From the FDA Drug Label
7 DRUG INTERACTIONS
7.2 Valproic Acid Case reports in the literature have shown that co-administration of carbapenems, including meropenem, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures Although the mechanism of this interaction is unknown, data from in vitro and animal studies suggest that carbapenems may inhibit the hydrolysis of valproic acid’s glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing the serum concentrations of valproic acid.
Yes, meropenem can cause increased elimination of valproic acid, resulting in decreased serum concentrations of valproic acid, which may lead to breakthrough seizures. The exact mechanism is unknown, but it is thought that meropenem may inhibit the hydrolysis of valproic acid's glucuronide metabolite back to valproic acid 1.
- Key points:
- Meropenem co-administration with valproic acid can decrease valproic acid concentrations
- This interaction may increase the risk of breakthrough seizures
- Supplemental anti-convulsant therapy should be considered if meropenem is necessary 1
From the Research
Yes, meropenem (Merrem) significantly decreases valproic acid (Depakote) levels through increased elimination, with a reported decrease of 90.8 and 93.5% in valproic acid serum levels during concomitant administration with meropenem 2. When these medications are used together, valproic acid levels can drop by 60-100% within 24 hours of starting meropenem, potentially leading to loss of seizure control or mood stabilization. This interaction occurs because meropenem inhibits valproic acid's reabsorption in the kidneys and may enhance its metabolism through glucuronidation. The effect is not dose-dependent and persists throughout meropenem therapy. Some key points to consider include:
- Patients requiring both medications should have valproic acid levels monitored frequently, though dose adjustments are often ineffective during concurrent therapy 3.
- Alternative antibiotics that don't interact with valproic acid (such as ceftriaxone) should be considered when possible.
- If meropenem is necessary, clinicians should monitor for breakthrough seizures or mood symptoms and consider temporary alternative treatments for the condition managed by valproic acid until meropenem therapy is complete 4. It is also worth noting that the interaction between meropenem and valproic acid has been observed in multiple studies, with a significant decrease in valproic acid plasma concentrations reported in all patients 5, 6, 3. Overall, the evidence suggests that meropenem can significantly decrease valproic acid levels, and clinicians should be aware of this potential interaction to minimize the risk of adverse effects.