CEREBYX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CEREBYX (CEREBYX).
Fosphenytoin is a prodrug of phenytoin, which stabilizes neuronal membranes by blocking voltage-gated sodium channels, thereby inhibiting repetitive firing of action potentials.
| Metabolism | Fosphenytoin is rapidly and completely converted to phenytoin by phosphatases in the liver and other tissues. Phenytoin is primarily metabolized by CYP2C9 and CYP2C19. |
| Excretion | Renal excretion of unchanged drug and metabolites accounts for approximately 80% of the dose; about 20% is eliminated in feces via biliary excretion. |
| Half-life | The terminal elimination half-life of fosphenytoin (converted to phenytoin) is approximately 15 hours (range 10-20 hours) in adults with normal hepatic function; after conversion, phenytoin half-life is dose-dependent and averages 22 hours (range 7-42 hours) at therapeutic concentrations. |
| Protein binding | Fosphenytoin: 95-99% bound to albumin and alpha-1-acid glycoprotein (AAG); phenytoin: 90-95% bound primarily to albumin, with increased free fraction in hypoalbuminemia or uremia. |
| Volume of Distribution | Fosphenytoin: 0.04-0.06 L/kg (primarily intravascular); phenytoin: 0.6-0.8 L/kg (total body water) after conversion, indicative of extensive tissue distribution. |
| Bioavailability | Intravenous: 100% (complete conversion to phenytoin); Intramuscular: 100% absorbed but with slower and variable conversion to phenytoin (peak phenytoin levels at 30-60 minutes). |
| Onset of Action | Intravenous: 15-30 minutes after infusion (time to therapeutic phenytoin levels); Intramuscular: 30-60 minutes. |
| Duration of Action | Duration of anticonvulsant effect is approximately 12-24 hours after a single IV dose, corresponding to the time phenytoin remains at therapeutic concentrations; maintenance dosing every 6-8 hours may be needed due to rapid initial distribution. |
Loading dose: 15-20 mg PE/kg IV/IM (max 1500 mg PE); maintenance: 4-6 mg PE/kg/day IV/IM divided q12h or q8h. Switch to oral phenytoin at equivalent dose.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl <10 mL/min: reduce loading dose to 10-15 mg PE/kg; maintenance: 3-5 mg PE/kg/day. Hemodialysis: supplement 1-2 mg PE/kg post-dialysis. Monitor free phenytoin levels. |
| Liver impairment | Child-Pugh A or B: reduce loading dose by 25-50%; Child-Pugh C: contraindicated. Use lower maintenance doses and monitor free phenytoin levels due to hypoalbuminemia. |
| Pediatric use | Loading dose: 15-20 mg PE/kg IV/IM; maintenance: 5-7 mg PE/kg/day divided q8-12h. Neonates: loading 15-20 mg PE/kg, maintenance 4-8 mg PE/kg/day. |
| Geriatric use | Use lower loading doses (10-15 mg PE/kg) and maintenance (3-5 mg PE/kg/day). Monitor free phenytoin levels due to hypoalbuminemia and reduced clearance. Avoid IM use if possible. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CEREBYX (CEREBYX).
| Breastfeeding | Breastfeeding is generally considered compatible. Fosphenytoin is extensively protein-bound and minimally excreted into breast milk. The M/P ratio is approximately 0.1-0.2. The American Academy of Pediatrics classifies it as compatible with breastfeeding. Monitor infant for sedation, poor feeding, and rash. |
| Teratogenic Risk | First trimester: Increased risk of major congenital malformations (e.g., orofacial clefts, neural tube defects) with an estimated risk of 6-9%. Second and third trimesters: Risk of hemorrhagic disease of the newborn due to vitamin K deficiency; neonatal withdrawal syndrome; potential for fetal hydantoin syndrome including dysmorphic facies, growth retardation, and neurodevelopmental delays. |
■ FDA Black Box Warning
The rate of intravenous administration should not exceed 150 mg PE/min because of the risk of severe hypotension and cardiac arrhythmias. Continuous monitoring of ECG, blood pressure, and respiratory function is required during IV infusion.
| Serious Effects |
Hypersensitivity to fosphenytoin, phenytoin, or any component; sinus bradycardia, sinoatrial block, second- and third-degree AV block, or Adams-Stokes syndrome; concurrent use with delavirdine.
| Precautions | Risk of hypotension and cardiac arrhythmias, especially with rapid IV infusion. Use caution in patients with hepatic impairment, porphyria, and hypothyroidism. Phenytoin may cause acute hepatotoxicity, blood dyscrasias, and gingival hyperplasia. Do not administer intramuscularly for status epilepticus due to erratic absorption. |
| Food/Dietary | Avoid alcohol: can increase side effects and decrease seizure control. Avoid grapefruit juice: may alter drug metabolism. Take with food if GI upset occurs; avoid high doses of vitamin D supplementation without medical advice due to potential bone loss. Maintain consistent dietary calcium and vitamin D intake. |
Loading safety data…
| Fetal Monitoring | Monitor serum phenytoin levels (maintain therapeutic range), liver function, complete blood count, and folate levels. Perform detailed fetal ultrasound for structural anomalies. Assess vitamin K-dependent clotting factors in the neonate and administer prophylactic vitamin K at birth. |
| Fertility Effects | Limited data suggest possible reduction in fertility due to alterations in sex hormone metabolism and menstrual irregularities. Enzyme-inducing antiepileptic drugs may reduce efficacy of hormonal contraceptives due to CYP450 induction, increasing risk of unplanned pregnancy. |
| Clinical Pearls | Cerebyx (fosphenytoin) is a prodrug of phenytoin, requiring conversion by phosphatases; monitor for hypotension and arrhythmias during IV infusion, especially in elderly or hemodynamically compromised patients; rate should not exceed 150 mg PE/min; IM administration is an option when IV access is limited, but causes local irritation; preferred for patients with low albumin or hyperbilirubinemia due to reduced protein binding interference; levels must be interpreted as phenytoin equivalent (PE); renal/hepatic impairment may prolong conversion. |
| Patient Advice | This medication is used to prevent or treat seizures. · Do not stop taking this medicine suddenly, as seizures may worsen. · Report any signs of allergic reaction: rash, fever, swollen glands, or mouth sores. · Avoid alcohol and grapefruit juice while on this medication. · Use effective contraception as fosphenytoin may reduce birth control effectiveness. · Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Regular blood tests are needed to monitor drug levels and liver function. · Notify your doctor if you experience coordination problems, dizziness, or unusual eye movements. |