Pro-Epanutin (Fosphenytoin)
Injectable antiepileptic for emergency seizure management and neurosurgical prophylaxis
Pro-Epanutin (fosphenytoin) is an injectable antiepileptic medication used in hospital settings for the emergency treatment of status epilepticus, seizure prevention during and after neurosurgery or head injury, and as a short-term parenteral substitute for oral phenytoin therapy. As a prodrug of phenytoin, it is rapidly converted to the active drug in the body and requires continuous cardiac monitoring during administration.
Quick Facts
Key Takeaways
- Pro-Epanutin (fosphenytoin) is a prodrug of phenytoin used exclusively in hospital settings for status epilepticus, perioperative seizure prevention, and short-term replacement of oral phenytoin therapy.
- It can be given both intravenously (IV) and intramuscularly (IM), offering a significant advantage over phenytoin which can only be given IV due to its alkaline pH and tissue toxicity.
- Continuous ECG, blood pressure and respiratory monitoring are mandatory during infusion and for at least 30 minutes afterwards due to the risk of hypotension and cardiac arrhythmias.
- Doses are expressed in phenytoin sodium equivalents (PE) so that the same number of milligrams PE corresponds directly to milligrams of oral phenytoin sodium, simplifying dose conversion.
- Pro-Epanutin is contraindicated in patients with heart rhythm disorders, acute intermittent porphyria, and those taking the antiretroviral delavirdine. It carries a significant risk of birth defects during pregnancy.
What Is Pro-Epanutin and What Is It Used For?
Quick Answer: Pro-Epanutin contains fosphenytoin sodium, a prodrug that is rapidly converted to the antiepileptic drug phenytoin after injection. It is used in adults and children aged 5 years and older for the emergency treatment of status epilepticus, seizure prevention around neurosurgery and head trauma, and as a temporary parenteral substitute when phenytoin cannot be taken orally.
Pro-Epanutin belongs to the hydantoin class of antiepileptic drugs (AEDs). Its active ingredient, fosphenytoin sodium, is a water-soluble phosphate ester prodrug of phenytoin. After intravenous or intramuscular administration, endogenous phosphatases rapidly cleave the phosphate group, releasing phenytoin into the bloodstream. This conversion occurs with a half-life of approximately 15 minutes, meaning therapeutic phenytoin levels are achieved quickly in emergency situations.
The primary indication for Pro-Epanutin is the treatment of status epilepticus – a life-threatening condition defined as continuous seizure activity lasting longer than five minutes, or two or more seizures without full recovery of consciousness between them. In this context, Pro-Epanutin is typically administered after initial treatment with a benzodiazepine such as diazepam or lorazepam has been given. The International League Against Epilepsy (ILAE) and the American Epilepsy Society (AES) guidelines recognise fosphenytoin as a second-line agent for established status epilepticus.
Pro-Epanutin is also indicated for the control and prevention of seizures during and after neurosurgery (craniotomy procedures) and following traumatic brain injury. Post-traumatic seizures occur in approximately 5–7% of hospitalised head injury patients within the first week, and prophylactic phenytoin (via fosphenytoin) has been shown to reduce early seizure incidence. The landmark study by Temkin et al. (1990), published in the New England Journal of Medicine, demonstrated a significant reduction in early post-traumatic seizures with phenytoin prophylaxis.
Additionally, Pro-Epanutin serves as a short-term parenteral replacement for patients who are unable to take oral phenytoin. This may occur during the perioperative period, in patients with severe gastrointestinal dysfunction, or in critically ill individuals who cannot swallow medications. Because the dose of Pro-Epanutin is expressed in phenytoin sodium equivalents (PE), the transition between oral phenytoin and parenteral fosphenytoin is straightforward – the same number of milligrams can be used.
A key clinical advantage of fosphenytoin over direct intravenous phenytoin is its more favourable side-effect profile at the injection site. Phenytoin injection has a pH of approximately 12 and contains propylene glycol, which frequently causes pain, burning, and tissue necrosis (including the serious condition known as “purple glove syndrome”). Fosphenytoin, with its near-neutral pH, causes substantially less local irritation and can also be administered intramuscularly – an option not available with phenytoin.
What Should You Know Before Receiving Pro-Epanutin?
Quick Answer: Pro-Epanutin must not be given to patients with cardiac conduction disorders, acute intermittent porphyria, or those taking delavirdine. Special caution is required in patients with liver disease, heart disease, kidney disease, or low serum albumin. Continuous cardiac monitoring is mandatory. The drug carries significant teratogenic risk and should be used with extreme caution during pregnancy.
