Keppra - Instructions For Use, Price, Reviews, Tablets, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Keppra

Keppra: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. For violations of liver function
11. 11. Drug interactions
12. 12. Analogs
13. 13. Terms and conditions of storage
14. 14. Terms of dispensing from pharmacies
15. 15. Reviews
16. 16. Price in pharmacies

Latin name: Keppra

ATX code: N03AX14

Active ingredient: levetiracetam (levetiracetam)

Producer: UCB Pharma (Belgium)

Description and photo update: 2019-13-08

Prices in pharmacies: from 461 rubles.

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Keppra is an anticonvulsant, antiepileptic drug that is active against both generalized and focal epileptic seizures.

Release form and composition

Keppra is available in the following dosage forms:

• Concentrate for preparation of solution for infusion: transparent colorless solution (5 ml in glass vials, 5 vials in blisters, 2 packs in a cardboard box);
• Film-coated tablets (blue - 250 mg, light yellow - 500 mg, white - 1000 mg): oval, biconvex, on one side there is a risk separating the engraving "ucb" and the dosage (ucb | 250, ucb | 500, ucb | 1000), white at the break, homogeneous (10 pcs. In blisters / blisters / blisters, 3 or 6 blisters / packs in a cardboard box);
• Oral solution: transparent, almost colorless liquid with a characteristic odor (300 ml each in dark glass vials, complete with a white polypropylene screw cap with childproof function and a measuring syringe (polyethylene / polystyrene), 1 set in a cardboard box)).

The composition of 5 ml of a concentrate for the preparation of Keppra's infusion solution includes:

• Active ingredient: levetiracetam - 500 mg;
• Auxiliary components: sodium chloride - 45 mg, sodium acetate trihydrate - 8.2 mg, 10% glacial acetic acid - until a pH of 5.5 is reached, water for injection - up to 5 ml.

The composition of 1 Keppra tablet includes:

• Active ingredient: levetiracetam - 250 mg, 500 mg, 1000 mg;
• Auxiliary components (250/500/1000 mg, respectively): silicon dioxide - 5.188 / 10.375 / 20.75 mg, croscarmellose sodium - 10.75 / 21.5 / 43 mg, macrogol 6000 - 2.5 / 5/10 mg, magnesium stearate - 0.313 / 0.625 / 1.25 mg;
• Film coating (250/500/1000 mg, respectively): Opadry 85F20694 - 8.063 mg / Opadry 85F32004 - 16.125 mg / Opadry 85F18422 - 32.25 mg.

The composition of 1 ml of Keppra oral solution includes:

• Active ingredient: levetiracetam - 100 mg;
• Auxiliary components: sodium citrate - 1.05 mg, citric acid monohydrate - 0.06 mg, methyl parahydroxybenzoate - 2.7 mg, propyl parahydroxybenzoate - 0.3 mg, ammonium glycyrrhizate - 1.5 mg, 85% glycerol - 235.5 mg, maltitol - 300 mg, acesulfame potassium - 4.5 mg, grape flavor 501040A - 0.3 mg, purified water - 504 mg.

Pharmacological properties

Pharmacodynamics

Keppra's active component, levetiracetam, belongs to pyrrolidone derivatives (S-enantiomer of α-ethyl-2-oxo-1-pyrrolidine-acetamide). Its chemical structure is different from other known antiepileptic drugs. The same applies to the mechanism of action of the drug, which is currently insufficiently studied.

In vivo and in vitro studies have shown that levetiracetam does not alter the basic properties of cells and does not affect normal transmission. In experiments in vitro, it was revealed that levetiracetam affects the intraneuronal level of Ca ^{2+ ions}, partially slowing down their flow through the N-type channels and reducing the degree of calcium release from intraneuronal stores. Also, the active component of Keppra partially normalizes the currents through glycine and GABA-dependent channels, which have been reduced by carbolines and zinc.

