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

Excipients: core: corn starch 20.0 mg, cellulose microcrystalline 159.2 mg, talc 3.2 mg, silicon colloidal dioxide 4.8 mg, sodium carboxymethyl starch 8.0 mg, magnesium stearate 4.8 mg; shell: hypromellose 3.0 mg, titanium dioxide 0.92 mg, talc 1.83 mg, macrogol 0.33 mg.

Description:

White or almost white, drop-shaped, biconvex, film-coated tablets with embossed "100" on one side and embossed "BLOn the other side, two layers are visible on the cross section: the core and the shell, the core of the tablet is white or almost white.

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 the angiotensin II receptor (subtype AT₁) for oral administration. Does not inhibit kinase II - an enzyme that catalyzes the reaction of the conversion of angiotensin I into angiotensin II.

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), kinase II, and, accordingly, does not prevent the destruction of bradykinin, therefore side effects mediated by bradykinin (eg, angioedema) are rare.

When using losartan, the absence of negative feedback influence on renin secretion leads to an increase in renin plasma activity. Increase in renin activity lead to an increase in angiotensin II in blood plasma. However, antihypertensive activity and a decrease in aldosterone concentration blood plasma persist, which indicates an effective blockade of angiotensin II receptors. 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 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.

Pharmacokinetics:

Ingestion losartan is well absorbed from the gastrointestinal tract (GIT) and at the same time is metabolized by "primary passage" through liver by carboxylation with the participation of isoenzyme CYP2C9 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. More than 9% of losartan and its active metabolite bind to blood plasma proteins, mainly albumin. The volume of distribution of losartan is 34 liters. Losartan practically does not penetrate the blood-brain barrier. Approximately 14% of losartan administered to a patient intravenously or inwardly becomes an active metabolite. 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 terminal half-life (T1 / 2) 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 C14 with isotope labeled 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.

With the clearance of creatinine (CC) above 10 ml / min. the concentration of losartan in the blood plasma does not differ from that in normal kidney function.

In patients on hemodialysis, the area under the concentration-time curve (AUC) approximately 2 times higher than in patients with normal renal function.

Neither losartan, nor its active metabolite is removed from the body by hemodialysis.

Concentrations of losartan and its active metabolite in the blood plasma of elderly patients with hypertension did not differ significantly from the values of these parameters in young male patients with 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. This pharmacokinetic difference is not clinically relevant.

Indications:

- Arterial hypertension;

- reducing the risk of cardiovascular disease and mortality in patients with hypertension and left ventricular hypertrophy;

- Diabetes mellitus type 2 with proteinuria (reduced risk of hypercreatininemia and proteinuria).

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

Contraindications:

Hypersensitivity to the components of the drug; severe hepatic insufficiency (more than 9 on the Child-Pugh scale); age to 18 years; pregnancy and lactation.

Carefully:

Carefully: hyperuricemia and / or gout, a burdened allergic anamnesis (in some patients angioedema has developed earlier with the intake of other drugs, including angiotensin-converting enzyme (ACE) inhibitors) and bronchial asthma, systemic blood diseases (including systemic lupus erythematosus), decreased the volume of circulating blood (BCC) (including against the background of high doses of diuretics), arterial hypotension, simultaneous use of non-steroidal anti-inflammatory drugs (NSAIDs), including inhibition tori cyclooxygenase-2 (COX-2), advanced age, coronary heart disease.

Pregnancy and lactation:

The use of Prezartan® 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, taking Prezartan® should be stopped immediately.

It is not known whether losartan with breast milk. Do not take Prezartan ® during lactation. If Prasartan® is needed during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Inside, regardless of food intake, the frequency of intake -1 times a day.

To ensure the following dosing regimen, it is possible to use the drug losartan in dosage form: tablets of 25 mg (including risk) and 50 mg.

With arterial hypertension the initial daily dose is 25 mg, the average daily dose is 50 mg, the frequency of administration is 1 time per day. The maximum antihypertensive effect develops in 3-6 weeks after the start of the preparation Prezartan ®. If necessary, the dose of the drug can be increased to 100 mg per day. In this case, the drug can be taken 2 times a day.

When administered to patients receiving high doses of diuretics, the initial dose should be reduced to 25 mg per day.

Patients with impaired liver function should be given lower doses of the preparation Prezartan®.

Patients with liver failure (less than 9 on the Child-Pugh scale), with, carrying out the hemodialysis procedure, as well as patients older than 75 years it is recommended to lower the initial dose of the drug - 25 mg once a day.

Prezartan® can be administered together with other antihypertensive drugs.

