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Active ingredients
Losartan
Release form
Pills
Composition
Active ingredient: Losartan (Losartan) Active ingredient concentration (mg): 50
Pharmacological effect
Antihypertensive drug. Specific antagonist of angiotensin II receptors (subtype AT1). Does not inhibit kininase II - an enzyme that catalyzes the reaction of converting angiotensin I to angiotensin II. Reduces the OPSS, the concentration in the blood of adrenaline and aldosterone, blood pressure, pressure in the pulmonary circulation; reduces afterload, has a diuretic effect. Interferes with the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure. Losartan does not inhibit ACE-kininase II and, accordingly, does not prevent the destruction of bradykinin, therefore side effects indirectly associated with bradykinin (for example, angioedema) occur quite rarely. In patients with arterial hypertension without diabetes mellitus with proteinuria (more than 2 g / day) , the use of the drug significantly reduces proteinuria, excretion of albumin and immunoglobulin G. Stabilizes the level of urea in the blood plasma. Does not affect the autonomic reflexes and does not have a long-term effect on the concentration of norepinephrine in the blood plasma. Losartan in a dose of up to 150 mg / day does not affect the level of triglycerides, total cholesterol and HDL cholesterol in serum in patients with arterial hypertension. At the same dose, losartan does not affect fasting blood glucose. After a single oral administration, the hypotensive effect (systolic and diastolic blood pressure decreases) reaches a maximum after 6 hours, then gradually decreases within 24 hours. The maximum hypotensive effect develops in 3-6 weeks after starting the drug.
Pharmacokinetics
Absorption When taken orally, losartan is well absorbed, and at the same time undergoes metabolism during the first passage through the liver by carboxylation with the participation of the cytochrome CYP2C9 isoenzyme with the formation of an active metabolite. Systemic bioavailability of losartan is about 33%. Cmax of losartan and its active metabolite are reached in serum approximately 1 h and 3-4 h after ingestion, respectively.Meal does not affect the bioavailability of losartan. Distribution Over 99% of losartan and its active metabolite binds to plasma proteins, mainly albumin. Vd losartan - 34 l. Losartan practically does not penetrate the BBB. Metabolism Approximately 14% of losartan, administered to the patient in / in, or ingested, turns into an active metabolite. Withdrawal The plasma clearance of losartan is 600 ml / min, and the active metabolite is 50 ml / min. The renal clearance of losartan and its active metabolite is 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 exhibit linear pharmacokinetics when administered orally in doses up to 200 mg. After ingestion, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a final T1 / 2 of losartan about 2 hours, and an active metabolite about 6-9 hours When taking the drug at a dose of 100 mg / day, neither losartan nor the active metabolite is significantly accumulated in the blood plasma. Losartan and its metabolites are excreted through the intestines and the kidneys. In healthy volunteers, after oral administration of losartan, labeled with 14C-isotope, about 35% of the radioactive label is found in the urine and 58% - in the feces. , and the active metabolite is 1.7 times higher than in healthy male volunteers. With KK> 10 ml / min, the concentration of losartan in the blood plasma does not differ from that of normal kidney function. In patients who need hemodialysis, 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. Concentration of losartan and its active metabolite in plasma in elderly men with arterial hypertension do not differ significantly from the values of these parameters in young men with arterial hypertension. The values of plasma concentrations of losartan in women with arterial hypertension are 2 times higher than the corresponding values tions in men with hypertension.Concentrations of the active metabolite in men and women do not differ. This pharmacokinetic difference has no clinical significance.