One of the probable mechanisms of action is based on the experimentally confirmed binding of SV2A synaptic vesicles with a glycoprotein that is part of the gray matter of the spinal cord and brain. It is believed that in this way an anticonvulsant effect is achieved, expressed in the prevention of hypersynchronization of neural activity. The effect of levetiracetam on glycine receptors and GABA receptors has also been observed through their modulation by various endogenous agents. Taking the drug does not lead to a change in normal neurotransmission, however, it helps to suppress epileptiform neuronal outbreaks induced by the GABA agonist bikuculin and the excitation of glutamate receptors. Keppra is effective both for focal,and with generalized epileptic seizures (epileptiform manifestations or photoparoxysmal reactions are implied).

Pharmacokinetics

Pharmacokinetics of levetiracetam does not depend on the time of day, race and gender. The substance is distinguished by good solubility and high penetrating power. After oral administration, levetiracetam is well absorbed from the gastrointestinal tract and absorbed completely, and this process is linear. Due to this, the content of the substance in the blood plasma can be predicted taking into account the taken dose of levetiracetam, expressed in mg / kg of body weight. The degree of absorption is not affected by the dose size and meal time. The bioavailability of levetiracetam reaches 100%. Its maximum plasma level is recorded 1.3 hours after taking the drug orally at a dose of 1000 mg and after a single dose is 31 μg / ml, and after repeated administration (2 times a day) - 43 μg / ml. When Keppra is taken twice, the equilibrium state is achieved 2 days after the start of treatment.

Levetiracetam and its main metabolite bind to plasma proteins by less than 10%. The volume of distribution is approximately 0.5-0.7 l / kg. There is no information on tissue distribution of the substance.

Levetiracetam is metabolized primarily by enzymatic hydrolysis of the acetamide group (24% of the dose taken). The primary metabolite ucb L057, which has no pharmacological activity, is formed without the participation of liver cytochrome P ₄₅₀. Keppra's active ingredient does not change the enzymatic activity of hepatocytes.

In vitro, levetiracetam and its main metabolite do not inhibit the main forms of cytochrome P ₄₅₀ (CYP3A4, 1A2, 2A6, 2E1, 2C9, 2D6, and 2C19), nor do they inhibit the activity of epoxide hydroxylase and glucuronyl transferase (UGT1A6 and UGT1A1). Taking levetiracetam also does not affect the glucuronidation of valproic acid, which is carried out in vitro.

The half-life of the substance from the blood plasma of an adult is approximately 7 ± 1 hour and is not determined by the dosage regimen and the route of administration. The average total clearance is 0.96 ml / min / kg. 95% of levetiracetam is excreted in the urine. The renal clearance of this substance and its metabolite is 0.6 and 4.2 ml / min / kg, respectively.

In elderly patients, an increase in the half-life of 40% is observed: usually it is 10-11 hours, which is due to renal dysfunction in this category of patients.

In patients with renal dysfunctions, there is a correlation between the clearance of Keppra's active component and its primary metabolite with creatinine clearance. Therefore, in renal failure, dose selection is necessary depending on the QC indicator. In adult patients diagnosed with end-stage renal failure, the half-life reaches 25 hours between dialysis sessions, and during dialysis is 3.1 hours. During a dialysis session lasting 4 hours, up to 51% of levetiracetam is excreted from the body.

In patients with mild to moderate liver dysfunctions, clinically significant changes in the clearance of levetiracetam are not observed. In most patients with severe liver dysfunctions and concomitant renal failure, a decrease in the clearance of levetiracetam by more than 50% was recorded.

In children aged 4–12 years, the half-life after a single dose of Keppra at a dose of 20 mg / kg of body weight is 6 hours. The total clearance of levetiracetam in patients of this age group is approximately 30% higher and is determined by body weight.

After repeated oral administration at a dose of 20-60 mg / kg of body weight in children 4-12 years of age, the maximum level of levetiracetam in blood plasma is reached after 30-60 minutes, and its concentration increases linearly and in direct proportion to the dose taken.

Indications for use

According to the instructions, Keppra is used simultaneously with other drugs to treat the following conditions / diseases:

• Epilepsy: partial seizures with or without secondary generalization in adults and children over 1 month old (oral solution), 4 years old (infusion solution, tablets);
• Juvenile myoclonic epilepsy: myoclonic seizures in adults and children over 12 years old;
• Idiopathic generalized epilepsy: primary generalized convulsive (tonic-clonic) seizures in adults and children over 12 years of age.

