Pharmacodynamics
Antihypertensive agent. It is a non-peptide angiotensin II receptor blocker. It has high selectivity and affinity for receptors of the AT1 type (with the participation of which the main effects of angiotensin II are realized). By blocking these receptors, losartan prevents and eliminates the vasoconstrictor effect of angiotensin II, its stimulating effect on the secretion of aldosterone by the adrenal glands and some other effects of angiotensin II. It is characterized by a long action (24 hours or more), due to the formation of its active metabolite.
Pharmacokinetics
After oral administration, losartan is rapidly absorbed from the digestive tract. Bioavailability is about 33%. It is metabolized during the ""first passage"" through the liver with the formation of a carboxyl metabolite, which has a more pronounced pharmacological activity than losartan, and a number of inactive metabolites. Cmax in the plasma of losartan and the active metabolite is reached after 1 h and 3-4 hours, respectively. The binding to plasma proteins of losartan and the active metabolite is high - more than 98%. T1 / 2 of losartan and the active metabolite in the final phase is about 1.5-2.5 hours and 3-9 hours, respectively. Losartan is excreted in the urine and feces (with bile) unchanged and in the form of metabolites. About 35% is excreted in the urine and about 60% - with feces.
Contraindications
Pregnancy, lactation, childhood and adolescence up to 18 years, hypersensitivity to losartan.
Side effects
From the cardiovascular system: dizziness, orthostatic hypotension. From the side of metabolism: hyperkalemia. Allergic reactions: angioedema (including swelling of the face, lips, pharynx and / or tongue), urticaria. From the digestive system: diarrhea, increased ALT activity. From the side of the central nervous system: headache. Dermatological reactions: itching. Other: impaired renal function, myalgia.
Interaction
With simultaneous use with diuretics in high doses, arterial hypotension is possible. With simultaneous use with potassium preparations, potassium-sparing diuretics, the risk of developing hyperkalemia increases. With simultaneous use with indomethacin, a decrease in the effectiveness of losartan is possible. There is a message about the development of lithium intoxication with simultaneous use with lithium carbonate. With simultaneous use with orlistat, the antihypertensive effect of losartan decreases, which can lead to a significant increase in blood pressure, the development of a hypertensive crisis. With simultaneous use with rifampicin, the clearance of losartan increases and its effectiveness decreases.
Dosage and administration
The method of application and the dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. The compliance of the dosage form of a particular preparation with the indications for use and the dosage regimen should be strictly observed. The average dose for oral administration is 50 mg 1 time / day. If necessary, the dose can be reduced to 25 mg / day or increased to 100 mg / day, in the latter case, it is possible to use 2 times / day.
Special instructions
Caution should be used in case of arterial hypotension, a decrease in bcc, impaired water-electrolyte balance, bilateral renal artery stenosis or stenosis of a single kidney artery, and renal / hepatic failure Patients who have a deficiency of fluid and / or sodium, before starting treatment, it is necessary to correct the water-electrolyte disturbances or apply a lower initial dose. In patients with dehydration (for example, receiving high-dose diuretics), symptomatic arterial hypotension may occur at the beginning of losartan treatment. In case of impaired renal function, a dose reduction of losartan may be required. In patients with a history of liver disease, losartan should be used in low doses. With cirrhosis of the liver, the concentration of losartan in the blood plasma increases significantly. During the treatment period, the level of potassium in the blood should be regularly monitored, especially in elderly patients, with impaired renal function. The simultaneous use of losartan with potassium-sparing diuretics should be avoided. Safety and efficacy of losartan in children have not been established.