Cerebyx

Generic Name: Fosphenytoin Sodium
Class: Hydantoins
VA Class: CN400
Chemical Name: 5,5-Diphenyl-3-[(phosphonooxy)methyl]-2,4-imidazoleidinedione disodium salt
Molecular Formula: C^₁₆H^₁₃N^₂Na^₂O^₆P
CAS Number: 92134-98-0

Introduction

Hydantoin-derivative anticonvulsant; prodrug of phenytoin.^{1 2 4 6}

Uses for Cerebyx

Seizure Disorders

Short-term (up to 5 days) parenteral therapy when the usual means of phenytoin administration is unavailable, inappropriate, or deemed less advantageous.¹ Used for the treatment of generalized convulsive status epilepticus,^{1 4 5 6 10 19} for the prevention and treatment of seizures occurring during neurosurgery, and as a short-term parenteral replacement for oral phenytoin.^{1 7 27}

IV fosphenytoin sodium is associated with fewer infusion site reactions (e.g., erythema, pain, burning, swelling, pruritus, soft tissue damage, phlebitis, necrosis) and less frequent need for infusion rate reduction, interruption, and/or changes of infusion sites than IV phenytoin sodium,^{1 2 4 6 9 10 14 15 18 19 22} but with a higher incidence of paresthesia and pruritus.^{1 2 6 7 9 10 14 22}

Use fosphenytoin rather than phenytoin for IM administration.^{1 2 6 9 10 27}

Not indicated for the treatment of absence seizures or seizures associated with hypoglycemia or other metabolic causes.¹

Cerebyx Dosage and Administration

General

• 
  

  When administering IV loading doses, continuous ECG, BP, and respiratory monitoring is essential during the period of maximal plasma phenytoin concentrations (about 10–20 minutes postinfusion).^{1 24}

  
  

Administration

Administer by IV infusion^{1 2 4 5 6 9 10 19 27} or by IM injection.^{1 2 6 9 10 23 27 30}

IV Administration

Dilution

Dilute in 5% dextrose injection or 0.9% sodium chloride injection to provide a solution containing 1.5–25 mg PE/mL.¹

Rate of Administration

Infuse loading dose for status epilepticus at rate of 100–150 mg PE/minute.¹

IM Administration

Administered once daily in 1 or 2 injection sites in clinical studies.¹ Some patients may require more frequent IM dosing.¹

IM administration is not recommended for initial treatment of status epilepticus.¹ If IV access is impossible, loading doses of fosphenytoin sodium have been given IM for other indications.¹

Dosage

Available as fosphenytoin sodium; dosage expressed in terms of phenytoin sodium equivalents (PE).¹ Always prescribe and dispense in terms of PE.¹

Each mmol of fosphenytoin is converted into 1 mmol of phenytoin; however, because of differences in molecular weight, each 75 mg of fosphenytoin sodium is equivalent to only 50 mg of phenytoin sodium.^{1 2}

IV and IM dosages (in terms of PE) are the same; ^{24 25} total daily doses of parenteral fosphenytoin sodium (in terms of PE) generally are equivalent to those of oral phenytoin sodium.¹

Adults

Seizure Disorders

Status Epilepticus

IV

15–20 mg PE/kg, followed by maintenance doses of fosphenytoin sodium or parenteral or oral doses of phenytoin.¹ Concomitant therapy with an IV benzodiazepine usually is necessary for initial control of status epilepticus.^{1 4}

Nonemergent Loading and Maintenance Dosages

IV or IM

Initiation of anticonvulsant therapy: 10–20 mg PE/kg.¹

Initial maintenance dosage: 4–6 mg PE/kg daily.¹

Conversion from Oral Phenytoin to Parenteral Fosphenytoin

IV or IM

Same total daily dose (in terms of PE) as oral phenytoin sodium.¹ However, plasma phenytoin concentrations may be slightly higher with parenteral fosphenytoin sodium than with oral phenytoin sodium (Dilantin) capsules due to different bioavailabilities (90 and 100%, respectively, in terms of phenytoin concentrations).¹