As a monotherapy (drug of choice), Keppra is used for partial seizures with or without secondary generalization in adults and adolescents from 16 years of age with newly diagnosed epilepsy.

The concentrate for the preparation of a solution for infusion is used temporarily when oral forms of the drug cannot be taken for any reason.

Contraindications

• Children's age: up to 1 month - solution for oral administration (efficacy and safety of the drug have not been established), up to 4 years - infusion solution, tablets;
• Hypersensitivity to pyrrolidone derivatives, including levetiracetam, as well as other components.

Keppra therapy is carried out with caution in elderly patients (from 65 years), with liver diseases in the stage of decompensation and renal failure.

Instructions for use of Keppra: method and dosage

The duration of the course of treatment and the choice of Keppra's dosage form is made by the attending physician.

Oral solution, film-coated tablets

Keppra's solution and tablets are taken orally, dividing the daily dose into 2 equal doses; the tablets should be taken with sufficient liquid.

As a drug of choice for monotherapy of partial seizures with or without secondary generalization in adults and adolescents over 16 years of age: the initial dose is 500 mg per day, divided into 2 doses of 250 mg. After 2 weeks, the dose can be increased to the basic therapeutic dose - 1000 mg per day, divided into 2 doses of 500 mg each. The maximum daily dose is 3000 mg, divided into 2 doses of 1500 mg.

As part of complex therapy for children from 1 month to six months, Keppra is prescribed in the form of a solution for oral administration in an initial therapeutic dose of 7 mg / kg 2 times a day. Depending on the clinical efficacy and tolerability, the dose may be increased to 21 mg / kg 2 times a day. It is allowed to change the dose plus / minus 7 mg / kg 2 times a day every 2 weeks until the minimum effective dose is reached.

The recommended dosage of the solution for oral administration to children up to six months is 2 times a day, depending on the child's body weight (initial dose / maximum dose):

• 4 kg - 28-84 mg (0.3-0.85 ml);
• 5 kg - 35-105 mg (0.35-1.05 ml);
• 7 kg - 49-147 mg (0.5-1.5 ml).

In children and adolescents aged from six months to 17 years, with a body weight of up to 50 kg, therapy begins with a dose of 10 mg / kg 2 times a day. Depending on the tolerability of the drug and the clinical response, the dose may be increased to 30 mg / kg 2 times a day (the dose can be changed by 10 mg / kg every 2 weeks; the minimum effective dose must be used).

For children weighing 50 kg or more, the dosage regimen is the same as for adult patients.

The recommended dosage of Keppra for children from six months is 2 times a day, depending on the child's body weight (initial dose / maximum dose):

• 6 kg - 60-180 mg (0.6-1.8 ml);
• 10 kg - 100-300 mg (1-3 ml);
• 15 kg - 150-450 mg (1.5-4.5 ml);
• 20 kg - 200-600 mg (2-6 ml);
• 25 kg - 250-750 mg;
• from 50 kg - 500-1500 mg.

Children over 4 years old should start therapy with a dose of 20 mg / kg per day, divided into 2 doses (10 mg / kg 2 times a day). Dose change by 20 mg / kg of body weight per day is carried out every 2 weeks until the recommended dose is reached - 60 mg / kg per day (30 mg / kg 2 times a day). If the recommended daily dose is intolerant, it may be reduced. The minimum effective dose should be used.

Keppra is used in the most suitable dosage and dosage form, depending on the patient's weight and the required therapeutic dose.

Children weighing less than 20 kg are recommended to start therapy with Keppra in the form of an oral solution.

Dosing of the solution for oral administration is carried out with a measuring syringe with a nominal capacity of 10 ml (1 g of levetiracetam) with a division value of 25 mg (0.25 ml), which is included in the delivery kit of the drug. The dose of the drug, metered for administration, is diluted in 200 ml of water.

