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1

&NA;. "Fosphenytoin." Reactions Weekly &NA;, no. 1379 (2011): 19. http://dx.doi.org/10.2165/00128415-201113790-00069.

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Fischer, James H., Tejal V. Patel, and Patricia A. Fischer. "Fosphenytoin." Clinical Pharmacokinetics 42, no. 1 (2003): 33–58. http://dx.doi.org/10.2165/00003088-200342010-00002.

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&NA;. "Fosphenytoin." Reactions Weekly &NA;, no. 1076 (2005): 9. http://dx.doi.org/10.2165/00128415-200510760-00028.

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&NA;. "Fosphenytoin." Reactions Weekly &NA;, no. 913 (2002): 7. http://dx.doi.org/10.2165/00128415-200209130-00020.

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Holliday, Stephen M., Paul Benfield, and Greg L. Plosker. "Fosphenytoin." PharmacoEconomics 14, no. 6 (1998): 685–90. http://dx.doi.org/10.2165/00019053-199814060-00008.

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6

&NA;. "Fosphenytoin." Drugs & Therapy Perspectives 4, no. 9 (1994): 7–8. http://dx.doi.org/10.2165/00042310-199404090-00003.

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7

&NA;. "Fosphenytoin." Reactions Weekly &NA;, no. 949 (2003): 11. http://dx.doi.org/10.2165/00128415-200309490-00041.

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8

&NA;. "Fosphenytoin." Dimensions of Critical Care Nursing 20, no. 3 (2001): 12. http://dx.doi.org/10.1097/00003465-200105000-00004.

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9

Luer, Mark. "Fosphenytoin." Neurological Research 20, no. 2 (1998): 178–82. http://dx.doi.org/10.1080/01616412.1998.11740502.

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10

Cheshire, William P. "Fosphenytoin." Journal of Pain and Symptom Management 21, no. 6 (2001): 506–10. http://dx.doi.org/10.1016/s0885-3924(01)00269-x.

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11

Eriksson, Kai, Tapani Keränen, and Reetta Kälviäinen. "Fosphenytoin." Expert Opinion on Drug Metabolism & Toxicology 5, no. 6 (2009): 695–701. http://dx.doi.org/10.1517/17425250902997975.

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12

Knapp, Lloyd E., and Alan R. Kugler. "Clinical Experience With Fosphenytoin in Adults: Pharmacokinetics, Safety, and Efficacy." Journal of Child Neurology 13, no. 1_suppl (1998): S15—S18. http://dx.doi.org/10.1177/0883073898013001051.

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Fosphenytoin, a prodrug of phenytoin, is rapidly and completely converted to phenytoin in adults after intravenous or intramuscular administration and is significantly better tolerated than parenteral phenytoin. Fosphenytoin is highly plasma-protein bound and, when present in sufficient concentration, will displace phenytoin from plasma proteins. The clinical utility is that fosphenytoin may be used to achieve therapeutic phenytoin concentrations more rapidly than intravenous phenytoin infused at its maximum recommended rate. In a clinical study of generalized convulsive status epilepticus, fo
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13

Kugler, Alan R., Thomas M. Annesley, Gerald D. Nordblom, Jeffrey R. Koup, and Stephen C. Olson. "Cross-reactivity of fosphenytoin in two human plasma phenytoin immunoassays." Clinical Chemistry 44, no. 7 (1998): 1474–80. http://dx.doi.org/10.1093/clinchem/44.7.1474.

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Abstract The cross-reactivity of fosphenytoin, a phosphate ester prodrug of phenytoin, was investigated in the Abbott phenytoin TDx®/TDxFLxTM fluorescence polarization immunoassay (TDx) and the Behring Diagnostics phenytoin Emit® 2000 enzyme-multiplied immunoassay (Emit). The first part of our study investigating cross-reactivity utilized in vitro correlation of the two immunoassays with a validated and specific phenytoin HPLC method used to assay plasma samples prepared in several phenytoin and fosphenytoin concentration combinations. Fosphenytoin cross-reacted with both immunoassays, but to
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14

Fischer, James H., Michael J. Cwik, Mark S. Luer, Carolyn B. Sibley, and Kelly L. Deyo. "Stability of Fosphenytoin Sodium with Intravenous Solutions in Glass Bottles, Polyvinyl Chloride Bags, and Polypropylene Syringes." Annals of Pharmacotherapy 31, no. 5 (1997): 553–59. http://dx.doi.org/10.1177/106002809703100505.

