Losakar - instructions for use, dose, side effects, contraindications

Composition:Each film-coated tablet contains active ingredient: losartan potassium, respectively, 12.5 mg, 50 mg and 100 mg.
Excipients: lactose monohydrate 25,27 / 25,5 / 51 mg, corn pregelatinized corn starch 10.48 / 20.95 / 41.9 mg, microcrystalline cellulose 26.27 (52.5 / 105 mg and magnesium stearate 0.52 / 1, 05 / 2.1 mg.
Shell composition: giprolose 0,9 / 1,8 / 3,6 mg, hypromellose 0,9 / 1,8 / 3,6 mg, dye brilliant blue 2/0/0 μg, titanium dioxide 0,44 / 0,9 / 1, 8 mg.

Description:Tablets 12.5 mg: round tablets covered with a film coating of blue color; On a cross-section - white or almost white color.
Tablets 50 and 100 mg: Round tablets covered with a film shell of white or almost white color; On a cross-section - white or almost white color.

Pharmacotherapeutic group:Angiotensin II receptor antagonist.

ATX: & nbsp

C.09.C.A.01 Losartan

C.09.C.A Angiotensin II antagonists

Pharmacodynamics:A hypotensive drug, is a specific antagonist of angiotensin II receptors (type₁). Angiotensin II selectively binds to AT₁ receptors found in many tissues (in the smooth muscle tissues of blood vessels, in the adrenal gland, in the kidneys and in the 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 route of synthesis. Unlike some peptide angiotensin II antagonists losartan does not have the effects of an agonist. Losartan selectively binds to the AT₁receptors and does not bind or block receptors of other hormones and ion channels, which play an important role in regulating the function of the cardiovascular system. Besides, losartan does not inhibit angiotensin-converting enzyme (ACE), which contributes to the degradation of bradykinin.Consequently, effects that are not directly related to the blockade of AT₁-receptors, in particular, the enhancement of effects associated with exposure to bradykinin or angioedema (losartan 1.7%, placebo 1.9%), are not related to the action of losartan.
With prolonged (6-week) treatment of patients with arterial hypertension losartan at a dose of 100 mg / day, there was a 2-3-fold increase in angiotensin II activity at the time of maximum plasma concentration (C_max) drug in the blood plasma; in some patients, an even greater increase in losartan concentration was observed, especially with a short duration of treatment (2 weeks). However, antihypertensive activity and a decrease in plasma aldosterone concentrations occurred at 2 and 6 weeks of therapy, indicating an effective blockade of angiotensin II receptors. After abolition of losartan, the plasma renin activity and angiotensin II activity decreased to the baseline values observed 3 days prior to taking the drug.
A study comparing the effects of 20 mg and 100 mg of losartan with the effects of an ACE inhibitor on the response to angiotensin I, angiotensin II, and bradykinin showed that losartan blocks the effects of angiotensin I and angiotensin II, without affecting the effects of bradykinin, which is due to the specific mechanism of action of losartan. In contrast, ACE inhibitors block the response of angiotensin I and increase the response to bradykinin without affecting the severity of the response to angiotensin II, which demonstrates the pharmacodynamic difference between losartan and ACE inhibitors.
The concentration of losartan and its active metabolite in the blood plasma, as well as the antihypertensive effect of losartan increase with increasing dose of the drug. Because losartan and its active metabolite are antagonists of angiotensin II receptors, they both determine the antihypertensive effect. In a study with a single dose of 100 mg of losartan in healthy volunteers (men), the use of the drug both in patients with a diet limited in table salt and in patients consuming a lot of table salt did not affect the glomerular filtration rate, the effective renal plasma flow and the filtration fraction. Losartan has a natriuretic effect, which was more pronounced with a low-sal diet and, apparently, was not associated with the suppression of early sodium reabsorption in the proximal renal tubules. Losartan also caused a transient increase in the excretion of uric acid by the kidneys.
In postmenopausal women with hypertension, who took losartan potassium in a dose of 50 mg / day for 4 weeks, there was no effect of therapy on the renal and systemic levels of prostaglandins.
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 G excretion.
Stabilizes the concentration of urea 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 up to 150 mg per day does not affect the concentration of triglycerides, total cholesterol and high-density lipoprotein cholesterol (HDL) in the blood serum in patients with arterialhypertension. In the same dose, losartan does not affect the concentration of glucose in the blood on an empty stomach.