Prescribing Limits

Adults

Seizure Disorders

Do not infuse loading dose at a rate >150 mg PE/minute.¹

Safety and efficacy for >5 days have not been systematically evaluated.¹

Special Populations

Geriatric Patients

Reduced or less frequent doses may be necessary.¹

Cautions for Cerebyx

Contraindications

• 
  

  Known hypersensitivity to fosphenytoin or any ingredient in the formulation, phenytoin, or other hydantoins.¹

  
  


• 
  

  Sinus bradycardia, sinoatrial block, second- or third-degree AV block, Adams-Stokes syndrome.¹

  
  

Warnings/Precautions

Warnings

Always express dosage of fosphenytoin sodium in terms of PE;¹ therefore, do not adjust recommended dosage when switching from phenytoin sodium to fosphenytoin sodium or vice versa.¹

Status Epilepticus Dosing Regimen

Administration of the recommended IV dose generally takes 5–7 minutes; administration of equimolar doses of phenytoin sodium takes 15–20 minutes.¹

IV route is preferred if the primary goal is rapid achievement of therapeutic phenytoin concentrations.¹

Discontinuance of Fosphenytoin

Do not discontinue abruptly; reduce dosage, discontinue drug, or make drug substitution gradually.¹ However, if an allergic or hypersensitivity reaction occurs, rapid substitution with an anticonvulsant that is structurally unrelated to hydantoins may be necessary.¹

Cardiovascular Effects

Potential for hypotension, especially after IV administration of high doses or rapid IV infusions.¹ Careful cardiac monitoring is needed when administering IV loading doses.¹ If hypotension occurs, may need to reduce the administration rate or discontinue the drug.¹

Use with caution in patients with hypotension or severe heart failure.¹

Contraindicated in patients with some cardiac conduction disorders. (See Contraindications under Cautions.)¹

Hepatic Effects

Acute hepatotoxicity, including infrequent cases of acute hepatic failure, reported with phenytoin.¹ If acute hepatotoxicity occurs, discontinue fosphenytoin immediately and do not resume.¹

Hematologic Effects

Adverse hematologic effects (e.g., thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, pancytopenia with or without bone marrow suppression), sometimes fatal, reported with phenytoin.¹

Development of local or generalized lymphadenopathy (e.g., benign lymph node hyperplasia, pseudolymphoma, lymphoma, Hodgkin’s disease) associated with phenytoin.¹ If lymphadenopathy develops, observe patient closely for an extended period; if possible, use alternative anticonvulsant.¹

Fetal/Neonatal Morbidity and Mortality

Fosphenytoin is embryotoxic and teratogenic in animals.¹ Phenytoin may cause fetal harm (e.g., congenital malformations, adverse developmental outcomes) in pregnant women.¹

Life-threatening bleeding disorders secondary to decreased concentrations of vitamin K-dependent clotting factors may occur in neonates exposed to phenytoin in utero; administration of vitamin K to the mother prior to delivery and to the neonate after birth prevents these disorders.¹

Sensitivity Reactions

Possible increased risk of developing toxic epidermal necrolysis or Stevens-Johnson syndrome with phenytoin in individuals of Asian ancestry who carry the human leukocyte antigen (HLA)-B*1502 allele.^{32 33 34} Precaution relating to presence of the HLA-B*1502 allele applies to fosphenytoin because fosphenytoin is converted to phenytoin.³² FDA is evaluating the relationship between use of phenytoin and serious dermatologic reactions in individuals with the HLA-B*1502 allele.³² Screening for presence of HLA-B*1502 allele before initiating fosphenytoin or phenytoin therapy not recommended at this time.³² Fosphenytoin or phenytoin should not be used as an alternative to carbamazepine in HLA-B*1502-positive patients.³²

If rash occurs, discontinue fosphenytoin.¹

Do not resume fosphenytoin if the rash is exfoliative, purpuric, or bullous or if lupus erythematosus, Stevens-Johnson syndrome, or toxic necrolysis is suspected; consider alternative anticonvulsant therapy.¹

If the rash is a milder type (measles-like or scarlatiniform), may restart fosphenytoin after the rash has completely disappeared; however, if rash recurs when fosphenytoin is restarted, further fosphenytoin or phenytoin therapy is contraindicated.¹

Exercise caution when using structurally similar compounds (e.g., barbiturates, succinimides, oxazolidinediones) in patients who have experienced phenytoin hypersensitivity.¹

