Pagluverin^® (Tablets) Instructions for Use

Instructions
Dosage forms

ATC Code

N03AX (Other antiepileptic drugs)

Clinical-Pharmacological Group

Combined anticonvulsant drug

Pharmacotherapeutic Group

Antiepileptic agent

Pharmacological Action

A combined antiepileptic agent.

Phenobarbital interacts with the barbiturate site of the benzodiazepine-GABA receptor complex, thereby increasing the sensitivity of GABA receptors to GABA, leading to the opening of neuronal channels for chloride ions, which results in their increased influx into the cell.

It reduces the excitability of neurons in the epileptogenic focus and the spread of nerve impulses.

It exhibits antagonism towards a number of excitatory mediators (glutamate and others).

It suppresses the sensory zones of the cerebral cortex, reduces motor activity, depresses cerebral functions, including the respiratory center.

It reduces the tone of the gastrointestinal smooth muscles.

It has anticonvulsant, sedative, hypnotic, and antispasmodic effects.

Caffeine increases the reflex excitability of the spinal cord, stimulates the respiratory and vasomotor centers, and stimulates metabolic processes in organs and tissues, including muscle tissue and the central nervous system.

Papaverine hydrochloride is an antispasmodic and has a hypotensive effect.

It reduces the tone and relaxes the smooth muscles of internal organs and blood vessels.

Calcium Gluconate replenishes the deficiency of calcium ions, which are necessary for the process of nerve impulse transmission.

Bromisoval has a sedative and moderate hypnotic effect.

Pharmacokinetics

Phenobarbital is absorbed slowly and completely.

C_max in blood plasma is determined after 1-2 hours, plasma protein binding is 50%.

It is metabolized in the liver, induces hepatic microsomal enzymes CYP3A4, CYP3A5, CYP3A7 (the rate of enzymatic reactions increases by 10-12 times).

It accumulates in the body.

T_1/2 is 2-4 days.

It is excreted by the kidneys in the form of a glucuronide, about 25% is excreted unchanged.

It penetrates into breast milk and through the placental barrier.

Caffeine: absorption is good and occurs throughout the intestine.

C_max in blood plasma is reached after 50-75 minutes.

It is rapidly distributed to all organs and tissues, penetrates the blood-brain barrier and placenta.

Binding to blood proteins (albumin) is 25-36%.

More than 90% is metabolized in the liver; in children of the first years of life, up to 10-15% is metabolized.

In adults, about 80% of the caffeine dose is metabolized to paraxanthine, about 10% to theobromine, and about 4% to theophylline.

These compounds are subsequently demethylated to monomethylxanthines and then to methylated uric acids.

T_1/2 in adults is 3.9-5.3 hours (sometimes up to 10 hours).

Excretion of caffeine and its metabolites is carried out by the kidneys.

Papaverine: bioavailability averages 54%.

Plasma protein binding is 90%.

It is well distributed and penetrates histohematic barriers.

It is metabolized in the liver.

T_1/2 is 0.5-2 hours (can be extended up to 24 hours).

It is excreted by the kidneys as metabolites.

Calcium Gluconate: approximately 1/5-1/3 is absorbed in the small intestine.

About 20% is excreted by the kidneys, the remaining amount is removed with the intestinal contents (actively secreted by the wall of the terminal part of the gastrointestinal tract).

Indications

Epilepsy.

ICD codes

Open the list of ICD codes

ICD-10 code	Indication
G40	Epilepsy

ICD-11 code	Indication
8A6Z	Epilepsy or epileptic seizures, unspecified

Dosage Regimen

The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen.

Administer the tablets orally.

For adults, take 2 to 4 tablets per dose, 2 to 3 times daily.

The total daily dose should not exceed 12 tablets.

For children under 10 years of age, the maximum daily dose is 5 tablets.

Divide the total daily dose for children into 2 or 3 administrations.

Adjust the dosage individually based on the clinical response and tolerability.

Adhere strictly to the prescribed dosing schedule to maintain stable drug levels.

Do not exceed the recommended maximum daily dose.

Adverse Reactions

From the nervous system lethargy, drowsiness, ataxia.

From the skin skin rashes.

