Hyperchloremic, Normal Anion-Gap, Metabolic Acidosis Due to Topiramate

Literature Review

The metabolic adverse effects of topiramate have been well documented in the pediatric population,^[4,5] but case reports in the adult population are limited.^{[6,7,8,9,10,11]} Published reports that evaluated topiramate-associated hyperchloremic, normal anion-gap, metabolic acidosis were identified via a MEDLINE search (1966-May 2007) and included six cases in adults. Search terms included topiramate, metabolic acidosis, Topamax, and hyperchloremia.

The first case involved a 22-year-old mentally handicapped man with a history of recurrent respiratory infections who developed metabolic acidosis after four months of taking topiramate 800 mg daily for Lennox-Gastaut syndrome.^[6] The patient had symptoms of fatigue, lethargy, hypotonia, and hyperventilation. His arterial blood gas revealed a pH of 7.3 (reference range, 7.35-7.45), and his serum bicarbonate concentration was 19 meq/L (reference range, 22-26 meq/L). Metabolic acidosis resolved after withdrawal of topiramate, although the authors did not report details of the timeline to resolution.

Wilner et al.^[7] reported the development of metabolic acidosis in a 52-year-old man taking topiramate 200 mg daily for partial complex seizures. The patient developed metabolic acidosis while undergoing a right temporal lobectomy for intractable seizures. He reported no symptoms of metabolic acidosis prior to surgery, but did report one to two weeks of diarrhea preceding the day of surgery. On the day of surgery, his metabolic acidosis was evidenced by an arterial blood gas pH of 7.29 (reference range, 7.35-7.45) and a serum bicarbonate concentration of 18 meq/L (reference range, 22-30 meq/L) and serum chloride concentration of 115 meq/L (reference range, 96-108 meq/L), both of which were within normal limits three days before (24 meq/L and 108 meq/L, respectively). The metabolic acidosis was resolved three days following surgery after a decrease in the topiramate dose to 100 mg daily and the administration of sodium bicarbonate. The patient's laboratory values were all within normal limits one month later while he was still taking the lower dose of topiramate.

Metabolic acidosis was reported in a 20-year-old man taking topiramate 400 mg daily for nine months, in addition to phenytoin and valproic acid for a seizure disorder.^[8] The patient had acute mental status changes that included disorientation, somnolence, and headache for two weeks. He had no apparent changes in baseline risk for the development of metabolic acidosis. Four days prior to admission, he was seen in the emergency department for the mental status complaints. A serum chemistry analysis was significant for concentrations of chloride, 109 meq/L (reference range, 98-106 meq/L), and bicarbonate, 22 meq/L (reference range, 25-35 meq/L). On the day of hospital admission, his serum chloride concentration rose to 120 meq/L and his bicarbonate concentration decreased to 12 meq/L. In addition, his serum ammonia concentration was 138 mmol/L (reference range, 13-34 mmol/L), which was reported to decrease during his hospital stay. The serum bicarbonate concentration reached a nadir of 8 meq/L and the chloride peaked at 122 meq/L on hospital day 3, at which time a continuous infusion of sodium bicarbonate was added. Topiramate was tapered over a five-day period, and the metabolic acidosis and mental status changes resolved 48 hours after topiramate discontinuation.

Metabolic acidosis was reported in a 58-year-old man taking topiramate 25 mg daily for four days followed by 50 mg daily for the three days leading up to a scheduled craniotomy for refractory temporal lobe epilepsy.^[9] The topiramate was prescribed in addition to carbamazepine. The patient developed metabolic acidosis during surgery, although there were no additional changes in baseline risk factors for the development of metabolic acidosis reported. The patient's arterial blood gases revealed a pH of 7.29 (reference range, 7.35-7.45) and a bicarbonate concentration of 20 meq/L (reference range, 23-28 meq/L). Metabolic acidosis resolved within a few hours of administering 50 meq of a sodium bicarbonate concentration with a pH of 7.36 and bicarbonate of 24 meq/L. One day following surgery, topiramate was reduced to 25 mg daily and titrated up by 25 mg daily every two weeks to a final dose of 100 mg daily without recurrence of metabolic acidosis.

Metabolic acidosis was reported in a 46-year-old woman taking topiramate 100 mg daily for three months prescribed for vertigo.^[10] The patient came to the emergency department with noncardiac chest pain and was diagnosed with metabolic acidosis with an arterial blood gas pH of 7.31 (reference range, 7.35-7.45), a serum bicarbonate concentration of 9.5 meq/L (reference range, 22-30 meq/L), and a chloride concentration of 107 meq/L (reference range, 98-106 meq/L). The topiramate was discontinued on hospital day 5, but there was still evidence of metabolic acidosis seven days later evidenced by a serum bicarbonate concentration of 11 meq/L. The patient's laboratory values were all within normal limits, including a serum bicarbonate concentration of 24 meq/L five weeks after the discontinuation of topiramate.

The final case involved a 47-year-old woman taking topiramate 150 mg daily for 12 months for migraine headaches.^[11] Metabolic acidosis was discovered after routine laboratory monitoring. The patient reported muscle weakness and bone pain, and physical examination revealed joint sensitivity and a 6-kg weight loss over a 4-month period. Laboratory data revealed a serum bicarbonate concentration of 19 meq/L (reference range not provided). The authors reported that all laboratory data were normal before the initiation of topiramate but did not report any follow-up laboratory data after discontinuing topiramate.

Am J Health Syst Pharm. 2008;65(15):1430-1434. © 2008  American Society of Health-System Pharmacists

Cite this: Hyperchloremic, Normal Anion-Gap, Metabolic Acidosis Due to Topiramate - Medscape - Aug 01, 2008.