Enkorat chrono - instructions for use, dose, side effects, contraindications

active substances: sodium valproate 133.5 mg, 200.0 mg and 333.0 mg, valproic acid (equivalent to sodium valproate) 58.0 (66.5) mg, 87.0 (100.0) mg, 145.0 (167, 0) mg;

Excipients: Hypromellose-K100M (Methocel-K100M) 50.0 mg / 72.0 mg / 75.0 mg, hypromellose-K15M (Methocel-K15M) 20.0 mg / 27.0 mg / 45.0 mg, starch (dried) 13.0 mg / 21.250 mg / 45.250 mg, talc purified 21.875 mg / 32.40 mg / 43.753 mg, magnesium stearate 5.438 mg / 7.950 mg / 13.130 mg, silicon dioxide colloidal 20.0 mg / 30.0 mg / 45.0 mg;

shell composition: methyl methacrylate, dimethylaminoethyl methacrylate and butyl methacrylate copolymer (Eudragit E-100) 2.350 mg / 3.0 mg / 4.70 mg, titanium dioxide 1.875 mg / 2.40 mg / 3.753 mg, macrogol-6000 0.47 mg / 0.60 mg / 0.94 mg, color: sunset yellow 0.45 mg / 0.57 mg / 0.90 mg.

Description:

Tablets 200 mg and 300 mg: Round, biconvex tablets, covered with a film shell of orange color.

Tablets 500 mg: Capsule, biconvex tablets, covered with a film shell of orange color.

Pharmacotherapeutic group:antiepileptic agent

ATX: & nbsp

N.03.A.G.01 Valproic acid

Pharmacodynamics:

Antiepileptic agent, has a central muscle relaxant and sedative effect.Sodium valproate increases the content of GABA (gamma-aminobutyric acid) in the central nervous system (CNS), which correspondingly increases the content of GABA in the postsynaptic neurons. In addition, sodium valproate affects the transfer of potassium ions through neuronal membranes. As a result of this influence, the excitability and convulsive readiness of the brain zones is reduced.

It improves the mental state and mood of patients, has antiarrhythmic activity.

Pharmacokinetics:

Suction

Valproic acid in the form of tablets, prolonged action characterized by the absence of absorption of latent time, slow absorption, bioavailability identical, lower (25%), but relatively more stable plasma concentration between 4 and 14 hours.

Food slightly reduces the rate of absorption; bioavailability is about 100%. Maximum plasma concentrations are attained within 2-8 hours after oral application of tablets with prolonged action.

Equilibrium concentration. The equilibrium concentration in plasma is achieved in 2-4 days receive (depending on the interval between doses).

Distribution

The connection with blood plasma proteins - 90-95% (at a plasma concentration of up to 50 mg / l), at a concentration of 50-100 mg / l decreases to 80-85%; with uremia, hypoproteinemia and liver cirrhosis, binding to plasma proteins is also reduced. Therapeutic efficacy manifests itself when the concentration of valproic acid in the blood plasma is 40-100 mg / l. At the same time, the pharmacological and therapeutic effects of this prolonged-action drug do not always depend on its plasma concentration. The volume of distribution is 0.2 liters / kg of body weight.

Metabolism and excretion

Valproic acid (1-3%) and its metabolites (in the form of conjugates, oxidation products, including ketometabolites) are excreted by the kidneys; small amounts are excreted with feces and with exhaled air. No presystemic metabolism was observed for this drug. Penetrates through the placental barrier and the blood-brain barrier; is excreted in breast milk (concentration in breast milk is 1-10% concentration in the mother plasma).

The time for prluvnoveniya is 8-22 hours. When combined with other drugs, half-life can be 6-8 hours due to the induction of metabolic enzymes, in patients with impaired liver function of elderly patients and children under 18 months can be significantly longer.

Indications:

In adults as a monotherapy or in combination with other antiepileptic drugs:

- treatment of generalized epilepsy, especially with the following types of seizures (absences, clonic, tonic, myoclonic, tonic-clonic, atonic);

- treatment of partial epilepsy (partial seizures with secondary generalization or without it);

- changes in character and behavior (caused by epilepsy);

- specific syndromes (Vesta, Lennox-Gastaut);

- manic-depressive psychosis with a bipolar course, resistant to treatment with Li + drugs or other drugs.

Children as a monotherapy or in combination with other antiepileptic drugs:

- treatment of generalized epilepsy, especially with the following types of seizures (absences, clonic, tonic, myoclonic, tonic-clonic, atonic);

- treatment of partial epilepsy (partial seizures with secondary generalization or without it);

- specific syndromes (Vesta, Lennox-Gastaut);

- febrile convulsions, children's teak.

Contraindications:

Individual intolerance to the drug,severe impairment of pancreatic function, hepatic insufficiency, acute and chronic hepatitis, hemorrhagic diathesis, porphyria, severe thrombocytopenia, lactation period, disorder of urea cycle exchange (including family history), children with body weight less than 20 kg (for this dosage form), it is not recommended to use the drug in combination with mefloquine; St. John's wort perforated; lamotrigine.