Step-by-step instructions for dosing the oral solution using a measuring syringe:

1. Open the Keppra bottle by pressing the cap and turning it counterclockwise;
2. Insert the syringe adapter into the neck of the vial and, making sure of good fixation, place the syringe into the adapter;
3. Turn the bottle upside down;
4. Draw a small amount of solution into the syringe by pulling the plunger down, then push the plunger up to remove air bubbles;
5. Fill the syringe with the solution by pulling the plunger down to the division corresponding to the dose prescribed by the doctor;
6. Turn the bottle upside down, remove the syringe from the adapter;
7. Introduce the contents of the syringe into a baby bottle or glass of water, pushing the plunger all the way;
8. Drink the contents of a baby bottle or glass completely;
9. Rinse the syringe with water;
10. Close the bottle with a plastic cap.

Infusion solution

Keppra is injected intravenously over 15 minutes; the daily dose of the solution is divided into 2 equal administrations.

One bottle of concentrate for solution for infusion contains 500 mg of levetiracetam (100 mg / ml). The concentrate should be diluted with at least 100 ml solvent.

Instructions for dosing Keppra's solution (solvent volume - 100 ml, infusion time - 15 minutes, frequency of administration - 2 times a day):

• 250 mg: 2.5 ml (¹ / ₂ ampoules 5 ml) - 500 mg per day;
• 500 mg: 5 ml (1 ampoule 5 ml) - 1000 mg per day;
• 1000 mg: 10 ml (2 ampoules of 5 ml) - 2000 mg per day;
• 1500 mg: 15 ml (3 ampoules of 5 ml) - 3000 mg per day.

It is recommended to use as solvents: Ringer's lactate solution for injection, 0.9% sodium chloride solution for injection, 5% dextrose solution for injection.

The solution is chemically stable for 24 hours at a temperature of 15-25 ° C in polyvinyl chloride bags. However, from the point of view of microbiological sterility, the drug should be used immediately after reconstitution.

If necessary, the solution can be stored at 2-8 ° C throughout the day, provided that the dilution was done under aseptic conditions. The user is responsible for the microbiological purity.

The dosage regimen of the solution for infusion is fully consistent with that described for oral forms. The transition from intravenous (IV) administration to oral administration of Keppra and vice versa can be done while maintaining the frequency of use and dose.

Features of Keppra's use in renal failure: since levetiracetam is excreted from the body by the kidneys, when prescribing the drug to elderly patients and patients with renal failure, it is necessary to adjust the dose depending on creatinine clearance (CC).

For men, CC is calculated using the following formula:

CC (ml / min) = (140 - age (number of years)) × body weight (kg) / 72 × Cl (mg / dl.)

Cl is the concentration of serum creatinine.

For women, CC is calculated by multiplying the result by a factor of 0.85.

Correction of the QC value taking into account the body surface area (BSP):

Cl (ml / min) / 1.73 m ² = Cl (ml / min) × 1.73 / PPT (m ²).

The recommended dosage regimen depending on the degree of renal failure (CC values):

• Norm (CC more than 80) - 500-1500 mg 2 times a day;
• Latent (CC 50-79) - 500-1000 mg 2 times a day;
• Compensated (CC 30-49) - 250-750 mg 2 times a day;
• Intermittent (CC less than 30) - 250-500 mg 2 times a day;
• Terminal (patients on hemodialysis) - 500-1000 mg once a day.

On the first day of therapy for patients on hemodialysis, it is recommended to take a saturating dose of Keppra - 750 mg. Further, after dialysis, an additional 250-500 mg of levetiracetam should be taken / administered.

With renal failure in children, the dose of levetiracetam is adjusted taking into account the degree of renal failure and the recommendations given for adults.

No dose adjustment is required for mild and moderate liver dysfunction. In the case of decompensated liver dysfunctions and renal failure, the CC value may not reflect the real degree of renal dysfunction, therefore, with CC less than 70 ml / min, the daily dose should be reduced by 50%.

Side effects

The most common adverse reactions are drowsiness, nasopharyngitis, headache, dizziness and fatigue.

