Phenytoin
Mechanism :
Phenytoin is an anticonvulsant which elevates the seizure threshold in the motor cortex by limiting the post-tetanic potentiation (PTP) of synaptic transmission. It exerts this effect by preventing the excessive accumulation of intracellular sodium during tetanic stimulation by either reducing the passive influx of sodium or increasing the efficiency of the sodium pump.
Indication :
- Epilepsy
- Status epilepticus
- Neuropathic pain
- Choreoathetosis
- Myotonia
- Arrhythmias where first line treatment not effective
- Tetralogy of Fallot - post operative
Contraindications :
Known hypersensitivity to hydantoin products. Because of its effect on ventricular automaticity, IV phenytoin is contraindicated in sinus bradycardia, sinoatrial block, second and third-degree AV block, patients with Adams-Stokes syndrome.
Dosing :
Status epilepticus:
Loading dose: 15-20 mg/kg IV as a single or in divided doses; may administer 5-10 mg/kg additionally 10 mins after the loading dose. Maintenance: 4-8 mg/kg IV in divided doses two times/day.
Antiepileptic:
Loading doses:
Neonates: 5 mg/kg/day PO in 2 divided dose.
6 months-16 years: 5 mg/kg/day PO in 2-3 divided doses.
Maintenance doses:
6 months-4 years: 8-10 mg/kg/day PO in divided doses 2-3 times daily.
4-17 years: 7.5-9 mg/kg/day PO in divided doses 2-3 times daily.
7-10 years: 7-8 mg/kg/day PO in divided doses 2-3 times daily.
10-16 years: 6-7 mg/kg/day PO in divided doses 2-3 times daily.
Adverse Effect :
Dose dependent: Fatigue, irritability, headache, nystagmus, ataxia, dyskinesia, lethargy, slurred speech, vertigo. Gum hypertrophy, hirsutism, osteomalacia, coarse facies, cognitive dysfunction, folate deficiency have been reported on chronic use.
Interaction :
Amiodarone, Chloramphenicol, Cimetidine, Disulfiram, Erythromycin, Fluconazole, Fluoxetine, Isoniazid, Ketoconazole, Methylphenidate, Omeprazole, Phenylbutazone, Salicylates, Sulfonamides, Trazodone, Warfarin and Acute Alcohol Ingestion: Drugs may increase phenytoin serum levels.
Carbamazepine, Chronic Alcohol Abuse, Diazoxide, Rifampin and Theophylline: Drugs may decrease phenytoin levels.
Phenobarbital, Valproic Acid, and Sodium Valproate: Drugs may either increase or decrease phenytoin serum levels. Similarly, the effect of phenytoin on phenobarbital, valproic acid and sodium valproate serum levels is unpredictable.
Corticosteroids, Diazoxide, Digitalis Glycosides, Doxycycline, Estrogens, Furosemide, Levodopa, Methadone, Oral Contraceptives, Quinidine, Theophylline, Vitamin D and Warfarin: Drugs efficacy is impaired by phenytoin.
Sucralfate, Enteral Feeds, Antacids or Calcium Preparations: Administration of phenytoin should be separated by at least 3 hours to prevent a decrease in phenytoin absorption.
I.V. Phenytoin with Lidocaine or Propranolol: Concurrent use of i.v. phenytoin with lidocaine or propranolol may produce additive cardiac depressant effects.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
20-50 | Dose as in normal renal function |
10-20 | Dose as in normal renal function |
<10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
CAPD | Not dialysed. Dose as in normal renal function |
HD | Not dialysed. Dose as in normal renal function |
HDF/High flux | Dialysed. Dose as in normal renal function |
CAV/VVHD | Unknown dialysability. Dose as in normal renal function |
Hepatic Dose :
Reduction of phenytoin dose may be required based on serum phenytoin concentrations and clinical response.