Indications
Arterial hypertension; Chronic heart failure (as part of combination therapy, with intolerance or failure of therapy with ACE inhibitors); Reducing the risk of cardiovascular diseases (including stroke) and mortality in patients with arterial hypertension and left ventricular hypertrophy; Diabetic nephropathy with hypercreatitis and proteinuria (the ratio of urine albumin to creatinine is more than 300 mg / g) in patients with type 2 diabetes mellitus and concomitant arterial hypertension (decreased progression of diabetic nephropathy to a terminal chronic renal failure)
Contraindications
Hypersensitivity to the components of the drug; Pregnancy and lactation; Age up to 18 years (efficacy and safety have not been established). With caution: arterial hypotension, reduced blood volume, impaired water electrolyte balance, bilateral renal artery stenosis or arterial stenosis of the only kidney renal / hepatic failure.
Precautionary measures
Do not exceed the recommended dose. With caution, you should use the drug for arterial hypotension, lower BCC, impaired water and electrolyte balance, bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, for renal / hepatic failure.
Use during pregnancy and lactation
Data on the use of the drug Lozap during pregnancy is not. However, it is known that drugs acting directly on the RAAS, when used in the second and third trimesters of pregnancy, can cause a defect of development or even death of a developing fetus. Therefore, when pregnancy occurs, the use of the drug Lozap should be immediately stopped. If you need to use Lozapa during lactation, you should decide whether to stop breastfeeding or to stop treatment with the drug.
Dosage and administration
The drug is taken orally, regardless of the meal. Frequency of use - 1 time / day. In hypertension, the average daily dose is 50 mg.In some cases, to achieve a greater therapeutic effect, the daily dose may be increased to 100 mg in 2 or 1 dose. The initial dose for patients with chronic heart failure is 12.5 mg 1 time / day. As a rule, the dose is increased with a weekly interval (ie, 12.5 mg / day, 25 mg / day, 50 mg / day) to an average maintenance dose of 50 mg 1 time / day, depending on the tolerance of the drug. When prescribing the drug to patients receiving diuretics in high doses, the initial dose of the drug Lozap should be reduced to 25 mg 1 time / day. For elderly patients there is no need for dose adjustment. When prescribing the drug in order to reduce the risk of cardiovascular diseases (including stroke) and mortality in patients with hypertension and hyp left ventricular rtrofiey initial dose is 50 mg / day. In the future, hydrochlorothiazide may be added at a low dose and / or the dose of Lozap may be increased to 100 mg / day in 1-2 doses. For patients with concomitant type 2 diabetes with proteinuria, the initial dose of the drug is 50 mg 1 time / day, then the dose increase to 100 mg / day (taking into account the degree of blood pressure reduction) in 1-2 doses. Patients with a history of liver disease, dehydration, during the hemodialysis procedure, as well as patients over 75 years old are recommended a lower initial dose of the drug - 25 mg (1 / 2 tab. 50 mg) 1 time / day.
Side effects
Side effects of losartan are usually transient and do not require discontinuation of the drug. When using losartan for the treatment of essential hypertension in controlled studies, among all side effects, only the incidence of vertigo differed from placebo by more than 1% (4.1% versus 2.4%). The dose-dependent orthostatic effect, characteristic of antihypertensive agents, was less observed in losartan than in 1% of patients. The side effects observed with the use of the drug are classified into categories depending on the frequency of their occurrence: very often ≥ 1/10; often> 1/100, ≤ 1/10; sometimes ≥ 1/1000, ≤ 1/100; rarely ≥ 1/10000, ≤ 1/1000; very rarely ≤ 1/10000, including individual messages. Side effects occurring with a frequency of more than 1%: Common symptoms Losartan (n = 2085) Placebo (n = 535) Asthenia, fatigue 3.8 3.9 Pain in the chest 1, 1 2.6 Peripheral edema 1.7 1.9 Cardiovascular system Heart beat 1.0 0.4 Tachycardia 1.0 1.7 Digestive system Abdominal pain 1.7 1.7 Diarrhea 1.9 1.9 Dispericap enough phenomena 1.1 1.5 Stomach 1, 8 2.8 Musculoskeletal