Contraindications

Severe hepatic and/or renal impairment; drug dependence (including history); hyperkinesis; myasthenia; severe anemia; porphyria; diabetes mellitus; adrenal hypofunction; hyperthyroidism; depression; bronchial obstructive diseases; active alcoholism; pregnancy; lactation period; hypersensitivity to the components of the combination.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and during the lactation (breastfeeding) period.

Use in Hepatic Impairment

Contraindication — hepatic impairment.

Use in Renal Impairment

Contraindication — renal impairment.

Pediatric Use

If it is necessary to prescribe the drug to children, the dose of the drug should be checked and the instructions for use should be carefully studied.

Special Precautions

The drug should be used with caution in debilitated patients (high risk of paradoxical agitation, depression, and confusion even when prescribed at usual doses).

In patients with mild hypercalciuria, decreased glomerular filtration rate, or a history of nephrolithiasis, therapy should be carried out under the control of urinary calcium levels, which is due to the presence of calcium gluconate in this combination.

Alcohol consumption is not recommended during therapy.

Effect on the ability to drive vehicles and operate machinery

During treatment, one should refrain from performing work that requires speed of psychomotor reactions (including driving a car).

Drug Interactions

Phenytoin and valproates increase the serum concentration of phenobarbital.

The effect of phenobarbital is reduced when taken simultaneously with reserpine and is increased when combined with amitriptyline, nialamide, diazepam, chlordiazepoxide.

It reduces the effectiveness of oral contraceptives and salicylates.

It reduces the blood levels of indirect anticoagulants, corticosteroids, griseofulvin, doxycycline, estrogens, and other drugs metabolized in the liver via oxidation (accelerates their metabolism).

It enhances the effect of ethanol, neuroleptics, narcotic analgesics, muscle relaxants, sedatives, and hypnotics.

Acetazolamide, by alkalinizing the urine, reduces the renal reabsorption of phenobarbital and weakens its effect.

It reduces the antibacterial activity of antibiotics and sulfonamides, and the antifungal effect of griseofulvin.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.

Medical Disclaimer

Brand (or Active Substance), Marketing Authorisation Holder, Dosage Form

Pagluverin^®-2 [Usolye-Sibirskiy Chemical and Pharmaceutical Plant, JSC (Russia)]
Tablets: 10, 20, 30, 40, 50, 60, 80, 100, or 120 pcs.

Marketing Authorization Holder

Usolye-Sibirskiy Chemical and Pharmaceutical Plant, JSC (Russia)

Dosage Form

Pagluverin^®-2

Tablets: 10, 20, 30, 40, 50, 60, 80, 100, or 120 pcs.

Dosage Form, Packaging, and Composition

Tablets white, round, with a bevel and a score.

	1 tab.
Phenobarbital	35 mg
Bromisoval	100 mg
Caffeine sodium benzoate	7.5 mg
Papaverine hydrochloride	15 mg
Calcium Gluconate	250 mg

Excipients : potato starch – 78.4 mg, calcium stearate – 4.1 mg.

10 pcs. – blister packs – cardboard packs.
10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (4) – cardboard packs.
10 pcs. – blister packs (5) – cardboard packs.
10 pcs. – blister packs (6) – cardboard packs.
10 pcs. – blister packs (8) – cardboard packs.
10 pcs. – blister packs (10) – cardboard packs.
10 pcs. – blister packs (12) – cardboard packs.
10 pcs. – blister packs (200) – cardboard boxes (for hospitals).
10 pcs. – blister packs (400) – cardboard boxes (for hospitals).
10 pcs. – blister packs (500) – cardboard boxes (for hospitals).
10 pcs. – blister packs (600) – cardboard boxes (for hospitals).
10 pcs. – blister packs (800) – cardboard boxes (for hospitals).
10 pcs. – blister packs (1000) – cardboard boxes (for hospitals).
10 pcs. – jars – cardboard packs.
20 pcs. – jars – cardboard packs.
30 pcs. – jars – cardboard packs.
40 pcs. – jars – cardboard packs.
50 pcs. – jars – cardboard packs.
60 pcs. – jars – cardboard packs.
80 pcs. – jars – cardboard packs.
100 pcs. – jars – cardboard packs.
120 pcs. – jars – cardboard packs.