Fosphenytoin


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : IM/IV Tonic-clonic status epilepticus As PSE: As adjunct to benzodiazepine: Loading dose: 15 mg/kg as a single dose by IV infusion. Maintenance: Initial: 4-5 mg/kg/day in 1-2 divided doses by IM inj or IV infusion. Seizures Except status epilepticus: As PSE: 10-15 mg/kg as a single dose by IM inj or IV infusion. Maintenance: Initial: 4-5 mg/kg/day in 1-2 divided doses by IM inj or IV infusion.
Dosage Details
Parenteral
Tonic-clonic status epilepticus
Adult: As phenytoin Na equivalents (PSE): As adjunctive therapy w/ benzodiazepine (e.g. diazepam): Loading dose: 15 mg/kg as a single dose by IV infusion at a rate of 100-150 mg/min. Maintenance: Initially, 4-5 mg/kg daily in 1-2 divided doses by IM inj or IV infusion at a rate of 50-100 mg/min. Subsequent doses are dependent on patient response and trough plasma-phenytoin levels.
Child: As PSE: ≥5 yr 15 mg/kg as a single dose by IV infusion at a rate of 2-3 mg/kg/min. Max rate of infusion for loading dose: 3 mg/kg/min or 150 mg/min. Maintenance: 4-5 mg/kg daily in 1-4 divided doses at a rate of 1-2 mg/kg/min, max 100 mg/min. Subsequent doses are dependent on patient response and trough plasma-phenytoin levels.
Elderly: Lower loading dose and/or infusion rate, and lower or less frequent maintenance dose.

