Lozartan - Teva

General characteristics. Structure:

Active agent: лозартан potassium of 25 mg / 50 mg / 100 mg;
excipients:

lactoses monohydrate of 4,50 mg / 9,00 mg / 18,00 mg;
cellulose of microcrystallic 39,50 mg / 79,00 mg / 158,00 mg;
starch of prezhelatinizirovanny 30,25 mg / 60,50 mg / 121,00 mg;
magnesium stearate of 0,75 mg / 1,50 mg / 3,00 mg;

Cover of Opadrv II85F18422 white:
the polyvinyl alcohol which is (partially hydrolyzed) 1,200 mg / 2,400 mg / 4,800 mg;
titanium dioxide (Е 171) 0,750 mg / 1,500 mg / 3,000 mg;
macrogoal of 0,606 mg / 1,212 mg / 2,424 mg;
talc of 0,444 mg / 0,888 mg / 1,776 mg.

 

Description
Tablets of 25 mg:
oval biconvex tablets of white color, film coated, with risky on both sides. On one of the parties an engraving "2" and "5".
Tablets of 50 mg:
oval biconvex tablets of white color, film coated. On one of the parties dividing risk, on another - an engraving "50".
Tablets of 100 mg:
oval biconvex tablets of white color, film coated. On one of the parties dividing risk, on another - an engraving "100".

Pharmacological properties:

Pharmacodynamics. Lozartan is a specific antagonist of receptors of angiotensin II (AT1 subtype) for intake. Angiotensin II selectively contacts the AT1 receptors which are in many fabrics (in smooth muscle fabrics of vessels, adrenal glands, kidneys and heart) and performs several important biological functions, including vasoconstriction and release of Aldosteronum. Angiotensin II also stimulates growth of smooth muscle cells.
Lozartan and him pharmacological an active metabolite (Е 3174) both in vitro, and in vivo block all physiological effects of angiotensin II, irrespective of a source or a way of synthesis. Lozartan selectively contacts AT1 receptors and does not communicate and does not block receptors of other hormones and ion channels playing an important role in regulation of function of cardiovascular system. Besides, лозартан does not inhibit an angiotensin-converting enzyme (APF) - a kininaza of II, and, respectively, does not interfere with destruction of bradikinin therefore the side effects indirectly connected with bradikinin (for example, a Quincke's disease) arise rather seldom.
At use of a lozartan, lack of influence of negative feedback on secretion of a renin leads to increase in activity of a renin of a blood plasma. Increase in activity of a renin leads to increase in concentration of angiotensin II in a blood plasma. However anti-hypertensive activity and decrease in concentration of Aldosteronum of a blood plasma remain that P. Lozartan points to effective blockade of receptors of angiotensin and his active metabolite have big affinity to angiotensin I receptors, than to angiotensin I receptors. The active metabolite is 10-40 times more active than a lozartan.
After a single dose inside hypotensive action (systolic and diastolic arterial pressure decreases) reaches a maximum in 6 hours, then within 24 hours gradually decreases. The maximum hypotensive effect develops in 3-6 weeks after the beginning of administration of drug.
At patients with arterial hypertension without the accompanying diabetes mellitus with a proteinuria (more than 2 g/days), drug use authentically reduces a proteinuria, excretion of albumine and immunoglobulin G. Stabilizes the content of urea in a blood plasma. Does not influence vegetative reflexes, and does not make long impact on concentration of noradrenaline in a blood plasma.
Lozartan in a dose of 150 mg a day does not influence concentration of triglycerides, the general cholesterol and cholesterol of lipoproteins of the high density (LPVGT) in blood serum at patients with arterial hypertension. In the same dose лозартан does not influence concentration of glucose in blood on an empty stomach.