Carefully:

Oppression of bone marrow hemopoiesis (leukopenia, thrombocytopenia, anemia), organic brain diseases, liver and pancreatic disease in history; hypoproteinemia, mental retardation in children, congenital fermentopathy, kidney failure, pregnancy, children under 3 years old.

Pregnancy and lactation:

In pregnancy, the development of generalized tonic-clonic epileptic seizures, epileptic status with the development of hypoxia may be a risk factor for death for both the mother and the fetus.

AT experimental research in mice, rats and rabbits, a teratogenic effect is shown.

According to available data, in humans, valproate mainly causes disruption of the development of the neural tube: myelomeningocele, spina bifida (1-2%). Cases of facial dysmorphia and developmental limb development abnormalities (especially limb shortening), as well as developmental defects of the cardiovascular system are described.

The risk of malformations is higher with combined antiepileptic therapy than with monotherapy with sodium valproate. However, it is rather difficult to establish a causal relationship between the developmental defects of the fetus and other factors (including genetic, social, environmental factors).

In view of the foregoing, during pregnancy, the use of the drug is only possible if the intended benefit to the mother exceeds the potential risk to the fetus.

If a woman is planning a pregnancy, the indications for antiepileptic treatment should be revised.

In pregnancy, do not interrupt the antiepileptic treatment with valproate if it is effective. In such cases, monotherapy is recommended; The minimum effective daily dose should be divided into several doses.

In addition to anti-epileptic therapy, folic acid preparations (at a dose of 5 mg / day) can be added, they minimize the risk of developing neural tube defects. However, regardless of whether the patient receives folate or not, in any case, a special antenatal control of the state of the neural tube or other malformations should be carried out.

Valproate can cause hemorrhagic syndrome in newborns, which, apparently, is associated with hypofibrinogenemia.

There have been cases of development of fetal affinity with lethal outcome. Perhaps this is due to a decrease in a number of clotting factors. Newborns should be monitored for platelet count, plasma fibrinogen levels, and blood coagulation factors.

Valproate is excreted in breast milk in low concentrations (from 1% to 10% of the concentration in the blood plasma). According to the literature and on the basis of a small clinical experience, it is possible to plan breastfeeding during treatment with Choro's Encrorate in the form of monotherapy taking into account its safety profile (especially hematological disorders).

Dosing and Administration:

Dosage regimen of the drug Chrono is selected individually depending on the age and weight of the patient, as well as taking into account the individual sensitivity to the drug. The drug is taken orally. The daily dose should be taken in 1 or 2 doses, preferably during meals. Tablets should be swallowed whole, washed down with a small amount of water.

Monotherapy

Adults: the initial dose is 600 mg / day. Increase the dosage by 200 mg every three days until the optimal effect is achieved. Take 1-2 times a day. The maximum recommended dose is 1-2 g.

Children weighing over 20 kg. The initial dose is 400 mg / day. Increase the dosage gradually until optimal, usually 20-30 mg / kg once a day or in two separate doses.

Children weighing up to 20 kg. It is not necessary to apply Encore Chrono to children of this category.

Elderly patients. It is characteristic that the volume of distribution increases, and the volume of the plasma decreases. However, with normal liver and kidney function, this increase in the amount of free drug is clinically insignificant. Dosage regimen Chronic enchorat in elderly patients is similar to the dosing regimen in adults and is selected individually.In patients who have the necessary therapeutic effect achieved with the treatment of Enkorat tablets, it is possible to apply Enkorat Chrono in the appropriate daily dosage.

Side effects:

From the side of the central nervous system: tremor, changes in behavior, mood or mental state (depression, fatigue, hallucinations, aggressiveness, hyperactive state, psychoses, unusual agitation, motor anxiety or irritability), ataxia, dizziness, drowsiness, headache, encephalopathy, dysarthria, enuresis, stupor, impaired consciousness, coma.

From the sense organs: diplopia, nystagmus, flashing of "flies" before the eyes.

From the digestive system: nausea, vomiting, gastralgia, decreased appetite or increased appetite, diarrhea, hepatitis, constipation, pancreatitis, up to severe lesions with a lethal outcome (in the first 6 months of treatment, usually 2-12 weeks).

On the part of the organs of hematopoiesis and the system of hemostasis: oppression of bone marrow hematopoiesis (anemia, leukopenia), thrombocytopenia, reduction of fibrinogen and platelet aggregation, leading to the development of hypocoagulation (accompanied by prolonged bleeding time, petechial hemorrhages, bruises, bruises, bleeding, etc.).

From the side of metabolism: decrease or increase in body weight.

Allergic reactions: skin rash, hives, angioedema, photosensitization, malignant exudative erythema (Stevens-Johnson syndrome).

Laboratory indicators: hypercortinemia, hyperammonia, hyperglycinemia, hyperbilirubinemia, a slight increase in the activity of "liver" transaminases, LDH (dose-dependent).

