Products Affected - Description
Fosphenytoin 75 mg/mL (50 mg PE/mL), Fresenius Kabi
2 mL vial (NDC 63323-0403-02)
10 mL vial (NDC 63323-0403-10)
Fosphenytoin 75 mg/mL (50 mg PE/mL), Hospira
2 mL vial, 25 count (NDC 00409-4857-02)
10 mL vial, 10 count (NDC 00409-4857-10)
Fosphenytoin 75 mg/mL (50 mg PE/mL), West-Ward
2 mL vial (NDC 00641-6136-25)
10 mL vial (NDC 00641-6137-10)
Reason for the Shortage
- Akorn discontinued fosphenytoin injection in 2011.1
- Fresenius Kabi recalled numerous lots of fosphenytoin due to particulate matter potentially from glass delamination and consistent with glass particulates observed in samples. Fresenius Kabi has a letter discussing the lot numbers and what to do with affected product.2
- American Regent discontinued fosphenytoin injection in late-2010.3
- Bedford discontinued fosphenytoin in May, 2011 to concentrate on the manufacturing of other products.4
- Hospira states the shortage is due to manufacturing delays.5,6
- Pfizer discontinued the Cerebyx 500 mg presentation in September, 2009 and the 1 gram presentation in early-February, 2010.7
- Pfizer launched Cerebyx 2 mL and 10 mL vials in October 2013.7
- Teva, Apotex, Baxter, GeneraMedix, and Wockhardt have discontinued their fosphenytoin presentations.8-12
Cerebyx 75 mg/mL (50 mg PE/mL), Pfizer7
2 mL vial (NDC 00069-6001-25)
10 mL vial (NDC 00069-6001-21)
Estimated Resupply Dates
- Hospira has all fosphenytoin 75 mg/mL presentations on back order and the company cannot estimate a release date.6
- Fresenius Kabi has fosphenytoin 75 mg/mL 2 mL and 10 mL vials on back order and the company estimates a release date of 3rd quarter 2014.2
- West-Ward has fosphenytoin 75 mg/mL 2 mL and 10 mL vials on back order and the company cannot estimate a release date.13
Implications for Patient Care
Fosphenytoin is labeled for the treatment or prevention of seizures occurring during neurosurgery, treatment of status epilepticus, and as a short term substitution for oral phenytoin when other means of phenytoin administration are unavailable or inappropriate.14
- Fosphenytoin and phenytoin are not equivalent in terms of dosing. However, fosphenytoin concentrations and dosing recommendations are expressed as phenytoin equivalents (PE) and orders for fosphenytoin should be written and dispensed as phenytoin equivalents. Fosphenytoin 75 mg/mL, also expressed as fosphenytoin 50 mg PE/mL, is equivalent to IV phenytoin 50 mg/mL.14
- Maximum administration rates differ for fosphenytoin and phenytoin. Fosphenytoin has a maximum administration rate of 150 mg PE/minute. The maximum recommended phenytoin administration rate is 50 mg/minute in adults and 1-3 mg/kg/minute in neonates and pediatric patients.14,15
- Phenytoin injection is a vesicant and should be administered via a central line when possible.15 Rapid infusion can lead to cardiac or respiratory arrest. Continued administration through the same vein may increase risk of vascular injury or soft tissue damage.16 Use of a 20-gauge or larger IV catheter, infusion through a well-placed line in a vein no smaller than the antecubital fossa vein, and a reduced administration rate may decrease the risk of injuries.16 The dilution of phenytoin is controversial and is not recommended due to increased risk of phenytoin precipitation.15, 17
Alternative Agents & Management
- The choice of an alternative agent must be patient-specific and based on the clinical situation, venous access, renal and hepatic function, and other comorbid conditions.
- Use oral phenytoin whenever possible. If IV phenytoin is necessary, the same total daily dose can be given IV. Carefully monitor plasma phenytoin concentrations due to increased bioavailability with IV preparation.14,15
- Table 1 provides some alternative treatment options for selected clinical situations.
- Table 2 provides some alternative treatment options for the treatment of status epilepticus or acute repetitive seizures in neonates, infants, and children.
- Akorn, Customer Service (personal communication).March 4, 12, and 24, April 6, 13, and 26, and May 18, October 12, December 6, 2010; May 25, June 3, July 13, and August 10, 2011.
- Fresenius Kabi, Customer Service (personal communication and website). March 4, 12, and 24, April 6, 13, and 27, May 19 and 28, June 15, July 16, 22, and 23, August 27, October 14 and 20, November 16, December 20, 2010; January 27, March 2, April 20, May 25, July 14, August 8, October 3, November 30, 2011; January 4, February 22, March 22, April 10, 19, and 23, June 12, July 16, August 7 and 13, October 24, November 9, December 21, 2012; January 14, February 5, March 6 and 27, April 29, May 9 and 28, June 17, July 16, August 12, September 10, October 29, 2013; January 27, February 28, April 11, May 6, June 3 and 23, and July 11, 2014.
- American Regent, Customer Service (personal communication). January 4 and 27, March 3, April 18, and May 25, July 14 and 22, August 8 and 11, October 3, and November 30, 2011; January 3 and February 23, 2012.
- Bedford, Customer Service (personal communication). March 4, 12, and 24, April 28, October 13, and December 14, 2010; April 18 and May 3, 2011.
- Hospira. Product Recall notice (written communication). May 24, 2010.