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OBJECTIVE: To determine the stability of fosphenytoin sodium admixtures with NaCl 0.9% injection and dextrose 5% (D5W) injection when stored in glass or polyvinyl chloride (PVC) containers, to evaluate the compatibility of fosphenytoin with 11 other intravenous solutions, and to determine the stability of fosphenytoin repackaged in polypropylene syringes. METHODS: Dilutions of fosphenytoin sodium 1, 8, and 20 mg phenytoin sodium equivalents (PE)/mL were prepared in NaCl 0.9%, D5W, and 11 other intravenous fluids. Aliquots of each solution in NaCL 0.9% or D5W were transferred to three glass bot
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15

Boucher, Bradley A., Claudio A. Feler, J. Christine Dean, et al. "The Safety, Tolerability, and Pharmacokinetics of Fosphenytoin after Intramuscular and Intravenous Administration in Neurosurgery Patients." Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 16, no. 4 (1996): 638–45. http://dx.doi.org/10.1002/j.1875-9114.1996.tb03646.x.

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Study Objective. To evaluate the safety, tolerability, and pharmacokinetic profile of fosphenytoin, a water‐soluble phenytoin prodrug, after intramuscular and intravenous administration.Design. Open‐label study of intramuscular administration, and double‐blind, randomized study of intravenous administration.Setting. Six and ten hospitals throughout the United States for the intramuscular and intravenous multicenter studies, respectively.Patients. Neurosurgical patients who required anticonvulsant prophylaxis or treatment.Interventions. In the intramuscular study, 118 patients received loading
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16

Boucher, Bradley A. "Fosphenytoin: A Novel Phenytoin Prodrug." Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 16, no. 5 (1996): 777–91. http://dx.doi.org/10.1002/j.1875-9114.1996.tb02996.x.

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Fosphenytoin is a phenytoin prodrug that received an approvable letter from the Food and Drug Administration in February 1996. It was designed to overcome many of the shortcomings associated with parenteral phenytoin sodium. Specifically, fosphenytoin is a highly water‐soluble, phosphate ester of phenytoin that has no known pharmacologic activity before its conversion to phenytoin. Dosing of fosphenytoin uses phenytoin equivalents (PE) to minimize dosage errors when converting from the conventional formulation. Pharmacokinetic studies documented that the agent is rapidly and completely convert
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17

&NA;. "Fosphenytoin/phenytoin." Reactions Weekly &NA;, no. 1223 (2008): 14–15. http://dx.doi.org/10.2165/00128415-200812230-00043.

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18

&NA;. "FOSPHENYTOIN (CEREBYX)." American Journal of Nursing 97, no. 1 (1997): 62. http://dx.doi.org/10.1097/00000446-199701000-00042.

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19

Chioffi, Susan M., Timothy F. Lassiter, Ann C. Scates, and Beth M. McLendon. "FOSPHENYTOIN FACTS." American Journal of Nursing 99, no. 8 (1999): 14. http://dx.doi.org/10.1097/00000446-199908000-00007.

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20

Browne, Thomas R. "Fosphenytoin (Cerebyx)." Clinical Neuropharmacology 20, no. 1 (1997): 1–12. http://dx.doi.org/10.1097/00002826-199702000-00001.

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21

Ramsay, R. Eugene, and B. J. Wilder. "PARENTERAL FOSPHENYTOIN." Neurologist 5, no. 4 (1998): S35. http://dx.doi.org/10.1097/00127893-199809010-00006.

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22

Chioffi, Susan M., Timothy F. Lassiter, Ann C. Scates, and Beth M. McLendon. "Fosphenytoin Facts." American Journal of Nursing 99, no. 8 (1999): 14. http://dx.doi.org/10.2307/3472163.

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23

Horowitz, B. Zane. "Fosphenytoin farewell?" Annals of Emergency Medicine 43, no. 3 (2004): 398–400. http://dx.doi.org/10.1016/j.annemergmed.2003.11.007.

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24

Mueller, Eric W., and Bradley A. Boucher. "Fosphenytoin: Current Place in Therapy." Journal of Pediatric Pharmacology and Therapeutics 9, no. 4 (2004): 265–73. http://dx.doi.org/10.5863/1551-6776-9.4.265.

