Dilantin

General information

Dilantin is an anticonvulsant drug belonging to the class of hydantoin anticonvulsants. It is used to control various types of seizures due to its ability to stabilize the electrical activity of neurons in the brain. The main active ingredient - phenytoin - effectively reduces the frequency and severity of seizures, which makes the drug an important tool in the therapy of epilepsy and other neurological conditions accompanied by seizures.

Trade name

Dilantin

International Nonproprietary Name (INN)

Phenytoin

Form of release

The drug is available in the following forms:

• Capsules with prolonged release: 100 mg;
• Chewable tablets (Dilantin Infatabs): 50 mg;
• Suspension for oral administration (Dilantin-125): 125 mg/5 mL.

Composition

The active substance: phenytoin (in capsules - in the form of phenytoin sodium).

Auxiliary components depend on the form of release:

• Capsules: lactose monohydrate, corn starch, magnesium stearate, talc; capsule shell contains gelatin, titanium dioxide, dyes (eg, iron oxide);
• Chewable tablets: sucrose, mannitol, flavorings, microcrystalline cellulose, magnesium stearate;
• Suspension: sugar syrup, glycerin, sodium carboxymethylcellulose, flavorings, ethanol (less than 0.5%), purified water.

Each form has its own characteristics, allowing the treatment to be adapted to the individual needs of the patient.

Pharmacologic properties

Pharmacodynamics

Phenytoin, the active ingredient of Dilantin, exerts anticonvulsant action by stabilizing neuronal membranes. It blocks potential-dependent sodium channels in nerve cell membranes, which prevents excessive propagation of electrical impulses in the brain. This mechanism is particularly effective in generalized tonic-clonic seizures and partial seizures. The drug reduces the frequency and intensity of pathological discharges, preventing their transition into convulsive activity. At the same time, phenytoin does not have a significant sedative effect, which distinguishes it from some other anticonvulsants.

The mechanism of action is associated with slowing down the recovery of sodium channels after depolarization, which reduces the excitability of neurons. The effect of the drug is enhanced at high concentrations and in conditions of hyperactivity of nervous tissue, characteristic of epileptic foci. Dilantin also has some antiarrhythmic action, which is sometimes used in cardiology, although it is not a major indication.

Pharmacokinetics

Absorption

After oral administration, phenytoin is absorbed from the gastrointestinal tract with a bioavailability of about 90%. The time to reach maximum plasma concentration (Tmax) varies: for capsules - 4-12 hours, for chewable tablets - 2-4 hours, for suspension - 1-3 hours. Food intake may slow absorption, especially for prolonged-release capsules, but does not affect the total bioavailability.

Distribution

Phenytoin binds actively to plasma proteins (90-95%), predominantly to albumin. The volume of distribution is 0.6-0.8 L/kg, indicating good penetration into tissues, including brain. The free fraction of the drug (5-10%) is pharmacologically active, and its levels may increase in the presence of hypoalbuminemia or competition with other drugs for binding.

The free fraction of the drug (5-10%) is pharmacologically active, and its levels may increase with hypoalbuminemia or competition with other drugs for binding.

Metabolism

Phenytoin metabolism occurs in the liver with the participation of cytochrome P450 enzymes, predominantly CYP2C9 and CYP2C19. The main metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin, has no pharmacologic activity and is excreted in conjugated form. The process of metabolism has a non-linear character: at high doses, enzymes are saturated, which leads to slower clearance and increased concentration of the drug in the blood.

Excretion

The half-life of phenytoin varies from 7 to 42 hours and depends on the dose and individual characteristics of the patient. The main route of excretion is the kidneys (about 70% in the form of metabolites), the rest is excreted with bile and feces. In case of hepatic or renal dysfunction, excretion may slow down, requiring dosage adjustment.

Indications for use

Dilantin is prescribed for the treatment and prevention of the following conditions:

• Generalized tonic-clonic seizures (grand mal);
• Partial seizures with complex symptomatology (psychomotor, temporal);
• Prevention and treatment of seizures occurring during or after neurosurgical operations;
• Convulsion control in epilepsy.

The drug is not effective in absences (petit mal) and myoclonic seizures, so its use is limited to certain types of epileptic seizures.