Pharmacokinetics. Absorption
At intake лозартан it is well absorbed from the digestive tract (DT) and at the same time is exposed to metabolism at "the first passing" through a liver by a carboxylation with the participation of CYP2C9 isoenzyme with formation of an active metabolite.
System bioavailability of a lozartan makes approximately 33%g the Maximum concentration of a lozartan and its active metabolite are reached in blood serum approximately in 1 hour and in 3-4 hours after intake, respectively. Meal does not influence bioavailability of a lozartan.
Distribution
More than 99% of a lozartan and its active metabolite contact proteins of a blood plasma, generally albumine. The volume of distribution of a lozartan - 34 l. Lozartan practically does not get through a blood-brain barrier.
Metabolism
About 14% of the lozartan entered to the patient intravenously or inside turn into an active metabolite.
Removal
The plasma clearance of a lozartan and its active metabolite makes about 600 ml/min. and 50 ml/min., respectively. The renal clearance of a lozartan and its active metabolite makes about 74 ml/min. and 26 ml/min., respectively. At intake about 4% of the accepted dose it is removed by kidneys in not changed look and about 6% are removed by kidneys in the form of an active metabolite. The linear pharmacokinetics at intake in doses to 200 mg is inherent to Lozartan and his active metabolite.
After intake plasma concentration of a lozartan and its active metabolite decrease polieksponentsialno with a final elimination half-life of a lozartan about 2 hours, and an active metabolite - about 6-9 hours. At administration of drug in a dose of 100 mg a day лозартан, its active metabolite is kumulirut considerably in a blood plasma.
Lozartan and his metabolites are brought out of an organism through intestines and kidneys.
After intake of marked C14 isotope of a lozartan, about 35% of a radioactive label are found in healthy volunteers in urine and 59% - in Calais.
Pharmacokinetics at special groups of patients
Patients with alcoholic cirrhosis of easy and moderate severity had a concentration of a lozartan by 5 times, and than an active metabolite - is 1,7 times higher, than at healthy male volunteers.
At the clearance of creatinine (CC) higher than 10 ml/min. concentration of a lozartan in a blood plasma does not differ from that at normal function of kidneys.
At the patients needing a hemodialysis value of the area under a curve "concentration time" (AUC) is approximately twice higher, than at patients with normal function of kidneys.
лозартан, its active metabolite is removed from an organism by means of a hemodialysis.
Concentration of a lozartan and its active metabolite in a blood plasma at elderly men with arterial hypertension significantly do not differ from values of these parameters at young men with arterial hypertension.
Values of plasma concentration of a lozartan at women with arterial hypertension exceed the corresponding values at men with arterial hypertension twice. Concentration of an active metabolite at men and women do not differ.

Indications to use:

- arterial hypertension;
- chronic heart failure (as a part of a combination therapy, at intolerance or inefficiency of therapy by APF inhibitors);
- decrease in risk of development of cardiovascular diseases (including a stroke) and mortality at patients with arterial hypertension and a hypertrophy of a left ventricle;
- a diabetic nephropathy or a giperkreatininemiya and a proteinuria (a ratio of albumine of urine and creatinine more than 300 mg/days) at patients with a diabetes mellitus 2 types and the accompanying arterial hypertension (decrease in progressing of a diabetic nephropathy to a terminal chronic renal failure).

Route of administration and doses:

Drug Lozartan - Tev is accepted inside irrespective of meal.
Tablets are swallowed, without chewing, washing down with water. Frequency rate of reception - 1 time a day.
Arterial hypertension
At arterial hypertension the average daily dose makes 50 mg of 1 times/days. For achievement of bigger therapeutic effect, the dose is increased to 100 mg of 1 times a day.
Chronic heart failure
The initial dose for patients with chronic heart failure makes 12,5 mg of 1 times a day. As a rule, the dose increases with a week interval (that is 12,5 mg/days, 25 mg/days and 50 mg/days) to an average maintenance dose of 50 mg of 1 times a day, depending on portability of drug the patient.
Dose adjustment of drug is not required from patients of advanced age.
Decrease in risk of development of cardiovascular diseases (including a stroke) and mortality at patients with arterial hypertension and a hypertrophy of a left ventricle
The initial dose of drug makes 50 mg of 1 times/days. Further the hydrochlorothiazide in low doses can be added or the drug dose Lozartan - Teva to 100 mg in one or two receptions taking into account a lowering of arterial pressure (ABP) is increased.
To patients with the accompanying diabetes mellitus 2 types with a proteinuria: drug Lozartan - Tev is appointed in an initial dose - 50 mg of 1 times a day with further increase in a dose to 100 mg/days (taking into account extent of decrease in the ABP) in one or in two steps.
At patients with reduced OTsK (for example, at reception of diuretics in high doses) the recommended initial dose of drug Lozartan - Teva makes 25 mg of 1 times/days.
To patients with a liver failure (less than 9 points on a scale of Chayld-Pyyu), when holding a procedure of a hemodialysis, and also to patients 75 years are more senior lower initial dose of drug - 25 mg of 1 times a day is recommended.
Safety and efficiency of drug at children up to 18 years is not established. Experience of use of drug for patients with a heavy liver failure therefore drug is not recommended at this category of patients does not suffice (see the section "Contraindications").