Pharmacokinetics:Suction. Ingestion losartan is well absorbed from the gastrointestinal tract (GIT) and is subjected to the effect of "primary passage" through the liver, resulting in the formation of an active carboxylated metabolite and inactive metabolites. Systemic bioavailability of losartan is approximately 33%. Mean maximum plasma concentrations (C_max) of losartan and its active metabolite are achieved after 1 hour and 3-4 hours, respectively. When losartan was taken during a normal meal, there was no clinically significant effect on the profile of losartan concentration in the blood plasma.
Distribution. Lozartan and its active metabolite bind to plasma proteins (mainly albumin) by more than 99%. V_d losartan is 34 liters. Losartan practically does not penetrate the blood-brain barrier.
Metabolism. Approximately 1.4% of the dose of losartan (when administered orally and in / in the introduction) is converted to its active metabolite. After oral or intravenous administration, losartan, labeled¹⁴C, the radioactivity of circulating blood plasma is primarily associated with the presence in it of losartan and its active metabolite. Biologically inactive metabolites are also formed, incl. two basic, resulting from the hydroxylation of the butyl side chain, and one secondary is N-2-tetrazole-glucuronide.
Excretion. 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 taking losartan, about 4% of the dose is excreted unchanged by the kidneys and about 6% of the dose is excreted by the kidneys in the form of an active metabolite. Losartan and its active metabolite have a linear pharmacokinetics when ingested at doses up to 200 mg.
After oral administration, the plasma concentrations of losartan and its active metabolite decrease polyexponentially with a finite elimination half-life (T_1/2) about 2 and 6-9 hours, respectively. With a single dose of 100 mg losartan, nor its active metabolite significantly accumulate in the blood plasma.
The excretion of losartan and its metabolites occurs through the intestine and kidneys. After ingestion of losartan, labeled¹⁴C, about 35% of the radioactive label is found in urine and 58% in feces. After iv introduction of losartan, labeled ¹⁴C, approximately 43% of the radioactive label is detected in the urine and 50% in the feces.
Pharmacokinetics in specific patient groups
The concentrations of losartan and its active metabolite in blood plasma in elderly patients with arterial hypertension do not significantly differ from these indices in younger patients with arterial hypertension.
Concentrations of losartan in blood plasma were 2 times higher in women with arterial hypertension compared with men with arterial hypertension. The concentrations of active metabolite in men and women did not differ. This apparent pharmacokinetic difference is not clinically significant.
When taking losartan inwards in patients with cirrhosis of the alcoholic genesis. mild and moderate severity of concentration of losartan and its active metabolite in blood plasma were 5 and 1.7 times (respectively) more than in young healthy male volunteers.
Concentrations of losartan in blood plasma in patients with creatinine clearance (CC) above 10 ml / min did not differ from. those in individuals with normal renal function. In patients who need hemodialysis, the area under the concentration-time curve (AUC) is approximately 2 times higher 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 on hemodialysis. Losartan and its active metabolite can not be removed by hemodialysis.

Indications:- arterial hypertension;
- A reduction in the risk of associated cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy, manifested by a decrease in the combined incidence of cardiovascular mortality, stroke and myocardial infarction.
- diabetic nephropathy or hypercreatinemia and proteinuria (urine albumin and creatinine ratio more than 300 mg / day) in patients with type 2 diabetes and concomitant arterial hypertension (reduction in the progression of diabetic nephropathy to terminal chronic renal failure).
- Chronic heart failure with ineffective treatment with ACE inhibitors.

Contraindications:- hypersensitivity to the components of the drug;
- severe hepatic insufficiency (more than 9 points on the Child-Pugh scale);
- lactose intolerance, lactase deficiency and glucose-galactose malabsorption;
- Pregnancy;
- lactation period;
- age to 18 years.

Carefully:Arterial hypotension, reduced volume of circulating blood (BCC), disturbance of water-electrolyte balance, bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, renal failure, liver failure (less than 9 on the Child-Pugh scale); with simultaneous use with the following medicinal products (see section Interactions with other medicinal products):
- beta-blockers and sympatholytics;
- diuretics;
- hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin;
- rifampin and fluconazole;
- lithium carbonate;
- potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone), potassium supplements and salts containing potassium;
- Non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2).

