fosphenytoin

Action and Spectrum

Actions and Spectrum: 

fosphenytoin is a prodrug of the anticonvulsant medication phenytoin. When administered, fosphenytoin is converted into phenytoin, which then acts on the brain to prevent seizures. 

The spectrum of action of fosphenytoin is quite broad, as it can be used to prevent and treat seizures of various types, including generalized tonic-clonic seizures, partial seizures, and status epilepticus.

Phenytoin works by stabilizing neuronal membranes and decreasing the activity of voltage-gated sodium channels in the brain, thereby reducing the abnormal electrical activity that leads to seizures. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

IV, adults 

Nystagmus (44%) 

Dizziness (31%) 

Pruritus (49%) 

Ataxia (11%) 

Somnolence (20%) 

Adults and children 

General 

Injection-site reaction, Chills, Fever, Face edema, Injection-site pain, Infection 

Musculoskeletal 

Leg cramps, myalgia, arthralgia, myopathy 

Nervous  

Dysarthria, Intracranial hypertension, reflexes increased, thinking abnormal, Speech disorder, Nervousness. 

Skin 

Rash 

Respiratory 

Pneumonia 

Digestive 

Constipation 

Cardiovascular 

Hypertension 

IV, children and adolescents 

Nystagmus (18%) 

Vomiting (21%) 

IM 

Nystagmus (15%) 

1-10% 

IV, adults 

Pelvic pain (4%) 

Extrapyramidal syndrome (4%) 

Incoordination (4%) 

Dry mouth (4%) 

Tongue disorder (4%) 

Paresthesia (4%) 

Vasodilatation (6%) 

Hypotension (8%) 

Stupor (8%) 

Tinnitus (9%) 

Nausea (9%) 

Tremor (3%) 

Diplopia (3%) 

Taste perversion (3%) 

Agitation (3%) 

Dysarthria (2%) 

Hypesthesia (2%) 

Vomiting (2%) 

Brain edema (2%) 

Vertigo (2%) 

Asthenia (2%) 

Deafness (2%) 

Amblyopia (2%) 

Headache (2%) 

Back pain (2%) 

IV, children and adolescents 

Rash (5%) 

Somnolence (6%) 

Ataxia (10%) 

Nervousness (7%) 

Hypotension (5%) 

Pruritus (6%) 

Fever (8%) 

Adults and children 

General 

injection-site hemorrhage, sepsis, injection-site inflammation, photosensitivity reaction 

injection-site edema, malaise, generalized edema, shock, cachexia, flu syndrome, cryptococcosis. 

Nervous 

CNS depression, confusion, twitching, akathisia, positive Babinski sign, circumoral paresthesia, hemiplegia, hypotonia, convulsion, extrapyramidal syndrome, insomnia, meningitis, depersonalization, depression, hypokinesia, hyperkinesia, paralysis, psychosis, aphasia, emotional lability, coma, hyperesthesia, myoclonus, personality disorder, acute brain syndrome, encephalitis, subdural hematoma, encephalopathy, hostility, amnesia, and neurosis. 

Urogenital 

Urinary retention, oliguria, dysuria, genital edema, kidney failure, polyuria, urethral pain, urinary incontinence, albuminuria, vaginitis, and vaginal moniliasis 

Special senses 

Visual field defect, eye pain, conjunctivitis, photophobia, hyperacusis, mydriasis, ear pain, taste loss, and parosmia 

Skin 

Contact dermatitis, pustular rash,urticaria, maculopapular rash, skin discoloration 

skin nodule, sweating.  

IM 

Somnolence (7%) 

Reflexes decreased (3%) 

Ataxia (8%) 

Pruritus (3%) 

Dizziness (5%) 

Incoordination (8%) 

Paresthesia (4%) 

Headache (9%) 

Vomiting (3%) 

Asthenia (9%) 

Nausea (5%) 

Tremor (10%)

Black Box Warning

Black Box Warning: 

The black box warning for fosphenytoin is related to the risk of cardiovascular adverse reactions, including severe hypotension and arrhythmias, particularly when the drug is administered too rapidly or in excessive doses. 

The black box warning specifically cautions that fosphenytoin should be administered slowly and in a manner that allows for cardiac monitoring, especially in patients with a history of cardiovascular disease. It also warns that the drug should not be used to treat certain types of arrhythmias, such as atrial fibrillation or flutter. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity: fosphenytoin should not be used in patients allergic to the drug or to phenytoin. 
• Bradycardia: fosphenytoin can cause bradycardia, which is a slow heart rate. Therefore, it should not be used in patients with a history of bradycardia or other cardiac conduction abnormalities, unless they have a pacemaker in place. 
• Heart block: fosphenytoin can worsen heart block, which is a condition where the electrical impulses that regulate the heartbeat are disrupted. Therefore, it should not be used in patients with second- or third-degree heart block. 
• Porphyria: fosphenytoin can trigger an acute attack of porphyria, which is a rare genetic disorder that affects the production of heme, a component of hemoglobin. Therefore, it should not be used in patients with this condition. 
• Preexisting hypotension: fosphenytoin can cause a drop in blood pressure, which can be dangerous in patients with preexisting hypotension. 