Major Toxicities

Sensory Disturbances

Severe burning, pruritus, and/or paresthesia (mainly in groin) reported with IV administration; symptoms generally persist for up to 14 or 24 hours for severe or mild reactions, respectively.^{1 2}

Patients receiving doses of 20 mg PE/kg at a rate of 150 mg PE/minute are likely to experience some discomfort; reducing or temporarily stopping the infusion may decrease the incidence and intensity.¹

Phosphate Content

Each mg PE provides 0.0037 mmol of phosphate; consider the phosphate content in patients who require phosphate restriction (e.g., patients with severe renal impairment).¹

General Precautions

Hyperglycemia

Hyperglycemia reported with phenytoin.¹

CNS Effects

Plasma phenytoin concentrations sustained above the optimal range may produce confusional states (e.g., delirium, psychosis, encephalopathy); rarely, irreversible cerebellar dysfunction may develop.¹

Determine plasma phenytoin concentrations at the first sign of acute toxicity.¹ If concentrations are excessive, reduce the fosphenytoin dosage; if symptoms persist, discontinue the drug.¹

Folate Concentrations

Phenytoin may reduce serum folate concentrations.¹

Monitoring Plasma Phenytoin Concentrations

Dosage of fosphenytoin (in PE) usually is selected to achieve total plasma phenytoin concentrations of 10–20 mcg/mL (unbound phenytoin concentrations of 1–2 mcg/mL).¹

Do not monitor plasma phenytoin concentrations until conversion of fosphenytoin to phenytoin is essentially complete (about 2 hours after conclusion of an IV infusion or 4 hours after an IM injection).^{1 2 6}

Unbound phenytoin fraction may be increased in patients with renal or hepatic impairment or hypoalbuminemia.¹ Interpret total plasma phenytoin concentrations with caution in these patients; consider monitoring unbound plasma phenytoin concentrations.¹

Specific Populations

Pregnancy

Category D.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Potential for increased seizure frequency during pregnancy due to alteration of phenytoin pharmacokinetics.¹ Monitor plasma phenytoin concentrations and adjust dosage accordingly; restoration of the patient’s usual dosage will probably be necessary postpartum.¹

Lactation

Not known whether fosphenytoin is distributed into milk.¹ Phenytoin is distributed into milk; nursing is not recommended in women receiving fosphenytoin.¹

Pediatric Use

Safety¹ and efficacy²⁴ not established in children.^{1 24}

Limited pharmacokinetic data in children 5–10 years of age with status epilepticus indicate that plasma fosphenytoin, total phenytoin, and unbound phenytoin concentration-time profiles following IV loading doses are similar to those achieved in adult patients with status epilepticus receiving comparable doses.^{1 8}

Geriatric Use

Not systematically evaluated in geriatric adults.¹

Hepatic Impairment

Use with caution.¹ Following IV administration, conversion of fosphenytoin to phenytoin may be increased without a similar increase in phenytoin clearance; the increases in plasma phenytoin concentrations may be associated with an increased incidence and severity of adverse effects.¹

Interpret total plasma phenytoin concentrations with caution.¹ (See Monitoring Plasma Phenytoin Concentrations under Cautions.)

Phenytoin may exacerbate porphyria; use with caution in patients with this disease.¹

Renal Impairment

Use with caution.¹ Following IV administration, conversion of fosphenytoin to phenytoin may be increased without a similar increase in phenytoin clearance; the increases in plasma phenytoin concentrations may be associated with an increased incidence and severity of adverse effects.¹

Interpret total plasma phenytoin concentrations with caution.¹ (See Monitoring Plasma Phenytoin Concentrations under Cautions.)

