Phenytoin

Generic name: phenytoin (oral)

Brand names: Dilantin, Phenytek

Drug classes: antiarrhythmics; hydantoin anticonvulsants.

What is phenytoin?

Phenytoin is an anticonvulsant, also known by its brand name Dilantin. It belongs to a class of drugs called hydantoins and has been widely used since the 1930s for the treatment of various types of seizures.Phenytoin is a medication primarily used to treat seizures (convulsions) in conditions such as epilepsy.

How do phenytoins work?

Phenytoin works by stabilizing the neuronal cell membrane and reducing the repetitive firing of action potentials. It primarily acts by inhibiting voltage-gated sodium channels in the brain, thereby decreasing the influx of sodium ions and stabilizing the neuronal membranes. This inhibitory effect on sodium channels helps prevent the abnormal electrical activity in the brain that leads to seizures.

Pharmacokinetics

Absorption:
● well-absorbed from the gastrointestinal tract.
● Peak plasma concentrations in 2 to 4 hours.
● Food can influence absorption.
Distribution:
● high protein binding, primarily to albumin.
● wide distribution, including the central nervous system.
Metabolism:
● Metabolized in the liver, primarily by CYP2C9.
● Formation of the main metabolite, para-hydroxyphenytoin.
● Saturation kinetics are observed at higher doses.

Elimination:
● Elimination half-life varies (12 to 36 hours).
● zero-order kinetics at higher concentrations.
● Minimal renal excretion (<5%).
Excretion:
● A small portion is excreted unchanged in urine.
Therapeutic Drug Monitoring:
● Narrow therapeutic index.
● Regular monitoring of plasma levels is necessary to optimize dosing and prevent toxicity.

Therapeutic uses:

Phenytoin is indicated for the treatment of various types of seizures and related conditions. Here is a detailed list of indications for phenytoin:
Epilepsy:
● Generalized Tonic-Clonic Seizures (Grand Mal): Phenytoin is effective in controlling generalized tonic-clonic seizures, which involve the entire brain and typically manifest with loss of consciousness and
convulsions.
● Complex Partial Seizures (Psychomotor or Temporal Lobe Seizures): Phenytoin is also used for complex partial seizures, which affect a specific region of the brain and may involve altered consciousness or unusual behaviors.
● Simple Partial Seizures: While not as commonly used for simple partial seizures, phenytoin may be considered in certain cases.

Status Epilepticus:
Phenytoin may be used in the management of status epilepticus, a medical emergency characterized by prolonged or repeated seizures without recovery of consciousness between them.
Prophylaxis After Neurosurgery:
Phenytoin is sometimes prescribed as a prophylactic measure to prevent seizures in individuals who have undergone neurosurgical procedures, as these patients may be at an increased risk of postoperative seizures.

Prophylaxis for Seizures Associated with Head Injury:
In some cases, phenytoin may be used to prevent seizures in individuals who have sustained a head injury, especially if there is an increased risk of developing post-traumatic seizures.
Arrhythmias Associated with Digoxin Toxicity:
Phenytoin has been used in the management of certain arrhythmias that can occur as a result of digitalis (digoxin) toxicity.

Side effects of phenytoin:

The more common side effects that can come with phenytoin include:
● Nausea
● Vomiting
● Dizziness
● Drowsiness
● Gingival hyperplasia (overgrowth of the gums)
● Tremors
● Constipation
● Confusion
● Headache

Serious side effects include:
● Skin rash (especially Stevens-Johnson syndrome)
● Liver problems
● Blood disorders
● Allergic reactions
● Mental/mood changes

Drug-Drug interaction:

Phenytoin can interact with various drugs, affecting its levels or the levels of co-administered medications.

1. Drugs that inhibit phenytoin metabolism can lead to increased phenytoin levels. Examples include:
   ● Cimetidine may increase phenytoin levels.
   ● Fluconazole: Can elevate phenytoin concentrations

2. Drugs that induce the activity of phenytoin-metabolizing enzymes can decrease phenytoin levels. Examples include:
● Carbamazepine: may reduce phenytoin efficacy.
● Rifampin: Can accelerate phenytoin metabolism.

3. Interactions with other antiepileptic drugs (AEDs) can occur. For example:
● Valproic acid: can increase phenytoin levels; monitor for toxicity.
● Lamotrigine: Phenytoin may reduce lamotrigine levels.

4. Phenytoin may decrease the efficacy of hormonal contraceptives, increasing the risk of unintended pregnancies.
5. Concurrent use with phenytoin may increase diazepam levels, potentially leading to increased sedation.
6. Medications affecting gastric acid, such as proton pump inhibitors and H2 blockers, can influence phenytoin absorption.
7. Phenytoin may interfere with the absorption of folic acid, necessitating supplementation.

