Divalproex (valproate) and Imipenem and cilastatin interaction

Divalproex (valproate) and Imipenem and cilastatin: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Imipenem and cilastatin (PRIMAXIN IV) label · effective 2024-07-05

Major

The concomitant use of PRIMAXIN and valproic acid/divalproex sodium is generally not recommended ( 5.3 , 7.3 ).

Warnings and precautionsnames Divalproex (valproate)View label on DailyMed
Major

The concomitant use of PRIMAXIN and valproic acid/divalproex sodium is generally not recommended.

Warnings and precautionsnames Divalproex (valproate)View label on DailyMed
Major

Valproic acid/divalproex sodium: Concomitant use with PRIMAXIN is generally not recommended.

Drug interactionsnames Divalproex (valproate)View label on DailyMed
Moderate

Increased Seizure Potential Due to Interaction with Valproic Acid: Co-administration of PRIMAXIN, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations.

Warnings and precautionsnames Divalproex (valproate)View label on DailyMed
Moderate

Increased Seizure Potential Due to Interaction with Valproic Acid Case reports in the literature have shown that co-administration of carbapenems, including PRIMAXIN, to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations.

Warnings and precautionsnames Divalproex (valproate)View label on DailyMed

From the Divalproex (valproate) (Depakote ER) label · effective 2026-03-31

Moderate

Interaction with Carbapenem Antibiotics Carbapenem antibiotics (for example, ertapenem, imipenem, meropenem; this is not a complete list) may reduce serum valproate concentrations to subtherapeutic levels, resulting in loss of seizure control.

Warnings and precautionsnames Imipenem and cilastatinView label on DailyMed
Moderate

Carbapenem Antibiotics A clinically significant reduction in serum valproic acid concentration has been reported in patients receiving carbapenem antibiotics (for example, ertapenem, imipenem, meropenem; this is not a complete list) and may result in loss of seizure control.

Drug interactionsnames Imipenem and cilastatinView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.