Fosphenytoin

Fosphenytoin Brand Name– Cerebyx

What is Fosphenytoin

Fosphenytoin is a water-soluble, parenteral prodrug of phenytoin. Intravenous (IV) or intramuscular (IM) fosphenytoin may be substituted short-term for oral phenytoin in situations where oral phenytoin is not appropriate or advantageous.

Unlike phenytoin, fosphenytoin is soluble in standard intravenous solutions and is rapidly absorbed via the IM route.

Fosphenytoin has fewer local adverse effects and does not contain propylene glycol; thus, IV doses can be given at a faster rate. Since fosphenytoin is converted to phenytoin in vivo, systemic adverse effects are generally similar between the two products.

While fosphenytoin represents an improvement over phenytoin in terms of infusion-related reactions, fosphenytoin causes transient, infusion-related, paresthesias and pruritus not seen with phenytoin.

These effects disappear upon stopping or lowering the rate of infusion.

Fosphenytoin is more expensive than corresponding doses of generic phenytoin but is an attractive alternative when IV access is limited or tenuous.

Fosphenytoin was approved by the FDA in August 1996 for patients 18 years and older.

Approval was expanded to include pediatric patients from neonates to 17 years of age in March 2017

Indications

  1. partial seizures
  2. seizure prophylaxis
  3. status epilepticus
  4. tonic-clonic seizures

NOTE: The dose, concentration, and infusion rate for fosphenytoin should always be prescribed and dispensed as phenytoin equivalents (PE). Fosphenytoin’s dose is expressed as PE to avoid the need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin doses

Side Effects

  1. acute generalized exanthematous pustulosis (AGEP)
  2. agitation
  3. agranulocytosis
  4. akathisia
  5. amblyopia
  6. amnesia
  7. anaphylactoid reactions
  8. anemia
  9. angioedema
  10. anorexia
  11. aphasia
  12. apnea
  13. arthralgia
  14. asthenia
  15. ataxia
  16. atrial flutter
  17. back pain
  18. bradycardia
  19. bronchospasm
  20. bullous rash
  21. bundle-branch block
  22. cardiac arrest
  23. cerebral edema
  24. chills
  25. coma
  26. confusion
  27. conjunctivitis
  28. constipation
  29. contact dermatitis
  30. cough
  31. cyanosis
  32. dehydration
  33. depression
  34. diabetes insipidus
  35. diarrhea
  36. diplopia
  37. dizziness
  38. drowsiness
  39. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
  40. dysarthria
  41. dysgeusia
  42. dyspepsia
  43. dysphagia
  44. dyspnea
  45. dysuria
  46. ecchymosis
  47. edema
  48. elevated hepatic enzymes
  49. emotional lability
  50. encephalopathy
  51. eosinophilia
  52. epistaxis
  53. erythema multiforme
  54. exfoliative dermatitis
  55. fever
  56. flatulence
  57. folate deficiency
  58. gastritis
  59. GI bleeding
  60. gingival hyperplasia
  61. headache
  62. hearing loss
  63. heart failure
  64. hemoptysis
  65. hepatic failure
  66. hepatomegaly
  67. hirsutism
  68. hostility
  69. hyperacusis
  70. hyperesthesia
  71. hyperglycemia
  72. hyperhidrosis
  73. hyperkalemia
  74. hyperkinesis
  75. hyperphosphatemia
  76. hyperreflexia
  77. hypersalivation
  78. hypertension
  79. hypertrichosis
  80. hyperventilation
  81. hypoesthesia
  82. hypokalemia
  83. hypophosphatemia
  84. hyporeflexia
  85. hypotension
  86. hypotonia
  87. hypoxia
  88. ileus
  89. infection
  90. infusion-related reactions
  91. injection site reaction
  92. insomnia
  93. jaundice
  94. leukocytosis
  95. leukopenia
  96. lupus-like symptoms
  97. lymphadenopathy
  98. maculopapular rash
  99. malaise
  100. meningitis
  101. migraine
  102. muscle cramps
  103. myalgia
  104. myasthenia
  105. mydriasis
  106. myoclonia
  107. myopathy
  108. nausea
  109. neutropenia
  110. nystagmus
  111. ocular pain
  112. oliguria
  113. orthostatic hypotension
  114. osteomalacia
  115. otalgia
  116. palpitations
  117. pancytopenia
  118. paresthesias
  119. parosmia
  120. pelvic pain
  121. peripheral vasodilation
  122. petechiae
  123. pharyngitis
  124. photophobia
  125. photosensitivity
  126. pneumothorax
  127. polyuria
  128. proteinuria
  129. pruritus
  130. psychosis
  131. pulmonary embolism
  132. purpura
  133. QT prolongation
  134. rash
  135. renal failure (unspecified)
  136. rhinitis
  137. seizures
  138. sinus tachycardia
  139. sinusitis
  140. skin discoloration
  141. skin necrosis
  142. Stevens-Johnson syndrome
  143. stroke
  144. subdural hematoma
  145. suicidal ideation
  146. syncope
  147. tenesmus
  148. teratogenesis
  149. thrombocytopenia
  150. tinnitus
  151. toxic epidermal necrolysis
  152. tremor
  153. urethral pain
  154. urinary incontinence
  155. urinary retention
  156. urticaria
  157. vaginitis
  158. ventricular fibrillation
  159. vertigo
  160. visual impairment
  161. vitamin D deficiency
  162. vomiting
  163. xerostomia

