Lirta - instructions for use, doses, side effects, contraindications

Excipients: lactose monohydrate 96.495 mg, pregelatinized starch 26,400 mg, croscarmellose sodium 7,200 mg,povidone-K25 6,750 mg, silicon dioxide colloid, anhydrous 2,400 m,; butylhydroxytoluene (E321) 0.480 mg, glyceride dibehenate 2,400 mg;

sheath: dry mixture Sepisperse 5212 Rose 10,000 mg [hypromellose (E 464) 55-65%; cellulose microcrystalline (E 460) 5-15%, titanium dioxide (E 171) 25-30%, iron dye red oxide (E 172) - max. 3%].

Description:

Round, biconvex tablets, covered with a film coat of grayish-pink color, with a risk on one side. On the cross section, the nucleus is white or almost white in color.

Pharmacotherapeutic group:Antiaggregant agent

ATX: & nbsp

B.01.A. C.04 Clopidogrel

Pharmacodynamics:

Clopidogrel is a prodrug, one of its metabolites is an inhibitor of platelet aggregation. Clopidogrel must be metabolized by enzymes CYP450 with the formation of an active metabolite, which inhibits platelet aggregation. Active metabolite clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its receptor P2Y₁₂ on platelet and subsequent ADP-dependent activation of the glycoprotein complex GPIIb/IIIa, which leads to inhibition of platelet aggregation. Thanks to irreversible binding,platelets remain immune to ADP stimulation for the remainder of their life (approximately 7-10 days), and the restoration of normal platelet function occurs at a rate corresponding to the rate of platelet renewal.

Clopidogrel also inhibits platelet aggregation caused by other agonists (other than ADP) by blocking the amplification of platelet activity upon release of ADP.

Since the active metabolite is formed by the action of enzymes CYP450, some of which are polymorphic or are inhibited by other drugs, adequate platelet inhibition will not occur in all patients.

With a daily intake of clopidogrel at a dose of 75 mg, a significant inhibition of ADP-induced platelet aggregation is noted from the first day of administration, which gradually increases for 3-7 days and then reaches a constant level (when the equilibrium state is reached). In the equilibrium state, platelet aggregation is suppressed on average by 40-60%. After stopping the use of clopidogrel, platelet aggregation and bleeding time gradually return to the baseline, on average, for 5 days.

Clopidogrel is able to prevent the development of atherothrombosis in any localization of atherosclerotic vascular lesions, in particular, in the lesions of cerebral, coronary or peripheral arteries.

Pharmacokinetics:

Suction

With a single and repeated oral administration at a dose of 75 mg / day clopidogrel quickly absorbed.

Mean values of maximum concentrations (C_mOh) of unchanged clopidogrel in blood plasma (approximately 2.2-2.5 ng / ml after a single oral dose of 75 mg) were achieved approximately 45 minutes after taking the drug. Based on the data on excretion of the metabolite of clopidogrel in the urine, the absorption of clopidogrel is not less than 50%.

Distribution

In vitro Clopidogrel and its main circulating non-active metabolite in the blood reversibly bind to blood plasma proteins (98% and 94%, respectively) and this bond is unsaturated in a wide range of concentrations.

Metabolism

Clopidogrel is extensively metabolized in the liver. In conditions in vitro and in vivo Clopidogrel is metabolized according to two main metabolic pathways: the first is mediated by esterases leading to hydrolysis to its inactive carboxylic acid derivatives (85% of circulating metabolites) and the second pathway is mediated by cytochromes P450. at first clopidogrel metabolized to the intermediate metabolite 2-oxo-clopidogrel. Subsequent metabolism of the intermediate metabolite of 2-oxo-clopidogrel leads to the formation of an active metabolite, the thiol derivative of clopidogrel. In vitro this metabolic pathway is mediated by CYP3A4, CYP2C19, CYP1A2 and CYP2B6. Active thiol metabolite of clopidogrel, which was isolated in studies in vitro, quickly and irreversibly binds to platelet receptors, thus suppressing platelet aggregation.

FROM_mOh active metabolite of clopidogrel after receiving its loading dose of 300 mg is 2 times higher than C_mOh after 4 days of taking a maintenance dose of clopidogrel 75 mg. In this case, when taking 300 mg clopidogrel C_mOh is achieved within about 30-60 minutes.