Contraindication of phenytoin:

● Hypersensitivity: Individuals with a known hypersensitivity to phenytoin or other hydantoins should not use this medication.
● Sinus Bradycardia, Atrioventricular Block, or Adams-Stokes Syndrome: Phenytoin may worsen these conditions, so caution is needed.
● Porphyria: It is contraindicated in patients with a history of porphyria, a group of rare genetic disorders affecting the nervous system or skin.

Phenytoin warning

Hypersensitivity and Serious Skin Reactions:

Phenytoin use has been associated with severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. These reactions can be life-changing and require instant medical supervision. If a skin rash develops,especially in the early stages of treatment, the medication should be discontinued.

Hematologic Effects:
Phenytoin may cause blood disorders, such as leukopenia, thrombocytopenia, and aplastic anemia. Regular monitoring of complete blood counts (CBC) is recommended, and patients should report any signs of infection or unusual bleeding.
Hepatic Effects:
Phenytoin can affect liver function, leading to elevated liver enzymes. Liver function should be monitored regularly, and the drug may need to be discontinued if significant liver dysfunction occurs.

Teratogenicity:
Phenytoin is known to be teratogenic, meaning it can cause birth defects if used during pregnancy.Women of childbearing potential should use effective contraception during phenytoin therapy, and healthcare providers should carefully consider the risks and benefits of continuing or discontinuing the medication for pregnant women.

Risk of Gingival Hyperplasia:
Phenytoin use has been associated with gingival hyperplasia (overgrowth of the gums). Good oral hygiene practices, including regular dental check-ups, are recommended to help manage this side effect.

Suicidal Thoughts and Behavior:
Antiepileptic drugs, including phenytoin, have been associated with an increased risk of suicidal thoughts and behavior. Patients and caregivers should be vigilant for any signs of mood changes, depression, or suicidal ideation and seek prompt medical attention if such symptoms occur.

Phenytoin dosage form

Phenytoin is available in various dosage forms, allowing flexibility in
administration. Here’s a brief overview of the different forms:
Oral Capsules:
● Phenytoin is commonly available in oral capsule form.
● Capsules come in different strengths, allowing for individualized
dosing.

Oral Suspension:
● A liquid formulation of phenytoin is available for those who have
difficulty swallowing capsules.
● The suspension should be shaken well before measuring a dose.
Injection:
● Phenytoin can be administered intravenously in emergency situations.
such as status epilepticus.
● Intravenous administration requires special attention to infusion rates
and potential risks, and it’s typically done in a healthcare setting.

Dosing of phenytoin:

1) Adult Dosing:
Epilepsy (Seizure Control):
● Initial: 100 mg three times daily.
● Maintenance: 300–400 mg per day in divided doses.
Status Epilepticus:
● Loading Dose: 15–20 mg/kg given intravenously at a rate not
exceeding 50 mg/minute.

● Maintenance: Followed by a maintenance dose of 5 mg/kg/day given
in two or three divided doses.

2) Pediatric Dosing:
Epilepsy (Seizure Control):
● Initial: 5 mg/kg/day in two to three divided doses.
● Maintenance: 4–8 mg/kg/day in divided doses.
Status Epilepticus:
● Loading Dose: 15–20 mg/kg given intravenously at a rate not
exceeding 1–3 mg/kg/minute.
● Maintenance: Followed by a maintenance dose of 5 mg/kg/day given
in two or three divided doses.

3) Special Populations:
Elderly:
● The elderly may require lower initial and maintenance doses due to
potential age-related changes in drug metabolism.
Hepatic Impairment:
● Dosing adjustments may be needed for individuals with liver disease.
Lower doses or extended dosing intervals may be considered.
Renal Impairment:
● Phenytoin is primarily metabolized by the liver, and renal impairment
may not significantly affect its elimination. However, dosage
adjustments may be necessary in severe renal impairment.

If you miss a dose,

Still, take it as soon as you remember. If you miss a dose,. However, skip the missed dose and renew your regular schedule if it’s nearly time for your next dose. Do not double up on doses to make up for a missed one without consulting your healthcare provider.

Take as directed

When taking phenytoin, it’s crucial to follow your healthcare provider’s instructions carefully. The dosage forms cater to different patient needs, preferences, and conditions, providing options for effective and convenient administration. The choice of dosage form is often determined by the healthcare provider based on the patient’s specific circumstances.