Common Adverse Effects

Nystagmus, dizziness, pruritus, paresthesia, headache, somnolence, ataxia.^{1 2 6 7}

Interactions for Cerebyx

Phenytoin is metabolized by CYP isoenzymes.¹ Phenytoin induces hepatic enzymes.¹

No drugs are known to interfere with conversion of fosphenytoin to phenytoin.¹

Drug interactions that occur with phenytoin expected to occur with fosphenytoin.¹

Protein-bound Drugs

Potential for fosphenytoin or phenytoin to displace or to be displaced by other protein-bound drugs.¹ Use with caution.¹

Drugs Affecting Hepatic Microsomal Enzymes

CYP inhibitors: Potential for increased plasma phenytoin concentrations.¹

Specific Drugs

Drug	Interaction	Comments
Alcohol, acute intake	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Alcohol, chronic intake	Possible decreased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Amiodarone	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Anticoagulants	Efficacy of anticoagulants, including warfarin, impaired1 Possible increased plasma phenytoin concentrations when administered with dicumarol (no longer commercially available in US)1	Monitor plasma phenytoin concentration if pharmacokinetic interaction suspected1
Antidepressants, tricyclic	Increased risk of seizures1	Adjust fosphenytoin dosage as necessary1
Carbamazepine	Possible decreased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Chloramphenicol	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Chlordiazepoxide	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Corticosteroids	Efficacy of corticosteroids impaired1
Diazepam	Pharmacokinetic (including protein binding) interaction unlikely1
Disulfiram	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Doxycycline	Efficacy of doxycycline impaired1
Estrogens	Possible increased plasma phenytoin concentrations1 Efficacy of estrogens impaired1	Monitor plasma phenytoin concentration if interaction suspected1
Ethosuximide	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Fluoxetine	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Furosemide	Efficacy of furosemide impaired1
Histamine H2-receptor antagonists (cimetidine)	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Halothane	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Isoniazid	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Methylphenidate	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Oral contraceptives	Efficacy of oral contraceptives impaired1
Phenobarbital	Possible increased or decreased plasma phenytoin or phenobarbital concentrations1	Monitor plasma concentrations if interaction suspected1
Phenothiazines	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Rifampin	Efficacy of rifampin impaired1
Quinidine	Efficacy of quinidine impaired1
Salicylates	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Succinimides	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Sulfonamides	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Theophylline	Efficacy of theophylline impaired1
Tolbutamide	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Trazodone	Possible increased plasma phenytoin concentrations1	Monitor plasma phenytoin concentration if interaction suspected1
Valproic acid and Valproate sodium	Possible increased or decreased plasma concentrations of phenytoin or valproic acid1	Monitor plasma concentrations if interaction suspected1

Cerebyx Pharmacokinetics

Absorption

Bioavailability

Completely converted to phenytoin following IV or IM administration; conversion half-life is 15 minutes.^{1 2}

Completely bioavailable following IM administration.¹ Peak plasma phenytoin concentrations are achieved in about 3 hours.¹ Concentrations are similar to those achieved with oral phenytoin sodium.¹

Onset

IV loading doses of 15–20 mg PE/kg infused at maximally tolerated rates (100–150 mg PE/minute) result in therapeutic plasma concentrations of unbound phenytoin (about 1–2 mcg/mL) within about 10 minutes.^{1 2 4 6 7 19 25 26}

Onset of action in controlling status epilepticus is similar to that of IV phenytoin sodium.^{4 26}

Distribution

Plasma Protein Binding

Fosphenytoin: 95–99%.¹

Phenytoin: 88%.¹

Fosphenytoin displaces phenytoin from binding sites.¹ In the presence of fosphenytoin, the fraction of unbound phenytoin increases; 70% of phenytoin is bound during the period required for conversion of fosphenytoin to phenytoin (0.5–1 hour postinfusion).¹

Special Populations

In patients with renal or hepatic impairment or hypoalbuminemia, fraction of unbound phenytoin is increased.¹

Elimination

Metabolism

Fosphenytoin is rapidly metabolized to phenytoin by blood and tissue phosphatases.² Each mmol of fosphenytoin is metabolized to one mmol of phenytoin.¹

Phenytoin is metabolized by hepatic CYP isoenzymes (saturable process).¹ A small percentage of individuals metabolize phenytoin slowly.¹

Elimination Route

Phenytoin is excreted in urine principally as metabolites.¹

Half-life

Phenytoin: 12–28.9 hours.¹

Special Populations

Following IV administration in patients with renal and/or hepatic impairment or hypoalbuminemia, fosphenytoin clearance to phenytoin may be increased without a similar increase in phenytoin clearance.¹