Excretion

Within 120 hours after ingestion by a human ¹⁴C-labeled clopidogrel about 50% is excreted through the kidneys and approximately 46% is excreted through the intestine. After a single oral dose of 75 mg half-life (T_1/2) Clopidogrel is approximately 6 hours. After a single administration and reception of repeated doses of clopidogrel (T_1/2) its main circulating in the blood inactive metabolite is 8 hours.

Pharmacogenetics

Using isoenzyme CYP2C19 are formed as an active metabolite, as well as an intermediate metabolite - 2-oxo-clopidogrel. Pharmacokinetics and antiplatelet effect of the active metabolite clopidogrel, in the study of platelet aggregation ex vivo, vary depending on the genotype of the isoenzyme CYP2C19. Gene allele CYP2C19 * 1 is responsible for the normally functioning metabolism, whereas the gene alleles CYP2C19 * 2 and CYP2C19 * 3 are responsible for reduced metabolism. Alleles of genes CYP2C19 * 2 and CYP2C19 * 3 cause a decrease in metabolism in the majority of representatives of the Caucasoid (85%) and Mongoloid races (99%). Other alleles associated with a lack or decrease in metabolism are less common and include, but are not limited to, gene alleles CYP2C19 * 4, * 5, * 6, * 7 and * 8. Patients with low isoenzyme activity CYP2C19, should have the two alleles of the gene with loss of function. Published frequencies of occurrence of phenotypes of persons with low isoenzyme activity CYP2C19 are 2% in Caucasians, 4% in Negroid people and 14% in Chinese. To determine the patient's isoenzyme genotype CYP2C19 there are corresponding tests.

According to a cross-sectional study (40 volunteers) and according to a meta-analysis of six studies (335 volunteers), which included individuals with very high,intermediate and low isoenzyme activity CYP2C19, there were no significant differences in the exposure of the active metabolite and in the mean platelet aggregation inhibition (IAT) (induced by ADP) in volunteers with very high, high and intermediate isoenzyme activity CYP2C19 was not identified. In volunteers with low isoenzyme activity CYP2C19, the exposure of the active metabolite decreased compared to volunteers with a high isoenzyme activity CYP2C19.

When volunteers with low isoenzyme activity CYP2C19 received a treatment regimen of 600 mg loading dose / 150 mg maintenance dose (600 mg/150 mg), the exposure of the active metabolite was higher than when taking the 300 mg / 75 mg treatment regimen. In addition, the IAT was similar to that in groups of patients with a higher metabolic rate by isoenzyme CYP2C19, who received a treatment regimen of 300 mg / 75 mg.

However, in studies with clinical outcomes, the dosing regimen of clopidogrel for patients in this group (patients with low isoenzyme activity CYP2C19) is not yet installed.

Clinical studies conducted to date have not had a sufficient sample size to detect differences in clinical outcome in patients with lowactivity of the isoenzyme СUR2С19.

Indications:

Prevention of atherothrombotic complications:

- in adults with myocardial infarction (from the first days to 35 days after myocardial infarction), ischemic stroke (in the period from 7 days to 6 months) or with the diagnosed occlusive disease of the peripheral arteries.

- in adults with acute coronary syndrome:

- without segment elevation ST (unstable angina or myocardial infarction without tooth formation Q), including patients who underwent stenting with percutaneous coronary intervention, in combination with acetylsalicylic acid (ASA);

- with segment lift ST (acute myocardial infarction), in combination with ASA with drug treatment and the possibility of carrying out thrombolytic therapy.

Prevention of atherothrombotic and thromboembolic complications, including stroke, with atrial fibrillation (atrial fibrillation) in adults with atrial fibrillation (atrial fibrillation), which have at least one risk factor for vascular complications, can not take indirect anticoagulants and have a low risk of bleeding (in combination with ASA).

Contraindications:

If you have any of these diseases, consult a doctor before taking the drug.

- Hypersensitivity to the active substance and / or to any of the auxiliary components of the drug.

- severe hepatic impairment;

- acute pathological bleeding, eg bleeding from peptic ulcers or intracranial hemorrhage;

- rare hereditary intolerance to galactose, lactase deficiency, glucose-galactose malabsorption syndrome;

- pregnancy and the period of breastfeeding;

- children under 18 years of age (safety and efficacy not established).

Carefully:

If you have any of these diseases, consult a doctor before taking the drug.

