Drug-Drug Interaction


VALPROATE/CHITOSAN

MECHANISM OF ACTION
The exact mechanism is unknown. Chitosan may bind to valproate in the gastrointestinal tract, preventing its absorption or chitosan may decrease the enterohepatic recirculation of chitosan by decreasing enteric bacteria.(1)

DISCUSSION
In a case report, a 35 year-old female had been seizure-free for three years on a regimen of valproate (500 mg twice daily, 52 mcg/ml) and phenobarbital. The patient developed seizures within 5 days of initiating chitosan (500 mg twice daily) on two separate occasions. Seizures remitted following discontinuation of chitosan. During the second trial of chitosan, valproate levels were undetectable while phenobarbital levels were therapeutic. Valproate levels returned to baseline 4 days after chitosan discontinuation.(1)

CLINICAL EFFECTS
Concurrent use of chitosan may decrease levels and effectiveness of valproate, resulting in an increase in seizures.

SEVERITY LEVEL
9-Undetermined Severity - Alternative Therapy Interaction: Assess the risk to the patient and take action as needed.

PATIENT MANAGEMENT
Patients maintained on valproate derivatives should be cautioned that the use of chitosan may increase their risk of seizures. Consider monitoring valproate levels and instruct patients to discontinue chitosan if seizures occur.

PREDISPOSING FACTORS
None determined.

REFERENCE

  1. Striano P, Zara F, Minetti C, Striano S. Chitosan may decrease serum .Striano P, Zara F, Minetti C, Striano S. Chitosan may decrease serum valproate and increase the risk of seizure reappearance. BMJ 2009; 339:b3751.