In geriatric patients, phenytoin clearance may be decreased.¹

Stability

Storage

Parenteral

Injection

2–8°C.¹ Do not store at room temperature for >48 hours.¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible
Amino acid injection 10%
Dextrose 5% in Ringer’s injection, lactated
Dextrose 5% in sodium chloride 0.45%
Dextrose 5 or 10% in water
Hetastarch 6% in sodium chloride 0.9%
Mannitol 20%
Plasma-Lyte A, pH 7.4
Ringer’s injection, lactated
Sodium chloride 0.9%

Drug Compatibility

Admixture CompatibilityHID

Compatible
Potassium chloride

Y-Site CompatibilityHID

Compatible
Lorazepam
Phenobarbital sodium
Incompatible
Fenoldopam mesylate
Midazolam HCl

ActionsActions

• 
  

  Prodrug of phenytoin.^{1 2 4 6} Pharmacologic effects include those of phenytoin.^{1 2 6}

  
  

Advice to Patients

• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Fosphenytoin Sodium

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection	75 mg (equivalent to 50 mg phenytoin sodium [PE]) per mL*	Cerebyx	Pfizer
			Fosphenytoin Sodium

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions April 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Parke-Davis. Cerebyx (fosphenytoin sodium) injection prescribing information. New York, NY; 2002 Feb.

2. Browne TR, Kugler AR, Eldon MA. Pharmacology and pharmacokinetics of fosphenytoin. Neurology. 1996; 46(Suppl 1):S3-7. [IDIS 368224] [PubMed 8649612]

3. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; 2001 Aug 21. From FDA web site.

4. Lowenstein DH, Alldredge BK. Status Epilepticus. N Engl J Med. 1998; 14:970-6.

5. Allen FH Jr, Runge JW, Legarda S et al. Safety, tolerance, and pharmacokinetics of intravenous fosphenytoin (Cerebyx) in status epilepticus. Epilepsia. 1995; 36(Suppl 4):90.

6. Boucher BA. Fosphenytoin: a novel phenytoin prodrug. Pharmacotherapy. 1996; 16:777-91. [IDIS 374567] [PubMed 8888074]

7. Meek PD, Davis SN, Collins M et al. Guidelines for the nonemergency use of parenteral phenytoin products: proceedings of an expert panel consensus process. Arch Intern Med. 1999; 159:2639-44. [IDIS 440708] [PubMed 10597754]

8. Pellock JM. Fosphenytoin use in children. Neurology. 1996; 46(Suppl 1):S14-6.

9. Fierro LS Savulich DH, Benezra DA. Safety of fosphenytoin sodium. Am J Health-Syst Pharm. 1996; 53:2707-12. [IDIS 375372] [PubMed 8931812]

10. DeToledo JC, Ramsay RE. Fosphenytoin and phenytoin in patients with status epilepticus: improved tolerability versus increased costs. Drug Safety. 2000; 22:459-66. [PubMed 10877039]

11. Labiner DM. Data vs opinion, phenytoin vs fosphenytoin: the saga continues. Arch Intern Med. 1999; 159:2631-2. [IDIS 440706] [PubMed 10597752]

12. Nightingale SL. Cerebyx labels changed. JAMA. 1999, 281:786.

13. Sigmund W II. Dear health care professional letter regarding revisions to the Cerebyx (fosphenytoin sodium) prescribing information concerning inadvertent overdosage of fosphenytoin sodium because the manufacturer’s label on the vial was misread. Morris Plains, NJ: Parke Davis; 1999 Jan 28.

14. Paloucek FP. Fosphenytoin safety and economics. Am J Health-Syst Pharm. 1996; 53:2702. [IDIS 375371] [PubMed 8931811]

15. Holliday SM, Benfield P, Plosker GL. Fosphenytoin: pharmacoeconomic implications of therapy. Pharmacoeconomics. 1998; 14:685-90. [PubMed 10346419]

16. Touchette DR, Rhoney DH. Cost-minimization analysis of phenytoin and fosphenytoin in the emergency department. Pharmacotherapy. 2000; 20:908-16. [IDIS 450897] [PubMed 10939551]

