Encorate Chrono (Tablets) Instructions for Use

Marketing Authorization Holder

Sun Pharmaceutical Industries, Ltd. (India)

ATC Code

N03AG01 (Valproic acid)

Active Substance

Valproic acid (Rec.INN registered by WHO)

Dosage Forms

	Encorate Chrono	Controlled-release film-coated tablets, 200 mg: 30 pcs.
		Controlled-release film-coated tablets, 300 mg: 30 pcs.
		Controlled-release film-coated tablets, 500 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Controlled-release film-coated tablets orange in color, round, biconvex.

Excipients: Hypromellose-K100M (Methocel-K100M), Hypromellose-K15M (Methocel-K15M), Starch (dried), Purified Talc, Magnesium Stearate, Colloidal Silicon Dioxide.

Coating composition Methacrylate, Dimethylaminoethyl Methacrylate and Butyl Methacrylate Copolymer (Eudragit E100), Titanium Dioxide, Polyethylene Glycol 6000, Sodium Lauryl Sulfate, Sunset Yellow FCF dye.

10 pcs. – aluminum strips (3) – cardboard packs.

Controlled-release film-coated tablets orange in color, round, biconvex.

Excipients: Hypromellose-K100M (Methocel-K100M), Hypromellose-K15M (Methocel-K15M), Starch (dried), Purified Talc, Magnesium Stearate, Colloidal Silicon Dioxide.

Coating composition Methacrylate, Dimethylaminoethyl Methacrylate and Butyl Methacrylate Copolymer (Eudragit E100), Titanium Dioxide, Polyethylene Glycol 6000, Sodium Lauryl Sulfate, Sunset Yellow FCF dye.

10 pcs. – aluminum strips (3) – cardboard packs.

Controlled-release film-coated tablets orange in color, capsule-shaped, biconvex.

Excipients: Hypromellose-K100M (Methocel-K100M), Hypromellose-K15M (Methocel-K15M), Starch (dried), Purified Talc, Magnesium Stearate, Colloidal Silicon Dioxide.

Coating composition Methacrylate, Dimethylaminoethyl Methacrylate and Butyl Methacrylate Copolymer (Eudragit E100), Titanium Dioxide, Polyethylene Glycol 6000, Sodium Lauryl Sulfate, Sunset Yellow FCF dye.

10 pcs. – aluminum strips (3) – cardboard packs.

Clinical-Pharmacological Group

Anticonvulsant drug

Pharmacotherapeutic Group

Anticonvulsant agent

Pharmacological Action

Sodium valproate increases the content of GABA (gamma-aminobutyric acid) in the brain, which accordingly increases the GABA content in postsynaptic neurons.

In addition, sodium valproate affects the transfer of potassium ions through neuronal membranes. The result of such an effect is the suppression of the occurrence, as well as the spread of epileptic excitation through neurons.

Valproate has anticonvulsant activity in various types of epilepsy in humans. The drug does not have pronounced hypnotic and sedative effects, and also does not have a depressant effect on the respiratory center.

Encorate Chrono does not have a negative effect on blood pressure, heart rate, kidney function, and body temperature.

Pharmacokinetics

Absorption of the drug is rapid and complete. C_max in plasma is reached within 2-8 hours after oral administration of controlled-release tablets.

80-90% of the drug is bound to plasma proteins, T_1/2 is 8-22 hours. Therapeutic efficacy is manifested at a plasma concentration of valproic acid of 40-100 mg/l.

At the same time, the pharmacological and therapeutic effects of this controlled-release drug do not always depend on its plasma concentration. V_d – 0.2 l/kg of body weight.

The drug is metabolized in the liver and excreted in the urine. No presystemic metabolism has been noted for this drug.

Indications

Treatment of generalized or partial epilepsy, especially in the following types of seizures

• Absences;
• Myoclonic;
• Tonic-clonic;
• Atonic.

Partial epilepsy

• Simple or combined seizures;
• Secondary generalized seizures.

Specific syndromes (West, Lennox-Gastaut)

ICD codes

Dosage Regimen

The dosage regimen is selected individually depending on the age and weight of the patient.

Monotherapy

Adults initial dose – 600 mg/day. Increase the dosage by 200 mg every three days until the optimal effect is achieved.

Tablets should be swallowed whole with a small amount of water. Take 1-2 times a day. The maximum recommended dose is 1-2 g.

Children weighing over 20 kg initial dose – 400 mg/day. Gradually increase the dosage until the optimal one is reached, usually 20-30 mg/kg once a day or in two divided doses.