Caution 

• Pregnancy and breastfeeding: fosphenytoin may be harmful to a developing fetus, so it should only be used in pregnant women if the potential benefits outweigh the risks. It may also be excreted in breast milk, so breastfeeding should be avoided while taking fosphenytoin. 
• Liver disease: fosphenytoin is metabolized by the liver, caution in patients with liver disease, as they may be at increased risk of toxicity. 
• Kidney disease: fosphenytoin is excreted by the kidneys, caution in patients with kidney disease, as they may be at increased risk of toxicity. 
• Elderly patients: Elderly patients may be more susceptible to the side effects of fosphenytoin, such as dizziness, confusion, and sedation, so they should be monitored closely while taking the medication. 
• Drug interactions: fosphenytoin may interact with other medications, such as oral contraceptives, warfarin, and corticosteroids, so healthcare professionals should review a patient’s medication history carefully before prescribing fosphenytoin. 
• Seizure control: fosphenytoin is used to prevent and treat seizures, but it is important to monitor a patient’s seizure control while they are taking the medication, as it may require adjustments in dosing or other medications. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned. 

Lactation:   

Excreted into human milk is Not known.  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.       
• Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.        
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.        
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology:

fosphenytoin is a prodrug of phenytoin, meaning that it is metabolized in the body to produce phenytoin, which is the active form of the drug. The pharmacology of fosphenytoin and phenytoin is similar, but there are some differences in their pharmacokinetics, which may affect their clinical use. 

Pharmacodynamics: 

Mechanism of Action: Phenytoin works by stabilizing neuronal membranes and reducing the spread of abnormal electrical activity in the brain, which can cause seizures. It appears to work by blocking voltage-dependent sodium channels in the neurons, thereby reducing the influx of sodium ions and stabilizing the neuronal membrane. 

Pharmacokinetics: 

Absorption 

fosphenytoin exhibits complete bioavailability when administered via intramuscular injection. Maximum plasma concentration is achieved at the end of the infusion when given through intravenous route. When administered intramuscularly, the plasma concentration is lower, but the effect is more sustained than intravenous due to the time required for absorption of fosphenytoin from the injection site. Peak plasma concentration is reached approximately 30 minutes after the intramuscular administration. 

Distribution 

The human plasma proteins, primarily albumin, bind protein at a rate of approximately 95-99%, while the volume of distribution is between 4.3-10.8 L. 

Metabolism 

Upon administration, fosphenytoin undergoes rapid hydrolysis, converting it to phenytoin. Phenytoin is metabolized in the liver and gives rise to various metabolites. 

Elimination and Excretion 

The half-life of fosphenytoin, resulting from its conversion to phenytoin, is approximately 15 minutes. fosphenytoin or its metabolites are not excreted in the urine. 

Adminstartion

Administration: 

IV/IM administration 

fosphenytoin is usually administered by injection into a vein (intravenously), although it can also be given by intramuscular injection in certain situations. Here are some general guidelines for the administration of fosphenytoin: 

• fosphenytoin should be given slowly, over a period of at least 30 minutes, to minimize the risk of cardiovascular adverse reactions. Rapid administration can cause severe hypotension and arrhythmias. 
• The dose of fosphenytoin is based on the patient’s weight and the indication for treatment. The maximum recommended loading dose is 20 mg phenytoin equivalents per kilogram of body weight. 
• fosphenytoin should be administered with caution in patients with cardiac disease or those who are receiving other medications that can affect cardiac function. 
• fosphenytoin should not be mixed with other medications or solutions, as this can cause precipitation or inactivation of the drug. 
• fosphenytoin should be stored at room temperature and protected from light. 
• When administering fosphenytoin intravenously, it is important to use a large bore needle or catheter to minimize the risk of tissue irritation or necrosis. 
• During and after administration patients should be monitored closely for signs of adverse reactions, such as hypotension, arrhythmias or hypersensitivity reactions. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: fosphenytoin 

Pronounced: [ fos-FEN-i-toyn ] 

Why do we use fosphenytoin? 

fosphenytoin is a medication used for the prevention and treatment of seizures in patients with epilepsy or other neurological disorders. Here are some specific uses of fosphenytoin: 

• Status epilepticus: fosphenytoin can be used in the emergency treatment of status epilepticus, which is a medical emergency characterized by prolonged or repeated seizures. 
• Prophylaxis of seizures: fosphenytoin can be used to prevent seizures before and after neurosurgery, during diagnostic procedures involving the brain, or in other situations where seizure activity is anticipated. 
• Substitution for phenytoin: fosphenytoin can be used as a substitute for phenytoin when oral administration is not possible, such as in patients with swallowing difficulties or gastrointestinal dysfunction. 
• Convulsive status epilepticus in children: fosphenytoin can be used to treat convulsive status epilepticus in children when other treatments have failed or are not feasible. 
• Acute treatment of seizures: fosphenytoin can be used for the acute treatment of seizures, especially in patients who cannot tolerate phenytoin.