Contraindications
Pro-Epanutin is absolutely contraindicated in the following situations, and must not be administered under these circumstances:
- Hypersensitivity to fosphenytoin sodium, phenytoin, or any of the excipients
- Cardiac conduction disorders including sinoatrial block, second-degree and third-degree atrioventricular (AV) block, and Adams-Stokes syndrome. Phenytoin has sodium channel-blocking properties that can worsen pre-existing conduction abnormalities and potentially cause complete heart block or asystole.
- Acute intermittent porphyria – a rare genetic disorder affecting haem biosynthesis. Phenytoin is a potent inducer of hepatic cytochrome P450 enzymes and can precipitate acute porphyric attacks, which may be life-threatening.
- Concurrent use of delavirdine – an antiretroviral non-nucleoside reverse transcriptase inhibitor (NNRTI) used in HIV treatment. Phenytoin significantly reduces delavirdine plasma concentrations through CYP3A4 induction, potentially leading to virological failure and development of resistance.
Warnings and Precautions
Healthcare providers should exercise particular caution when administering Pro-Epanutin in the following circumstances. A careful risk-benefit assessment should be performed before initiating treatment:
Hepatic impairment: Phenytoin is extensively metabolised by the liver, primarily through the CYP2C9 and CYP2C19 enzyme systems. In patients with liver disease, the rate of conversion of fosphenytoin to phenytoin may be altered, and the free (unbound) fraction of phenytoin in plasma may be increased. This can lead to enhanced pharmacological effects and toxicity at seemingly therapeutic total phenytoin levels. Dose reduction and more frequent monitoring of free phenytoin levels are recommended.
Renal impairment: In patients with kidney disease, the binding of phenytoin to plasma proteins is often reduced, leading to higher free phenytoin levels. Furthermore, the phosphate load from fosphenytoin conversion should be considered in patients with renal insufficiency. Dose adjustments based on free phenytoin level monitoring are advisable.
Hypoalbuminaemia: Phenytoin is approximately 90% protein-bound, primarily to albumin. In patients with low serum albumin levels (common in critically ill, elderly or malnourished patients), the free fraction of phenytoin is increased. Total phenytoin levels may appear within the therapeutic range while the free level is actually supratherapeutic. Measuring free phenytoin levels is essential in these patients.
Diabetes: Phenytoin may inhibit insulin release and can cause hyperglycaemia. Blood glucose monitoring should be intensified in diabetic patients receiving Pro-Epanutin.
Severe cutaneous adverse reactions (SCARs): Rarely, phenytoin and fosphenytoin may cause serious skin reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalised exanthematous pustulosis (AGEP). The risk may be elevated in individuals of Chinese, South-East Asian, Japanese, Malaysian or Thai ancestry who carry the HLA-B*1502 allele or the CYP2C9*3 variant. Pharmacogenomic testing should be considered in these populations before initiating treatment. If a severe skin reaction occurs, fosphenytoin must be permanently discontinued.
Angioedema: Cases of facial swelling, including swelling of the lips, gums, tongue and throat with potential for life-threatening airway obstruction, have been reported with phenytoin and fosphenytoin. Patients who develop signs of angioedema should receive immediate medical attention.
Pregnancy and Breastfeeding
The management of epilepsy during pregnancy requires specialist oversight. The risks of uncontrolled seizures during pregnancy include maternal injury, placental abruption, premature labour, and foetal hypoxia. However, the teratogenic risk of phenytoin is well-documented, and international guidelines from the ILAE and the European Medicines Agency (EMA) recommend that phenytoin should not be used as a first-line treatment in women of childbearing potential whenever effective alternatives exist.
If Pro-Epanutin is used during pregnancy, there is also a risk of neonatal haemorrhage due to phenytoin-induced vitamin K deficiency. Prophylactic vitamin K administration to the mother in the last month of pregnancy and to the newborn at delivery is recommended. Careful neonatal monitoring is essential.
Breastfeeding: Phenytoin is excreted in breast milk. Pro-Epanutin should not be used during breastfeeding. Discuss alternative feeding options with your healthcare provider.
Contraception: Phenytoin is a potent inducer of hepatic enzymes (CYP3A4) and significantly reduces the effectiveness of hormonal contraceptives, including combined oral contraceptives, progestogen-only pills, implants and patches. Women of childbearing potential should discuss reliable non-hormonal contraceptive methods (such as copper intrauterine devices) with their healthcare provider.
