Phenytoin Infusion Revisited: Stability and Administration

Abstract

Background: Manufacturers of phenytoin injection recommend that it be given without dilution by direct IV injection. Direct IV injection presents well-recognised side effects which can be minimised by giving phenytoin as an infusion. Aim: To assess the stability of Phenytoin Injection (DBL) in sodium chloride 0.9% prepared for infusion in Viaflex bags and a Buretrol extension set. Method: Admixtures containing 3, 6 and 10 mg/mL of phenytoin were prepared in sodium chloride 0.9% and stored in Viaflex bags, extension sets and beakers exposed to air (controls) for 6 hours. The concentration of phenytoin in the Viaflex bags was measured by UV absorption spectrophotometry. All the admixtures were inspected for microscopic particulate matter and the pH measured at intervals over 6 hours. Results: In the Viaflex bags there were no changes in the phenytoin concentration, minimal change in pH(< 0.1) and no particulate matter over 6 hours. In the extension sets and beakers, particulate matter was minimal at 2 hours and extensive beyond this time. There was an overall decrease of 0.30 and 0.32 pH units in samples from the extension sets and beakers. Conclusion: Phenytoin Injection (DBL) can be given as an IV infusion in sodium chloride 0.9% provided it is prepared in a Viaflex bag and infused within 2 hours of preparation.

Review article: Phenytoin use and efficacy in the ED

“…If required, phenytoin may be added to sodium chloride 0.9% to achieve a concentration range of 3–10 mg/mL and infuse via an in‐line filter over 30 min. The infusion must be prepared immediately before use and infused within one hour.’ Phenytoin injection should never be diluted in dextrose‐containing solutions as it will precipitate 23–25 …”

“…22 However, there is concern that diluting phenytoin can cause precipitation (crystals form spontaneously at lower pH) and manufacturers recommend that it is given by direct injection. 4 This concern results from conflicting results from older studies, 23 which displayed varying methodology. A small study with sound methodology undertaken in 2004 has confirmed that dilution of phenytoin in 0.9% saline to 3-10 mg/mL produces a stable solution that is free of crystals for at least 2 h. 23 The Australian Drugs Handbook 16 states that dilution is 'generally not recommended because of low solubility and resultant precipitation.…”

“…4 This concern results from conflicting results from older studies, 23 which displayed varying methodology. A small study with sound methodology undertaken in 2004 has confirmed that dilution of phenytoin in 0.9% saline to 3-10 mg/mL produces a stable solution that is free of crystals for at least 2 h. 23 The Australian Drugs Handbook 16 states that dilution is 'generally not recommended because of low solubility and resultant precipitation. If required, phenytoin may be added to sodium chloride 0.9% to achieve a concentration range of 3-10 mg/mL and infuse via an in-line filter over 30 min.…”

“…Phenytoin injection should never be diluted in dextrose-containing solutions as it will precipitate. [23][24][25] Unfortunately, although it is clear that diluting phenytoin is safe, there is still insufficient evidence to confirm or refute that diluting parenteral phenytoin reduces adverse effects. There are no high-quality studies comparing the incidence of adverse cardiovascular effects when giving phenytoin diluted or undiluted; and there are only small uncontrolled studies that report varying incidences of cardiovascular adverse effects with diluted phenytoin infusions.…”

“…The study by Milne et al states that a filter is desirable but not necessary if solution is made up according to guidelines. 23 There are no high-quality studies to guide us in this area.…”