Lozartan-Teva - instructions for use, dose, side effects, contraindications

Composition:For 1 tablet:
1 tablet contains: active substance: Losartan potassium 25 mg / 50 mg / 100 mg; Excipients: lactose monohydrate 4.50 mg / 9.00 mg / 18.00 mg; cellulose microcrystalline 39.50 mg / 79.00 mg / 158.00 mg; pregelatinized starch 30.25 mg / 60.50 mg / 121.00 mg; magnesium stearate 0.75 mg / 1.50 mg / 3.00 mg; Shell Opacity 1185F 18422 white: polyvinyl alcohol (partially hydrolysed) 1,200 mg / 2,400 mg / 4,800 mg; titanium dioxide (E 171) 0.750 mg / 1.500 mg / 3,000 mg; macrogol 0.606 mg / 1.212 mg / 2.424 mg; talc 0.444 mg / 0.888 mg / 1.776 mg.

Description:Tablets 25 mg: oval biconvex tablets of white color, film-coated, with a risk on both sides. On one side is engraving "2" and "5".
Tablets 50 mg: oval biconvex tablets of white color, covered with a film membrane. On one side is the dividing risk, on the other is the engraving "50".
Tablets 100 mg: oval biconvex tablets of white color, covered with a film membrane. On one side is the dividing risk, on the other is the engraving "100".

Pharmacotherapeutic group:Angiotensin II receptor antagonist.

ATX: & nbsp

C.09.C.A.01 Losartan

C.09.C.A Angiotensin II antagonists

Pharmacodynamics:Losartan is a specific antagonist of angiotensin II receptors (subtype AT₁) for oral administration. Angiotensin II selectively binds to AT₁receptors located in many tissues (vascular smooth muscle, adrenal gland, kidneys and the heart) and performs several important biological functions, including vasoconstriction and the release of aldosterone. 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. Losartan selectively binds to the AT₁-receptors and does not bind, and ns blocks the 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) - kininase II, and, accordingly, does not interfere with the destruction of bradykinin, therefore side effects mediated by bradykinin (eg, angioedema) are rare.
When losartan is used, the absence of negative feedback influence the secretion of renin 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, antihypertensive activity and a decrease in plasma aldosterone concentration persist, indicating an effective blockade of angiotensin II reviewers. Losartan and its active metabolite have a greater affinity for the 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 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 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 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 at a dose of 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 hypertension. At the same dose losartan does not affect the concentration of glucose in the blood on an empty stomach.

Pharmacokinetics:Suction. Ingestion losartan It is well absorbed from the gastrointestinal tract (GIT) and at the same time is metabolized at the "first passage" through the liver by carboxylation with the participation of the CYP2C9 isoenzyme with the formation of an active metabolite.
Systemic bioavailability of losartan is approximately 33%.
The maximum concentration of losartan and its active metabolite is reached in the blood serum after approximately 1 hour and 3-4 hours after ingestion, respectively. Eating does not affect the bioavailability of losartan.
Distribution. More than 99% of losartan and its active metabolite bind to plasma proteins, mainly albumin. The volume of distribution of losartan is 34 liters. Losartan practically does not penetrate the blood-brain barrier.
Metabolism. Approximately 14% of losartan administered to a patient intravenously or inwardly becomes an active metabolite.
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 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 oral administration, the plasma concentrations of losartan and its active metabolite decrease polyexponentially with a final half-life of losartan about 2 hours, and the active metabolite - about 6-9 hours. When taking the drug at a dose of 100 mg per day, neither losartan, nor its active metabolite significantly not cumulate in blood plasma.
Losartan and its metabolites are excreted through the intestine and the kidneys.
In healthy volunteers after ingestion of a labeled C¹⁴ 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 area under the concentration-time curve (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 of these parameters in young men with arterial hypertension.
Values of plasma concentrations of losartan in women with arterial hypertension are 2 times higher than the corresponding values in men with arterial hypertension.The concentrations of the active metabolite in men and women do not differ.

Indications:- arterial hypertension;
- chronic heart failure (as part of combination therapy, with intolerance or inefficiency of therapy with PSA inhibitors);
- reduction in the risk of developing cardiovascular diseases (including stroke) and mortality in patients with hypertension and left ventricular hypertrophy;
- Diabetic nephropathy or hypercritropinemia 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).

