Encorate (Tablets) Instructions for Use

Marketing Authorization Holder

Sun Pharmaceutical Industries, Ltd. (India)

ATC Code

N03AG01 (Valproic acid)

Active Substance

Valproic acid

Dosage Forms

	Encorate	Enteric-coated tablets, 200 mg: 100 pcs.
		Enteric-coated tablets, 300 mg: 100 pcs.

Dosage Form, Packaging, and Composition

Enteric-coated tablets pink, round, biconvex.

Excipients: colloidal silicon dioxide, microcrystalline cellulose, corn starch, polyvinylpyrrolidone K30, calcium silicate, magnesium stearate, purified talc, sodium starch glycolate (type A), hypromellose 2910, dibutyl phthalate, methacrylic acid copolymer (type C), titanium dioxide, Ponceau 4R lacquer dye, Sunset Yellow FCF lacquer dye.

10 pcs. – strips made of aluminum foil (10) – cardboard packs.

Enteric-coated tablets pink, round, biconvex.

Excipients: colloidal silicon dioxide, microcrystalline cellulose, corn starch, polyvinylpyrrolidone K30, calcium silicate, magnesium stearate, purified talc, sodium starch glycolate (type A), hypromellose 2910, dibutyl phthalate, methacrylic acid copolymer (type C), titanium dioxide, Ponceau 4R lacquer dye, Sunset Yellow FCF lacquer dye.

10 pcs. – strips made of aluminum foil (10) – cardboard packs.

Clinical-Pharmacological Group

Anticonvulsant drug

Pharmacotherapeutic Group

Antiepileptic agent

Pharmacological Action

An antiepileptic drug that has a central muscle relaxant and sedative effect.

The mechanism of action is associated with an increase in the GABA content in the CNS (due to inhibition of GABA transaminase, as well as a decrease in the reuptake of GABA in the brain), resulting in reduced excitability and convulsive readiness of the motor zones of the brain.

According to another hypothesis, it acts on the sites of postsynaptic receptors, mimicking or enhancing the inhibitory effect of GABA.

A possible direct effect on membrane activity is associated with changes in potassium conductivity.

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

Pharmacokinetics

When administered orally, it is well absorbed from the gastrointestinal tract. Bioavailability is about 100%.

C_max in blood plasma is reached 3-4 hours after administration. C_ss is achieved on days 2-4 of administration (depends on the intervals between doses).

Therapeutic concentrations in blood plasma range from 50-150 mg/l. Plasma protein binding is 90%.

It penetrates the placental and blood-brain barriers; it is excreted in breast milk (the concentration in breast milk is 1-10% of the concentration in the maternal blood plasma). The content in the cerebrospinal fluid correlates with the value of the fraction not bound to proteins.

T_1/2 varies from 6 to 16 hours. It is metabolized in the liver to form a glucuronide.

It is excreted mainly by the kidneys as a metabolite; small amounts of the drug are excreted in the feces and exhaled air.

Indications

• Epilepsy – minor seizures (absences, complex absences);
• Major convulsive seizures;
• Focal seizures.

ICD codes

Dosage Regimen

Orally during meals, doses are set individually. The tablet should be swallowed whole, without breaking, without chewing. Do not change the dose and treatment regimen without consulting a doctor.

Adults: the drug is prescribed at an initial daily dose of 0.3-0.6 g in 2 doses. The dose is gradually increased by 0.1-1.15 g/day every 3-4 days until the desired effect is achieved. The maximum daily dose is 2.4 g.

Children weighing less than 40 kg: the drug is prescribed at a daily dose of 20 mg/kg.

Children weighing 40 kg and more: the maximum daily dose is 40 mg/kg of body weight. The frequency of administration is 2 times/day.

Discontinuation of treatment is carried out with a gradual dose reduction over 1-2 years. If therapy is effective, dose recalculation depending on the child’s body weight may not be performed if there is no deterioration in the ECG.

Adverse Reactions

From the digestive system: at the beginning of treatment, transient disorders are possible: anorexia, stomach pain, nausea, vomiting, diarrhea, increased appetite; rarely – constipation, pancreatitis up to severe lesions with a fatal outcome.

From the CNS: lethargy, ataxia, tremor, changes in behavior, mood or mental state (depression, feeling of fatigue, hallucinations, aggressiveness, hyperactive state, psychoses, unusual agitation, motor restlessness or irritability), dizziness, drowsiness, headache, dysarthria, enuresis, stupor, impaired consciousness, coma.

From the senses: diplopia, nystagmus, flickering of flies before the eyes.

From the liver: a transient increase in the activity of liver enzymes is possible, observed during the first few months of treatment and often not manifested by any clinical symptoms (frequency about 40%). The risk of developing these side effects depends on the dose of the drug; when the dose is reduced, these effects decrease or disappear. Very rarely, the development of fulminant hepatitis with a fatal outcome is observed, and it is far from always possible to detect previous changes in liver function indicators.

Allergic reactions: skin rash, alopecia, urticaria, angioedema, photosensitization, malignant exudative erythema (Stevens-Johnson syndrome) are possible.

From the endocrine system: dysmenorrhea, secondary amenorrhea, breast enlargement, galactorrhea.