From the endocrine system: dysmenorrhea, secondary amenorrhea, enlargement of the mammary glands, galactorrhea.

Other: peripheral edema, alopecia.

Overdose:

There have been reports of rare cases of drug overdose. At the same time, nausea, vomiting, dizziness, diarrhea, respiratory depression, hyporeflexia, miosis, coma were observed.

Treatment: gastric lavage (not later than 10-12 hours), reception of activated charcoal, forced diuresis. If necessary - inpatient treatment with the use of symptomatic therapy, hemodialysis.

Interaction:

Valproic acid enhances effects, incl. by-side, other antiepileptic medicines (LS) (phenytoin, lamotrigine), antidepressants, antipsychotic drugs (neuroleptics), anxiolytics, barbiturates, monoamine oxidase inhibitors, thymoleptics, ethanol.

Addition of valproate to clonazepam in single cases can lead to an increase in the expression of absent status.

With the simultaneous use of valproic acid with barbiturates or primidone, there is an increase in the concentration of the latter in the plasma.

Increases the half-life of lamotrigine (suppresses liver enzymes, slows the metabolism of lamotrigine, so that its half-life extends to 70 hours in adults and up to 45-55 hours in children).

Reduces zidovudine clearance by 38%, while its half-life does not change.

Tricyclic antidepressants, monoamine oxidase inhibitors, antipsychotic drugs (neuroleptics) and other drugs that reduce the threshold of convulsive activity, reduce the effectiveness of the drug Enkorata Chrono.

When the combination of Enchorate Chrono with salicylates, the effects of valproic acid are enhanced (displacement from the bond with plasma proteins), enhances the effect of antiplatelet agents (acetylsalicylic acid) and indirect anticoagulants.

When combined with phenobarbital, phenytoin, carbamazepine, mefloquine, the content of valproic acid in the blood serum decreases (acceleration of metabolism).

Felbamate increases the concentration of valproic acid in the plasma by 35-50% (dose adjustment is necessary).

With the simultaneous use of the drug Enkorat Chrono with ethanol and other drugs that depress the central nervous system (tricyclic antidepressants, monoamine oxidase inhibitors and antipsychotic drugs), it is possible to increase the depression of the central nervous system.

Ethanol and other hepatotoxic drugs increase the likelihood of developing liver damage.

Chronico's Enchorate does not induce the induction of "liver" enzymes and does not reduce the effectiveness of oral contraceptives.

Myelotoxic drugs - increased risk of oppression of bone marrow hematopoiesis.

Valproic acid can both increase and decrease the concentration of ethosuximide in the blood serum due to changes in metabolism.

Meropenem reduces the plasma concentration of valproic acid, which can lead to a decrease in anticonvulsant effect.

With simultaneous application with topiramate, the risk of hyperammonemia and encephalopathy increases.

Special instructions:

During treatment, it is advisable to monitor the activity of "hepatic" transaminases, bilirubin concentrations, peripheral blood picture, blood platelets, the state of the blood coagulation system, the activity of amylase (every 3 months, especially when combined with other antiepileptic drugs).

Patients who receive other antiepileptic drugs, transfer to the reception of the drug Choro Acetate should be carried out gradually, reaching a clinically effective dose after 2 weeks, after which the gradual elimination of other antiepileptic drugs is possible. In patients who have not been treated with other antiepileptic drugs, a clinically effective dose should be achieved after 1 week.

The risk of developing side effects from the liver is increased when combined anticonvulsant therapy, as well as in children.

Do not drink beverages that contain ethanol.

Before the surgical intervention, a general blood test (including platelet numbers), bleeding time, coagulogram indices is required.

If there is a symptomatology of the "acute" abdomen before the onset of surgery, it is recommended to determine the concentration of amylase in the blood to exclude acute pancreatitis.

During treatment it is necessary to take into account the possible distortion of the results of urinalysis in diabetes mellitus (due to an increase in the content of keto products), thyroid function indices.

With the development of any acute serious side effects, it is necessary to immediately discuss with the doctor the advisability of continuing or discontinuing treatment.

To reduce the risk of dyspeptic disorders, it is possible to take antispasmodics and enveloping drugs.

A sharp discontinuation of valproic acid may lead to an increase in epileptic seizures.

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

During the treatment period, care must be taken when driving vehicles and engaging in other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of prolonged action, film-coated, 200 mg, 300 mg and 500 mg.

Packaging:

10 tablets per strip, made of aluminum foil.

3 strips, together with instructions for use, are placed 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:П N014475 / 01-2002

Date of registration:16.10.2008

The owner of the registration certificate:San Pharmaceutical Industries Co., Ltd.San Pharmaceutical Industries Co., Ltd. India

Manufacturer: & nbsp

Sun Pharmaceutical Industries, Ltd. India

Representation: & nbspSAN PHARMACEUTICAL INDUSTRIES LTD. SAN PHARMACEUTICAL INDUSTRIES LTD. India

Information update date: & nbsp10.12.2015

Illustrated instructions

Instructions

Enchorat Chrono (Encorate chrono)