Unusual presentation of iatrogenic phenytoin toxicity in a newborn.
BACKGROUND
Medication errors may produce severe toxicity resulting in hospitalization. This can be compounded if the physician obtains the wrong concentration from a reference manual and a pharmacy miscalculates the conversion. We report a child presenting with ileus, hypothermia and lethargy after receiving supratherapeutic dosing of phenytoin after a concentration miscalculation.


METHODS
A one-month-old infant presented to the Emergency Department with progressive worsening of abdominal distension, diminished activity, and a one day history of difficulty feeding secondary to a decreased level of consciousness. The past medical history was significant for neonatal Group B Strep meningitis with seizures. Among the child's discharge medications was a prescription for phenytoin (30 mg/5 mL) 2.5 cc by mouth three times daily. On exam, the child was hypothermic with pink mottled skin, poor responsiveness, prolonged capillary refill, abdominal distension with hypoactive bowel sounds, and a dysconjugate gaze. The Initial phenytoin serum concentration was 91.8 mcg/mL. She was admitted to the PICU and was started on ampicillin and cefotaxime for R/O sepsis. Phenytoin was withheld and subsequent serum concentrations revealed an extremely slow elimination (mcg/mL vs. time pair coordinates were 78.2/13.3h; 74.3/62.3h; 43.7/109.6h; 10.8/160.9h) reflecting zero-order kinetics. Post discontinuing antibiotics, phenytoin levels decreased at rates expected. She was discharged after resolution of symptoms. The MD who had written the phenytoin prescription had based it on the Harriet Lane Handbook, 2000 Ed. The 30 mg/5 mL formulation has been unavailable in the US for several years. A community pharmacy substituted the 125 mg/5 mL formulation, but miscalculated the dosage to be 1.6 cc (40 mg) tid.


CONCLUSIONS
Abdominal distension and ileus may be presenting symptoms in children at toxic phenytoin levels. Ampicillin and cefotaxime may effect the elimination rate of phenytoin at such levels. We report one of the highest phenytoin levels recorded after therapeutic misadventure. Physicians must be aware of inaccuracies in reference manuals that may result in dosing errors.
Lowry
Jennifer A
JA
Cardinal Glennon Regional Poison Center, Saint Louis University School of Medicine, St. Louis, MO, USA. jlowry@cmh.edu
Vandover
John C
JC
DeGreeff
Jan
J
Scalzo
Anthony J
AJ
D000005:Abdomen; D000284:Administration, Oral; D000667:Ampicillin / Q000009:adverse effects / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000927:Anticonvulsants / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D002439:Cefotaxime / Q000009:adverse effects / Q000493:pharmacokinetics; D004347:Drug Interactions; D062787:Drug Overdose / Q000209:etiology*; D005260:Female; D006801:Humans; D045823:Ileus / Q000139:chemically induced / Q000503:physiopathology; D007231:Infant, Newborn; D008508:Medication Errors; D016920:Meningitis, Bacterial / Q000150:complications / Q000188:drug therapy; D010672:Phenytoin / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D012640:Seizures / Q000188:drug therapy / Q000209:etiology
D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D010672:Phenytoin; D000667:Ampicillin; D002439:Cefotaxime