Losartan Macleodz - instructions for use, dose, side effects, contraindications

Starch (45.5 mg / 33.0 mg), lactose (38.0 mg / 25.0 mg), povidone-K30 (2.0 mg / 2.0 mg), microcrystalline cellulose (13.0 mg / 13 , 0 mg), magnesium stearate (1.00 mg / 1.05 mg).

Film Sheath:

Hypromellose (1.5 mg / 1.5 mg), talc (0.45 mg / 0.45 mg), titanium dioxide (0.40 mg / 0.40 mg), propylene glycol (0.15 mg / 0.15 mg), diethylphthalate (0.30 mg / 0.30 mg), sunset sunset yellow (sunset yellow) (0.05 mg in tablet 25 mg), dye green (Pia Green dye) (0.05 mg in tablet 50 mg).

Description:

Tablets 25 mg: The capsule-shaped, biconvex tablets covered with a film cover of orange color, with the squeezed out inscription "25" on the one hand and risk on the other hand.

Tablets 50 mg: The capsule-shaped, biconvex tablets covered with a film membrane of green color, with the squeezed out inscription "50" on one side and risk on the other side.

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.

Lozartan and its pharmacologically active metabolite (e 3174) as in vitro, and in vivo block all the physiological effects of angiotensin II, regardless of the source or route of synthesis. Losartan selectively communicates with 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), 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 are preserved, which indicates an effective blockade of angiotensin II receptors. Losartan and its active metabolite have a greater affinity for angiotensin I receptors than for angiotensin receptors II. The active metabolite in 10-40 times more active losartan.

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 excretion G.

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 in 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 arterial 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 by "primary passage" through the liver by carboxylation with the participation of the isoenzyme СUR2С9 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 finite half-life 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 labeled C14 with isotope of losartan, about 35% of the radioactive label is found in the urine and 59% - in the 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 pharmacokinetic curve "concentration-time" (AUC) is approximately 2 times higher than in patients with normal renal function.

Neither losartan, nor its active metabolite, is not 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 arterialhypertension is 2 times higher than the corresponding values in men with hypertension; the concentrations of the active metabolite in men and women are not different.

Indications:

- Arterial hypertension

- Chronic heart failure (as part of combination therapy, with intolerance or inefficiency of therapy with ACE inhibitors)

- Reducing the risk of developing cardiovascular diseases, (including stroke) and mortality in patients with hypertension and left ventricular hypertrophy.

- Diabetic nephropathy or hypercreatininaemia and proteinuria (urine albumin and creatinine ratio greater than 300 mg / day) in patients with type 2 diabetes and concomitant arterial hypertension (decreased progression of diabetic nephropathy to terminal chronic renal failure).

Contraindications:

- Hypersensitivity to the components of the drug;

- bVariability;

- PThe period of lactation;

- age up to 18 years;

- thepatic impairment (more than 9 on the Child-Pugh scale);

- Mr.hereditary intolerance to galactose, lactase deficiency, or glucose-galactose malabsorption syndrome.

Carefully:

Apply the drug with arterial hypotension, reduced volume of circulating blood (BCC), violations of water-electrolyte balance, bilateral stenosis renal arteries or stenosis of the artery of a single kidney, renal failure, hepatic insufficiency (less than 9 on the Child-Pugh scale).

Pregnancy and lactation:

The use of the drug Losartan Macleodz during pregnancy is contraindicated.

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 a pregnancy, the drug Lozartan Macleodz should be discontinued immediately.

It is not known whether losartan with breast milk. It is not recommended to take Lozartan Macleodz during lactation. If the drug Lozartan Macleodz is needed during lactation, then breastfeeding should be discontinued.

Dosing and Administration:

The drug Losartan Macleodz is taken orally regardless of the meal. 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 once a 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 tablet 25 mg) once a day. Typically, the dose increases with a weekly interval (i.e., 12.5 mg / day, 25 mg / day and 50 mg / day) to an average maintenance dose of 50 mg 1 time per day, depending on the patient's 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 dose of the drug Losartan Macleodz to 100 mg in one or two doses, taking into account the reduction in blood pressure (BP).

Patients with concomitant type 2 diabetes mellitus with proteinuria: the drug Losartan Macleodz is prescribed in an initial dose of 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 Losartan Macleodz is 25 mg 1 time / day.

Patients with hepatic insufficiency (less than 9 on the Child-Pugh scale), during the procedure of hemodialysis, as well as patients older than 75 years it is recommended to lower the initial dose of the drug - 25 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").

The drug does not have the features of the action at the first admission or when it is withdrawn, but it is necessary to control blood pressure, as with any hypotensive drug.

Admission of antihypertensive drugs should be carried out at the same time as prescribed by the doctor to increase the therapeutic effect.

If you miss a dose, you need to take the next dose of the drug at the time closest to the time of the usual drug intake or while remembering that you missed the appointment,having moved the time of taking the next dose. Do not take twice the dose of the drug.