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Fosphenytoin is a parenteral phosphate ester prodrug of phenytoin developed to overcome the limitations associated with parenteral administration of phenytoin. Despite potential clinical advantages, pharmacoeconomic concerns have prevented widespread substitution of parenteral phenytoin with fosphenytoin. The purposes of this descriptive review are to (1) highlight recent clinical and pharmacoeconomic data regarding the therapeutic decision to use phenytoin or fosphenytoin for the parenteral management of acute seizures, and (2) discuss the implications of fosphenytoin use in neonatal and pedi
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25

Roberts, William L., Barun K. De, John P. Coleman, and Thomas M. Annesley. "Falsely Increased Immunoassay Measurements of Total and Unbound Phenytoin in Critically Ill Uremic Patients Receiving Fosphenytoin." Clinical Chemistry 45, no. 6 (1999): 829–37. http://dx.doi.org/10.1093/clinchem/45.6.829.

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Abstract Background: Fosphenytoin, a phosphate ester prodrug of phenytoin, is metabolized to phenytoin in vivo. Phenytoin metabolites accumulate in renal insufficiency and cross-react in some phenytoin immunoassays. Our aim was to determine the accuracy of phenytoin immunoassays in renal patients treated with fosphenytoin. Methods: We measured phenytoin with HPLC and with the aca, ACS:180, TDx phenytoin II, Vitros, and AxSYM methods. Specimens were collected 2–120 h after fosphenytoin administration from 17 patients with renal insufficiency. Results: The AxSYM, TDx phenytoin II, ACS:180, and V
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26

Clark, Sarah L., Megan R. Leloux, Ross A. Dierkhising, Gregory D. Cascino, and Sara E. Hocker. "IV fosphenytoin in obese patients." Neurology: Clinical Practice 7, no. 1 (2016): 45–52. http://dx.doi.org/10.1212/cpj.0000000000000322.

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AbstractBackground:Previous studies evaluated the disposition of IV phenytoin loading doses and found that obese patients had increased drug distribution into excess body weight, larger volumes of distribution, and longer half-lives when compared to their nonobese counterparts. We assess the safety and efficacy of fosphenytoin loading doses in patients with different body mass indices (BMIs).Methods:A retrospective chart review was conducted in 410 patients who received fosphenytoin. Patients were divided into 2 groups: BMI <30 (nonobese) and BMI ≥30 (obese). Patient demographics, fosphenyt
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27

Prusakov, Ashley B., Anup D. Patel, and Justin W. Cole. "Impact of Obesity on Fosphenytoin Volume of Distribution in Pediatric Patients." Journal of Child Neurology 33, no. 8 (2018): 534–36. http://dx.doi.org/10.1177/0883073818770801.

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The impact of body habitus on fosphenytoin pharmacokinetics is poorly understood in pediatric patients. This retrospective, single-center review examined differences in fosphenytoin volume of distribution (VD) between children with normal and obese body habitus. From 2013 to 2015, patients 2 to 18 years of age who received a loading dose of fosphenytoin were identified. Thirty-seven patients met inclusion criteria. Mean total serum phenytoin concentration was 25.3 ± 6.5 μg/mL in the nonobese group and 29.5 ± 7.6 μg/mL in the obese group ( P = .09). VD was not significantly different between ob
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28

Alix, Veronica, Mansi James, Anthony H. Jackson, Paul F. Visintainer, and Rachana Singh. "Efficacy of Fosphenytoin as First-Line Antiseizure Medication for Neonatal Seizures Compared to Phenobarbital." Journal of Child Neurology 36, no. 1 (2020): 30–37. http://dx.doi.org/10.1177/0883073820947514.

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Currently used treatment protocols for neonatal seizures vary among centers with limited evidence to support the choice of a given antiseizure medication. Because of concerns about the potential negative impact of phenobarbital on long-term neurodevelopment outcomes, our unit transitioned to fosphenytoin as the first-line antiseizure medication. A retrospective observational cohort study was conducted to compare the acute and long-term outcomes of fosphenytoin and phenobarbital as first-line antiseizure medication for neonatal seizure treatment. The 2 study groups had similar baseline characte
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29

Graves, Nina. "Pharmacoeconomic Considerations in Treatment Options for Acute Seizures." Journal of Child Neurology 13, no. 1_suppl (1998): S27—S29. http://dx.doi.org/10.1177/0883073898013001081.