Contraindications:Hypersensitivity to the components of the drug; severe hepatic insufficiency (more than 9 on the Child-Pugh scale); simultaneous use with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus and / or renal dysfunction (glomerular filtration rate less than 60 ml / min / 1.73 m), age to 18 years; hereditary intolerance to galactose, lactase deficiency or glucose-galactose malabsorption syndrome; pregnancy and lactation.

Carefully:Arterial hypotension, reduced circulating blood volume (BCC), disturbance of water-electrolyte balance, bilateral stenosis of the renal arteries or stenosis of the single kidney artery, renal failure, condition after kidney transplantation, liver failure (less than 9 points on the Child-Pugh scale), aortic and mitral stenosis, hypertrophic obstructive cardiomyopathy, heart failure with concomitant severe impairment of kidney function, severe chronic heart failure IV functional class but as NYHA classification of heart failure with life-threatening arrhythmias, ischemic heart disease, cerebrovascular disease, primary aldosteronism, angioedema in history.

Pregnancy and lactation:The use of the drug Losartan-Teva during pregnancy is contraindicated.
The use of drugs that affect RAAS (renin-angiotensin-aldosterone system) in the second and third trimester of pregnancy reduces kidney function and increases the incidence and mortality of the fetus and newborns.The development of oligohydramnion can be associated with fetal lung hypoplasia and deformities of the bones of the skeleton. Possible adverse events in newborns include hypoplasia of the skull bones, anuria, arterial hypotension, renal failure and death. When diagnosing pregnancy, the drug should be immediately canceled. The above undesirable outcomes are usually due to the use of drugs that affect RAAS in the second and third trimester of pregnancy. Most epidemiological studies to study the development of fetal abnormalities after the use of antihypertensive drugs in the first trimester of pregnancy have revealed differences between drugs that affect RAAS and other antihypertensive drugs. When prescribing antihypertensive therapy for pregnant women, it is important to optimize the possible outcomes for the mother and fetus. If it is not possible to select alternative therapy instead of therapy with drugs that affect RAAS, it is necessary to inform the patient about the possible risk of therapy for the fetus.It is necessary to conduct periodic ultrasound examinations to assess the intra-amniotic space. Depending on the week of pregnancy, appropriate fetal tests are necessary.
It is not known whether losartan with breast milk. It is not recommended to take Lozartan-Teva during lactation. If the drug Lozartan-Teva is needed during lactation, then breastfeeding should be discontinued.

Dosing and Administration:The drug Losartan-Teva is taken orally regardless of food intake. Tablets are swallowed, not liquid, squeezed with water. Multiplicity of admission - 1 time per day.
Arterial hypertension
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 once a day.
Chronic heart failure
The initial dose for patients with chronic heart failure is 12.5 mg (1/2 tablets of 25 mg) once a day. Typically, the dose increases with a weekly interval (i.e., 12.5 (1/2 tablets of 25 mg), mg / day, 25 mg / day and 50 mg / day) to an average maintenance dose of 50 mg once daily, in dependence on patient 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, you can add hydrochlorothiazide in low doses or increased the dose of the drug Losartan-Teva to 100 mg in one or two doses, taking into account the decrease in blood pressure (BP).
Patients with concomitant type 2 diabetes mellitus with proteinuria: Lozargan-Teva is prescribed in the initial dose - 50 mg once a 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 Lozartan-Teva is 25 mg 1 time / day.
Patients with hepatic insufficiency (less than 9 on the Child-Pugh scale), during the hemodialysis procedure, and also for patients older than 75 years it is recommended to lower the initial dose of the drug - 25 mg once a day.
Safety and efficacy of the drug in children under 18 years of age have not been established.
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").