- Moderate hepatic impairment;

- chronic renal failure (limited clinical experience of use);

- with injuries, surgical interventions;

- diseases in which there is a predisposition to the development of bleeding (especially gastrointestinal or intraocular);

- with the simultaneous administration of non-steroidal anti-inflammatory drugs, including,selective inhibitors of cyclooxygenase-2 (COX-2);

- with simultaneous administration of warfarin, heparin and glycoprotein inhibitors IIb /IIIa;

- with a hereditary decrease in the function of the isoenzyme CYP2C19 because they have less active metabolite of clopidogrel in recommended doses at recommended doses and less pronounced its antiplatelet effect, and therefore, when taking the usually recommended doses of clopidogrel in acute coronary syndrome or percutaneous coronary intervention, a higher frequency of cardiovascular complications than in patients with normal activity of isoenzyme СUR2С19.

Pregnancy and lactation:

Pregnancy

As a precaution, the use of clopidogrel during pregnancy is not recommended because of the lack of clinical data on the use of clopidogrel by pregnant women.

Animal studies do not indicate a direct or indirect adverse effect on pregnancy, embryonic / intrauterine development, delivery or postnatal development.

Lactation

It is not known whether clopidogrel with human breast milk.Studies in animals have shown that clopidogrel excreted in breast milk. As a precautionary measure it is not recommended to apply clopidogrel during lactation. If necessary, clopidogrel therapy is recommended to stop breastfeeding.

Dosing and Administration:

The drug is taken orally, regardless of food intake. A drug clopidogrel appoint adults and patients of advanced age.

Adults and elderly people with normal activity of isoenzyme СUR2С19

Myocardial infarction, ischemic stroke and diagnosed peripheral arterial occlusive disease

The drug is prescribed in a dose of 75 mg once a day. In patients with myocardial infarction, treatment can begin from the first days to 35 days after myocardial infarction; and in patients with ischemic stroke in the period from 7 days to 6 months.

Acute coronary syndrome without segment elevation ST (unstable angina or myocardial infarction without tooth formation Q)

Treatment with clopidogrel should begin with a single dose of 300 mg loading dose, and then continue at a dose of 75 mg once a day (in combination with ASA in doses of 75-325 mg per day).Since the use of ASA at higher doses is associated with an increased risk of bleeding, the recommended dosage for ASC should not exceed 100 mg. The optimal duration of treatment has not been formally established. The maximum favorable effect is observed by the 3rd month of treatment. The course of treatment is up to 1 year.

Acute coronary syndrome with segment elevation ST (acute myocardial infarction with tooth formation ST)

Clopidogrel is prescribed in a dose of 75 mg once a day with an initial single dose 300 mg loading dose in combination with acetylsalicylic acid in combination or without thrombolytics. In patients older than 75 years, treatment clopidogrel om should be started without taking a loading dose. Combination therapy starts as soon as possible after the onset of symptoms and lasts for at least 4 weeks. The benefits of a combination of clopidogrel with ASA for more than 4 weeks were not investigated under these conditions.

Atrial fibrillation (atrial fibrillation)

Clopidogrel should be taken once a day at a dose of 75 mg. In combination with clopidogrel, you should start and then continue taking ASA (75-100 mg per day).

Patients with genetically determined reduced activity of isoenzyme СУР2С19

Low isoenzyme activity CYP2C19 is associated with a decrease in the antiplatelet effect of clopidogrel. The mode of application of higher doses (600 mg - loading dose, then 150 mg once a day daily) in patients with low isoenzyme activity CYP2C19 increases the antiplatelet effect of clopidogrel (see the section "Pharmacokinetics"). However, at the present time in clinical studies that take into account clinical outcomes, the optimal dosing regimen for clopidogrel has not been established for patients with reduced metabolism due to genetically determined low isoenzyme activity CYP2C19.

Special patient groups

Elderly people

In elderly volunteers (over 75 years old), when compared with young volunteers, there was no difference in platelet aggregation and bleeding time. Do not require dose adjustment for the elderly.

Children

The safety and efficacy of clopidogrel in children and adolescents have not been established.

Patients with impaired renal function

After repeated use of clopidogrel at a dose of 75 mg per day in patients with severe renal disease (creatinine clearance from 5 to 15 ml / min), inhibition of ADP-induced platelet aggregation (25%) was lower than that of healthy volunteers, however, lengthening bleeding time was similar to that of healthy volunteers who received clopidogrel in a dose of 75 mg per day. In addition, all patients had good tolerability of the drug.

