Avoid phenytoin suspension in patients with feeding tubes

Avoid phenytoin suspension in patients with feeding tubes: Excerpt from Avoiding Common Pediatric Errors

John T. Berger, III, MD

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Phenytoin is an important medication for the treatment of primary and secondary generalized tonic–clonic seizures, partial seizures, and status epilepticus. Consistent serum concentrations of phenytoin are essential for maintaining effective seizure control. Phenytoin, however, has several properties including nonlinear pharmacokinetics, a narrow therapeutic window, and uneven absorption that pose challenges for maintaining steady serum concentrations. Consistent administration and formulation will reduce the variability.

Phenytoin's metabolism has nonlinear (Michaelis-Menten) kinetics. At low serum concentrations, a fixed percentage of drug is metabolized in a given time (first-order kinetics). At higher serum levels (at the high end of the normal therapeutic range), a fixed amount of drug is metabolized per unit time (zero-order kinetics), because the metabolic pathways are saturated. Consequently, when serum levels are high, even a small dose increase may produce a very big increase in serum levels. Additionally, factors such as hepatic dysfunction and fever can alter phenytoin clearance. Phenytoin interacts with many drugs, which may increase or decrease concentrations of it or other concomitantly used anticonvulsants.

The administration of phenytoin suspension in conjunction with enteral nutrition through nasogastric (NG) feeding tubes has been associated with erratic phenytoin absorption, subtherapeutic concentrations, and breakthrough seizures. Postulated mechanisms include chelation to proteins and electrolytes in the enteral feeding, binding to NG tubing, and alterations in gastrointestinal pH, resulting in precipitation of phenytoin. If possible, continuous NG feeds should be held for 2 hours before and 2 hours after phenytoin administration to avoid decreased serum levels. The suspension should be diluted and the nasogastric tube should be thoroughly irrigated after administration.

Phenytoin suspension is reported to settle and result in uneven drug distribution and subsequently variability in drug delivery. The only study to address the question showed that even poorly shaken suspensions maintained uniform concentrations for up to 4 weeks. More important to variable dosingmaybeinaccuratemeasuringoftheconcentratedsuspension,assmall variations in volume may produce a large change given phenytoin's pharmacokinetics. Parents should be instructed not only to shake the suspension priortoeachdosebutalsotomeasurecarefully.Commerciallyavailablebrand and generic phenytoin products may differ in phenytoin content and other formulation characteristics that can affect bioavailability. These differences may occasionally result in an increase or decrease in serum phenytoin levels, which in turn might adversely affect seizure control or cause toxicity when patients are switched from one preparation to another. Additional serum monitoring is warranted when substituting new formulations of phenytoin.

Suggested Readings

Bader MK. Case study of two methods for enteral phenytoin administration. J NeurosciNurs. 1993;25(4):233–242.
Sarkar MA, Garnett WR, Karnes HT. The effects of storage and shaking on the settling properties of phenytoin suspension. Neurology. 1989;39(2 Pt 1):207–209.
Soryal I, Richens A. Bioavailability and dissolution of proprietary and generic formulations of phenytoin. J Neurol Neurosurg Psychiatry. 1992;55(8):688–691.

Book Source Details

• Book Title: Avoiding Common Pediatric Errors
• Author(s): Anthony D Slonim MD, DrPH; Lisa Marcucci MD
• Year of Publication: 2008
• Copyright Details: Avoiding Common Pediatric Errors, Copyright © 2008 Lippincott Williams & Wilkins.

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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

More About This Book: Title: Avoiding Common Pediatric Errors Authors: Anthony D Slonim MD, DrPH; Lisa Marcucci MD Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7489-6

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