Driving and Operating Machinery
Pro-Epanutin may cause dizziness, drowsiness, visual disturbances and impaired coordination. Patients should not drive or operate machinery until these effects have fully resolved. In practice, as Pro-Epanutin is administered in hospital settings, this applies primarily to the period following hospital discharge.
How Does Pro-Epanutin Interact with Other Drugs?
Quick Answer: Phenytoin (the active metabolite of fosphenytoin) has extensive drug interactions due to its potent enzyme-inducing properties and its own metabolism by CYP2C9 and CYP2C19. Many drugs can increase or decrease phenytoin levels, and phenytoin itself reduces the effectiveness of numerous medications including oral contraceptives, warfarin, corticosteroids and immunosuppressants.
Phenytoin has one of the most extensive drug interaction profiles of any medication. It is a potent inducer of CYP3A4, CYP2B6 and other hepatic enzymes, and is itself primarily metabolised by CYP2C9 and CYP2C19. Because phenytoin follows non-linear (Michaelis-Menten) pharmacokinetics, even small changes in its metabolism can lead to disproportionately large changes in plasma concentrations – potentially causing either toxicity or loss of seizure control. Therapeutic drug monitoring (TDM) of phenytoin levels is essential when adding, removing or changing the dose of interacting medications.
Major Interactions
| Drug / Class | Effect | Clinical Significance |
|---|---|---|
| Delavirdine | Phenytoin induces CYP3A4, dramatically reducing delavirdine levels | Contraindicated – risk of virological failure and HIV resistance |
| Warfarin | Complex bidirectional interaction; phenytoin initially inhibits then induces warfarin metabolism | Close INR monitoring required; dose adjustment often needed |
| Oral contraceptives | Phenytoin induces CYP3A4, reducing oestrogen and progestogen levels | Contraceptive failure risk; use non-hormonal alternatives |
| Valproic acid | Displaces phenytoin from protein binding and inhibits its metabolism; phenytoin reduces valproate levels | Monitor free phenytoin and valproate levels; dose adjustment likely |
| Carbamazepine | Mutual enzyme induction; both drug levels may decrease | Monitor levels of both drugs; dose increases may be required |
| Cyclosporine / Tacrolimus | Phenytoin induces CYP3A4, markedly reducing immunosuppressant levels | Risk of transplant rejection; intensive level monitoring mandatory |
| Corticosteroids | Phenytoin enhances steroid metabolism via CYP3A4 induction | Reduced steroid efficacy; higher steroid doses may be needed |
Other Notable Interactions
| Drug / Class | Effect | Recommendation |
|---|---|---|
| Theophylline | Mutual metabolism increase; both levels may fall | Monitor levels of both drugs |
| Antifungals (fluconazole, voriconazole) | Inhibit CYP2C9; increase phenytoin levels | Reduce phenytoin dose; monitor levels |
| Proton pump inhibitors (omeprazole) | CYP2C19 inhibition; may increase phenytoin levels | Monitor phenytoin levels when starting or stopping |
| St John’s Wort (Hypericum perforatum) | Induces CYP enzymes; may reduce phenytoin levels | Avoid concurrent use; do not stop abruptly |
| Folate / Vitamin D supplements | Phenytoin impairs folate and vitamin D metabolism | Supplementation often recommended with chronic use |
| Neuromuscular blocking agents | Phenytoin may reduce the duration of neuromuscular blockade | Monitor depth of blockade; dose adjustments during surgery |
Alcohol: Chronic heavy alcohol use induces CYP enzymes and can lower phenytoin levels, potentially reducing seizure control. Conversely, acute alcohol intoxication may inhibit phenytoin metabolism, raising levels and increasing toxicity risk. Patients should be counselled about the unpredictable effects of alcohol on their medication.
Laboratory test interference: Phenytoin can affect various laboratory measurements including thyroid function tests (reduced T4 levels), blood glucose, calcium and vitamin D levels. Healthcare providers should be aware of these effects when interpreting laboratory results.
What Is the Correct Dosage of Pro-Epanutin?
Quick Answer: Pro-Epanutin is administered in hospital under continuous monitoring. Doses are expressed in phenytoin sodium equivalents (PE). For status epilepticus in adults, the typical loading dose is 15–20 mg PE/kg IV at a maximum rate of 100–150 mg PE/min, followed by maintenance doses of 4–5 mg PE/kg/day. For children aged 5 and above, dosing per kg is similar but administration is IV only.
