Drug Interaction Between Phenytoin and Valproic Acid in a Child With Refractory Epilepsy

2013 ◽  
Vol 27 (2) ◽  
pp. 214-216 ◽  
Author(s):  
Indira Valadê Carvalho ◽  
Renata Cavalcanti Carnevale ◽  
Marília Berlofa Visacri ◽  
Priscila Gava Mazzola ◽  
Rosiane de Fátima Lopes Ambrósio ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Drug Interaction ◽  
Serum Concentration ◽  
Refractory Epilepsy ◽  
Free Drug ◽  
Epilepsy Syndrome ◽  
Concomitant Treatment ◽  
Case Description ◽  
Phenytoin Toxicity

Introduction: There are no published reports on pediatric phenytoin toxicity, resulting from the drug interaction between phenytoin and valproic acid. Case description: A 12-year-old patient with refractory epilepsy syndrome presented with phenytoin toxicity, following a concomitant treatment with phenytoin, valproic acid, and lamotrigine. The phenytoin concentration detected in the capsules used by the patient was in accordance with the prescribed dose and was appropriate for the age and weight of the patient. However, a supratherapeutic phenytoin serum concentration was observed (21.92 µg phenytoin/mL of blood). Consequently, the phenytoin dose was reduced, and the patient was monitored; 24 hours later the patient did not present with any signs/symptoms of toxicity. Discussion: Despite the appropriate phenytoin concentration in the capsules, the patient presented with phenytoin toxicity. This toxicity likely resulted from the drug interaction between phenytoin and valproic acid that leads to phenytoin displacement from plasmatic proteins and inhibits phenytoin metabolism, thereby increasing the concentration of free drug in the serum.

scholarly journals Meropenem-induced Valproic Acid Elimination: A Case Report of Clinically Relevant Drug Interaction

2017 ◽  
Vol 118 (2-3) ◽  
pp. 105-109 ◽  
Author(s):  
Martin Šíma ◽  
Jan Hartinger ◽  
Jan Rulíšek ◽  
Robert Šachl ◽  
Ondřej Slanař
Keyword(s):  
Valproic Acid ◽  
Drug Interaction ◽  
Case Report ◽  
Serum Concentration ◽  
Dose Escalation ◽  
Treated Patient ◽  
Case Reports ◽  
Concomitant Administration ◽  
Serum Levels ◽  
Population Kinetic

We present two case reports of drug interaction between valproic acid and meropenem. In comparison with expected population-kinetic based serum levels, we observed 90.8 and 93.5% decrease in valproic acid serum levels during concomitant administration with meropenem. If carbapenems need to be administered to valproic acid treated patient, other anticonvulsant addition seems to be the appropriate as most probably the valproic acid dose escalation would not be sufficient to achieve therapeutic serum concentration.

scholarly journals Valproate Interaction With Carbapenems: Review and Recommendations

2019 ◽  
Vol 55 (3) ◽  
pp. 181-187
Author(s):  
Osama Al-Quteimat ◽  
Alla Laila
Keyword(s):  
Valproic Acid ◽  
Drug Interaction ◽  
Serum Concentration ◽  
Health Care Providers ◽  
Cochrane Library ◽  
Therapeutic Drug ◽  
Potential Drug Interaction ◽  
Potential Drug ◽  
Care Providers ◽  
Carbapenem Antibiotic

Introduction: Valproic acid is a commonly used antiepileptic drug. Combining valproate derivatives with carbapenem antibiotics is associated with a potential drug interaction that decreases serum concentration of valproate and may expose the patient to uncontrolled seizure risk from valproate subtherapeutic concentration. Raising awareness of this drug interaction among health care providers including emergency department physicians, neurologists, and pharmacists is highly needed. The aim of this article was to review the current literature about the potential drug interaction resulting from combining valproate derivatives with carbapenem antibiotics and to establish therapeutic recommendations regarding their use together. Methods: A review of the literature was conducted using Medline (through PubMed), Ovid, Embase, Cochrane library using the following keywords: valproate, valproic acid, carbapenem, ertapenem, doripenem, meropenem, imipenem, and valproate drug interaction. In addition, a manual search through major journals for articles referenced in PubMed was performed. Related publications from January 1998 till November 2018 were included in the initial search. Relevant publications were reviewed, and data regarding patients, type of carbapenem used, valproic acid dosing and level, interaction severity, and clinical outcome were summarized. Results and Discussion: Few clinical trials and multiple case reports have shown that carbapenem antibiotics including meropenem, ertapenem, imipenem, and doripenem can decrease the serum concentration of valproate derivatives leading to a subtherapeutic serum concentration and seizures in some patients. Valproic acid serum concentration may be significantly decreased with addition of a carbapenem antibiotic but generally return toward normal shortly after discontinuation of the carbapenem antibiotic. Conclusions: Generally, the concurrent use of carbapenem antibiotics with valproate derivatives should be avoided due to the potential of drug-drug interaction that results in subtherapeutic valproate serum concentration. Other antimicrobial agents should be considered as alternatives to carbapenems but if a concurrent carbapenem is necessary, using an additional antiepileptic agent is recommended. Therapeutic drug monitoring of valproate serum concentrations is warranted when a carbapenem-valproic acid combination therapy is unavoidable.