Features of use:

Prior to drug use Lozartan - Tev it is necessary to carry out correction of OTsK or to begin treatment with use of drug in lower dose.
The drugs making impact on RAAS can increase concentration of urea in blood and concentration of serumal creatinine at patients with a bilateral stenosis of renal arteries or a stenosis of an artery of the only kidney.
During treatment it is regularly necessary to control the content of potassium in blood, especially at patients of advanced age, at a renal failure.

Influence on ability to manage vehicles and to work with the equipment.
Special clinical trials on drug impact assessment on ability to manage vehicles and to work with the equipment were not conducted. It must be kept in mind a possibility of emergence of drowsiness and dizziness therefore it is necessary to be careful when working, requiring special attention, especially in an initiation of treatment, at increase in a dose of drug and at control of vehicles.

Side effects:

Side effects of a lozartan usually passing also do not demand drug withdrawal.
At use of a lozartan for treatment of arterial hypertension in controlled researches, among side effects only the frequency of development of dizziness differed from placebo more than for 1% (4,1% against 2,4%).
The Dozozavisimy hypotensive action characteristic of antihypertensives, at use of a lozartan was noted less than at 1% of patients.
The side effects observed at drug use are qualified on category depending on the frequency of their emergence: very often - not less than 10%; often - more than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; seldom - not less than 0,01%, but less than 0,1%; very seldom - less than 0,01%, including separate messages.

The side effects meeting with frequency more than 1%
                                                     Lozartan (n=2085)    of Placebo (n=535) 
General symptoms                                    
Adynamy, fatigue                                                      3,8 3,9
Pain in a thorax                                          1,1 2,6
Peripheral hypostases                                                      1,7 1,9
Cardiovascular system                     
Heart consciousness                                                   1,0 0,4
Tachycardia                                                                         1,0 1.7
Alimentary system
Abdominal pain                                                                     1,7 1.7
Diarrhea                                                                               1,9 1,9
Dispepsichesky frustration                                             1,1 1,5
Nausea                                                                             1,8 2,8
Musculoskeletal system
Dorsodynia, legs                                                            1,6 1,1
Spasms of gastrocnemius muscles                                               1,0 1,1
Neurology/psychiatry
Dizziness                                                                  4,1 2,4
Headache                                                                   14,1 17,2
Sleeplessness                                                                         1,1 0,7
Respiratory system
Cough, bronchitis                                                                3,1 2,6
Congestion of a nose                                                             1,3 1,1
Pharyngitis                                                                            1,5 2,6
Sinusitis                                                                               1,0 1,3
Upper respiratory tract infections                              6,5 5,6

The side effects meeting with frequency less than 1%
From cardiovascular system: orthostatic hypotension (dozozavisimy), nasal bleeding, bradycardia, arrhythmias, stenocardia, vasculitis, myocardial infarction.
From the alimentary system: anorexia, dryness of a mucous membrane of an oral cavity, dentagra, vomiting, meteorism, gastritis, lock, hepatitis, abnormal liver function.
From integuments: a xeroderma, an erythema, ecchymomas, a photosensitization, the increased sweating, an alopecia.
Allergic reactions: urticaria, skin rash, an itch, a Quincke's disease (including the hypostasis of a throat and language causing obstruction of respiratory tracts and/or a face edema, lips, a throat).
From system of a hemopoiesis: anemia (insignificant decrease in hemoglobin and a hematocrit, on average on 0,11 g of % and 0,09 volume of %, respectively, seldom having clinical value), thrombocytopenia, an eosinophilia, Shenleyn-Genokh's purpura.
From a musculoskeletal system: arthralgia, arthritis, shoulder, knee pain, fibromyalgia.
From a nervous system and sense bodys: concern, frustration of a dream, drowsiness, memory disturbances, peripheral neuropathy, paresthesias, giposteziya, a tremor, an ataxy, a depression, a faint, a ring in ears, disturbance of taste, a vision disorder, conjunctivitis, migraine.
From urinogenital and reproductive system: imperative desires on an urination, infections of urinary tract, a renal failure, decrease in a libido, impotence.
Others: gout.
Laboratory indicators: often - a hyperuricemia (content of potassium in a blood plasma more than 5,5 mmol/l); infrequently - increase in concentration of urea and residual nitrogen and creatinine in blood serum; very seldom - moderate increase in activity of "hepatic" transaminases: aspartate aminotransferases (ACT) and alaninaminotranspherase (ALT), hyperbilirubinemia.