All doses of Pro-Epanutin are expressed in phenytoin sodium equivalents (PE). This means that 1 mg PE of fosphenytoin delivers the same amount of active phenytoin as 1 mg of phenytoin sodium taken orally. The concentration of Pro-Epanutin solution is 75 mg fosphenytoin sodium per ml, which is equivalent to 50 mg PE/ml. This PE-based dosing system simplifies the transition between parenteral fosphenytoin and oral phenytoin.
Adults
Status Epilepticus
Pro-Epanutin is given after initial benzodiazepine treatment (diazepam or lorazepam). The loading dose is 15–20 mg PE/kg administered as an intravenous infusion at a maximum rate of 100–150 mg PE/min. Following the loading dose, maintenance doses of 4–5 mg PE/kg/day may be given intravenously or intramuscularly. If seizures are not controlled with Pro-Epanutin, other treatments should be initiated.
Neurosurgery / Head Injury Prophylaxis
A loading dose of 10–15 mg PE/kg is administered intravenously or intramuscularly. This is followed by maintenance doses of 4–5 mg PE/kg/day via either route. The duration of prophylaxis is typically 7 days for post-traumatic seizure prevention, as supported by the Temkin et al. evidence base.
Temporary Replacement for Oral Phenytoin
When Pro-Epanutin is used as a substitute for oral phenytoin, no loading dose is needed. The dose in mg PE is the same as the patient’s usual oral phenytoin sodium dose in mg. It can be given intravenously or intramuscularly.
Children (Aged 5 Years and Older)
The dosing of Pro-Epanutin per kilogram of body weight is the same for children from 5 years of age as for adults. However, in children, Pro-Epanutin must be administered only as an intravenous infusion (not intramuscularly). The maximum infusion rate in children should not exceed 2 mg PE/kg/min or 100 mg PE/min, whichever is lower. Cardiovascular monitoring requirements are the same as for adults.
Pro-Epanutin is not approved for use in children under 5 years of age. Limited safety data are available in this age group, and the pharmacokinetic profile of fosphenytoin in very young children has not been fully characterised.
Elderly Patients and Special Populations
In patients over 65 years, the dose of Pro-Epanutin may need to be reduced and the intravenous infusion rate slowed. Elderly patients are at increased risk of cardiovascular adverse effects including hypotension and cardiac arrhythmias. They are also more likely to have reduced albumin levels, hepatic function and renal function, all of which affect phenytoin pharmacokinetics.
Similarly, dose reduction and slower infusion rates should be considered in critically ill patients, those with hepatic or renal impairment, and patients with hypoalbuminaemia. Free phenytoin level monitoring is strongly recommended in these populations.
Overdose
An overdose of Pro-Epanutin is a medical emergency requiring immediate intervention. Symptoms of phenytoin toxicity progress with increasing plasma concentrations:
- Nystagmus typically appears first at levels above 20 mcg/ml
- Ataxia and dysarthria at levels above 30 mcg/ml
- Lethargy and confusion at levels above 40 mcg/ml
- Coma, respiratory depression and cardiovascular collapse at very high levels
There is no specific antidote for phenytoin. Treatment is supportive and includes airway management, cardiovascular support, and monitoring of phenytoin levels. Equipment for managing cardiac arrest should be immediately available during Pro-Epanutin administration. In rare cases, sustained elevated phenytoin levels have resulted in irreversible cerebellar damage.
What Are the Side Effects of Pro-Epanutin?
Quick Answer: The most common side effects include nystagmus, dizziness and itching (affecting more than 1 in 10 patients). Common effects include drowsiness, headache, tremor, nausea, low blood pressure and pain at the injection site. Serious but rare adverse effects include Stevens-Johnson syndrome, DRESS, purple glove syndrome, blood disorders and severe cardiac arrhythmias.
Like all medicines, Pro-Epanutin can cause side effects, although not everyone experiences them. The side effects are largely attributable to phenytoin, the active metabolite, and are concentration-dependent. Many adverse effects resolve when phenytoin levels return to the therapeutic range. A unique and relatively common phenomenon with intravenous fosphenytoin administration is the occurrence of temporary itching, burning, warmth or tingling in the groin area during or shortly after injection; this is related to the drug itself rather than the vehicle and typically resolves spontaneously or with slowing of the infusion rate.
