Fosphenytoin, also known as fosphenytoin

sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...

, and sold under the brand name Cerebyx among others, is a water-soluble

phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anticonvulsant, anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence se ...

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

that is administered intravenously to deliver phenytoin, potentially more safely than intravenous

. It is used in the acute treatment of convulsive

status epilepticus Status epilepticus (SE), or status seizure, is a medical condition with abnormally prolonged seizures. It can have long-term consequences, manifesting as a single seizure lasting more than a defined time (time point 1), or 2 or more seizures over ...

. Fosphenytoin was developed in 1996.

Medical uses

Fosphenytoin is approved in the United States for the short-term (five days or fewer) treatment of epilepsy when more widely used means of phenytoin administration are not possible or are ill-advised, such as

endotracheal intubation Tracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic tube into the trachea (windpipe) to maintain an open airway or to serve as a conduit through which to administer certain drugs. It is frequently ...

or some other type of repeated seizures; cluster seizure, vomiting, and/or the patient is unalert or not awake or both.

Other

In 2003, it was reported that even though

anticonvulsant Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatme ...

s are often very effective in

mania Mania, also known as manic syndrome, is a Psychiatry, psychiatric Abnormality (behavior), behavioral syndrome defined as a state of Abnormality (behavior), abnormally elevated arousal, affect (psychology), affect, and energy level. During a mani ...

, and acute mania requires rapid treatment, fosphenytoin had no antimanic effect.

Metabolism

One milli mole of phenytoin is produced for every millimole of fosphenytoin administered; the

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

of fosphenytoin also yields

phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...

and

formaldehyde Formaldehyde ( , ) (systematic name methanal) is an organic compound with the chemical formula and structure , more precisely . The compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde. It is stored as ...

, the latter of which is subsequently metabolized to

formate Formate (IUPAC name: methanoate) is the conjugate base of formic acid. Formate is an anion () or its derivatives such as ester of formic acid. The salts and esters are generally colorless. Fundamentals When dissolved in water, formic acid co ...

, which is in turn metabolized by a folate dependent mechanism.

Side effects

Side effects are similar to intravenous phenytoin and include hypotension, cardiac

arrhythmias Arrhythmias, also known as cardiac arrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – above 100 beats ...

, CNS adverse events (

nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) Eye movement (sensory), eye movement. People can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in visual impairment, re ...

, dizziness, sedation/somnolence,

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

and

stupor Stupor is the lack of critical mental function and a level of consciousness, in which an affected person is almost entirely unresponsive and responds only to intense stimuli such as pain. The word derives from the Latin '' stupor'' ("numbness, in ...

), and local dermatological reactions. Purple glove syndrome probably occurs with fosphenytoin but possibly at lower frequency than with intravenous phenytoin. Fosphenytoin can cause

hyperphosphatemia Hyperphosphatemia is an electrolyte disorder in which there is an elevated level of phosphate in the blood. Most people have no symptoms while others develop calcium deposits in the soft tissue. The disorder is often accompanied by low calci ...

in end-stage

renal failure Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney fa ...

patients.

History

Phenytoin, in both its acidic and sodium salt forms, is erratically bioavailable whether it is injected or taken orally due to its high

melting point The melting point (or, rarely, liquefaction point) of a substance is the temperature at which it changes state of matter, state from solid to liquid. At the melting point the solid and liquid phase (matter), phase exist in Thermodynamic equilib ...

, weak

acidity An acid is a molecule or ion capable of either donating a proton (i.e. hydrogen cation, H+), known as a Brønsted–Lowry acid, or forming a covalent bond with an electron pair, known as a Lewis acid. The first category of acids are the ...

, and its being only sparingly

soluble In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solubi ...

in water. Simply putting patients on other drugs is not always an option; this was especially true before 1993, when the number of

s available was much more limited. One solution was to develop a prodrug that did not have these drawbacks. Fosphenytoin was approved by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) in August 1996, for use in epilepsy.

References

{{Authority control Anticonvulsants CYP3A4 inducers Hydantoins Prodrugs Drugs developed by Pfizer