Side effects from systems and organs, depending on the frequency of occurrence (≥1 / 10 - very often; ≥1 / 100- <1/10 - often; ≥1 / 1000- <1/100 - infrequently; ≥1 / 10,000 - <1/1000 - rarely; <1/10 000 - extremely rare):

• Hepatobiliary system: infrequently - changes in liver function tests; rarely - hepatitis, liver failure;
• Respiratory system: often - cough;
• Immune system: rarely - DRESS syndrome (drug-induced hypersensitivity syndrome with eosinophilia);
• Invasions and infections: very often - rhinopharyngitis; rarely - infection;
• Skin: often - rash; infrequently - eczema, itching, alopecia; rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme;
• Musculoskeletal system: infrequently - myalgia, muscle weakness;
• Blood and lymphatic system: infrequently - leukopenia, thrombocytopenia; rarely - agranulocytosis, pancytopenia (in some episodes with bone marrow suppression), neutropenia;
• Nervous system: very often - headache, drowsiness; often - imbalance, convulsions, dizziness, tremors, lethargy; infrequently - memory impairment, amnesia, impaired coordination / ataxia, decreased concentration, paresthesia; rarely - dyskinesia, choreoathetosis, hyperkinesia;
• Metabolism: often - anorexia; infrequently - decrease or increase in body weight;
• General disorders: often - asthenia / fatigue;
• Organ of vision: infrequently - blurred vision, diplopia;
• Hearing organ: often - dizziness (vertigo);
• Digestive system: often - diarrhea, dyspepsia, abdominal pain, nausea, vomiting; rarely - pancreatitis;
• Mental disorders: often - hostility / aggressiveness, depression, anxiety, insomnia, irritability, nervousness; infrequently - suicidal intentions, suicidal attempts, behavioral disorders, psychotic disorders, hallucinations, confusion, anger, emotional lability, agitation, mood swings, panic attacks; rarely - personality disorder, violation of the thinking process, suicide;
• Injuries, complications of procedures: infrequently - accidental injuries.

In general, the safety profiles of levetiracetam in different age groups of children and adults are similar.

After discontinuation of levetiracetam, hair restoration was observed in some cases.

Overdose

Symptoms of Keppra's overdose are anxiety, drowsiness, blurred consciousness, agitation, aggressiveness, depression of the respiratory center, and coma. In the acute period of poisoning, it is necessary to artificially induce vomiting and rinse the stomach, and then take activated charcoal. There is no specific antidote for levetiracetam. If necessary, the patient is prescribed symptomatic therapy in a hospital using hemodialysis (the effectiveness of dialysis for Keppra's active component is 60%, and for its main metabolite - 74%).

special instructions

Under the influence of food, the completeness of absorption of levetiracetam does not change, but the rate of absorption is somewhat reduced.

If it is necessary to stop taking Keppra, it is recommended to cancel it in stages (reducing a single dose every 2-4 weeks by 500 mg). The dose reduction for children should not exceed 10 mg / kg 2 times a day every 2 weeks, and for children under six months - 7 mg / kg 2 times a day every 2 weeks.

During the transfer of patients to taking levetiracetam, concomitant antiepileptic drugs are recommended to be canceled gradually.

There are no data when using Keppra in children, indicating any negative effect on their sexual maturity and development, but the long-term effects of levetiracetam's effect on learning ability, growth, endocrine gland function, fertility, sexual and intellectual development of children remain unknown.

In case of kidney disease and decompensated liver disease, it is necessary to undergo a study of renal function before starting therapy, and a dose adjustment of the drug may be required.

Patients on a sodium-restricted diet should take into account that in the concentrate for the preparation of a solution for infusion, the sodium content in 1 ampoule is 0.83 mmol (19 mg).

There are reports of cases of suicidal intent, suicide and attempted suicide during the period of therapy with levetiracetam, therefore, patients should be warned about the need to immediately inform their doctor about any suicidal intentions or symptoms of depression.

There is no clinical experience with infusion of levetiracetam for more than 4 days.

Do not use Keppra if mechanical impurities appear in the solution or its color changes.

The oral solution is contraindicated for use in violation of fructose tolerance due to the content of maltitol.

The content of propyl parahydroxybenzoate and methyl parahydroxybenzoate in the oral solution may cause allergies (including delayed action).

Given the individual sensitivity to levetiracetam on the part of the central nervous system (cases of drowsiness have been recorded in some patients), during therapy one should refrain from activities that require the speed of psychomotor reactions and increased concentration of attention, incl. from driving vehicles.