Very Common
Affects more than 1 in 10 people
- Nystagmus (abnormal eye movements)
- Dizziness
- Pruritus (itching)
Common
Affects 1 in 10 to 1 in 100 people
- Mood changes
- Paraesthesia (tingling and prickling sensations)
- Ataxia (unsteadiness), somnolence (drowsiness), headache, tremor
- Abnormal or uncoordinated movements, slurred speech
- Blurred vision, taste disturbance, tinnitus (ringing in ears)
- Nausea, dry mouth, vomiting
- Pain or reaction at the injection site
- Fatigue, weakness, chills
- Decreased level of consciousness
- Hypotension (low blood pressure)
- Ecchymosis (bruising)
Uncommon
Affects 1 in 100 to 1 in 1,000 people
- Nervousness, confusion, abnormal thinking
- Peripheral neuropathy (numbness or tingling in hands and feet)
- Increased or decreased reflexes
- Diplopia (double vision), hearing impairment
- Reduced tongue sensation
- Skin rash (mild maculopapular eruptions)
- Muscle weakness, twitching, cramps
- Stevens-Johnson syndrome / Toxic epidermal necrolysis (SJS/TEN)
Not Known
Frequency cannot be estimated from available data
- Blood disorders: anaemia, leucopenia, thrombocytopenia, agranulocytosis
- Lymphadenopathy (swollen lymph nodes)
- DRESS syndrome (drug reaction with eosinophilia and systemic symptoms)
- AGEP (acute generalised exanthematous pustulosis)
- Systemic lupus erythematosus-like reactions
- Purple glove syndrome (discolouration, swelling and pain at IV site spreading distally)
- Angioedema (facial and throat swelling)
- Hepatitis and liver damage (jaundice)
- Gingival hyperplasia (gum overgrowth)
- Hyperglycaemia; decreased calcium, folate and vitamin D levels
- Osteoporosis and bone fractures (with long-term phenytoin use)
- Cerebellar atrophy (with prolonged toxic levels)
- Serious cardiac arrhythmias (including ventricular fibrillation)
- Coarsening of facial features, hirsutism (with chronic use)
- Nephritis (kidney inflammation)
- Priapism (painful persistent erection)
How Should Pro-Epanutin Be Stored?
Quick Answer: Pro-Epanutin should be stored in a refrigerator (2–8°C). Undiluted product may be kept at room temperature (up to 25°C) for a maximum of 24 hours. After dilution, use immediately. For single use only – discard any unused solution.
Pro-Epanutin concentrate for solution for injection/infusion must be stored in a refrigerator at 2–8°C. It should be kept out of the sight and reach of children. The undiluted product can be stored at room temperature (8–25°C) for up to 24 hours if needed, but should be returned to refrigeration if not used within this period.
Once diluted for intravenous infusion, Pro-Epanutin should be used immediately. The product is intended for single use only. Any unused solution remaining after opening the vial must be discarded. Do not use the product if the solution contains visible particles.
Check the expiry date printed on the carton and the vial before use. The expiry date refers to the last day of the stated month. Do not use Pro-Epanutin after this date.
What Does Pro-Epanutin Contain?
Quick Answer: Each ml of Pro-Epanutin contains 75 mg fosphenytoin sodium (equivalent to 50 mg PE phenytoin sodium). Excipients include water for injections, trometamol and hydrochloric acid. It is available in 2 ml (100 mg PE) and 10 ml (500 mg PE) glass vials.
The active substance is fosphenytoin sodium. Each millilitre of solution contains 75 mg fosphenytoin sodium, which is equivalent to 50 mg phenytoin sodium (expressed as 50 mg PE). Two vial sizes are available:
- 2 ml vial: Contains 150 mg fosphenytoin sodium (equivalent to 100 mg PE)
- 10 ml vial: Contains 750 mg fosphenytoin sodium (equivalent to 500 mg PE)
The other ingredients (excipients) are water for injections, trometamol (THAM, a buffering agent), and hydrochloric acid (for pH adjustment).
Appearance: Pro-Epanutin is a clear, colourless to slightly yellow sterile solution supplied in glass vials.
Sodium content: The 10 ml vial contains 85 mg sodium (4.25% of the WHO recommended maximum daily sodium intake for adults). The 2 ml vial contains 17 mg sodium (less than 1 mmol). When calculating total sodium load, any sodium chloride used for dilution should also be taken into account.
| Vial Size | Fosphenytoin Content | Phenytoin Equivalent (PE) | Pack Sizes |
|---|---|---|---|
| 2 ml | 150 mg | 100 mg PE | 5, 10, or 25 vials; multipack 50 vials (10 × 5) |
| 10 ml | 750 mg | 500 mg PE | 5 or 10 vials; multipack 25 vials (5 × 5) |
Not all pack sizes may be marketed. Pro-Epanutin is manufactured by Pfizer.