From the hematopoietic organs: anemia, thrombocytopenia, leukopenia, decreased fibrinogen content, platelet aggregation and blood clotting, accompanied by prolonged bleeding time, petechial hemorrhages, bruising, hematomas, bleeding.

From the metabolism: decrease or increase in body weight.

Laboratory indicators: hypercreatininemia, hyperbilirubinemia, hyperammonemia.

Other: peripheral edema.

Contraindications

• Severe impairment of liver and/or pancreatic function;
• Porphyria;
• Hemorrhagic diathesis;
• Severe thrombocytopenia;
• Leukopenia;
• Children under 3 years of age;
• Pregnancy;
• Lactation period;
• Hypersensitivity to the drug.

Use with caution in patients with a history of liver and pancreatic diseases, as well as bone marrow damage; impaired renal function; congenital enzymopathies; mentally retarded children; organic brain lesions, hypoproteinemia.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Contraindicated

• Severe impairment of liver function.

Use in Renal Impairment

Use with caution in case of impaired renal function.

Pediatric Use

Children weighing less than 40 kg: the drug is prescribed at a daily dose of 20 mg/kg.

Children weighing 40 kg and more: the maximum daily dose is 40 mg/kg of body weight. The frequency of administration is 2 times/day.

Discontinuation of treatment is carried out with a gradual dose reduction over 1-2 years. If therapy is effective, dose recalculation depending on the child’s body weight may not be performed if there is no deterioration in the ECG.

Contraindicated in children under 3 years of age.

Special Precautions

Before starting treatment and during treatment, it is recommended to monitor the functional state of the liver and pancreas, the peripheral blood picture, and blood clotting parameters. If liver and pancreatic function disorders or blood clotting disorders occur or are suspected, the drug should be discontinued.

During combination therapy with other anticonvulsant drugs, it is advisable to monitor, especially at the beginning of treatment, the concentration in the blood plasma of the other drug, as it may change under the influence of Encorate.

Patients who are receiving other antiepileptic drugs should be switched to valproic acid gradually, reaching a clinically effective dose after 2 weeks, after which a gradual withdrawal of other antiepileptic drugs is possible. In patients who have not been treated with other antiepileptic drugs, a clinically effective dose should be reached after 1 week.

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

The increased risk of bleeding in patients receiving anticoagulant or thrombolytic therapy should be taken into account.

During treatment with Encorate, a false-positive urine reaction to ketone bodies is possible.

There are reports of changes in the functional state of the thyroid gland during therapy with Encorate.

Before surgery, a complete blood count (including platelet count), determination of bleeding time, and coagulogram parameters are necessary.

If symptoms of an acute abdomen occur during treatment, before starting surgery, it is recommended to determine the level of amylase in the blood to exclude acute pancreatitis.

During treatment, the possible distortion of urine test results in diabetes mellitus (due to an increase in the content of ketone products), and thyroid function indicators should be taken into account.

If any acute serious side effects develop, it is necessary to immediately discuss with the doctor the advisability of continuing or stopping treatment.

To reduce the risk of dyspeptic disorders, the use of antispasmodics and enveloping agents is possible.

Effect on the ability to drive vehicles and mechanisms

When using the drug, one should refrain from potentially hazardous activities that require increased attention, rapid mental and motor reactions.

Overdose

Symptoms: increased severity of side effects – nausea, vomiting, dizziness, diarrhea, respiratory dysfunction, muscle hypotonia, hyporeflexia, miosis, coma.

Treatment: gastric lavage, maintenance of adequate diuresis, hemodialysis and hemoperfusion, symptomatic therapy.

Drug Interactions

Valproic acid enhances the effects, including side effects, of other antiepileptic drugs (phenytoin, lamotrigine), anxiolytics (tranquilizers), MAO inhibitors, thymoleptics, ethanol.

The addition of valproate to clonazepam in isolated cases can lead to an increase in the severity of absence status.

With the simultaneous use of valproic acid with barbiturates or primidone, an increase in their concentration in the blood plasma is noted.

Increases the T_1/2 of lamotrigine (inhibits liver enzymes, causes a slowdown in the metabolism of lamotrigine, as a result of which its T_1/2 is extended to 70 hours in adults and to 45-55 hours in children).

Reduces the clearance of zidovudine by 38%, while its T_1/2 does not change.

Tricyclic antidepressants, MAO inhibitors, antipsychotic drugs (neuroleptics), drugs that reduce the threshold of convulsive activity reduce the effectiveness of valproic acid.

When combined with salicylates, an enhancement of the effects of valproic acid is observed (displacement from plasma protein binding).

Enhances the effect of antiplatelet agents (acetylsalicylic acid) and indirect anticoagulants.

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

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

With the simultaneous use of valproic acid with ethanol and other drugs that depress the CNS (tricyclic antidepressants, MAO inhibitors and antipsychotic drugs), increased CNS depression is possible.

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

Valproic acid does not cause induction of liver enzymes and does not reduce the effectiveness of oral contraceptives.

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

When combined with myelotoxic agents, the risk of inhibition of bone marrow hematopoiesis increases.

Storage Conditions

Store in a place inaccessible to children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed 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.