Monitoring Parameters

  • CBC
  • LFTs
  • neurologic function
  • serum albumin
  • serum phenytoin concentrations

Contraindications

  • abrupt discontinuation
  • Adams-Stokes syndrome
  • agranulocytosis
  • alcoholism
  • Asian patients
  • AV block
  • barbiturate hypersensitivity
  • bone marrow suppression
  • bradycardia
  • breast-feeding
  • bundle-branch block
  • carbamazepine hypersensitivity
  • cardiac arrhythmias
  • cardiac disease
  • contraception requirements
  • dental disease
  • dental work
  • depression
  • diabetes mellitus
  • driving or operating machinery
  • encephalopathy
  • geriatric
  • hematological disease
  • hemolytic anemia
  • hepatic disease
  • hepatotoxicity
  • Hodgkin lymphoma
  • hydantoin hypersensitivity
  • hypoalbuminemia
  • hypoglycemia
  • hyponatremia
  • hypotension
  • hypothyroidism
  • infusion-related reactions
  • intravenous administration
  • jaundice
  • leukopenia
  • lymphoma
  • methemoglobin reductase deficiency
  • methemoglobinemia
  • myasthenia gravis
  • neonates
  • neutropenia
  • obstetric delivery
  • osteomalacia
  • osteoporosis
  • petit mal (absence) seizures
  • porphyria
  • pregnancy
  • psychosis
  • radiation therapy
  • renal disease
  • renal failure
  • renal impairment
  • reproductive risk
  • succinimide hypersensitivity
  • suicidal ideation
  • thrombocytopenia
  • thyroid disease
  • vitamin K deficiency

