Fosphenytoin
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| Systematic (IUPAC) name |
| (2,5-dioxo-4,4-diphenyl-imidazolidin-1-yl)methoxyphosphonic acid |
| Clinical data |
| Trade names |
Cerebyx |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a604036 |
| Pregnancy cat. |
D (US) |
| Legal status |
℞ Prescription only |
| Routes |
Intravenous, intramuscular |
| Pharmacokinetic data |
| Bioavailability |
100% (IM) |
| Protein binding |
95 to 99% |
| Metabolism |
Hepatic |
| Half-life |
15 minutes to convert to phenytoin |
| Excretion |
Renal (as phenytoin) |
| Identifiers |
| CAS number |
93390-81-9 Y |
| ATC code |
N03AB05 |
| PubChem |
CID 56339 |
| DrugBank |
DB00252 |
| ChemSpider |
50839 Y |
| UNII |
B4SF212641 Y |
| KEGG |
D07993 Y |
| ChEMBL |
CHEMBL919 N |
| Chemical data |
| Formula |
C16H15N2O6P |
| Mol. mass |
362.274 g/mol |
SMILES
- O=C3N(C(=O)C(c1ccccc1)(c2ccccc2)N3)COP(=O)(O)O
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InChI
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InChI=1S/C16H15N2O6P/c19-14-16(12-7-3-1-4-8-12,13-9-5-2-6-10-13)17-15(20)18(14)11-24-25(21,22)23/h1-10H,11H2,(H,17,20)(H2,21,22,23) Y
Key:XWLUWCNOOVRFPX-UHFFFAOYSA-N Y
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| N (what is this?) (verify) |
Fosphenytoin (fosphenytoin sodium injection, previously Cerebyx, Parke-Davis; Prodilantin, Pfizer Holding France[1]) is a water-soluble phenytoin prodrug that is administered intravenously to deliver phenytoin, potentially more safely than intravenous phenytoin. It is most commonly used in the acute treatment convulsive status epilepticus.
On 18 November 2004, Sicor (a subsidiary of Teva) received a tentative approval letter from the United States Food and Drug Administration for a generic version of fosphenytoin.[2]
Contents
- 1 Uses
- 1.1 Approved
- 1.2 Unapproved/off-label/investigational
- 2 Metabolism
- 3 Side effects
- 4 History
- 5 References
- 6 See also
Uses[edit]
Approved[edit]
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,[3] such as endotracheal intubation, status epilepticus or some other type of repeated seizures; vomiting, and/or the patient is unalert or not awake or both.[4]
Unapproved/off-label/investigational[edit]
In April 2003, Applebaum and colleagues at the Ben-Gurion University of the Negev in Beersheba reported that even though anticonvulsants are often very effective in mania, and acute mania requires rapid treatment, fosphenytoin had no antimanic effect even 60 minutes after administration of doses used in status epilepticus.[5]
Fosphenytoin was more successfully used to relieve pain refractory to opiates in a 37-year-old woman with neuroma, according to Dr. Gary J. McCleane of the Rampark Pain Center in Lurgan, Northern Ireland.[6] She was given 1,500 phenytoin equivalent units of fosphenytoin over a 24 hour period, producing pain relief that last three to fourteen weeks after each infusion, allowing her to use less opiates.[6]
Metabolism[edit]
One millimole of phenytoin is produced for every millimole of fosphenytoin administered; the hydrolysis of fosphenytoin also yields phosphate and formaldehyde, the latter of which is subsequently metabolized to formate, which is in turn metabolized by a folate dependent mechanism.[3]
Side effects[edit]
Side effects are similar to intravenous phenytoin and include hypotension, cardiac arrhythmias, CNS adverse events (nystagmus, dizziness, sedation/somnolence, ataxia and stupor), and local dermatological reactions. Purple glove syndrome probably occurs with fosphenytoin but possibly at lower frequency than with intravenous phenytoin. Fosphenytoin can cause hyperphosphatemia in end-stage renal failure patients.[7]
History[edit]
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, weak acidity, and its being only sparingly soluble in water.[8] Simply putting patients on other drugs is not always an option; this was especially true before 1993, when the number of anticonvulsants available was much more limited.[9] One solution was to develop a prodrug that did not have these drawbacks.
Fosphenytoin was approved by the Food and Drug Administration (FDA) on August 5, 1996 for use in epilepsy.[10]
References[edit]
- ^ "PRODILANTIN 75 mg/ml sol inj IM et p perf IV". VIDAL, l'information de référence sur les produits de santé. Retrieved 23 October 2005.
