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J Neurol Neurosurg Psychiatry. 1986 October; 49(10): 1142–1145.
PMCID: PMC1029047

Carbamazepine-viloxazine interaction in patients with epilepsy.


In six depressed epileptic patients stabilised on carbamazepine therapy, addition of the antidepressant agent viloxazine (300 mg/day for three weeks) induced a marked (average 55%) increase in steady-state plasma carbamazepine concentration. The concentration of the active metabolite carbamazepine-10,11-epoxide also increased during viloxazine therapy, but to a lesser extent (16%). In three patients, these effects were associated with symptoms of carbamazepine intoxication, which regressed rapidly when plasma carbamazepine and carbamazepine-10,11-epoxide levels returned to baseline values after discontinuation of viloxazine. In a seventh patient, viloxazine had to be discontinued after only two weeks because of severe side effects associated with a striking elevation of carbamazepine and carbamazepine 10,11-epoxide levels (by 197% and 137% respectively). Although viloxazine appears to be one of the few antidepressants which can be used safely in patients with epilepsy these results indicate that the drug should be prescribed with great caution in subjects treated with carbamazepine. The mechanism of the interaction probably involves inhibition of the metabolism of both carbamazepine and its active epoxide metabolite.

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Selected References

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  • Meldrum BS, Anlezark GM, Adam HK, Greenwood DT. Anticonvulsant and proconvulsant properties of viloxazine hydrochloride: pharmacological and pharmacokinetic studies in rodents and the epileptic baboon. Psychopharmacology (Berl) 1982;76(3):212–217. [PubMed]
  • Edwards JG, Glen-Bott M. Does viloxazine have epileptogenic properties? J Neurol Neurosurg Psychiatry. 1984 Sep;47(9):960–964. [PMC free article] [PubMed]
  • Pisani F, Narbone MC, Fazio A, Crisafulli P, Primerano G, D'Agostino AA, Oteri G, Di Perri R. Effect of viloxazine on serum carbamazepine levels in epileptic patients. Epilepsia. 1984 Aug;25(4):482–485. [PubMed]
  • Mihaly GW, Phillips JA, Louis WJ, Vajda FJ. Measurement of carbamazepine and its epoxide metabolite by high-performance liquid chromatography, and a comparison of assay techniques for the analysis of carbamazepine. Clin Chem. 1977 Dec;23(12):2283–2287. [PubMed]
  • Fazio A, Crisafulli P, Primerano G, D'Agostino AA, Oteri G, Pisani F. A sensitive gas chromatographic assay for the determination of serum viloxazine concentration using a nitrogen-phosphorus-selective detector. Ther Drug Monit. 1984;6(4):484–488. [PubMed]
  • Pacifici GM, Tomson T, Bertilsson L, Rane A. Valpromide/carbamazepine and risk of teratogenicity. Lancet. 1985 Feb 16;1(8425):397–398. [PubMed]
  • Meijer JW, Binnie CD, Debets RM, van Parys JA, de Beer-Pawlikowski NK. Possible hazard of valpromide-carbamazepine combination therapy in epilepsy. Lancet. 1984 Apr 7;1(8380):802–802. [PubMed]

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