Patients with impaired hepatic function

After daily for 10 days of taking clopidogrel at a daily dose of 75 mg in patients with severe liver damage, inhibition of ADP-induced platelet aggregation was similar to that of healthy volunteers. The mean bleeding time was also comparable in both groups.

Patients of different ethnicity

The prevalence of alleles of genes of isoenzyme СУР2С19, responsible for the intermediate and decreased metabolism of clopidogrel to its active metabolite, differs among representatives of different ethnic groups (see Section "Pharmacogenetics"). There are only limited data for representatives of the Mongoloid race on the impact of the genotype of the isoenzyme CYP2C19 on clinical outcome events.

Features of the drug during its cancellation:

Do not stop treatment without consulting a doctor. Contact your doctor or pharmacist if you decide to stop taking the drug.

Features of the actions of a doctor (paramedic), a patient with a pass of one or more doses of the drug:

- eIf less than 12 hours have elapsed after missing the next dose, the missed dose of the drug should be taken immediately, and then the following doses should be taken at the usual time;

- eIf more than 12 hours have passed after missing the next dose, the patient should take the next dose at the usual time. Do not take a double dose to replace the missed one.

Side effects:

Adverse reactions are given according to the frequency of their occurrence: very often (≥1/10), often (≥1/100 to <1/10); infrequently (≥1/1000 to <1/100); rarely (≥1/10000 to <1/1000); very rarely (<1/10000) and unknown (can not be estimated from the available data). Within each class of the organ system, adverse reactions are given in order of decreasing severity.

Bleeding is the most frequent reaction, most often it develops during the first month of treatment.

Violations of the blood and lymphatic system

- infrequently: thrombocytopenia, leukopenia, eosinophilia;

- rarely: neutropenia, including severe neutropenia;

- very rarely: thrombotic thrombocytopenic purpura (TTP), aplastic anemia, pancytopenia, agranulocytosis, severe thrombocytopenia, granulocytopenia, anemia.

Immune system disorders

- very rarely: serum sickness, anaphylactoid reactions.

Disorders of the psyche

- very rarely: hallucinations, confusion.

Disturbances from the nervous system

- infrequently: intracranial hemorrhage (there are reports of several fatal cases), headache, paresthesia, dizziness;

- very rarely: a taste disorder.

Disturbances on the part of the organ of sight

- infrequently: eye hemorrhage (conjunctival, in the tissue and retina of the eye). Disturbances from the ear and the labyrinth of the ear

- rarely: vertigo.

Disorders from the cardiovascular system

- often: hematoma;

- very rarely: heavy bleeding, bleeding from the operating wound, vasculitis, lowering blood pressure.

Disturbances from the respiratory system, chest and mediastinal organs

- often: epistaxis;

- very rarely: bleeding from the respiratory system (hemoptysis, pulmonary hemorrhage), bronchospasm, interstitial pneumonitis.

Disorders from the gastrointestinal tract

- very often: bleeding of the gastrointestinal tract, diarrhea, abdominal pain, indigestion;

- infrequently: peptic ulcer of stomach and duodenum, gastritis, vomiting, nausea, constipation, bloating;

- rarely: retroperitoneal bleeding;

- very rarely: gastrointestinal and retroperitoneal bleeding sometimes fatal, pancreatitis, colitis (including ulcerative or lymphocytic colitis), stomatitis.

Disturbances from the liver and bile ducts

- very rarely: acute hepatic insufficiency, hepatitis, deviation from the norm of indicators of the liver functionnor.

Disturbances from the skin and subcutaneous tissues

- often: bruises;

- infrequently: rash, itchy skin, purpura (subcutaneous hemorrhage);

- very rarely: bullous dermatitis (toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme), angioedema, erythematous rash, urticaria, eczema, flat lichen.

Disturbances from musculoskeletal and connective tissue

- very rarely: hemorrhages in the muscles and joints, arthritis, arthralgia, myalgia.

Disorders from the kidneys and urinary tract

- infrequently: hematuria;

- very rarely: glomerulonephritis, increasing the level of creatinine.

General disorders and disorders at the site of administration

- often: bleeding at the injection site.

- very rarely: fever.