Side effects:

The side effects of losartan are usually transient and do not require withdrawal of the drug.
When using losartan for the treatment of hypertension in controlled trials, only the incidence of dizziness differed from placebo by more than 1% (4.1% vs. 2.4%) among the side effects.
The dose-dependent hypotensive effect, characteristic of antihypertensive agents, was observed in less than 1% of patients with losartan.
Undesirable effects are classified according to the frequency of their development: very often (≥ 1/10), often (≥1 / 100, <1/10), infrequently (≥ 1/1000, <1/100), rarely (≥ 1 / 10000, <1/1000), very rarely (<1/10000), unknown frequency - the available data are insufficient to estimate the frequency of the side effect.
Table 1. Prevalence of adverse reactions from placebo-controlled clinical trials and post-registration follow-up

By-side reaction	Prevalence of adverse reactions according to indications for use								Other
	Arterial hypertension	Patients with hypertension and left ventricular hypertrophy		Chronic cardiac failure		Arterial hypertension and type 2 diabetes mellitus with impaired renal function		Post-registration observation
Disorders from the blood and lymphatic system
anemia					frequent				frequency unknown
thrombocytopenia									frequency unknown
Immune system disorders
allergic reaction, anaphylactic reactions, Quincke's edema¹ and vasculitis									rare
Disorders of the psyche
depression									frequency unknown
Disturbances from the nervous system
dizziness	frequent		frequent		frequent		frequent
drowsiness	infrequent
headache	infrequent				infrequent
sleep disturbance	infrequent
paresthesia					rare
migraine									frequency unknown
taste disorder									frequency unknown
Hearing disorders and labyrinthine disorders
vertigo	infrequent		frequent
noise in ears									frequency unknown
Heart Disease
sensation palpitation	infrequent
angina pectoris	infrequent
fainting					rare
ciliary arrhythmia					rare
sharp violation of cerebral blood circulation					rare
Vascular disorders
(orthostatic) marked decrease in blood pressure (including dose-dependent orthostatic effects)³	infrequent				frequent		frequent
Disturbances from the respiratory system, thorax and mediastinum
dyspnea					infrequent
cough					infrequent				frequency unknown
Disorders from the gastrointestinal tract
abdominal pain	infrequent
intestinal obstruction	infrequent
diarrhea					infrequent				frequency unknown
nausea					infrequent
vomiting					infrequent
Disturbances from the liver and bile ducts
pancreatitis									frequency unknown
hepatitis									sparse
liver dysfunction									frequency unknown
Disturbances from the skin and subcutaneous tissues
hives					infrequent				frequency unknown
itchy skin					infrequent				frequency unknown
rash	infrequent				infrequent				frequency unknown
photosensitization									frequency unknown
Disturbances from musculoskeletal and connective tissue
myalgia									frequency unknown
arthralgia									frequency unknown
rhabdomyolysis									frequency unknown
muscle spasm					infrequent
Disorders from the kidneys and urinary tract
impaired renal function					frequent
renal insufficiency					frequent
Violations of the genitals and mammary glands
erectile dysfunction/ impotence									frequency unknown
General disorders and disorders at the site of administration
asthenia	infrequent		frequent		infrequent		frequent
weakness	infrequent		frequent		infrequent		frequent
edema	infrequent
malaise									frequency unknown
Impact on the results of laboratory and instrumental studies
hyperkalemia	frequent				infrequent⁴		frequent⁵
an increase in the activity of alanine isotransferase (ALT)⁶	rare
increased concentrations of urea, creatinine and potassium in blood plasma					frequent
hyponatremia									frequency unknown
hypoglycemia							frequent

¹Including swelling of the larynx, vocal cords, face, lips, pharynx and / or tongue (which leads to impaired airway patency); in some of these patients, Quincke's edema was noted earlier in connection with the appointment of other drugs, including AMP inhibitors.

²Including hemorrhagic vasculitis (Shenlaine-Henoch disease).

³Especially in patients with hypovolemia, for example, in patients with severe heart failure or patients receiving diuretics in high doses.

⁴It is often noted in patients who received losartan in a dose of 150 m g instead of 50 mg.

⁵In a clinical study involving patients with type 2 diabetes mellitus and nephropathy, hyperkalemia> 5.5 mmol / L developed in 9.9% of patients who received losartan in tablets, and in 3.4% of patients receiving a placebo.

⁶Usually passes after the withdrawal of treatment.

The following additional adverse reactions were more frequent in patients who received losartan, than in patients receiving placebo (exact rates are unknown): back pain, urinary tract infections and flu-like symptoms. Disorders from the kidneys and urinary tract:
As a consequence of inhibition of RAAS in patients at risk, impaired renal function including acute renal failure was noted. These changes on the part of the kidney function can be reversible in the case of timely withdrawal of treatment.