- Hospira, Customer Service (website and personal communication). August 8, March 4, 12, and 24, April 6, 13, and 27, and May 18 and 27, June 14, July 20, October 12, 2010; January 20, February 25, April 18, May 25, June 3, July 12, August 8, October 3, November 30, 2011; January 3, February 20, March 21, April 10 and 23, June 11, July 16, August 6, October 24, November 9, December 26, 2012; January 16, February 5, March 6 and 25, April 29, May 13 and 28, June 18, July 18, August 12, September 9, October 30, 2013; January 27, March 3, April 14, May 6, June 6 and 23, and July 14, 2014.
- Pfizer, Customer Service (personal communication). March 12, 2010; October 29, 2013; January 24, February 28, April 11, May 6, June 6 and 23, and July 11, 2014.
- Teva Pharmaceuticals, Customer Service (personal communication). March 4, 12, and 24, and April 6, 2010.
- Apotex, Customer Service (personal communication). March 4, 2010.
- Baxter, Customer Service (personal communication). March 4, 2010; and March 2, 2011.
- GeneraMedix, Customer Service (personal communication). March 12, 2010.
- Wockhardt, Customer Service (personal communication). March 4 and 12, 2010.
- West-Ward, Customer Service (personal communication). November 18, December 20, 2010; January 27, March 3, April 18, May 25, August 10, October 4, 2011; January 6, February 23, March 21, April 6 and 24, June 14 and 29, August 6, October 24, November 9, December 17, 2012; January 11, February 5 March 6 and 25, April 22, May 10 and 28, June 10, July 12, August 9, September 6, October 25, 2013; January 24, February 27, April 11, May 6, June 4 and 23, and July 11, 2014.
- Fosphenytoin Injection product information. Lake Forest, IL: Hospira; 2006 August.
- Phenytoin Injection product information. Deerfield, IL: Baxter Healthcare Corporation; 2007 August.
- Meek PD et al. Guidelines for nonemergency use of parenteral phenytoin products: proceedings of an expert panel consensus. Arch Intern Med. 1999;159:2639-2644.
- McEvoy GK, Snow EK, Miller J, eds. AHFS 2010 Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2010.
- Aminoff MJ, Greenberg DA, Simon RR. Seizures and Syncope. In: Foltin J, Fernando N, eds. Clinical Neurology. 6th edition. New York, NY: McGraw-Hill Companies, Inc.; 2005: 263-84.
- Lexi-Comp Online. Hudson, OH: Lexi-Comp Inc.; 2010.
- Rubin DH, Kornblau DH, Conway EE, Caplen SM. Neurological Disorders. In: Marx JA, Hockberger RS, Walls RM, et al, eds. Rosen’s Emergency Medicine: concepts and clinical practice. 7th edition. Maryland Heights, MO: Mosby, Inc.; 2009. Accessed on May 28, 2010.
- Trinka E. Emergency treatment of status epilepticus: what is the relative value of the standard anticonvulsants phenytoin, fosphenytoin, phenobarbital, valproate, and levetiracetam. Epilepsia. 2009;50:40-43.
- Ruegg S, Naegelin Y, Hardmeier M, et al. Intravenous levetiracetam: treatment experience with the first 50 critically ill patients. Epilepsy Behav 2008;12(3):477–80.
- Knake S, et al. Intravenous levetiracetam in the treatment of benzodiazepine refractory status epilepticus. J Neurol Neurosurg Psychiatry. 2008;79:588-589.
- Milligan TA, Hurwitz A, Bromfield EB. Efficacy and tolerability of levetiracetam verus phenytoin after supratentorial neurosurgery. Neurology. 2008;71:665-669.
- Szaflarski JP, Sangha KS, Lindsell CJ, Shutter LA. Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Neurocrit Care. 2010;12:165-172.
- Pediatric Lexi-Drugs Online. Hudson, OH: Lexi-Comp Inc.; 2010.
- Abend NS, et al. Anticonvulsant medications in the pediatric emergency room and intensive care unit. Pediatric Emergency Care. 2008;24:705-18.
- Phelps SJ, Hak EB, Crill CM, eds. Pediatric Injectable Drugs: The Teddy Bear Book. 9th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2010.
- Young TE, Mangum B. Neofax 2009. 22nd edition. Montvale, NJ: Thomson Reuters; 2009.
- Custer JW, Rau RE, eds. The Harriet Lane Handbook. 18th edition. Philadelphia, PA: Mosby-Elsevier, 2009.
- Abend NS, Monk HM, Licht DJ, Dlugos DJ. Intravenous levetiracetam in critically ill children with status epilepticus or acute repetitive seizures. Pediatr Crit Care Med. 2009;10:505-10.
- Gallentine WB, Hunnicutt AS, Husain AM. Levetiracetam in children with refractory status epilepticus. Epilepsy & Behavior. 2009;14:215-18.
- Kirmani BF, Crisp ED, Kayani S, Rajab H. Role of intravenous levetiracetam in acute seizure management of children. Pediatr Neurol. 2009;41:37-39.
- Goraya JS, et al. Intravenous levetiracetam in children with epilepsy. Pediatr Neurol. 2008;38:177-180.
Updated July 14, 2014 by Michelle Wheeler, PharmD, Drug Information Specialist. Created May 28, 2010, by Megan Dryer, PharmD, Drug Information Specialist and M. Christina Beckwith, PharmD, Drug Information Specialist. Copyright 2014, Drug Information Service, University of Utah, Salt Lake City, UT.
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