Side effects:

From the nervous system and sense organs: ≥1% - dizziness, fatigue / fatigue, headache, insomnia; <1% - anxiety, sleep disturbance, drowsiness, memory disorders, peripheral neuropathies, paresthesia, hyposthenia, hyperesthesia, migraine, tremor, ataxia, depression, syncope, ringing in the ears, taste disturbance, vision change, conjunctivitis.

On the part of the respiratory system: ≥1% - nasal congestion, cough, upper respiratory tract infections (elevated body temperature, sore throat, etc.), sinusopathy, sinusitis, pharyngitis; <1% - dyspnea, bronchitis, rhinitis.

From the side of the digestive system: ≥1% - nausea, diarrhea, dyspeptic phenomena, abdominal pain, dryness of the oral mucosa; <1% - anorexia, toothache, vomiting, flatulence, gastritis, constipation.

From the side musculoskeletal system: ≥1% - convulsions, myalgia, pain in the back, chest, legs; <1% - arthralgia, shoulder pain, knee, arthritis, fibromyalgia.

Co side of the cardiovascular system and blood (hematopoiesis, hemostasis): <1% - orthostatic reactions (dose-dependent), hypotension, palpitation, tachy- or bradycardia, arrhythmias, angina pectoris, anemia, myocardial infarction.

From the genitourinary system: <1% - mandatory urination, urinary tract infection, impaired renal function, weakening of libido, impotence.

From the skin: <1% - dry skin, erythema, a rush of blood, photosensitization, increased sweating, alopecia.

Allergic reactions: <1% - urticaria, skin rash, itching, angioedema, incl. face, lips, throat and / or tongue.

Other: ≥1% - hyperkalemia; <1% - fever, gout, increase in the level of "liver" transaminases and bilirubin in the blood, vasculitis, hyperuricemia, thrombocytopenia, eosinophilia, purpura shenlein genotype, hypercreatininaemia.

Overdose:

Symptoms: a marked decrease in blood pressure, possibly a change in heart rate (tachycardia or bradycardia).

Measures to help with overdose

Gastric lavage, forced diuresis, symptomatic maintenance therapy. Hemodialysis is ineffective (nor losartan, nor its active metabolite is not excreted in hemodialysis).

Interaction:

The drug Losartan Macleodz can be used concurrently with other antihypertensive drugs.

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, digoxin, 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 joint use of losartan with potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium preparations, salts containing potassium, increases the risk of hyperkalemia.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2), can reduce the effect of diuretics or other antihypertensives.

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 need for joint use of drugs, it is necessary to regularly monitor the concentration of lithium in the blood plasma.

Special instructions:

For patients with chronic heart failure, in whom a stable effect was achieved as a result of the use of angiotensin converting enzyme inhibitors, it is not recommended to switch to angiotensin II receptor antagonists, incl. preparation Losartan Macleodz.

Patients with liver pathology (less than 9 on the Child-Pugh scale, and especially with cirrhosis), including in the history, should be given smaller doses.

In patients with dehydration (for example, receiving treatment with high doses of diuretics), at the beginning of treatment with losartan, symptomatic arterial hypotension may occur (it is necessary to correct dehydration before losartan is administered or to begin treatment at a lower dose).

In patients with impaired renal function, both with and without diabetes, electrolyte disorders (hyperkalemia) often develop, to which attention should be paid. In the presence of acute or chronic renal failure losartan may lead to impaired renal function with or without hyperkalemia.During treatment with losartan should regularly monitor the potassium content in the blood, especially in elderly patients and with violations of kidney function. It should avoid simultaneous use of losartan with potassium-sparing diuretics.

In elderly patients who use non-steroidal anti-inflammatory drugs, with simultaneous administration of diuretics or with impaired renal function, the use of losartan can lead to impaired renal function, including the possibility of acute renal failure. These effects are usually reversible. Periodically monitor renal function in patients taking losartan and non-steroidal anti-inflammatory drugs.

Data on the safety and efficacy of the drug in children are not sufficient.

Special precautions for the destruction of the drug

Special precautions for the destruction of an unused medicinal product or a drug with an expired shelf life is not required.

Effect on the ability to drive transp. cf. and fur:

The ability of the drug to influence the speed of psychomotor reactions and the ability to control transport or other technical means has not been studied.Care should be taken when dealing with potentially hazardous activities requiring increased attention and rapid psychomotor reactions.

Form release / dosage:

Film-coated tablets, 25 mg and 50 mg.

Packaging:

10 tablets per blister (PVC / aluminum foil).

For 5 blisters together with instructions for use in a cardboard box.

Storage conditions:

In a dry place, at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001111

Date of registration:03.11.2011

Expiration Date:03.11.2016

The owner of the registration certificate:McLeodz Pharmaceuticals Co., Ltd. McLeodz Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

MACLEODS PHARMACEUTICALS, Ltd. India

Representation: & nbspAdvansd Trading, OOOAdvansd Trading, OOO

Information update date: & nbsp30.11.2016

Illustrated instructions

Instructions

Losartan Macleodz (Losartan Macleods)