Frequently Asked Questions
Pro-Epanutin contains fosphenytoin, a prodrug that is rapidly converted to the antiepileptic drug phenytoin after injection. It is used for three main purposes: (1) emergency treatment of status epilepticus (prolonged, severe seizures), typically after benzodiazepines have been given; (2) prevention and control of seizures during and after neurosurgery or head injury; and (3) as a temporary injectable replacement when patients cannot take oral phenytoin. It is approved for adults and children aged 5 years and older, and is administered only in hospital settings.
Pro-Epanutin can be administered by intravenous (IV) infusion into a large vein or by intramuscular (IM) injection. When given intravenously, it must first be diluted. For children aged 5 and above, only the IV route is used. During and for 30 minutes after IV infusion, the patient's ECG, blood pressure and breathing are continuously monitored. The infusion rate is carefully controlled – the maximum rate for adults is 100–150 mg PE/min for status epilepticus and 50–100 mg PE/min for non-emergency indications.
The most common side effects (affecting more than 1 in 10 people) are nystagmus (involuntary eye movements), dizziness, and itching. Common side effects (affecting up to 1 in 10) include drowsiness, headache, tremor, nausea, vomiting, blurred vision, low blood pressure, bruising, tingling sensations, and pain at the injection site. A notable side effect unique to IV fosphenytoin is temporary itching, burning, or warmth in the groin area during infusion, which resolves spontaneously or when the infusion rate is reduced.
Pro-Epanutin carries a significant risk of birth defects when used during pregnancy. Documented malformations include fetal hydantoin syndrome (facial and limb abnormalities), cardiac defects, and an increased risk of neuroblastoma. However, stopping antiepileptic treatment without medical guidance can be equally dangerous, as uncontrolled seizures pose serious risks to both mother and fetus. Women of childbearing potential must use effective non-hormonal contraception while receiving this medication and should discuss their treatment options with a specialist epileptologist before becoming pregnant.
Fosphenytoin (Pro-Epanutin) is a water-soluble prodrug that is converted to phenytoin after injection. The key advantages of fosphenytoin over direct IV phenytoin include: a faster maximum infusion rate (up to 150 mg PE/min vs 50 mg/min), significantly less pain and irritation at the injection site, the ability to be given intramuscularly (phenytoin cannot due to tissue damage and erratic absorption), and a lower risk of the serious complication known as purple glove syndrome. Doses are expressed in phenytoin equivalents (PE) so that the same number of milligrams can be used when switching between the two formulations.
Both fosphenytoin and its active metabolite phenytoin have effects on cardiac conduction. Phenytoin blocks voltage-dependent sodium channels in the heart (similar to Class IB antiarrhythmic drugs), which can slow conduction and suppress automaticity. During rapid IV infusion, this can cause hypotension, bradycardia, heart block, and in severe cases, ventricular arrhythmias or cardiac arrest. These risks are greatest in elderly patients, children, critically ill patients, and those with pre-existing cardiac conditions. Continuous ECG, blood pressure and respiratory monitoring are therefore mandatory for the duration of the infusion and for at least 30 minutes after completion.
References
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- Glauser T, Shinnar S, Gloss D, et al. Evidence-based guideline: Treatment of convulsive status epilepticus in children and adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48-61. doi:10.5698/1535-7597-16.1.48
- Temkin NR, Dikmen SS, Wilensky AJ, et al. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med. 1990;323(8):497-502. doi:10.1056/NEJM199008233230801
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- National Institute for Health and Care Excellence (NICE). Epilepsies in children, young people and adults. NICE guideline [NG217]. Updated 2024.
- World Health Organization. WHO Model List of Essential Medicines – 23rd list (2023). Geneva: WHO; 2023.
- Boucher BA, Feler CA, Dean JC, et al. The safety, tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients. Pharmacotherapy. 1996;16(4):638-645.
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Editorial Team
This article was written and medically reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians in neurology, epileptology, emergency medicine, and clinical pharmacology. Our editorial process follows the GRADE evidence framework and adheres to international guidelines from the WHO, ILAE, AES and NICE.
Conflict of Interest: None. iMedic operates with no commercial funding and no pharmaceutical industry sponsorship. All content is independent and evidence-based.
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