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  • Nifedipine
  • Nilotinib
  • Nilutamide
  • Nimodipine
  • Nintedanib
  • Nisoldipine
  • Nitazoxanide
  • Nitisinone
  • Norethindrone
  • Norgestrel
  • Nortriptyline
  • Olanzapine
  • Olaparib
  • Ombitasvir; Paritaprevir; Ritonavir
  • Omeprazole
  • Omeprazole; Amoxicillin; Rifabutin
  • Omeprazole; Sodium Bicarbonate
  • Ondansetron
  • Oritavancin
  • Osilodrostat
  • Osimertinib
  • Ospemifene
  • Oxazepam
  • Oxcarbazepine
  • Oxybutynin
  • Oxycodone
  • Oxymorphone
  • Paclitaxel
  • Palbociclib
  • Paliperidone
  • Pancuronium
  • Panobinostat
  • Paricalcitol
  • Paroxetine
  • Pemigatinib
  • Pemoline
  • Penicillin G Benzathine; Penicillin G Procaine
  • Penicillin G Procaine
  • Pentobarbital
  • Perampanel
  • Perindopril; Amlodipine
  • Perphenazine; Amitriptyline
  • Pexidartinib
  • Phenelzine
  • Phenicol Derivatives
  • Phenobarbital
  • Phenothiazines
  • Phentermine; Topiramate
  • Pimavanserin
  • Pitolisant
  • Polatuzumab Vedotin
  • Pomalidomide
  • Ponatinib
  • Posaconazole
  • Pramlintide
  • Praziquantel
  • Prednisolone
  • Prednisone
  • Prilocaine
  • Prilocaine; Epinephrine
  • Primidone
  • Progesterone
  • Progestins
  • Propoxyphene
  • Propranolol
  • Protriptyline
  • Pyridoxine, Vitamin B6
  • Quazepam
  • Quetiapine
  • Quinidine
  • Quinine
  • Rabeprazole
  • Raltegravir
  • Ranolazine
  • Rapacuronium
  • Red Yeast Rice
  • Regorafenib
  • Remdesivir
  • Remifentanil
  • Repaglinide
  • Ribociclib
  • Ribociclib; Letrozole
  • Rifabutin
  • Rifampin
  • Rifapentine
  • Rilpivirine
  • Riluzole
  • Rimegepant
  • Riociguat
  • Ripretinib
  • Risperidone
  • Ritonavir
  • Rivaroxaban
  • Rocuronium
  • Roflumilast
  • Rolapitant
  • Romidepsin
  • Ropivacaine
  • Rucaparib
  • Rufinamide
  • Ruxolitinib
  • Salicylates
  • Saquinavir
  • Sarilumab
  • Saxagliptin
  • Secobarbital
  • Secukinumab
  • Sedating H1-blockers
  • Segesterone Acetate; Ethinyl Estradiol
  • Selegiline
  • Selpercatinib
  • Selumetinib
  • Sertraline
  • Sevoflurane
  • Sildenafil
  • Siltuximab
  • Simeprevir
  • Simvastatin
  • Simvastatin; Sitagliptin
  • Siponimod
  • Sirolimus
  • Sitagliptin
  • Sofosbuvir
  • Sofosbuvir; Velpatasvir
  • Sofosbuvir; Velpatasvir; Voxilaprevir
  • Sonidegib
  • Sorafenib
  • St. John’s Wort, Hypericum perforatum
  • Streptozocin
  • Succinylcholine
  • Sufentanil
  • Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole
  • Sulfinpyrazone
  • Sulfonylureas
  • Sunitinib
  • Suvorexant
  • Tacrolimus
  • Tadalafil
  • Tamoxifen
  • Tasimelteon
  • Tazemetostat
  • Telithromycin
  • Telotristat Ethyl
  • Temazepam
  • Temsirolimus
  • Teniposide
  • Tenofovir Alafenamide
  • Terbinafine
  • Tetracaine
  • Tezacaftor; Ivacaftor
  • Thalidomide
  • Theophylline, Aminophylline
  • Thiazolidinediones
  • Thiopental
  • Thiotepa
  • Thiothixene
  • Thyroid hormones
  • Tiagabine
  • Ticagrelor
  • Ticlopidine
  • Tinidazole
  • Tipranavir
  • Tizanidine
  • Tocilizumab
  • Tofacitinib
  • Tolvaptan
  • Topiramate
  • Toremifene
  • Trabectedin
  • Tramadol
  • Trandolapril; Verapamil
  • Tranylcypromine
  • Trazodone
  • Tretinoin, ATRA
  • Triamcinolone
  • Triazolam
  • Triclabendazole
  • Tricyclic antidepressants
  • Trimethoprim
  • Trimetrexate
  • Trimipramine
  • Triprolidine
  • Tubocurarine
  • Tucatinib
  • Ubrogepant
  • Ulipristal
  • Upadacitinib
  • Valacyclovir
  • Valbenazine
  • Valdecoxib
  • Valproic Acid, Divalproex Sodium
  • Vandetanib
  • Vecuronium
  • Vemurafenib
  • Venetoclax
  • Verapamil
  • Vigabatrin
  • Vilazodone
  • Vincristine
  • Vincristine Liposomal
  • Vorapaxar
  • Voriconazole
  • Vortioxetine
  • Voxelotor
  • Warfarin
  • Zafirlukast
  • Zalcitabine, ddC
  • Zaleplon
  • Zanubrutinib
  • Zidovudine, ZDV
  • Ziprasidone
  • Zolpidem
  • Zonisamide
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