 1% - dizziness, asthenia / fatigue, headache, insomnia; <1% - anxiety, sleep disturbance, drowsiness, memory disorders, peripheral neuropathies, paresthesia, hypostases,
hyperesthesia, migraine, tremor, ataxia, depression, syncope, ringing in the ears, taste disorder, vision change, conjunctivitis.
On the part of the respiratory system: > 1% - nasal congestion, cough, upper respiratory tract infections (elevated body temperature, sore throat), sinusopathy, sinusitis, pharyngitis; <1% - dyspnea, bronchitis, rhinitis.
On the part of the digestive system: > 1% - nausea, diarrhea, dyspeptic phenomena, abdominal pain, dryness of the oral mucosa; <1% - anorexia, toothache, vomiting, flatulence, gastritis, constipation.
From the musculoskeletal system: > 1% - convulsions, myalgia, pain in the back, chest, legs; <1% - arthralgia, shoulder pain, knee, arthritis, fibromyalgia.
From the cardiovascular system and blood (hematopoiesis, hemostasis): <1% - orthostatic reactions (dose-dependent), hypotension, palpitation, tachy- or bradycardia, arrhythmias, angina, anemia, myocardial infarction.
On the part of the genitourinary system: <1% - mandatory urges for urination, infection, urinary tract, impaired renal function, weakening of libido, impotence.
From the skin: <1% - dry skin, erythema, blood flow, photosensitivity, increased sweating, alopecia.
Allergic reactions: <1% - urticaria, skin rash; itching, angioedema, incl. face, lips, throat and / or tongue.
Other: > 1% - hyperkalemia; <1% - fever, gout, increased liver transaminases and bilirubin in the blood, vasculitis, hyperuricemia, thrombocytopenia, eosinophilia, purpura Shenlen-Henoch, hypercreatininaemia.
- lactation period;
- age up to 18 years;
- severe hepatic insufficiency (more than 9 points on the Child-Pugh scale);
- hereditary intolerance of galactose, lactase deficiency or glucose-galactose malabsorption syndrome;
- Hypersensitivity to the components of the drug.
With caution apply the drug with arterial hypotension, reduced bcc, violations of water-electrolyte balance, bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, kidney failure, liver failure (less than 9 on the Child-Pugh scale).
PREGNANCY AND LACTATION
The use of the drug Losartan Macleodz during pregnancy is contraindicated. It is known that drugs acting directly on the renin-angiotensin-aldosterone system (RAAS), with the application of III and III trimesters of pregnancy, can cause developmental defects or even death of the developing fetus. Therefore, when diagnosing pregnancy, the drug Lozartan Macleodz should be discontinued immediately.
It is not known whether losartan is excreted in breast milk. It is not recommended to take Lozartan Macleodz during lactation. If the drug Lozartan Macleodz is needed during lactation, then breastfeeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution apply the drug in bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, kidney failure.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
- severe hepatic insufficiency (more than 9 points on the Child-Pugh scale).
Use with caution in patients with liver failure (less than 9 on the Child-Pugh scale).
APPLICATION FOR CHILDREN
Contraindicated in children under 18 years.
APPLICATION IN ELDERLY PATIENTS
No dose adjustment is required in elderly patients .
Patients older than 75 years are recommended a lower initial dose of the drug - 25 mg 1 time / day.
For patients with chronic heart failure, in whom a stable effect was achieved as a result of the use of ACE inhibitors, it is not recommended to switch to angiotensin II receptor antagonists, incl. preparation Losartan Macleodz.
Patients with a liver pathology (less than 9 points on the scale. Chaid-Pugh, and especially with cirrhosis), incl. in the anamnesis, it is necessary to prescribe smaller doses.
In patients with dehydration (for example, receiving treatment with high doses of diuretics), at the beginning of treatment with losartan, symptomatic arterial hypotension may occur (it is necessary to correct dehydration before losartan is administered or to begin treatment at a lower dose).
In patients with renal dysfunction, with or without diabetes, electrolyte disorders (hyperkalemia) often develop, to which attention should be paid. In the presence of acute or chronic renal failure, losartan may lead to impaired renal function with or without hyperkalemia.
During the treatment with losartan should regularly monitor the potassium content in the blood, especially in elderly patients and with violations of kidney function. It should avoid simultaneous use of losartan with potassium-sparing diuretics.
In elderly patients using non-steroidal anti-inflammatory drugs, with simultaneous administration of diuretics, or with impaired renal function, the use of losartan may lead to impaired renal function, including the possibility of acute renal failure. These effects are usually reversible. Periodically monitor renal function in patients taking losartan and non-steroidal anti-inflammatory drugs.
Data on the safety and efficacy of the drug in children are not sufficient.
Impact on the ability to drive vehicles and manage mechanisms
The ability of the drug to influence the speed of psychomotor reactions and the ability to control transport or other technical means has not been studied. Care should be taken when dealing with potentially hazardous activities requiring increased attention and rapid psychomotor reactions.
Symptoms: a marked decrease in blood pressure, possibly a change in heart rate (tachycardia or bradycardia).
Treatment: gastric lavage, forced diuresis, symptomatic maintenance therapy. Hemodialysis is ineffective (neither losartan nor its active metabolite is excreted in hemodialysis).
The drug Losartan Macleodz can be used concurrently with other antihypertensive drugs.
Mutually enhances the effect of beta-blockers and sympatholytics.
The combined use of losartan with diuretics causes an additive effect.
There were no pharmacokinetic interactions of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin.
Reportedly, rifampicin and fluconazole reduce the concentration of the active metabolite in the blood plasma. The clinical significance of these interactions is still unknown.
As with other agents that inhibit angiotensin II or its effect, the combined use of losartan with potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium preparations, potassium-containing salts, increases the risk of hyperkalemia.
Non-steroidal. Anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2), can reduce the effect of diuretics and other antihypertensive agents.
With the combined use of antagonists of angiotensin II and lithium receptors, an increase in the concentration of lithium in blood plasma is possible. Given this, it is necessary to weigh the favor and. risk of co-administration, losartan with lithium salts. In case of necessity of joint application of preparations, it is necessary to regularly monitor the concentration of lithium in blood plasma.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
Shelf life of the drug is 3 years. In a dry place at a temperature of no higher than 25 В° C. Keep out of the reach of children.