scholarly journals Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy

Epilepsia ◽  
2015 ◽  
Vol 56 (8) ◽  
pp. 1246-1251 ◽  
Author(s):  
Alexandra L. Geffrey ◽  
Sarah F. Pollack ◽  
Patricia L. Bruno ◽  
Elizabeth A. Thiele
Keyword(s):  
Drug Interaction ◽  
Refractory Epilepsy ◽  
Drug Drug Interaction

scholarly journals Clinical studies on serum concentration of free fraction of phenytoin, carbamazepine and valproic acid.

1990 ◽  
Vol 16 (5) ◽  
pp. 277-287 ◽  
Author(s):  
JUN HOSOYA ◽  
HIDEYO NAGAOKA ◽  
SYU ISHIKAWA ◽  
YOSHITO NAKAGAWA ◽  
YOSHIAKI HIGASHITANI ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Serum Concentration ◽  
Clinical Studies ◽  
Free Fraction

scholarly journals P15 Lacosamide monitoring in the serum of children with refractory epilepsy

2019 ◽  
Vol 104 (6) ◽  
pp. e23.1-e23 ◽  
Author(s):  
N Kronenfeld ◽  
E Kohn ◽  
M Lezinger ◽  
N Brandriss ◽  
E Heyman ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Refractory Epilepsy ◽  
Medical Center ◽  
Serum Levels ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Trough Serum ◽  
Median Plasma ◽  
Antiepileptic Medications ◽  
Serum Monitoring

BackgroundLacosamide is indicated for various types of refractory epilepsy and as adjunctive therapy to other antiepileptic medications. Data on monitoring serum levels of lacosamide in pediatric patients is scarce.ObjectiveTo evaluate the correlation between serum levels of lacosamide and the tolerability in children with refractory epilepsy.MethodsThe medical records of 22 children with refractory epilepsy treated with lacosamide at Assaf Harofeh Medical Center were reviewed. Trough serum levels of lacosamide was measured using HPLC and correlated with its efficacy and safety.ResultsMean age of the children was 11 ± 4 (3–18) years. Median lacosamide daily dose was 9.3 (6.6–11) mg/kg and median plasma concentration was 7.1 (5.9–11.9) ug/ml. The therapeutic range of lacosamide serum concentration is 10 to 20 ug/ml. No change in seizures frequency was reported in 21.4% of children with lacosamide concentrations below 10 ug/ml. However, in 40% of the children, reduction of the seizures frequency was reported when serum concentration was above 10 ug/ml. No serious adverse events were reported during therapy. The prospective part of the study was initiated, and the first patients were recruited.ConclusionLarge studies, preferably prospective, on lacosamide serum monitoring including information on correlation with efficacy and safety are warranted.Disclosure(s)Nothing to disclose

VALPROIC ACID AND RISPERIDONE: A DRUG INTERACTION?

2003 ◽  
Vol 42 (1) ◽  
pp. 1-2 ◽  
Author(s):  
Janne Kutschera Sund ◽  
Trond Aamo ◽  
Olav Spigset
Keyword(s):  
Valproic Acid ◽  
Drug Interaction

scholarly journals Soybean greatly reduces valproic acid plasma concentrations: A food–drug interaction study

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Anu Marahatta ◽  
Bidur Bhandary ◽  
Seul-Ki Jeong ◽  
Hyung-Ryong Kim ◽  
Han-Jung Chae
Keyword(s):  
Valproic Acid ◽  
Drug Interaction ◽  
Plasma Concentrations ◽  
Interaction Study ◽  
Drug Interaction Study

Effect of food on the serum concentration profile of entericcoated valproic acid

Neurology ◽  
1988 ◽  
Vol 38 (8) ◽  
pp. 1319-1319 ◽  
Author(s):  
J. H. Fischer ◽  
A. N. Barr ◽  
F. P. Paloucek ◽  
J. V. Dorociak ◽  
A. L. Spunt
Keyword(s):  
Valproic Acid ◽  
Serum Concentration ◽  
Concentration Profile ◽  
Effect Of Food

Significant drug interaction: Phenytoin toxicity due to erlotinib

Lung Cancer ◽  
2007 ◽  
Vol 57 (3) ◽  
pp. 404-406 ◽  
Author(s):  
Tal Grenader ◽  
Maya Gipps ◽  
Linda Shavit ◽  
Alberto Gabizon
Keyword(s):  
Drug Interaction ◽  
Significant Drug Interaction ◽  
Phenytoin Toxicity
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