Interaction with other medicines:

It can be applied along with other antihypertensives. Mutually strengthens effect of beta adrenoblockers and sympatholytics. Combined use of a lozartan with diuretics causes the additive effect. Pharmacokinetic interactions of a lozartan with a hydrochlorothiazide, digoxin, warfarin, Cimetidinum, phenobarbital, ketokonazoly and erythromycin are noted. According to messages, rifampicin also flukonazolsnizhat concentration of an active metabolite in a blood plasma. Clinical value of these interactions is still unknown.
As well as at use of other means inhibiting angiotensin II or its action, combined use of a lozartan with kaliysberegayushchy diuretics (for example, Spironolactonum, Triamterenum, amiloride), the potassium drugs, salts containing potassium increases risk of a hyperpotassemia.
Non-steroidal anti-inflammatory drugs (NPVP), including the selection inhibitors of cyclooxygenase-2 (TsOG-2), can reduce effect of diuretics and other antihypertensives.
At combined use of antagonists of receptors of angiotensin II and lithium increase in concentration of lithium in a blood plasma is possible. Considering it, it is necessary to weigh advantage and risk of combined use of a lozartan with lithium salts. In case of need combined use of drugs, it is regularly necessary to control concentration of lithium in a blood plasma.

Contraindications:

Hypersensitivity to drug components; a heavy liver failure (more than 9 points on a scale of Chayld-Pyyu); age up to 18 years; hereditary intolerance of a galactose, deficit of lactase or sprue of glucose galactose; pregnancy and period of a lactation.

With care
Arterial hypotension, the reduced the volume of the circulating blood (VCB), disturbances of water and electrolytic balance, bilateral stenosis of renal arteries or stenosis of an artery of the only kidney, renal failure, liver failure (less than 9 points on a scale of Chayld-Pyyu).

Use at pregnancy and during breastfeeding
Drug use Lozartan - Teva at pregnancy is contraindicated. It is known that the drugs influencing directly the renin-angiotensin-aldosteronovuyu system (RAAS) at use in II and III trimesters of pregnancy, can cause defects of development or even смертьразвивающегося a fruit. Therefore when diagnosing pregnancy, administration of drug Lozartan - Teva should be stopped immediately.
It is unknown whether it is allocated лозартан with breast milk. Lozartan - Teva in the period of a lactation is not recommended to accept drug. If administration of drug Lozartan - Teva is necessary in the period of a lactation, then breastfeeding needs to be stopped.

Overdose:

Symptoms: the expressed decrease in the ABP and tachycardia; bradycardia can arise owing to parasympathetic stimulation.
Treatment: artificial diuresis, symptomatic therapy; the hemodialysis is not effective.

Storage conditions:

To store at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 3 years. Not to use after the date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 25 mg, 50 mg, 100 mg.
Tablets of 25 mg:
10 tablets in the blister from polyvinylchloride and aluminum folgi.3 or 5 blisters together with the application instruction in a cardboard pack.
Tablets of 50 mg:
14 tablets in the blister from polyvinylchloride and aluminum foil.
1 blister together with the application instruction in a cardboard pack.
10 tablets in the blister from polyvinylchloride and aluminum foil. 3 blisters together with the application instruction in a cardboard pack.
Tablets of 100 mg:
10 tablets in the blister from polyvinylchloride and aluminum foil.
3 blisters together with the application instruction in a cardboard pack.