Children weighing up to 20 kg. Encorate Chrono should not be used in children of this category.

Elderly patients typically, the volume of distribution increases and plasma volume decreases. However, with normal liver and kidney function, this increase in the amount of free drug is not clinically significant.

The dosage regimen of Encorate Chrono in elderly patients is similar to that in adults and is selected individually.

In patients who have achieved the required therapeutic effect with Encorate tablets, it is possible to use Encorate Chrono in the appropriate daily dosage.

Adverse Reactions

In rare cases, the following side effects have been reported

• Nausea, vomiting, diarrhea and/or constipation
• Hepatitis
• Pancreatitis
• Weight gain
• Skin rash, itching, photosensitivity, erythema multiforme, Stevens-Johnson syndrome
• Hair loss (in 2-12% of patients)
• Ataxia, tremor, impaired consciousness, coma
• Menstrual cycle disorders, secondary amenorrhea
• Anemia, hyperammonemia, hypercreatininemia, thrombocytopenia, neutropenia, leukopenia, decreased fibrinogen content, inhibition of platelet aggregation.

Contraindications

• Individual intolerance to the drug;
• Severe impairment of pancreatic and liver function;
• Acute hepatitis;
• Pregnancy, lactation;
• Porphyria;
• Thrombocytopenia;
• Children under 3 years of age.

Use in Pregnancy and Lactation

Prescribing the drug to pregnant women is possible only if the intended benefit to the mother outweighs the potential risk to the fetus. If the drug is taken during pregnancy, specialized prenatal monitoring of the fetus is mandatory.

The use of valproate during breastfeeding is not recommended.

Use in Hepatic Impairment

Contraindicated in severe liver dysfunction, acute hepatitis.

Pediatric Use

Encorate Chrono should not be used in children weighing less than 20 kg.

Geriatric Use

Elderly patients: typically, the volume of distribution increases and plasma volume decreases. However, with normal liver and kidney function, this increase in the amount of free drug is not clinically significant.

The dosage regimen of Encorate Chrono in elderly patients is similar to that in adults and is selected individually.

In patients who have achieved the required therapeutic effect with Encorate tablets, it is possible to use Encorate Chrono in the appropriate daily dosage.

Special Precautions

Caution should be exercised when working with machinery, as the drug impairs attention. Regular monitoring of transaminase levels, bilirubin, blood platelets, and amylase is necessary (every 3 months).

Valproic acid inhibits platelet aggregation, which increases the risk of increased blood clotting time during bleeding.

The possibility of developing complications associated with bleeding in operated patients receiving valproate should be considered.

In patients taking valproate for a long time, spontaneous hematomas and bleeding may develop. In such a case, the drug should be discontinued immediately.

Valproate can cause drug-induced pancreatitis and impaired liver function (usually within the first 6 months of use).

In this regard, it is necessary to monitor the condition of the pancreas during the first 6 months of treatment, perform liver tests, and monitor prothrombin levels.

Impaired liver function, liver failure during valproate therapy is sometimes observed in children with epilepsy and combined metabolic and degenerative diseases, organic pathology of brain tissue, and mental retardation.

If symptoms such as severe weakness, lethargy, swelling, vomiting, and jaundice occur, the use of the drug should be discontinued immediately. Use during pregnancy and lactation

Prescribing the drug to pregnant women is possible only if the intended benefit to the mother outweighs the potential risk to the fetus. If the drug is taken during pregnancy, specialized prenatal monitoring of the fetus is mandatory. The use of valproate during breastfeeding is not recommended.

Overdose

Rare cases of accidental or intentional overdose of the drug have been reported. In this case, nausea, vomiting, dizziness, diarrhea, respiratory depression, hyporeflexia, and coma were observed.

First aid: gastric lavage, intake of activated charcoal. If necessary, inpatient treatment with symptomatic therapy, hemodialysis.

Drug Interactions

Valproate enhances the effect of antipsychotic drugs, anticonvulsants, and antidepressants.

Unlike other anticonvulsant drugs, valproate does not cause induction of liver enzymes, so it does not reduce the effectiveness of oral contraceptives.

When valproate and warfarin are used together, the percentage of plasma protein binding of the latter decreases.

Valproate alters the plasma concentrations of phenytoin and lamotrigine.

In combination with anticoagulants and acetylsalicylic acid derivatives, inhibition of platelet aggregation increases.

Storage Conditions

Store in a dry, light-protected place, at a temperature not exceeding +25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 3 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.