Fosphenytoin
Mechanism :
Fosphenytoin is a prodrug of phenytoin and accordingly, its anticonvulsant effects are attributable to phenytoin
Indication :
- Epilepsy- Generalized Tonic Clonic Seizures
- Status epilepticus
Contraindications :
Known hypersensitivity to hydantoin products. Because of its effect on ventricular automaticity, i.v. phenytoin is contraindicated in sinus bradycardia, sinoatrial block, second and third-degree AV block, patients with Adams-Stokes syndrome.
Dosing :
The dosage of fosphenytoin is expressed in terms of
phenytoin equivalents (PE); 150 mg of fosphenytoin sodium is equivalent to 100 mg of
phenytoin sodium.
Loading doses:
15-20 mg/kg IV. Maintenance doses start 12 hours after loading doses. Usual maintenance doses are 4 to 8 mg/kg/day, in 2 or 3 divided doses. Maximum rate of infusion 150 mg/minute.
Adverse Effect :
Nystagmus dizziness, pruritus, somnolence, ataxia, transient pruritus, tinnitus, hypertension, fever, injection-site reaction, constipation, hypokalemia, pneumonia.
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 whose efficacy is impaired by phenytoin.
Sucralfate, Enteral Feeds, Antacids or Calcium Preparations: Administration of phenytoin with sucralfate, enteral feeds, antacids or calcium preparations 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 | Reduce dose or rate by 10–25% and monitor carefully (except for status epilepticus) |
| 10-20 | Reduce dose or rate by 10–25% and monitor carefully (except for status epilepticus) |
| <10 | Reduce dose or rate by 10–25% and monitor carefully (except for status epilepticus) |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unlikely to be dialysed. Dose as for GFR<10 mL/min |
| HD | Not dialysed. Dose as for GFR<10 mL/min |
| HDF/High flux | Unlikely to be dialysed. Dose as for GFR<10 mL/min |
| CAV/VVHD | Not dialysed. Dose as for GFR=10–20 mL/min |
Hepatic Dose :
Fosphenytoin is converted to phenytoin in the systemic circulation which is primarily metabolized in the liver. Patients with hepatic disease may have an increased fraction of unbound phenytoin. Except in the treatment of status epilepticus, a lower loading dose and/or infusion rate, and lower or less frequent maintenance dosing may be required in patients with hepatic disease or in those with hypoalbuminemia. A 10% to 25% reduction in dose or rate may be considered and careful clinical monitoring is required. Dosage adjustments may be required based upon serum phenytoin concentrations and clinical response.