Parenteral
Seizures
Adult: Except status epilepticus: As phenytoin Na equivalents (PSE): 10-15 mg/kg as a single dose by IM inj or IV infusion at a rate of 50-100 mg/min. Maintenance: Initially, 4-5 mg/kg daily in 1-2 divided doses by IM inj or IV infusion at a rate of 50-100 mg/min. Subsequent doses are dependent on patient response and trough plasma-phenytoin levels.
Child: Except status epilepticus: As PSE: ≥5 yr 10-15 mg/kg as a single dose by IV infusion at a rate of 1-2 mg/kg/min. Max rate of infusion for loading dose: 3 mg/kg/min or 150 mg/min. Maintenance: 4-5 mg/kg daily in 1-4 divided doses at a rate of 1-2 mg/kg/min, max 100 mg/min. Subsequent doses are dependent on patient response and trough plasma-phenytoin levels.
Elderly: Lower loading dose and/or infusion rate, and lower or less frequent maintenance dose.
Renal Impairment
Dose reduction or slower infusion may be needed.
Hepatic Impairment
Dose reduction or slower infusion may be needed.
Reconstitution
Dilute in dextrose 5% inj or NaCl 0.9% inj to provide a soln containing 1.5-2.5 mg PSE/mL.
Incompatibility
Y-site: Fenoldopam, midazolam.
Contraindications
Sinus bradycardia, SA block, 2nd- or 3rd-degree AV block, or Stokes-Adams syndrome. Concomitant use w/ delavirdine.
Special Precautions
Patient w/ phosphate restriction, hypoalbuminaemia, hypotension, severe myocardial insufficiency, DM. May exacerbate porphyria. Not effective for the treatment of absence seizures and seizures associated w/ hypoglycaemia or other metabolic causes. Avoid abrupt withdrawal. Renal and hepatic impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
Burning, itching, and paraesthesia, particularly in the groin area; oedema, discoloration, and pain distal at the inj site (purple glove syndrome); lymphadenopathy (local or generalised); confusional states (e.g. delirium, psychoses).
Potentially Fatal: Severe CV reactions (e.g. hypotension, cardiac arrhythmias) associated w/ rapid infusion, suicidal ideation and behaviour, serious skin reactions (e.g. exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis), anticonvulsant hypersensitivity syndrome (AHS), drug reaction w/ eosinophilia and systemic symptoms (DRESS), acute hepatotoxicity, haematopoietic complications (e.g. thrombocytopenia, leucopenia, granulocytopenia, agranulocytosis, pancytopenia).
IM/IV/Parenteral: D
Patient Counseling Information
May impair ability to drive or operate machinery.
MonitoringParameters
Monitor BP, cardiac and resp function; vital signs, haematologic and hepatic function, plasma phenytoin concentrations.
Overdosage
Symptoms: Initially, nystagmus, ataxia and dysarthria. Nausea, vomiting, lethargy, tachycardia, bradycardia, asystole, cardiac arrest, hypotension, syncope, hypocalcaemia, metabolic acidosis; resp or circulatory depression. Management: Supportive treatment. Haemodialysis may be considered.
Drug Interactions
Increased plasma levels w/ amiodarone, antiepileptics (e.g. ethosuximide), azoles (e.g. fluconazole), capecitabine, chloramphenicol, chlordiazepoxide, disulfiram, oestrogens, fluorouracil, fluoxetine, fluvastatin, fluvoxamine, H2-antagonists (e.g. cimetidine), halothane, isoniazid, methylphenidate, omeprazole, phenothiazines, salicylates, sertraline, succinimides, sulfonamides (e.g. sulfamethizole), ticlopidine, tolbutamide, trazodone. Decreased plasma levels w/ anticancer drugs usually in combination (e.g. bleomycin), carbamazepine, diazepam, diazoxide, folic acid, fosamprenavir, nelfinavir, reserpine, rifampicin, ritonavir, theophylline, vigabatrin. Altered (increased or decreased) plasma levels w/ phenobarbital, valproic acid, Na valproate. May impair the efficacy of corticosteroids, doxycycline, furosemide, irinotecan, OC, paclitaxel, paroxetine, quinidine, rifampicin, teniposide, theophylline, vit D. Increased and decreased prothrombin time/INR responses w/ warfarin. May decrease plasma levels of active metabolites of albendazole, certain HIV antivirals (e.g. efavirenz), atorvastatin, chlorpropamide, clozapine, ciclosporin, digoxin, methadone, mexiletine, nifedipine, nimodipine, nisoldipine, praziquantel, simvastatin, verapamil. May decrease serum levels of amprenavir (active metabolite of fosamprenavir), when given w/ fosamprenavir alone. May increase amprenavir concentration when given w/ fosamprenavir and ritonavir combination. May cause resistance to the neuromuscular blocking action of the non-depolarising neuromuscular blocking agents (e.g. pancuronium).
Potentially Fatal: May cause loss of virologic response and possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors.
Food Interaction
Acute alcohol intake may increase plasma phenytoin levels while chronic use may decrease plasma phenytoin levels. Decreased plasma levels w/ St John's wort.
Lab Interference
May decrease serum concentrations of T4. May produce low results in dexamethasone or metyrapone tests. May cause increased serum concentrations of glucose, alkaline phosphatase and γ-glutamyl transpeptidase (GGT).
Action
Description: Fosphenytoin is a diphosphate ester salt of phenytoin which acts as a water soluble prodrug of phenytoin. After admin, plasma esterases convert fosphenytoin to phosphate, formaldehyde, and phenytoin as the active moiety; phenytoin stabilises neuronal membranes and decreases seizure activity by increasing efflux or decreasing influx of Na ions across cell membranes in the motor cortex during generation of nerve impulses.
Pharmacokinetics:
Absorption: Bioavailability: 100% (IM). Time to peak plasma concentration: Immediately at the end of IV infusion; approx 30 min (IM).
Distribution: Plasma protein-binding: 95-99% (mainly to albumin).
Metabolism: Rapidly and completely hydrolysed to phenytoin.
Excretion: Via urine (as metabolites).
Chemical Structure

Chemical Structure Image
Fosphenytoin

Source: National Center for Biotechnology Information. PubChem Database. Fosphenytoin, CID=56339, https://pubchem.ncbi.nlm.nih.gov/compound/Fosphenytoin (accessed on Jan. 21, 2020)

Storage
Store between 2-8°C.
MIMS Class
ATC Classification
N03AB05 - fosphenytoin ; Belongs to the class of hydantoin derivatives antiepileptics.
References
Anon. Fosphenytoin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 11/12/2014.

Buckingham R (ed). Fosphenytoin Sodium. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/12/2014.

Cerebyx Injection Solution (Pfizer Laboratories). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 11/12/2014.

McEvoy GK, Snow EK, Miller J et al (eds). Fosphenytoin Sodium. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 11/12/2014.

Disclaimer: This information is independently developed by MIMS based on Fosphenytoin from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in