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Two pharmacoeconomic studies on the treatment of acute seizures have been conducted. In 1991, Kriel and colleagues surveyed parents of children with a history of cluster seizures, prolonged seizures, or status epilepticus who had been instructed in the use of rectal diazepam. A comparison of data before instruction with data after instruction showed a reduced need for emergency department visits with rectal diazepam. Instruction thus provided a pharmacoeconomic benefit, despite the cost of the product. In 1996, Marchetti and coworkers found that intravenous fosphenytoin was associated with few
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30

&NA;. "Fosphenytoin/phenytoin overdose." Reactions Weekly &NA;, no. 1391 (2012): 23. http://dx.doi.org/10.2165/00128415-201213910-00085.

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31

Kirschbaum, Karen, and Cheryle Gurk-Turner. "Phenytoin vs Fosphenytoin." Baylor University Medical Center Proceedings 12, no. 3 (1999): 168–72. http://dx.doi.org/10.1080/08998280.1999.11930167.

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32

Takeoka, Masanori, Kalpathy S. Krishnamoorthy, Teesta B. Soman, and Verne S. Caviness. "Fosphenytoin in Infants." Journal of Child Neurology 13, no. 11 (1998): 537–40. http://dx.doi.org/10.1177/088307389801301102.

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33

Annesley, Thomas M., Stephen Kurzyniec, Gerald D. Nordblom, et al. "Glucuronidation of Prodrug Reactive Site: Isolation and Characterization of Oxymethylglucuronide Metabolite of Fosphenytoin." Clinical Chemistry 47, no. 5 (2001): 910–18. http://dx.doi.org/10.1093/clinchem/47.5.910.

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Abstract Background: This investigation was undertaken to identify the structure of a novel immunoreactive metabolite derived from fosphenytoin that has been hypothesized previously as present in sera from renally impaired patients receiving this prodrug. Methods: The metabolite was isolated from uremic sera using solid-phase extraction and HPLC. Structural analysis was performed using HPLC–tandem mass spectrometry, nuclear magnetic resonance (NMR), deuterium exchange, and chemical derivatization. Immunoreactivity was evaluated using a fluorescence polarization immunoassay. Results: The metabo
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34

Bohannon, Kristin K., Noelle Leung, Aaron M. Cook, et al. "Evaluation of Two Fosphenytoin Loading Dose Regimens and Monitoring in Infants and Neonates Less Than Six Months of Age." Journal of Pediatric Pharmacology and Therapeutics 25, no. 7 (2020): 617–22. http://dx.doi.org/10.5863/1551-6776-25.7.617.

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OBJECTIVES The objectives of the study were to compare the free serum concentrations after different fosphenytoin loading dose strategies in patients younger than 6 months old and to investigate the frequency of seizure cessation following a loading dose of fosphenytoin. METHODS This retrospective cohort study included neonates and infants admitted to a 150-bed children's hospital between August 1, 2014, and February 1, 2018. Patients were included if they were younger than 6 months old and had a postload free phenytoin serum concentration collected during the specified time frame. Patients we
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35

Gadd, Nancy J. "Probable Anticonvulsant Hypersensitivity Syndrome Due to Fosphenytoin in a Pediatric Patient with Streptococcus pneumoniae Meningitis." Journal of Pediatric Pharmacology and Therapeutics 12, no. 4 (2007): 224–28. http://dx.doi.org/10.5863/1551-6776-12.4.224.

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An 8-year-old previously healthy girl with Streptococcus pneumoniae meningitis developed probable anticonvulsant hypersensitivity syndrome (AHS) within 5 days of starting fosphenytoin. She experienced fever, rash, periorbital edema, profound hepatotoxicity and coagulopathy. Her sudden and dramatic rise in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) to greater than 80 times the upper limit of normal in combination with an elevated INR were very concerning. Mortality from AHS has been correlated with the degree of hepatic involvement. Fosphenytoin was immediately disconti
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36

&NA;. "Esomeprazole/fosphenytoin/phenytoin interaction." Reactions Weekly &NA;, no. 1313 (2010): 19–20. http://dx.doi.org/10.2165/00128415-201013130-00065.

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37

Wainwright, Mark S. "Fat, Pharmacokinetics, and Fosphenytoin." Pediatric Critical Care Medicine 19, no. 8 (2018): 784–85. http://dx.doi.org/10.1097/pcc.0000000000001647.