- ^ "Fosphenytoin Sodium Approval History". Retrieved 20 October 2005.
- ^ a b Parke-Davis (2001). "Cerebyx: Fosphenytoin Sodium Injection - Labeling Revision" (PDF). Cerebyx Approval History. Warner-Lambert Company. Retrieved 20 October 2005. [dead link]
- ^ Johnson J, Wrenn K (2001). "Inappropriate fosphenytoin use in the ED". American Journal of Emergency Medicine 19 (4): 293–4. doi:10.1053/ajem.2001.24471. PMID 11447516. Fulltext options List of Library Holdings Worldwide
- ^ Applebaum J, Levine J, Belmaker RH (2003). "Intravenous fosphenytoin in acute mania" (PDF). Journal Clinical Psychiatry 64 (4): 408–9. doi:10.4088/JCP.v64n0408. PMID 12716241.
- ^ a b McCleane GJ (2002). "Intravenous infusion of fosphenytoin produces prolonged pain relief: a case report". The Journal of Pain 3 (2): 156–8. doi:10.1054/jpai.2002.123004. PMID 14622802. List of Library Holdings Worldwide
- ^ McBryde KD, Wilcox J, Kher KK (2005). "Hyperphosphatemia due to fosphenytoin in a pediatric ESRD patient". Pediatric Nephrology (Berlin, Germany) (PDF) 20 (8): 1182–5. doi:10.1007/s00467-005-1947-0. PMID 15965770.
- ^ Yamaoka Y, Roberts RD, Stella VJ (April 1983). "Low-melting phenytoin prodrugs as alternative oral delivery modes for phenytoin: a model for other high-melting sparingly water-soluble drugs". J Pharm Sci 72 (4): 400–5. doi:10.1002/jps.2600720420. PMID 6864479.
- ^ Anticonvulsants before 1993 Neuroland
- ^ "Cerebyx Approval History". Retrieved 20 October 2005.
See also[edit]
- hydantoin
- ethotoin
- mephenytoin
- phenytoin
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Anticonvulsants (N03)
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| GABAA receptor agonist |
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Barbiturates
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- Barbexaclone
- Metharbital
- Methylphenobarbital
- Pentobarbital
- Phenobarbital#
- Primidone
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Benzodiazepines
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- Clobazam
- Clonazepam
- Clorazepate
- Diazepam#
- Flutoprazepam
- Lorazepam
- Midazolam
- Nimetazepam
- Nitrazepam
- Temazepam
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| Other GABA agents |
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Aromatic allylic alcohols
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| Carbonic anhydrase inhibitor |
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Sulfa drugs
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- Acetazolamide
- Ethoxzolamide
- Sultiame
- Zonisamide
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| Channel blockers |
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Primarily sodium
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Hydantoins
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- Ethotoin
- Fosphenytoin
- Mephenytoin
- Phenytoin#
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Carboxamides
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- Carbamazepine#
- Eslicarbazepine acetate
- Oxcarbazepine
- Oxitriptyline
- Rufinamide
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Primarily calcium
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Succinimides
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- Ethosuximide#
- Mesuximide
- Phensuximide
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AMPA receptor
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Unknown/ungrouped
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- Phenyltriazine (Lamotrigine), Oxazolidinediones (Ethadione
- Paramethadione
- Trimethadione), Ureas (Phenacemide
- Pheneturide), Monosaccharide (Topiramate)
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| Channel openers |
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| Indirect GABA agents |
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Carboxylic acids/
Fatty acid derivatives
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- GABA transaminase inhibitor: Valproic acid# (Sodium valproate & Valproate semisodium)
- Valpromide
- Valnoctamide
- Valproate pivoxil
GABA reuptake inhibitor: Tiagabine
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GABA analogs
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- Gabapentin
- Pregabalin
- Progabide
- Tolgabide
- Vigabatrin
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Unknown/multiple/
unsorted |
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Carbamates/sulfamates
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- Carisbamate†
- Emylcamate
- Felbamate
- JNJ-26990990§
- Meprobamate
- Topiramate
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Pyrrolidines
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- Brivaracetam
- Levetiracetam
- Nefiracetam
- Seletracetam
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Propionates
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Aldehydes
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Bromides
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- Potassium bromide
- Sodium bromide
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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anat (n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp
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noco (m/d/e/h/v/s)/cong/tumr, sysi/epon, injr
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proc, drug (N1A/2AB/C/3/4/7A/B/C/D)
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