Cerefos
Cerefos Uses, Dosage, Side Effects, Food Interaction and all others data.
Cerefos is a water-soluble phenytoin prodrug used only in hospitals for the treatment of epileptic seizures. It works by slowing down impulses in the brain that cause seizures. Its main mechanism is to block frequency-dependent, use-dependent and voltage-dependent neuronal sodium channels, and therefore limit repetitive firing of action potentials.
Cerefos is a water-soluble phenytoin prodrug used for the treatment of epileptic seizures. Following parenteral administration of fosphenytoin, fosphenytoin is converted to the anticonvulsant phenytoin by endogenous phosphatases. Each 1.5 mg of fosphenytoin sodium is equivalent to 1.0mg of phenytoin sodium (PE equivalents); care should be taken to calculate the dose required in PE equivalents properly. Serious adverse effects such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN), and hematopoietic complications may occur and indicate an alternate antiepileptic should be used. Withdrawal of fosphenytoin sodium may precipitate seizures and should be done gradually.
| Trade Name | Cerefos |
| Availability | Prescription only |
| Generic | Fosphenytoin |
| Fosphenytoin Other Names | Fosfenitoina, Fosphenytoin, Fosphenytoine, Fosphenytoinum |
| Related Drugs | gabapentin, clonazepam, lorazepam, lamotrigine, diazepam, pregabalin, Lyrica, topiramate, Ativan, Valium |
| Type | Injection |
| Formula | C16H15N2O6P |
| Weight | Average: 362.2739 Monoisotopic: 362.066772734 |
| Protein binding | Fosphenytoin is extensively bound (95-99%) to human plasma proteins, primarily albumin, and displays saturable binding kinetics over a physiologically relevant range of fosphenytoin concentrations. Like fosphenytoin, phenytoin is extensively bound, again mainly to albumin, but can be displaced by fosphenytoin itself. Phenytoin is typically about 88% bound in the absence of fosphenytoin, but this drops to around 60% 0.5-1 hour following fosphenytoin infusion while fosphenytoin is being converted to phenytoin. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | Gland Pharma Limited |
| Available Country | India |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Cerefos is an antiepileptic agent used for the management of generalized convulsive status epilepticus and prevention and treatment of seizures occurring during neurosurgery.
Cerefos is indicated for the treatment of generalized tonic-clonic status epilepticus and for the prevention and treatment of seizures occurring during neurosurgery in adult patients. It can also be substituted, short-term, for oral phenytoin in patients aged two years and older when oral phenytoin administration is not possible.
Cerefos is also used to associated treatment for these conditions: Oral phenytoin treatment, Seizures, Generalized tonic-clonic status epilepticus, Refractory seizure disorders
How Cerefos works
Cerefos is a prodrug of phenytoin and accordingly, its anticonvulsant effects are attributable to phenytoin. Phenytoin acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. By promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of post-tetanic potentiation at synapses. Loss of post-tetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas.
Toxicity
Nausea, vomiting, lethargy, tachycardia, bradycardia, asystole, cardiac arrest, hypotension, syncope, hypocalcemia, metabolic acidosis, and death have been reported in cases of overdosage with fosphenytoin. The median lethal dose of fosphenytoin given intravenously in mice and rats was 156 mg PE/kg and approximately 250 mg PE/kg, or about 0.6 and 2 times, respectively, the maximum human loading dose on a mg/m2 basis. Signs of acute toxicity in animals included ataxia, labored breathing, ptosis, and hypoactivity.
Food Interaction
- Avoid alcohol. Acute alcohol consumption may increase phenytoin serum concentration, but chronic alcohol use may reduce phenytoin serum concentration.
- Avoid St. John's Wort. This herb may reduce the serum concentration of phenytoin.
Cerefos Alcohol interaction
[Moderate]
Acute consumption of alcohol may increase plasma phenytoin levels.
Chronic consumption of alcohol may decrease plasma phenytoin levels.
The mechanism of this interaction is related to induction of phenytoin metabolism by ethanol during chronic administration.
Other hydantoin derivatives may be similarly affected by ethanol.
Patients receiving phenytoin therapy should be warned about the interaction between phenytoin and ethanol and they should be advised to notify their physician if they experience worsening of seizure control or symptoms of toxicity, including drowsiness, visual disturbances, change in mental status, nausea, or ataxia.
Cerefos Drug Interaction
Major: sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprimModerate: lorazepam, lorazepam, meperidine, meperidine, valproic acid, valproic acid, valproic acid, valproic acid, midazolam, midazolamUnknown: glucose, glucose, levetiracetam, levetiracetam, phenytoin, phenytoin, pantoprazole, pantoprazole
Volume of Distribution
The volume of distribution of fosphenytoin increases with dose and rate, ranging between 4.3 and 10.8 L.
Elimination Route
Cerefos at 15 to 20 mg PE/kg infused at 100 to 150 mg PE/min intravenously yields free plasma phenytoin concentrations similar to an equivalent dose of phenytoin sodium administered at 50 mg/min. Single intravenous administration of fosphenytoin shows a linear increase in mean maximum total phenytoin concentration while the mean maximum unbound phenytoin concentrations increase with both dose and infusion rate. Cerefos is rapidly converted to phenytoin following intravenous administration with a half-life of 15 minutes; if administered intramuscularly, the peak plasma phenytoin concentration is not reached until three hours.
Half Life
Cerefos has a conversion half-life of approximately 15 minutes. The resulting phenytoin has a wide range of mean total half-life values (12 to 28.9 hours), with longer half-life times at higher administered doses.
Elimination Route
Phenytoin derived from fosphenytoin administration is excreted in the urine primarily as 5-(p-hydroxyphenyl)-5-phenylhydantoin and its glucuronide. There is little unchanged phenytoin (1%–5% of the administered dose), and essentially no fosphenytoin recovered in urine.
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