System Back pain,legs 1.6 1.1Survival of calf muscles 1.0 1.1 Neurology / psychiatryPitiatomy 4.1 2.4 Headache 14.1 17.2 Insomnia 1.1 0.7 Respiratory systemCough, bronchitis 3.1 2.6 Congestion of the nose 1.3 1 , 1 Pharyngitis 1.5 2.6> Sinusitis 1.0 1.3 Upper respiratory tract infections 6.5 5.6 Side effects occurring with a frequency of less than 1%: Cardiovascular: orthostatic hypotension (dose-dependent), epistaxis, bradycardia, arrhythmias, angina pectoris, vasculitis, myocardial infarction. On the part of the digestive tract: anorexia, dryness of the oral mucosa, toothache, vomiting, flatulence, gastritis, constipation, hepatitis, abnormal liver function. On the part of the skin: dry skin, erythema, ecchymosis, photosensitivity, increased sweating, alopecia. Allergic reactions: urticaria, skin rash, itching, angioedema (including laryngeal and tongue edema, causing airway obstruction and / or swelling of the face, lips, pharynx). On the part of the hemopoietic system: sometimes - anemia (a slight decrease in hemoglobin and hematocrit concentrations, on average by 0.11 g% and 0.09 volume%, respectively, rarely - having clinical significance), thrombocytopenia, eosinophilia, Schoenlein-Henoch suture. On the part of the musculoskeletal system: arthralgia, arthritis, pain in the shoulder, knee, fibromyalgia. On the part of the central nervous system and sensory organs: anxiety, sleep disturbance, drowsiness, memory disorders, peripheral neuropathy, paresthesia, hypoesthesia, tremor, ataxia, depression, syncope, tinnitus, impaired taste, visual disturbances, conjunctivitis, migraine. On the part of the urinary system: imperative urination to urinate, urinary tract infections, impaired renal function, decreased libido, impotence. Other: gout. Laboratory indicators: often: hyperkalemia (the level of potassium in the blood plasma is more than 5.5 mmol / l); sometimes - an increase in the level of urea and residual nitrogen or creatinine in the blood serum; very rarely - a moderate increase in liver transaminase activity: aspartate aminotransferase (AST) and alanine aminotransferase (ALT), hyperbilirubinemia.
Overdose
Symptoms: marked decrease in blood pressure, tachycardia; Bradycardia may appear due to parasympathetic (vagal) stimulation. Treatment: Forced diuresis, symptomatic therapy; hemodialysis is not effective.
Interaction with other drugs
The drug can be prescribed with other antihypertensive drugs. There is a mutual enhancement of the effects of beta-blockers and sympatholytic.The combined use of losartan with diuretics leads to an additive effect. Pharmacokinetic interactions between losartan and hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin are not observed. According to reports, rifampicin and fluconazole decreases the activity of an activity. The clinical significance of this interaction is not yet known. As with the use of other agents inhibiting angiotensin II or its action, the combined use of losartan with potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium preparations and salts containing potassium, increases the risk of hyperkalemia. , including selective COX-2 inhibitors, may reduce the effect of diuretics and other antihypertensive drugs. With the combined use of angiotensin II and lithium receptor antagonists, an increase in the end tration of lithium in blood plasma. Given this, it is necessary to weigh the benefits and risks of losartan co-administration with lithium salts. If necessary, the joint use should regularly monitor the concentration of lithium in the blood plasma.
special instructions
It is necessary to correct dehydration before prescribing Lozap or start treatment with a lower dose. Drugs affecting the RAAS can increase blood urea and serum creatinine in patients with bilateral renal artery stenosis or arterial stenosis of a single kidney. In patients With cirrhosis, the concentration of losartan in the blood plasma increases significantly, and therefore, in the presence of liver diseases in history, it should be prescribed in lower doses. During the period of treatment, the concentration of potassium in the blood should be regularly monitored, especially in elderly patients, in cases of impaired renal function. Use in pediatrics MechanismsLozap does not affect the ability to drive vehicles or work with mechanisms.