Suat BİÇER, Gülay ERDAĞ ÇİLER, Canan YILDIRIM KOCAMAN, Tuba GİRAY, Defne ÇÖL, Öznur KÜÇÜK, Zerrin YALVAÇ, Ayça VİTRİNEL

Seizure worsening caused by low serum valproate levels from an interaction between valproate and meropenem

Bu yazıda, meropenem ve valproat etkileşimine sekonder olarak serum valproat düzeyinin hızlı düşmesi sonucu nöbetleri alevlenen epileptik bir çocuk sunulmuştur. Hastanın tedavisine meropenem eklendikten ve iki doz kullanıldıktan sonra nöbet sıklığı ve somnolans durumunda artış ortaya çıkan hastanın serum valproat düzeyinde ani düşme görüldü. Nöbet sıklığındaki artışın valproat serum düzeyinin düşüşüne bağlı olduğu düşünüldü. Hastanın valproat dozu artırılarak meropenem tedavisi kesildikten iki gün sonra nöbetler sona erdi. Beş gün sonra serum valproat düzeyi üç katına, dört hafta sonra ise terapötik düzeylere yükseldi. Serum valproat düzeyinin düşmesine neden olan ilaç etkileşimine neden olmamak için, valproat kullanan epileptik hastalarda meropenem dikkatle uygulanmalı, iki ilacın birlikte kullanımı mutlaka gerekliyse hastanın klinik durumu ve serum valproat düzeyi yakından izlenmelidir.

Valproat ve meropenem arasındaki etkileşime bağlı olarak serum valproat düzeyinin düşmesinin ortaya çıkardığı nöbetler

We present an interaction of meropenem with valproate in an epileptic child, leading to seizure exacerbations owing to the rapid lowering of serum valproate concentration. An increase of seizure frequency and somnolence were observed in the patient after the addition of meropenem to the treatment, and a rapid decline of valproate serum concentrations was observed after two doses of meropenem. This decline was the most likely cause of the increase in seizure frequency. The dosage of valproate was raised and meropenem was stopped. Two days later, the seizures stopped. Five days later, the serum valproate concentrations raised to three fold, and they rose to therapeutic levels four weeks later. To avoid drug interaction that reduces the serum concentration of valproate, meropenem in epileptic patients using valproate for the treatment of epilepsy should be administered cautiously. If concominant administration is essential, close observation of serum concentration of valproate and clinical course of the patient are necessary.

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1. Nacarkucuk E, Saglam H, Okan M. Meropenem decreases serum level of valproic acid. Pediatr Neurol 2004; 31: 232-4. http://dx.doi.org/10.1016/j.pediatrneurol.2004.03.014
2. De Turck BJ, Diltoer MW, Cornelis PJ, et al. Lowering of plasma valproic acid concentrations during concomitant therapy with meropenem and amikacin. J Antimicrob Chemother 1998; 42: 563-4. http://dx.doi.org/10.1093/ jac/42.4.563
3. Calandra G, Lydick E, Carrigan J, Weiss L, Guess H. Factors predisposing to seizures in seriously ill infected patients receiving antibiotics: Experience with imipenem/cilastatin. Am J Med 1988; 84: 911-8.
4. Cunha BA. Meropenem in elderly and renally inpaired patients (corrected and republished in Int J Antimicrob Agents 1999; 11: 167-77). Int J Antimicrob Agents 1998; 10: 107-17. http:// dx.doi.org/10.1016/S0924-8579(98)00031-4
5. Nakamura Y, Nakahira K, Mizutani T. Decreased valproate level caused by VPA-glucuronidase inhibition by carbapenem antibiotics. Drug Metab Lett 2008; 2: 280-5. http://dx.doi. org/10.2174/187231208786734049
6. Nagai K, Shimizu T, Togo A, et al. Decrease in serum levels of valproic acid during treatment with a new carbapenem, panipenem/betamipron. J Antimicrob Chemother 1997; 39: 295-6. http://dx.doi.org/10.1093/jac/39.2.295
7. Spriet I, Meersseman W, De Troy E, Wilmer A, Casteels M, Willems L. Meropenem-valproic acid interaction in patients with cefepime-associated status epilepticus. Am J Health Syst Pharm 2007; 64: 54-8. http://dx.doi.org/10.2146/ajhp050512
8. Yoon H, Kim DH. Unusual drug reaction between valproate sodium and meropenem. Int J Clin Pharm 2013; 35: 316-8. http://dx.doi: 10.1007/s11096-013-9763-2.
9. Mann HI. Drug-associated disease: Cytochrome P450 interactions. Crit Care Clin 2006; 22: 329-45. http://dx.doi. org/10.1016/j.ccc.2006.02.004
10. Yokogawa K, Iwashita S, Kubota A, et al. Effect of meropenem on disposition kinetics of valproate and its metabolites in rabbits. Pharm Res 2001; 18: 1320-6.
11. Ogawa K, Yumoto R, Hamada N, Nagai J, Takano M. Interaction of valproic acid and carbapenem antibiotics with multidrug resistance-associated proteins in rat erythrocyte membranes. Epilepsy Res 2006; 71: 76-87. http://dx.doi. org/10.1016/j.eplepsyres.2006.05.016
12. Taha FA, Hammond DN, Sheth RD. Seizures from valproate- carbapenem interaction. Pediatric Neurology 2013; 49: 279- 81.