Application during pregnancy and lactation

Adequate clinical studies concerning the safety of prescribing levetiracetam to pregnant women and accompanied by strict control have not been carried out, therefore the drug is not recommended to be prescribed to such patients (with the exception of vital indications).

During pregnancy, the female body undergoes special physiological changes that can affect the content of levetiracetam in the blood plasma. A decrease in its concentration is often observed. This decrease is more pronounced in the first trimester (the indicator is 60% of the standard plasma concentration detected in the period preceding pregnancy).

Keppra's treatment of pregnant patients requires particularly careful monitoring of their condition. It should also be taken into account that interruptions in the course of antiepileptic therapy can provoke a worsening of the course of the disease, which adversely affects both the mother and the fetus.

Levetiracetam passes into breast milk, therefore it is recommended to stop breastfeeding during treatment. However, if the appointment of Keppra is necessary during lactation, the balance of the possible risks and benefits of such treatment should be carefully weighed against the importance of breastfeeding.

For violations of liver function

No dose adjustment is required in patients with mild to moderate liver dysfunction.

Drug interactions

• Antiepileptic drugs (carbamazepine, phenytoin, valproic acid, lamotrigine, phenobarbital, gabapentin, primidone and topiramate): do not mutually affect each other's plasma concentration;
• Anticonvulsants (inducers of liver microsomal enzymes): in children taking Keppra, the clearance of levetiracetam is increased by 22%;
• Probenecid, sulfonamides, non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate: the effect of levetiracetam when taken simultaneously with them is unknown; taking probenecid 4 times a day at 500 mg reduces the renal secretion of the primary metabolite;
• Oral contraceptives (levonorgestrel and ethinyl estradiol): when taken at a dose of 1000 mg per day, levetiracetam does not alter their pharmacokinetics;
• Warfarin and digoxin - levetiracetam, when taken in a dose of 2000 mg per day, does not change their pharmacokinetics;
• Warfarin, digoxin and oral contraceptives: do not affect the pharmacokinetics of levetiracetam;
• Topiramate: increases the risk of developing anorexia;
• Antacids: there is no data on their effect on the absorption of levetiracetam;
• Alcohol: no data on interaction with levetiracetam.

Analogs

Keppra's analogs are: Vimpat, Gabapeptin, Konvulsan, Lamictal, Lyrica, Lamotrigine, Topiramate, Tebantin, Tirapol, Komviron, Epiterra, Epitropil, Letiram, Levetinol, Levetiracetam Lupine.

Terms and conditions of storage

Keep out of the reach of children at a temperature not exceeding 25 ° C.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Keppra

Reviews about Keppra confirm the opinion that antiepileptic therapy with such a drug should be selected strictly individually and exclusively by an experienced doctor. In the absence of individual negative reactions to treatment and adherence to the rules of admission, the drug shows good results.

Price for Keppra in pharmacies

The approximate price of Keppra in the form of tablets is 867-903 rubles (dosage 250 mg, the package contains 30 pcs.), 1697-1771 rubles (dosage 500 mg, the package contains 30 pcs.), 3309-3517 rubles (dosage 500 mg, the package contains 60 pieces) or 3336–3550 rubles (dosage 1000 mg, the package contains 30 pieces). The oral solution can be purchased for an average of 3342–3528 rubles. The cost of a concentrate for preparing a solution for infusion is about 7797-8200 rubles (the package includes 10 vials of 5 ml).

Keppra: prices in online pharmacies

Drug name Price Pharmacy

Keppra 250 mg film-coated tablets 30 pcs. 461 r Buy

Keppra tablets p.p. 250mg 30 pcs. 556 r Buy

Keppra 500 mg film-coated tablets 30 pcs. 864 RUB Buy

Keppra 100 mg / ml oral solution 300 ml 1 pc. 1475 RUB Buy

Keppra 500 mg film-coated tablets 60 pcs. 1809 RUB Buy

Keppra tablets p.p. 500mg 60 pcs. 1956 RUB Buy

Keppra 100 mg / ml concentrate for solution for infusion 5 ml 10 pcs. 4553 RUB Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!