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38

Hutt, Nancy. "FOSPHENYTOIN for Seizure Control." American Journal of Nursing 99, no. 3 (1999): 52. http://dx.doi.org/10.1097/00000446-199903000-00037.

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39

Anderson, Becky L. "New Anticonvulsant Agent: Fosphenytoin." Baylor University Medical Center Proceedings 9, no. 3 (1996): 41–42. http://dx.doi.org/10.1080/08998280.1996.11929985.

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40

Pellock, J. M. "Fosphenytoin use in children." Neurology 46, Issue 6, Supplement 1 (1996): 14S—16S. http://dx.doi.org/10.1212/wnl.46.6_suppl_1.14s.

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41

Eldon, Michael A., Lloyd E. Knapp, and Alan R. Kugler. "CLINICAL PHARMACOKINETICS OF FOSPHENYTOIN." Neurologist 5, no. 4 (1998): S30. http://dx.doi.org/10.1097/00127893-199809010-00005.

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42

Paloucek, Frank P. "Fosphenytoin safety and economics." American Journal of Health-System Pharmacy 53, no. 22 (1996): 2702–6. http://dx.doi.org/10.1093/ajhp/53.22.2702.

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43

Fierro, Lesley S., Donna H. Savulich, and Diane A. Benezra. "Safety of fosphenytoin sodium." American Journal of Health-System Pharmacy 53, no. 22 (1996): 2707–12. http://dx.doi.org/10.1093/ajhp/53.22.2707.

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44

Morton, Lawrence Daniel. "Clinical Experience With Fosphenytoin in Children." Journal of Child Neurology 13, no. 1_suppl (1998): S19—S22. http://dx.doi.org/10.1177/0883073898013001061.

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Fosphenytoin, a phenytoin prodrug, can be administered in a variety of intravenous diluents and has a more neutral pH value than phenytoin. The pharmacokinetics, safety, and tolerability of fosphenytoin in children from 1 day to 16 years old have been evaluated in two multicenter studies. Data are available from 78 patients who received loading doses (62 with intravenous administration and 16 with intramuscular administration). In these studies, fosphenytoin was converted to phenytoin within 8.3 minutes (range, 2.5-18.5 minutes). In addition, no significant difference in conversion rates was n
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45

Pon, PharmD, Doreen, Joon Hwang, PharmD Candidate, Teresa Lo, PharmD Candidate, and Carin Van Zyl, MD, FACEP. "Decreased responsiveness to oxycodone: A case of a pharmacokinetic drug interaction?" Journal of Opioid Management 11, no. 4 (2015): 357. http://dx.doi.org/10.5055/jom.2015.0284.

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Concurrent administration of oxycodone and phenytoin may cause, through induction of CYP3A4 enzymes, decreased analgesic effects of oxycodone. However, no descriptions of this interaction exist. A patient who was on oxycodone for chronic back pain was admitted to the hospital. Five days after initiating fosphenytoin, the patient experienced a dramatic escalation in his pain and lack of response to oxycodone breakthrough doses. Changing oxycodone to hydromorphone resulted in significantly improved analgesia. Concurrent use of fosphenytoin and oxycodone may increase the conversion of oxycodone t
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46

Applebaum, Julia, Joseph Levine, and R. H. Belmaker. "Intravenous Fosphenytoin in Acute Mania." Journal of Clinical Psychiatry 64, no. 4 (2003): 408–9. http://dx.doi.org/10.4088/jcp.v64n0408.

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47

Millichap, J. Gordon. "Fosphenytoin in Infants and Children." Pediatric Neurology Briefs 12, no. 11 (1998): 87. http://dx.doi.org/10.15844/pedneurbriefs-12-11-11.

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48

Browne, T. R., A. R. Kugler, and M. A. Eldon. "Pharmacology and pharmacokinetics of fosphenytoin." Neurology 46, Issue 6, Supplement 1 (1996): 3S—7S. http://dx.doi.org/10.1212/wnl.46.6_suppl_1.3s.

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49

Pruitt, Alicia C. "More on fosphenytoin (Cerebyx) dosing." Journal of Emergency Nursing 24, no. 1 (1998): 6. http://dx.doi.org/10.1016/s0099-1767(98)90154-4.

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50

Stella, Valentino J. "A case for prodrugs: Fosphenytoin." Advanced Drug Delivery Reviews 19, no. 2 (1996): 311–30. http://dx.doi.org/10.1016/0169-409x(95)00112-k.

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