Contraindications

The use of Dilantin is prohibited in the following conditions:

• Hypersensitivity to phenytoin or other hydantoins (e.g., etotoin, fosphenytoin);
• Sinus bradycardia, sinoatrial block, grade II-III atrioventricular block (outside of cardiac monitoring);
• Acute liver failure or severe chronic liver disease;
• Porphyria (porphyrin metabolism disorder);
• Pregnancy (unless the benefit outweighs the risk);
• Breastfeeding;
• Simultaneous administration of delavirdine (an antiviral drug).

Patients with an allergy to the drug's components or a history of severe reactions to anticonvulsants should avoid using Dilantin.

Method of administration and dosage

How to take

Dilantin is taken orally. Capsules are swallowed whole, without chewing, drinking water (about 200 ml). Chewable tablets can be chewed or swallowed whole, suspension should be shaken before use. The drug can be taken independently of food, but taking it with food may reduce gastric irritation. Regularity of administration is important to maintain a stable concentration in the blood.

Dosages

Adults

• Starting dose: 100 mg 3 times daily (capsules) or equivalent in other forms;
• Supplemental dose: 300-400 mg/day, up to 600 mg/day if necessary;
• Single dose: if seizures are well controlled, switching to 300 mg once daily (prolonged-release capsules only) is possible.

Children

• Starting dose: 5 mg/kg/day in 2-3 doses;
• Supplemental dose: 4-8 mg/kg/day, maximum 300 mg/day;
• Children over 6 years of age: adult doses (300 mg/day) may be required.

Dose Adjustment

• Hiver failure: dose reduction by 25-50% in mild/moderate form, the drug is contraindicated in severe form;
• Renal insufficiency: correction is not required, but control of free fraction level is obligatory;
• Elderly patients: the initial dose is reduced to 3 mg/kg/day due to slow metabolism;
• Hypoalbuminemia: dosage is adjusted taking into account the level of free phenytoin in plasma.

Side effects

The following adverse reactions may accompany the use of Dilantin:

• Nervous system: dizziness, ataxia, nystagmus, somnolence, confusion;
• Gastrointestinal tract: nausea, vomiting, constipation, gingival hyperplasia;
• Cardiovascular system: hypotension, arrhythmias (with rapid administration);
• Skin: rash, Stevens-Johnson syndrome, toxic epidermal necrolysis;
• Heat: leukopenia, thrombocytopenia, agranulocytosis;
• Liver: enzyme elevation, hepatitis;
• Endocrine system: hyperglycemia, osteoporosis with prolonged use.

Most side effects are dose-dependent and subside with dose reduction.

Overdose

Symptoms

Overdose is manifested by nystagmus (at a concentration of 20 µg/mL), ataxia (30 µg/mL), confusion, coma (above 50 µg/mL). Nausea, vomiting, hypotension, respiratory depression may occur.

First aid measures

• Gastric lavage (within 1 hour after ingestion);
• Take activated charcoal;
• Symptomatic therapy (maintenance of respiration, BP control);
• Monitoring of phenytoin levels in the blood.

Hemodialysis is ineffective due to high protein binding.

Interaction with other drugs

Influence on the effect of other drugs

• Enhances the metabolism of warfarin, reducing its effect;
• Decreases the concentration of cyclosporine, corticosteroids, oral contraceptives;
• increases toxicity of methotrexate when taken together.

Compatibility with alcohol and food

Alcohol increases the sedative effect and toxicity of phenytoin, its use is not recommended. Food does not affect efficacy, but fatty foods may slow absorption.

Special Instructions

Use in pregnancy and breastfeeding

Dilantin is contraindicated in pregnancy due to the risk of birth defects (cleft lip, heart defects). Use is possible only for vital indications. Phenytoin penetrates into breast milk, therefore breastfeeding is prohibited.

Effect on driving and mechanisms

The drug may cause somnolence and ataxia, therefore driving and working with mechanisms are not recommended until the response to treatment is evaluated.

Particularities of use in the elderly and children

Elderly patients require a reduced initial dose and monitoring due to slower metabolism. In children, the drug is administered on a weight basis, but is not recommended before the age of 6 years without a strict indication.

Storage conditions

Store at a temperature of 20-25 ° C in a dry, protected from light, out of reach of children. Shelf life: 3 years for capsules and tablets, 2 years for suspension after opening.