Phenytoin

1. Introduction

Phenytoin is an anticonvulsant medication used to control seizures. It stabilises neuronal membranes and reduces seizure activity by limiting repetitive firing of action potentials via sodium channel modulation. Phenytoin is commonly prescribed for epilepsy and certain types of seizures but has a narrow therapeutic range requiring careful monitoring.

2. Indications

  • Generalised tonic-clonic seizures
  • Focal (partial) seizures
  • Status epilepticus (IV formulation)
  • Prevention of seizures following neurosurgery

3. Dosage

Adults:

  • Seizure control (oral):
    • Initial dose: 100 mg 2–3 times daily.
    • Maintenance dose: 300–400 mg/day in divided doses (maximum: 600 mg/day).
  • Status epilepticus (IV):
    • Loading dose: 15–20 mg/kg at a rate of ≤50 mg/min.
    • Maintenance dose: 100 mg every 6–8 hours.

Children:

  • Oral (seizure control):
    • Initial dose: 5 mg/kg/day in divided doses.
    • Maintenance dose: 4–8 mg/kg/day (maximum: 300 mg/day).
  • IV (status epilepticus):
    • Loading dose: 15–20 mg/kg infused at ≤1–3 mg/kg/min.

Elderly:

  • Start at the lower end of the dosing range due to altered metabolism and increased risk of side effects.

4. Administration

  • Oral formulations should be taken with food to reduce gastrointestinal upset.
  • Shake oral suspension well before use to ensure proper dosing.
  • IV phenytoin must be administered slowly to avoid cardiovascular complications.

5. Forms Available

  • Capsules: 30 mg, 100 mg, 200 mg
  • Oral suspension: 125 mg/5 mL
  • Intravenous solution: 50 mg/mL

6. Side Effects

6.1 Common Side Effects:

  • Drowsiness
  • Dizziness
  • Nausea or vomiting
  • Gingival hyperplasia (overgrowth of gums)
  • Hirsutism (excess hair growth)

6.2 Less Common Side Effects:

  • Skin rash
  • Coarsening of facial features (long-term use)
  • Headache

6.3 Rare but Serious Side Effects:

  • Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)
  • Agranulocytosis (low white blood cells)
  • Liver toxicity
  • Hypotension or arrhythmias (IV use)

7. Warnings

  • Narrow Therapeutic Range: Requires regular blood level monitoring to avoid toxicity (therapeutic range: 10–20 mcg/mL).
  • Severe Skin Reactions: Risk of SJS/TEN, especially in individuals with the HLA-B*1502 allele (more common in people of Asian descent).
  • Cardiovascular Risk: Rapid IV administration can cause severe hypotension or arrhythmias.

8. Precautions

  • Use cautiously in patients with hepatic impairment, as phenytoin is extensively metabolised by the liver.
  • Avoid abrupt discontinuation to prevent rebound seizures or status epilepticus.
  • Monitor for signs of bone mineral density loss during long-term therapy.

9. Interactions

  • CYP450 Inducers (e.g., carbamazepine): May reduce phenytoin levels.
  • CYP450 Inhibitors (e.g., fluconazole, valproic acid): May increase phenytoin levels and risk of toxicity.
  • Oral Contraceptives: Phenytoin may reduce contraceptive efficacy; alternative methods should be considered.
  • Alcohol: Acute intake increases phenytoin levels, while chronic use reduces them.

10. Monitoring Parameters

  • Monitor serum phenytoin levels regularly to maintain therapeutic range (10–20 mcg/mL).
  • Liver function tests (ALT, AST) periodically.
  • Complete blood count (CBC) to detect agranulocytosis or other haematological abnormalities.
  • Observe for signs of toxicity, such as nystagmus, ataxia, or confusion.

11. Use in Children

  • Safe when dosed according to weight. Monitor closely for signs of toxicity due to narrow therapeutic index.

12. Use in Pregnancy

  • Category D: Phenytoin is associated with foetal hydantoin syndrome (craniofacial abnormalities, growth retardation) and an increased risk of congenital defects. Use only if benefits outweigh risks.

13. Use in Elderly

  • Use cautiously due to altered pharmacokinetics, increased sensitivity to side effects, and higher risk of toxicity.

14. Use in Kidney Disease

  • Use cautiously, as phenytoin is highly protein-bound and levels may increase in hypoalbuminaemia.

15. Use in Liver Disease

  • Dose adjustments may be required due to altered metabolism. Regular monitoring of serum levels is recommended.

16. Patient Counselling Points

  • Take phenytoin exactly as prescribed. Do not skip doses, and avoid abrupt discontinuation.
  • Report any unusual symptoms, such as skin rash, fever, or persistent nausea, to your doctor immediately.
  • Maintain good oral hygiene to minimise gingival hyperplasia.
  • Avoid alcohol and over-the-counter medications without consulting your doctor.
  • Regular blood tests are needed to monitor phenytoin levels and prevent toxicity.

17. Table of Brand Names, Manufacturer, and Prices in USD

Brand NameManufacturerStrength/Dosage FormPrice (USD)
DilantinPfizer100 mg Capsule$25 (30 capsules)
EpanutinPfizer50 mg/mL IV Solution$40 (5 vials)
Generic PhenytoinVarious100 mg Capsule$15 (30 capsules)

18. 15 FAQs (Frequently Asked Questions)

1. What is Phenytoin used for?
Phenytoin is used to treat seizures, including tonic-clonic and focal seizures, and to prevent seizures during neurosurgery.

2. How does Phenytoin work?
It stabilises neuronal membranes by modulating sodium channels, preventing repetitive firing of action potentials.

3. What is the usual dose of Phenytoin for seizures?
Typically, 300–400 mg/day in divided doses for adults.

4. How is Phenytoin monitored?
Serum levels are monitored to maintain a therapeutic range of 10–20 mcg/mL.

5. Can children take Phenytoin?
Yes, it is safe when dosed according to weight (5–8 mg/kg/day).

6. Can Phenytoin cause drowsiness?
Yes, drowsiness is a common side effect, especially during dose adjustments.

7. Is Phenytoin safe during pregnancy?
Phenytoin is classified as Category D and carries a risk of congenital defects. Use only if necessary.

8. What should I do if I miss a dose?
Take the missed dose as soon as possible, unless it is close to the next dose. Do not double the dose.

9. Can Phenytoin be stopped suddenly?
No, abrupt discontinuation may trigger seizures or status epilepticus.

10. Can Phenytoin cause skin rashes?
Yes, rashes, including serious reactions like Stevens-Johnson syndrome, can occur.

11. Does Phenytoin interact with other drugs?
Yes, it interacts with oral contraceptives, anticoagulants, and CYP450-modulating drugs.

12. Can Phenytoin cause gum problems?
Yes, gingival hyperplasia is a common side effect.

13. How should Phenytoin be stored?
Store at room temperature, away from moisture and light.

14. Can I drink alcohol while on Phenytoin?
Avoid alcohol, as it can affect phenytoin levels and worsen side effects.

15. What are signs of Phenytoin toxicity?
Symptoms include nystagmus, ataxia, confusion, and slurred speech.