With chronic heart failure the initial dose for patients is 12.5 mg once a day. Typically, the dose titrated with a weekly interval (ie 12.5 mg per day, 25 mg per day, 50 mg per day) to an average maintenance dose of 50 mg 1 time per day, depending on the patient's tolerance of the drug. No dose adjustment is required in elderly patients. In patients with reduced BCC (for example, when taking diuretics in high doses) the recommended initial dose of the drug Prezartan ® is 25 mg 1 time / day.

Reducing the risk of cardiovascular disease and mortality in patients with hypertension and left ventricular hypertrophy, the initial dose is 50 mg once a day, further it is recommended to additionally appoint hydrochlorothiazide or increase the dose to 100 mg once a day (taking into account the degree of depression of blood pressure).

Diabetes mellitus type 2 with proteinuria: the initial dose is 50 mg once a day with a further increase in the dose to 100 mg / day (taking into account the degree of depression of blood pressure).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:

Side effects, occurring with a frequency of more than 1%:

Common violations: asthenia, fatigue, pain in the chest, peripheral edema.

From the side of the cardiovascular system: palpitation, tachycardia

From the digestive system: abdominal pain, diarrhea, dyspepsia, nausea.

From the musculoskeletal system: pain in the back, legs, cramps calf muscles.

From the nervous system: dizziness, headache, insomnia.

On the part of the respiratory system: cough, bronchitis, stuffy nose, pharyngitis, sinusitis, upper respiratory tract infections

Side effects, occurring with a frequency of less than 1%

From the cardiovascular system: orthostatic hypotension (dose-dependent), epistaxis, bradycardia, arrhythmias, angina pectoris, vasculitis, myocardial infarction.

From the digestive system: anorexia, dryness of the oral mucosa, toothache, vomiting, flatulence, gastritis, constipation, hepatitis, a violation of liver function.

From the skin: dry skin, erythema, ecchymosis, photosensitivity, increased sweating, alopecia.

Allergic reactions: urticaria, skin rash, itching, angioedema (including swelling of the larynx and tongue, causing airway obstruction and / or swelling of the face, lips, pharynx).

On the part of the hematopoiesis system: anemia (a slight decrease in hemoglobin and hematocrit, an average of 0.11 g% and 0.09% volume, respectively, rarely having clinical significance), thrombocytopenia, eosinophilia, purpura Shenlen-Genocha.

From the musculoskeletal system: arthralgia, arthritis, pain in the shoulder, knee, fibromyalgia.

From the nervous system and sensory organs: anxiety, sleep disorders, drowsiness, "memory impairment, peripheral neuropathy, paresthesia, hyposthenia, tremor, ataxia, depression, fainting, ringing in the ears, impaired taste, visual impairment, conjunctivitis, migraine.

From the genitourinary and reproductive system: imperative urge to urinate, urinary tract infection,impaired renal function, decreased libido, impotence.

Other: exacerbation of gout.

Laboratory indicators: often - hyperuricemia (the content of potassium in the blood plasma is more than 5.5 mmol / l); infrequently - increased concentrations of urea and residual nitrogen and creatinine in the blood serum; very rarely - a moderate increase in the activity of "liver" transaminases: aspartate aminotransferase (ACT) and alanine aminotransferase (ALT), hyperbilirubinemia.

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:

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, 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 other agents that inhibit angiotensin II or its effect, the combined use of losartan with potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium preparations, potassium-containing salts, increases the risk of hyperkalemia.

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of COX-2, can reduce the effect of diuretics and other antihypertensive agents: ACE inhibitors and angiotensin II receptor antagonists.

In patients with impaired renal function receiving NSAID therapy (including COX-2 inhibitors), angiotensin II receptor antagonist therapy can lead to further impairment of kidney function, including acute kidney failure, which is usually reversible. Simultaneous reception of these medicines should be carried out with caution in patients with impaired renal function.

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 benefit and risk of simultaneous 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 Prezartan ®, it is necessary to correct the BCC or start treatment with the drug at a lower dose.

Drugs that affect RAAS can increase the concentration of urea in the blood and serum 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.

Influence on the ability to drive vehicles and work with machinery.

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 coat of 100 mg.

Packaging:

Primary packaging: 10 or 14 tablets in a blister of aluminum foil and PVC film. Secondary packaging: 2 blisters for 14 tablets or 3 blisters for 10 tablets together with instructions for use in a cardboard box.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 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-001315

Date of registration:01.12.2011

Expiration Date:01.12.2016

The owner of the registration certificate:Ipka Laboratories Ltd.Ipka Laboratories Ltd. India

Manufacturer: & nbsp

IPCA LABORATORIES, Ltd. India

Representation: & nbspIPKA LABORATORIES LTD. IPKA LABORATORIES LTD. India

Information update date: & nbsp31.08.2016

Illustrated instructions

Instructions

Prezartan® (Presartan®)