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valproic acid oral

Valproic Acid/Carbapenem Antibiotics

This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

Medical warning:

Serious. These medicines may interact and cause very harmful effects. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

Your antibiotic may decrease how much valproic acid your body absorbs.

What might happen:

The amount of valproic acid in your blood may decrease. If you are taking valproic acid for epilepsy, your seizures may not be controlled.

What you should do about this interaction:

Let your healthcare professionals (e.g. doctor or pharmacist) know that you are taking these medicines together. Your doctor may want to check the amount of valproic acid in your blood and may need to adjust the dose of your medicine. If you are taking valproic acid for epilepsy, your doctor may want you to take another medicine while you are taking meropenem. If you experience a seizure, contact a healthcare professional right away.Your healthcare professionals may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

References:

1.Torii M, Takiguchi Y, Izumi M, Fukushima T, Yokota M. Carbapenem antibiotics inhibit valproic acid transport in Caco-2 cell monolayers. Int J Pharm 2002 Feb 21;233(1-2):253-6.
2.Nakajima Y, Mizobuchi M, Nakamura M, Takagi H, Inagaki H, Kominami G, Koike M, Yamaguchi T. Mechanism of the drug interaction between valproic acid and carbapenem antibiotics in monkeys and rats. Drug Metab Dispos 2004 Dec;32(12):1383-91.
3.Torii M, Takiguchi Y, Saito F, Izumi M, Yokota M. Inhibition by carbapenem antibiotic imipenem of intestinal absorption of valproic acid in rats. J Pharm Pharmacol 2001 Jun;53(6):823-9.
4.Santucci M, Parmeggiani A, Riva R. Seizure worsening caused by decreased serum valproate during meropenem therapy. J Child Neurol 2005 May; 20(5):456-7.
5.Omoda K, Murakami T, Yumoto R, Nagai J, Maeda Y, Kiribayashi Y, Takano M. Increased erythrocyte distribution of valproic acid in pharmacokinetic interaction with carbapenem antibiotics in rat and human. J Pharm Sci 2005 Aug;94(8):1685-93.
6.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 Sep;71(1):76-87.
7.Suzuki E, Yamamura N, Ogura Y, Nakai D, Kubota K, Kobayashi N, Miura S, Okazaki O. Identification of valproic Acid glucuronide hydrolase as a key enzyme for the interaction of valproic Acid with carbapenem antibiotics. Drug Metab Dispos 2010 Sep;38(9):1538-44.
8.Yokogawa K, Iwashita S, Kubota A, Sasaki Y, Ishizaki J, Kawahara M, Matsushita R, Kimura K, Ichimura F, Miyamoto K. Effect of meropenem on disposition kinetics of valproate and its metabolites in rabbits. Pharm Res 2001 Sep;18(9):1320-6.
9.Masuo Y, Ito K, Yamamoto T, Hisaka A, Honma M, Suzuki H. Characterization of inhibitory effect of carbapenem antibiotics on the deconjugation of valproic acid glucuronide. Drug Metab Dispos 2010 Oct;38(10):1828-35.
10.Spriet I, Goyens J, Meersseman W, Wilmer A, Willems L, Van Paesschen W. Interaction between valproate and meropenem: a retrospective study. Ann Pharmacother 2007 Jul;41(7):1130-6.
11.Coves-Orts FJ, Borras-Blasco J, Navarro-Ruiz A, Murcia-Lopez A, Palacios-Ortega F. Acute seizures due to a probable interaction between valproic acid and meropenem. Ann Pharmacother 2005 Mar;39(3):533-7.
12.De Turck BJ, Diltoer MW, Cornelis PJ, Maes V, Spapen HD, Camu F, Huyghens LP. Lowering of plasma valproic acid concentrations during concomitant therapy with meropenem and amikacin. J Antimicrob Chemother 1998 Oct; 42(4):563-4.
13.Mink S, Muroi C, Seule M, Bjeljac M, Keller E. Levetiracetam compared to valproic acid: plasma concentration levels, adverse effects and interactions in aneurysmal subarachnoid hemorrhage. Clin Neurol Neurosurg 2011 Oct;113(8):644-8.
14.Doribax (doripenem) US prescribing information. Shionogi, Inc. January, 2014.
15.Fudio S, Carcas A, Pinana E, Ortega R. Epileptic seizures caused by low valproic acid levels from an interaction with meropenem. J Clin Pharm Ther 2006 Aug;31(4):393-6.
16.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 Jan 1;64(1):54-8.
17.Clause D, Decleire PY, Vanbinst R, Soyer A, Hantson P. Pharmacokinetic interaction between valproic acid and meropenem. Intensive Care Med 2005 Sep;31(9):1293-4.
18.Nacarkucuk E, Saglam H, Okan M. Meropenem decreases serum level of valproic acid. Pediatr Neurol 2004 Sep;31(3):232-4.
19.Sala Pinol F, Padulles Zamora N, Hidalgo Albert E, Clemente Bautista S, Cabanas Poy MJ, Oliveras Arenas M, Balcells Ramirez J. Pharmacokinetic interaction between valproic acid and meropenem. An Pediatr (Barc) 2006 Jan;64(1):93-5.
20.Gu J, Huang Y. Effect of concomitant administration of meropenem and valproic acid in an elderly chinese patient. Am J Geriatr Pharmacother 2009 Feb;7(1):26-33.
21.Muzyk AJ, Candeloro CL, Christopher EJ. Drug interaction between carbapenems and extended-release divalproex sodium in a patient with schizoaffective disorder. Gen Hosp Psychiatry 2010 Sep-Oct; 32(5):560.e1-3.
22.Lunde JL, Nelson RE, Storandt HF. Acute seizures in a patient receiving divalproex sodium after starting ertapenem therapy. Pharmacotherapy 2007 Aug;27(8):1202-5.
23.Invanz (ertapenem) US prescribing information. Merck & Co., Inc. July, 2013.
24.Cabanes Mariscal MA, Sanchez Lopez P, Alvarez Herranz P, Chamorro Merino G. Pharmacokinetic interaction between valproic acid and ertapenem. Farm Hosp 2006 Sep-Oct;30(5):313-5.
25.Liao FF, Huang YB, Chen CY. Decrease in serum valproic acid levels during treatment with ertapenem. Am J Health Syst Pharm 2010 Aug;67(15):1260-4.
26.Perea Falomir M, Roura Poch P, Higueruelo Demason S, Garcia Gil VJ. Pharmacokinetic interaction between valproic acid and imipenem. Farm Hosp 2006 Sep-Oct;30(5):316-7.
27.Depakote (divalproex sodium) US prescribing information. AbbVie Inc. June, 2013.

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