MECHANISM OF ACTION
Pivalic acid is released after hydrolysis from several
prodrugs. In humans, formation and urinary excretion of pivaloylcarnitine
generated from pivaloyl-CoA is the major route of pivalate elimination.
DISCUSSION
There are reports of low carnitine levels caused by the long
term (> 6 months) resulting in neurological deficits caused by the
concurrent use of pivalic acid containing products.(2) The patient improved
after carnitine supplementation.
CLINICAL EFFECTS
Concurrent use of valproic acid or its derivatives and
pivmecillinam may increase the risk of low carnitine levels leading to
neurologic deficits with or without encephalopathy. Neurologic deficits may
present as changes in state of consciousness and/or cognitive function with
lethargy and vomiting. (1-2)
SEVERITY LEVEL
3-Moderate Interaction: Assess the risk to the patient and
take action as needed.
PATIENT MANAGEMENT
The UK manufacturer of pivmecillinam state that the use
of pivmecillinam and valproic acid and its derivatives should be avoided.
(1)
PREDISPOSING FACTORS
Patients with low carnitine levels.
REFERENCES