Overdose:Symptoms: marked decrease in blood pressure and tachycardia; Bradycardia can occur due to parasympathetic stimulation.
Treatment: forced diuresis, symptomatic therapy; hemodialysis is not effective.

Interaction:Double blockade of RAAS with the use of angiotensin II receptor antagonists (APA II), ACE inhibitors or aliskiren (direct renin inhibitor) may be accompanied by an increased risk of arterial hypotension, fainting, hyperkalemia and renal dysfunction (including acute renal failure) compared with monotherapy .Regular monitoring of blood pressure, the function of the nights and the content of electrolytes in the blood in patients taking both losartan and other drugs that affect RAAS.
Losartan should not be used concurrently with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus and / or renal dysfunction (glomerular filtration rate less than 60 ml / mip / 1.73 m²). The use of Lozartap-Teva in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended for other patients. Can be used concomitantly with other antihypertensive agents.
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, digoxip, 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 the use of other agents that inhibit angiotensin II or its effect, the combined use of losartan with potassium-sparing diuretics (eg, spironolactone, eplerenone (a derivative of spironolactone), triamterene, amiloride), potassium preparations, salts containing potassium, increases the risk of hyperkalemia. Non-steroidal anti-inflammatory drugs (PPVP), including selective inhibitors of pycloxygenase-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 the blood plasma is possible. Considering this, it is necessary to weigh the benefits and risks of joint use of 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.

Special instructions:Prior to the use of the drug Lozartan-Teva, it is necessary to correct the BCC or begin treatment with the use of the drug in a lower dose.
Hypersensitivity
Patients with an angioneurotic edema in the anamnesis (swelling of the face, lips, throat and / or tongue) should be under strict supervision.
Drugs that have an effect on RAAS can increase the concentration of urea in the blood and the serum creatinine concentration 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.
Ischemic heart disease (CHD) and cerebrovascular disease
As with any antihypertensive drug, a too sharp decrease in blood pressure in patients with ischemic heart disease and cerebrovascular disease can lead to myocardial infarction or ischemic stroke.
Kidney transplantation
Data on the use of losartan in patients who have recently undergone kidney transplantation are not available.
Stenosis of the aortic and mitral valve, hypertrophic obstructive cardiomyopathy
When using Lozartap-Teva. as with other vasodilators, caution should be exercised in patients with hypertrophic obstructive cardiomyopathy or hemodynamically significant stenosis of the aortic or mitral valve.
Heart failure
In patients with heart failure with or without kidney function, as with other drugs acting on RAAS, there is a risk of developing severe arterial hypotension and acute renal failure.
Practically there is no experience with losartan in the treatment of patients with heart failure and concomitant severe renal insufficiency, in patients with severe chronic heart failure (IV functional class according to the NYHA classification), as well as in patients with heart failure and life-threatening arrhythmias. With this in mind, caution should be exercised when administering Lozartan-Teva to these patient categories.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism are usually resistant to therapy with antihypertensive drugs that affect the RALS. In this regard, the drug Losartan-Teva is not recommended to appoint such patients.

Effect on the ability to drive transp. cf. and fur:No special clinical studies have been conducted 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 use caution when performing tasks that require special attention, especially at the beginning of treatment with increasing doses of the drug and the management transportyymi means.

Form release / dosage:Film-coated tablets, 25 mg, 50 mg, 100 mg.

Packaging:Tablets 25 mg: 10 tablets in a blister of PVC and aluminum foil. 3 or 5 blisters together with instructions for use in a cardboard pack.
Tablets 50 mg: 14 tablets in a blister made of polyvinyl chloride and aluminum foil. 1 blister together with instructions for use in a cardboard pack. 10 tablets in a blister made of polyvinylchloride and aluminum foil. 3 blisters together with instructions for use in a cardboard bundle.
Tablets 100 mg: 10 tablets in a blister made of polyvinyl chloride and aluminum foil. 3 blisters together with instructions for use in a cardboard bundle.

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 expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000090

Date of registration:15.12.2010 / 07.10.2016

Expiration Date:Unlimited

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Works Private, Ltd. Co. Hungary

Representation: & nbspTeva Teva Israel

Information update date: & nbsp2016-10-21

Illustrated instructions

Instructions

Losartan Teva (Losartan-Teva)