Acyclovir
Adverse Effect: decreased valproic acid plasma concentrations and potential increased seizure activity Clinical Management: Monitor patients for reduction in antiepileptic plasma levels. Consider alternative antiviral therapy.
Amitriptyline
Adverse Effect: Increased serum amitriptyline and Chlordiazepoxide levels Clinical Management: Clinicians should be aware of a possible interaction between valproic acid and amitriptyline. A lower dose of amitriptyline may be necessary if given concurrently with valproate.
Aspirin
Adverse Effect: Valproic acid toxicity (CNS depression, GI upset) Clinical Management: An occasional single dose of aspirin would not present a problem; however, with repeated doses, monitoring of valproic acid concentrations might be considered. An alternative analgesic/antiinflammatory agent such as naproxen might be considered if appropriate.
Carbamazepine
Adverse Effect: Carbamazepine toxicity (ataxia, nystagmus, diplopia, headache, vomiting, apnea, seizures, coma) and/or decreased valproic acid effectiveness Clinical Management: Monitor patients for signs of carbamazepine toxicity such as nausea, vomiting, drowsiness, and ataxia when valproic acid is added. Serum carbamazepine concentrations should also be measured, though clinicians should be aware of the increase in the concentration of the active metabolite, carbamazepine-epoxide, which is not routinely measured, but does contribute to the efficacy and toxicity of the drug. If carbamazepine is added to valproic acid therapy, monitor valproic acid levels; increased valproic acid dosage may be required.
Chlordiazepoxide
Adverse Effect: Increased serum Chlordiazepoxide levels Clinical Management: Clinicians should be aware of a possible interaction between valproic acid and Chlordiazepoxide . A lower dose of Chlordiazepoxide may be necessary if given concurrently with valproate.
Diazepam
Adverse Effect: An increased risk of diazepam toxicity (confusion, sedation, respiratory depression)
Erythromycin
Adverse Effect: Valproic acid toxicity (CNS depression, seizures) Clinical Management: If valproic acid and erythromycin are used concurrently, be alert for signs of valproate toxicity (CNS depression, seizures). Monitor valproic acid serum concentrations during and after erythromycin therapy.
Ethosuximide
Adverse Effect: An increased risk of ethosuximide toxicity
Fluoxetine
Adverse Effect: A change in valproic acid blood concentration Clinical Management: When fluoxetine and valproic acid are used concomitantly, measure valproic acid concentrations carefully.
INH
Adverse Effect: Valproic acid or isoniazid toxicity Clinical Management: Consider monitoring liver function tests periodically with therapy, as well as continued assessment of therapeutic efficacy of valproic acid. Monitor serum valproic acid trough concentrations as indicated. If toxicity occurs, an alternative anticonvulsant may be appropriate.
Lamotrigine
Adverse Effect: lamotrigine toxicity (fatigue, drowsiness, ataxia) and an increased risk of toxic epidermal necrolysis Clinical Management: Dosage reductions of lamotrigine are necessary with concurrent valproic acid therapy, in conjunction with other enzyme-inducing medications.
Lorazepam
Adverse Effect: increased lorazepam concentrations Clinical Management: When lorazepam and valproic acid are coadministered, the dose of lorazepam should be reduced by 50%.
Mefloquine
Adverse Effect: loss of seizure control Clinical Management: If mefloquine and valproic acid must be administered concurrently, monitor the levels of valproic acid. Adjustments of the valproic acid dose may be required. Also monitor the patient for seizure control.
Nimodipine
Adverse Effect: Nimodipine toxicity (dizziness, headache, flushing, peripheral edema) Clinical Management: Monitor for clinical or toxic effects of nimodipine (hypotension is most likely). Downward dose adjustment may be necessary to maintain desired cardiovascular response.
Phenobarbitone
Adverse Effect: Phenobarbital toxicity or decreased valproic acid effectiveness Clinical Management: With the addition of valproic acid therapy in a patient stabilized on phenobarbital, the patient should be monitored for signs of phenobarbital toxicity and serum phenobarbital level obtained. Phenobarbital dosage may need to be decreased in some cases. Due to increased valproic acid metabolism, periodic determinations of valproic acid concentrations should be considered.
Phenytoin
Adverse Effect: Increased risk of phenytoin toxicity (ataxia, hyperreflexia, nystagmus, tremor) Clinical Management: Monitor for signs of phenytoin toxicity with combined therapy; consideration might also be given to monitoring serum phenytoin levels when Sodium Valproate is added or discontinued from therapy and doses adjusted accordingly.
Primidone
Adverse Effect: severe central nervous system depression Clinical Management: All patients receiving concurrent primidone and valproic acid therapy should be watched for excessive central nervous system depression and neurological toxicity.
Rifampicin
Adverse Effect: reduced valproate levels Clinical Management: Monitor valproate levels and the patient for seizure control. An adjustment in the dose of valproate may be necessary when coadministered with rifampin.
Zidovudine
Adverse Effect: increased zidovudine plasma concentrations and potential zidovudine toxicity (asthenia, fatigue, nausea, hematologic abnormalities) Clinical Management: Monitor patients for signs and symptoms of zidovudine toxicity (asthenia, fatigue, nausea, hematologic abnormalities). It may be necessary to reduce zidovudine doses |