Laboratory research

- infrequently: an increase in bleeding time, a decrease in the number of neutrophils, a decrease in the number of platelets.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

Symptoms: prolongation of bleeding time and subsequent complications in the form of development of bleeding.

Giving help: When bleeding occurs, appropriate therapy should be performed. If rapid correction of prolonged bleeding time is necessary, transfusion of platelet mass is recommended. There is no specific antidote.

Interaction:

Oral anticoagulants: simultaneous use of clopidogrel with oral anticoagulants is not recommended, since such a combination can increase the intensity of bleeding.Although taking clopidogrel at a dose of 75 mg / day did not alter the pharmacokinetics of S-warfarin or the International Normalized Ratio (INR) in patients receiving long-term treatment with warfarin, concurrent administration of clopidogrel increases the risk of bleeding due to its independent additional effect on clotting.

Inhibitors of glycoprotein IIb/IIIa: simultaneous use of clopidogrel and blockers IIb /IIIa-receptor requires caution, especially in patients with an increased risk of bleeding (with trauma, surgery or other pathological conditions (cSee sections "With caution" and "Special instructions").

Acetylsalicylic acid (ASA): ASA does not change the inhibitory effect of the drug clopidogrel on ADP-induced platelet aggregation, but the drug clopidogrel potentiates the effect of ASA on collagen-induced platelet aggregation. However, simultaneous with clopidogrel, the intake of acetylsalicylic acid 500 mg twice a day for 1 day did not cause a significant increase in bleeding time caused by the use of clopidogrel.Between clopidogrel and ASA, pharmacodynamic interaction is possible, which leads to an increased risk of bleeding. Given this, caution should be exercised when they are used simultaneously, although in clinical trials patients received combination therapy with clopidogrel and acetylsalicylic acid for 1 year.

Heparin: according to a clinical study conducted on healthy volunteers, when taking clopidogrel simultaneously with heparin, there was no need to change the dose of heparin and its anticoagulant effect did not change. The simultaneous use of heparin did not alter the inhibitory effect of clopidogrel on platelet aggregation. Between the drug clopidogrel and heparin pharmacodynamic interaction is possible, which may increase the risk of bleeding, so caution is required with this combination.

Thrombolytics: safety of simultaneous application of clopidogrel. fibrin-specific or nonspecific thrombolytics and heparin was investigated in patients with acute myocardial infarction. The incidence of clinically significant bleeding was similar to that ofwhich was observed in the case of simultaneous use of thrombolytic agents and heparin with acetylsalicylic acid.

Non-steroidal anti-inflammatory drugs (NSAIDs): prescription of NPBC (including, inhibitors of COX-2) in conjunction with the drug clopidogrel requires caution. In a clinical study conducted with the participation of healthy volunteers, the simultaneous use of clopidogrel and naproxen increased latent gastrointestinal bleeding. However, due to the lack of research on the interaction of clopidogrel with other NSAIDs, it is currently unknown whether there is an increased risk of gastrointestinal bleeding when taking clopidogrel simultaneously with other HBBCs.

Other combination therapy

Because the clopidogrel metabolized to its active metabolite in part by CYP2C19, the use of drugs that inhibit the activity of this enzyme can lead to a decrease in the level of the active metabolite and a decrease in clinical efficacy. Drugs that inhibit CYP2C19: omeprazole and esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxcarbazepine and chloramphenicol.

Omeprazole 80 mg, prescribed once a day simultaneously with clopidogrel or with an interval of 12 hours between the use of these two drugs, reduces the level of the active metabolite in the blood plasma. Reduction was associated with inhibition of platelet aggregation. Esomeprazoleis expected to have a similar interaction with clopidogrel.

A less pronounced decrease in the level of the active metabolite in the blood plasma is observed with pantoprazole or lansoprazole.

The simultaneous use of drugs that inhibit CYP2C19 should be avoided (for example, omeprazole). If proton pump inhibitors are to be taken concomitantly with clopidogrel, a proton pump inhibitor with the least inhibited isoenzyme СУР2С19 should be used, such as pantoprazole.