Pregnancy and lactation:Losakor is contraindicated in pregnancy and lactation.
It is known that drugs acting directly on the renin-angiotensin-aldosterone system (RAAS), when used in the II and III trimesters of pregnancy, can cause developmental defects or even the death of the developing fetus. Therefore, when diagnosing pregnancy, taking Losakor should be stopped immediately. It is not known whether losartan with breast milk. It is not recommended to take Losakor during lactation. If taking Losakor is necessary during lactation, then breastfeeding should be discontinued.

Dosing and Administration:Inside, regardless of food intake, the tablets are swallowed, not liquid, squeezed with water. Multiplicity of admission - 1 time per day.
With arterial hypertension, the average daily dose is 50 mg 1 time / day. In some cases, to achieve a greater effect, the dose is increased to 100 mg in 2 divided doses or once a day. The maximum dose is 100 mg per day.
When administering the drug to patients receiving diuretics in high doses, the initial dose of the drug should be reduced to 25 mg (1/2 tablets 50 mg) once a day. There is no need to select an initial dose in elderly patients and in patients with renal insufficiency, including patients on dialysis. Patients with hepatic insufficiency (less than 9 on the Child-Pugh scale), as well as patients older than 75 years, are recommended a lower initial dose of the drug -25 mg (1/2 tablets 50 mg) once a 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 (see section "Contraindications").
To reduce the risk of cardiovascular disease and mortality in patients with hypertension and left ventricular hypertrophy, usually the initial dose is 50 mg once a day. In the future, you can add hydrochlorothiazide in low doses and / or the dose of Losacor is increased to 100 mg per day in one or two doses.
To protect kidney function in patients with type 2 diabetes and proteinuria, usually the initial dose is 50 mg once a day.Further it is recommended to increase the dose to 100 mg / day (taking into account the degree of decrease in blood pressure) in one or two doses.
The initial dose for patients with chronic heart failure is 12.5 mg once a day. Typically, the dose increases 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 patient's tolerance.

Side effects:Side effects of the frequency of occurrence are distributed as follows: very often (≥ 10%), often (≥ 1% and <10%), sometimes (≥0.1% and <1%), rarely (≥ 0.01% and < 0.1%), very rarely, including individual reports (<0.01%).
In patients with essential hypertension, the only side effect associated with taking the drug was dizziness, which was observed more often than with placebo and occurred in more than 1% of patients receiving Loxacor. In addition, less than 1% of patients had orthostatic reactions, depending on the dose of the drug. Rarely, rash was reported, but its incidence was less than with placebo.
Losacore is generally well tolerated by patients with left ventricular hypertrophy, patients with type 2 diabetes and proteinuria.The most frequent side effects associated with taking the drug were systemic and non-systemic dizziness, asthenia / weakness, marked decrease in blood pressure and hyperkalemia. Side effects, occurring with a frequency of development of more than 1%:
On the part of the body as a whole: pain in the stomach area of 1.7% (placebo 1.7%); weakness and fatigue 3.8% (placebo 3.9%), chest pain 1.1% (placebo 2.6%), peripheral edema 1.7% (placebo 1.9%).
From the cardiovascular system: a palpitation of 1% (placebo 0.4%); tachycardia 1% (placebo 1.7%).
From the digestive system: diarrhea 1.9% (placebo 1.9%); dyspepsia 1.1% (placebo 1.5%); nausea 1.8% (placebo 2.8%).
From the musculoskeletal system: back pain 1.6% (placebo 1.1%); muscle cramps 1% (placebo 1.1%). i
From the central nervous system: dizziness 4.1% (placebo 2.4%); headache 14.1% (placebo 17.2%); Insomnia 1.1% (placebo 0.7%).
From the respiratory system: cough 3.1 (placebo 2.6%); edema of the nasal mucosa 1.3% (placebo 1.1%); pharyngitis 1.5% (placebo 2.6%); sinusitis 1% (placebo 1.3%); upper respiratory tract infection 6.5% (placebo 5.6%).
Side effects, occurring with a development rate of less than 1%:
Allergic reactions: angioedema, including swelling of the larynx, glottis, causing airway obstruction, and / or edema of the face, lips, pharynx and / or tongue.
From the central nervous system: migraine.
From the musculoskeletal system: myalgia, arthralgia.
From the skin: urticaria, itching.
From the digestive system: hepatitis, a violation of the liver.
From the hematopoiesis: anemia, thrombocytopenia.
From the respiratory system: cough.
Laboratory indicators: often: hyperkalemia (the concentration of potassium in the blood plasma is more than 5.5 meq / l); sometimes - increasing the concentration of urea and residual nitrogen or creatinine in the blood serum; very rarely - a moderate increase in the activity of "hepatic" transaminases: aspartate aminotransferase (ACT) and alanine aminotransferase (ALT), hyperbilirubinemia.
In patients with dehydration (eg, receiving diuretic treatment in high doses), at the beginning of treatment with losartan, symptomatic arterial hypertension may occur. With cirrhosis of the liver, the concentration of losartan in the blood plasma increases significantly.
In general, the drug is well tolerated, the side effects are mild and transient and do not require withdrawal of the drug. The total frequency of Loxacor's side effects is comparable to that of placebo.