17. Marchetti A, Magar R, Fischer J et al. A pharmacoeconomic evaluation of intravenous fosphenytoin (Cerebyx) versus intravenous phenytoin (Dilantin) in hospital emergency departments. Clin Ther. 1996. 18:953-66. (IDIS 376632)

18. Armstrong EP, Sauer KA, Downey MJ. Phenytoin and fosphenytoin: a model of cost and clinical outcomes. Pharmacotherapy. 1999; 19:844-53. [IDIS 429096] [PubMed 10417033]

19. Bleck TP. Management approaches to prolonged seizures and status epilepticus. Epilepsia. 1999; 40(Suppl 1):S59-63. [IDIS 431654] [PubMed 10421562]

20. Matheson C. Reactions to fosphenytoin editorial and review article. Am J Health-Syst Pharm. 1997; 54:441-2. [IDIS 379822] [PubMed 9043571]

21. Cohen MR. Flawed dispensing practice and Cerebyx label confusion result in child’s death. Hosp Pharm. 1998; 33:828,831.

22. Sangha K, Privitera M. Fosphenytoin restrictions at the Health Alliance of Greater Cincinnati. Hosp Pharm. 1997;32:1293-4. (IDIS 396163)

23. Pryor FM, Gidal B, Ramsay RE et al. Fosphenytoin: phramacokinetics and tolerance of intramuscular doses. Epilepsia. 2001; 42:245-50. [IDIS 460662] [PubMed 11240597]

24. Pfizer, Morris Plains, NJ: Personal communication.

25. Reviewers’ comments (personal observations).

26. Kugler AR, Knapp LE, Eldon MA. Rapid attainment of therapeutic phenytoin concentrations following administration of loading doses of fosphenytoin: a metaanalysis. Neurology. 1996; 46(Suppl):A176. [IDIS 368224] [PubMed 8649612]

27. Boucher BA, Feler CA, Dean JC et al. The safety, tolerability, and pharmacokinetics of fosphenytoin: intramuscular and intravenous administration in neurosurgery. Pharmacotherapy. 1996; 16:638-45. [IDIS 370972] [PubMed 8840370]

28. Jamerson BD, Donn KH, Dukes GE et al. Absolute bioavailability of phenytoin after 3-phosphoryloxymethyl phenytoin disodium (ACC-9653) administration to humans. Epilepsia. 1990; 31:592-7. [IDIS 273305] [PubMed 2401249]

29. Leppik IE, Boucher BA, Wilder BJ et al. Pharmacokinetics and safety of a phenytoin prodrug given i.v. or i.m. in patients. Neurology. 1990; 40(3 Part 1):456-60. [IDIS 285422] [PubMed 2314588]

30. Uthman BM, Wilder BJ, Ramsay RE. Intramuscular use of fosphenytoin: an overview. Neurology. 1996; 46(Suppl 1):S24-28.

31. Sharpe R. Monsanto, FDA are trying to overcome confusion over name of arthritis drug. Wall St J. 1999 Apr 15.

32. Food and Drug Administration. Information for healthcare professionals phenytoin (marketed as Dilantin, Phenytek and generics) and Fosphenytoin (marketed as Cerebyx and generics). 2008 Nov 24. From FDA website. Accessed 2008 Nov 25.

33. Locharernkul C, Loplumlert J, Limotai C et al. Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with HLA-B*1502 allele in Thai population. Epilepsia. 2008; 49:2087-91. [PubMed 18637831]

34. Man CBL, Kwan P, Baum L et al. Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia. 2007: 48:1015-8.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:754-6.

More Cerebyx resources

• Cerebyx Side Effects (in more detail)
• Cerebyx Use in Pregnancy & Breastfeeding
• Cerebyx Drug Interactions
• Cerebyx Support Group
• 0 Reviews for Cerebyx - Add your own review/rating

• Cerebyx Prescribing Information (FDA)


• Cerebyx MedFacts Consumer Leaflet (Wolters Kluwer)


• Cerebyx Concise Consumer Information (Cerner Multum)


• Cerebyx Advanced Consumer (Micromedex) - Includes Dosage Information


• Fosphenytoin Prescribing Information (FDA)


• Fosphenytoin Professional Patient Advice (Wolters Kluwer)

Compare Cerebyx with other medications

• Epilepsy
• Status Epilepticus