A number of clinical studies with clopidogrel and other concomitantly prescribed drugs were conducted to study possible pharmacodynamic and pharmacokinetic interactions that showed that:

- with the simultaneous use of clopidogrel with atenolol and / or nifedipine, there was no clinically significant pharmacodynamic interaction;

- pharmacodynamic activity of clopidogrel did not change significantly when combined with phenobarbital, cimetidine or estrogens;

- pharmacokinetic indices of digoxin and theophylline did not change when they were used together with clopidogrel;

antacids did not reduce the absorption of clopidogrel;

- phenytoin and tolbutamide can be safely used simultaneously with clopidogrel (CAPR studyIE), despite the fact that the data obtained from studies with human liver microsomes indicate that the carboxylic metabolite clopidogrel can inhibit the activity of the CYP2C9 isoenzyme, which can lead to an increase in the plasma concentrations of certain drugs (phenytoin, tolbutamide and some NSAIDs ), which are metabolized by the CYP2C9 isoenzyme;

- Clinical studies did not reveal a clinically significant undesirable interaction of clopidogrel with angiotensin converting enzyme (ACE) inhibitors, diuretics, β-adrenoblockers, calcium channel blockers, lipid-lowering drugs, coronary vasodilators, antidiabetics (incl.insulin), antiepileptic drugs, and drugs for hormone replacement therapy and glycoprotein antagonists IIb / IIIa.

Special instructions:

When using clopidogrel, especially during the first weeks of treatment and / or after invasive cardiac procedures / surgical intervention, careful monitoring of patients should be carried out to exclude signs of bleeding, including concealed ones.

In connection with the risk of bleeding and hematological side effects, if clinical symptoms appearing during treatment are suspect for the occurrence of bleeding, it is urgent to do a clinical blood test, determine APTT, the number of platelets, the platelet function and perform other necessary studies.

A drug clopidogrel should be used with caution in patients who have an increased risk of bleeding associated with trauma, surgery or other pathological conditions, as well as with combination therapy with acetylsalicylic acid, NSAIDs (including COX-2 inhibitors), heparin or glycoprotein inhibitors IIb / IIIa.

Joint use of clopidogrel with oral anticoagulants (or warfarin) may increase the intensity of bleeding, so caution should be exercised when using clopidogrel and warfarin together (or oral anticoagulants).

At planned surgical interventions and, if the antiplatelet effect is temporarily undesirable, the course of treatment with the drug clopidogrel should be discontinued 7 days before surgery.

A drug clopidogrel should be used with caution in patients with a risk of bleeding (especially gastrointestinal and intraocular bleeding). Drugs that can cause damage to the gastrointestinal mucosa (such as ASA, non-steroidal anti-inflammatory drugs) in patients receiving clopidogrel, should be used with caution.

Patients should be warned that when taking clopidogrel (alone or in combination with acetylsalicylic acid) it may take longer to stop bleeding, and also if they have an unusual (localized or prolonged) bleeding, they should be informed about this to your doctor.Before any future operation and before starting any new drug, patients should inform the doctor (including the dentist) about taking clopidogrel. Very rarely there have been cases of idiopathic thrombocytopenic purpura (ITP) after taking clopidogrel (sometimes even briefly). This was characterized by thrombocytopenia and microangiopathic hemolytic anemia in combination with either neurologic symptoms, impaired renal function, or fever. The development of ITPs can pose a threat to life and require the adoption of urgent measures, including plasmapheresis.

The drug should be administered with caution in patients with impaired liver function.

Care should be taken when using the drug in patients with moderate hepatic disease, because of the risk of hemorrhagic diathesis.

The use of clopidogrel is not recommended for acute stroke with a prescription of less than 7 days, because There is no data on the use of the drug in this state.

The preparation Lirta® contains lactose. Patients with a rare hereditary intolerance to galactose,lactase deficiency Lappa or malabsorption syndrome glucose-galactose should not take the drug (see section "Composition").

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

A drug Lirta® does not significantly affect the ability to drive vehicles or work with mechanisms that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets coated with a film coating, 75 mg.

Packaging:

Primary packaging:

10 tablets per blister perforated from aluminum foil and PVC / TE / PVDC film.

Secondary packaging:

3 blisters (30 tablets), along with instructions for use, are placed in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002231

Date of registration:17.09.2013 / 22.04.2014

Expiration Date:17.09.2018

The owner of the registration certificate:Alkaloid, JSCAlkaloid, JSC Macedonia

Manufacturer: & nbsp

ALKALOID, AD Macedonia

Representation: & nbspALKALOID, AOALKALOID, AO

Information update date: & nbsp11.04.2018

Illustrated instructions

Instructions

Lirta® (Lirta®)