Overdose:Information on overdose is limited.
Symptoms: The most likely symptoms of an overdose are: a marked decrease in blood pressure and tachycardia; Bradycardia can occur due to parasympathetic stimulation. Treatment: symptomatic therapy. Losartan and its active metabolite are not removed from the bloodstream during hemodialysis.

Interaction:Mutually enhances the effect of beta-blockers and sympatholytics. The combined use of losartan with diuretics causes an additive effect. There was no clinically significant interaction of the drug with such drugs as hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketronazole and erythromycin.
Rifampin and fluconazole decrease the concentration of the active metabolite. The clinical significance of these interactions has not been studied.
There is a report on the development of lithium intoxication with simultaneous application of lithium carbonate.With simultaneous 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 benefits and risks of the joint use of losartan with lithium preparations. In case of necessity of joint application of preparations, it is necessary to regularly monitor the concentration of lithium in blood plasma.
As with other drugs that block the formation of angiotensin II and its effects, the concomitant use of potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone), potassium supplements and salts containing potassium, can lead to an increase in potassium in the serum.
Non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2), can reduce the effect of diuretics and other antihypertensive drugs. Therefore, the antihypertensive effect of angiotensin II receptor antagonists can be weakened by the simultaneous use of NSAIDs, including selective inhibitors of COX-2.
In some patients with impaired renal function who have been treated with NSAIDs, including selective COX-2 inhibitors,simultaneous use of angiotensin II receptor antagonists can cause further impairment of kidney function. Usually, this effect is reversible.

Special instructions:Perhaps the manifestation of such a symptom of hypersensitivity as angioedema.
Patients with a reduced osmotically active extracellular cation (BCC) (eg, receiving treatment with large doses of diuretics) may experience symptomatic arterial hypotension. Correction of such conditions should be carried out before the appointment of Losakor or start treatment with a lower dose.
During the period of treatment, the potassium content in the blood should be regularly monitored, especially in elderly patients, with renal dysfunction.
Violation of the water-electrolyte balance is characteristic of patients with renal insufficiency with diabetes mellitus or without diabetes mellitus, therefore, when prescribing a drug in this category of patients, special care should be taken.
In patients with cirrhosis of the liver, the concentration of losartan in the blood plasma is significantly increased, and therefore, in the presence of liver diseases in the history of the drug should be prescribed in lower doses.
Drugs that affect the renin-angiotensin-aldosterone system can increase the concentration of urea in the blood and creatinine in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney. During the treatment period, the potassium content in the blood should be regularly monitored, especially in elderly patients, with renal dysfunction.

Effect on the ability to drive transp. cf. and fur:There were no special clinical studies to assess the effect of the drug on the ability to drive vehicles and work with machinery. It should be borne in mind the possibility of drowsiness and dizziness, so you need to be careful when performing work that requires increased attention, especially at the beginning of treatment, with an increase in the dose of the drug and in the management of vehicles.

Form release / dosage:Tablets coated with a film sheath of 12.5; 50 and 100 mg.

Packaging:Tablets of 12.5 mg: 14 tablets per blister. 2 blisters together with instructions for use in a pack of cardboard.
Tablets of 50 and 100 mg: 10 tablets per blister. For 3 blisters together with instructions for use in a pack of cardboard.

Storage conditions:Store at a temperature not exceeding 25 ° C.
Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001127

Date of registration:03.11.2011

Expiration Date:Unlimited

The owner of the registration certificate:Adifarm, EADAdifarm, EAD Bulgaria

Manufacturer: & nbsp

ADIPHARM, EAD Bulgaria

Representation: & nbspADIFARMADIFARMBulgaria

Information update date: & nbsp2016-10-28

Illustrated instructions

Instructions

Losakar (Losacar)