Aliphatic carboxylic acid · Antiepileptic
Divalproex is a coordination compound of valproic acid with sodium valproate (1:1). It acts as a prodrug, delivering valproic acid, which exerts broad-spectrum anticonvulsant action through multiple mechanisms including Na+ channel inactivation, T-current attenuation, and GABA potentiation.
Increased risk of carbamazepine toxicity (dizziness, ataxia, diplopia) and decreased valproate levels, leading to loss of seizure control.
Avoid co-administration if possible. If unavoidable, monitor carbamazepine and valproate levels closely. Adjust doses as needed. Monitor for signs of toxicity.
Rapid and significant decrease in valproate levels, leading to loss of seizure control.
Avoid co-administration. If ertapenem is essential, consider alternative anticonvulsants or closely monitor valproate levels and increase valproate dose significantly. Monitor for seizure recurrence.
Rapid and significant decrease in valproate levels, leading to loss of seizure control.
Avoid co-administration. If imipenem/cilastatin is essential, consider alternative anticonvulsants or closely monitor valproate levels and increase valproate dose significantly. Monitor for seizure recurrence.
Increased risk of severe lamotrigine-related rash (Stevens-Johnson syndrome, toxic epidermal necrolysis) and other CNS adverse effects (dizziness, ataxia).
Reduce lamotrigine starting dose and titration rate significantly when co-administered with divalproex. Monitor closely for rash and other adverse effects. Consider therapeutic drug monitoring for lamotrigine.
Rapid and significant decrease in valproate levels, leading to loss of seizure control.
Avoid co-administration. If meropenem is essential, consider alternative anticonvulsants or closely monitor valproate levels and increase valproate dose significantly. Monitor for seizure recurrence.
Increased risk of phenobarbital toxicity (sedation, respiratory depression, coma).
Reduce phenobarbital dose significantly when co-administered with divalproex. Monitor phenobarbital levels and clinical signs of toxicity closely.
Increased risk of phenytoin toxicity (nystagmus, ataxia, lethargy) due to elevated free phenytoin levels, and decreased valproate levels, potentially leading to loss of seizure control.
Monitor free phenytoin levels (not total) and valproate levels closely. Adjust doses as needed. Monitor for signs of toxicity.
AUC of paliperidone increased by 50%.
Monitor for increased paliperidone effects.
Source: G&G 14e · p368
Increased risk of valproate-related adverse effects (e.g., thrombocytopenia, hyperammonemia) and increased bleeding risk.
Monitor valproate levels (especially free valproate if available) and platelet count. Use with caution, especially in patients with bleeding disorders or those on other anticoagulants/antiplatelets.
Increased risk of ethosuximide-related adverse effects (e.g., nausea, vomiting, drowsiness).
Monitor ethosuximide levels and clinical response. Adjust ethosuximide dose as needed.
Increased risk of olanzapine-related adverse effects (e.g., sedation, weight gain, metabolic effects).
Monitor for olanzapine adverse effects. Consider lower doses of olanzapine or closer monitoring when co-administered with divalproex.
Increased risk of risperidone-related adverse effects (e.g., extrapyramidal symptoms, sedation).
Monitor for risperidone adverse effects. Consider lower doses of risperidone or closer monitoring when co-administered with divalproex.
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Sources: KD Tripathi 7e·Verified: 2026-05-10 · House clinical team