Background:Valproate and meropenem are frequently used in the intensive care unit to treat seizures and serious infections, respectively. Several case reports have described a remarkable interaction between the drugs when administered concurrently. The interaction leads to a significant drop in plasma concentrations of valproate within 24 hours and relapse of seizures in some patients.Objective:To evaluate a consecutive population of hospitalized patients who were simultaneously treated with meropenem and valproate and assess the effect on epileptic activity.Methods:A retrospective study of an 18 month period was performed to assess the extent and clinical impact of this interaction. To assess the relevance of the interaction, the time-relationship between the drop in plasma concentrations and relapse in seizure activity and/or deterioration of electroencephalogram recordings was determined. We investigated other contributing preconvulsive cofactors and concomitant antiepileptic treatment. Drug interactio...

Interaction between Valproate and Meropenem: A Retrospective Study

β-lactam antibiotics are commonly prescribed antibiotic drugs. To describe the clinical characteristics, risk markers and outcomes of β-lactam antibiotic-induced neurological adverse effects, we performed a general literature review to provide updated clinical data about the most used β-lactam antibiotics. For selected drugs in each class available in France (ticarcillin, piperacillin, temocillin, ceftazidime, cefepime, cefpirome, ceftaroline, ceftobiprole, ceftolozane, ertapenem and aztreonam), a systematic literature review was performed up to April 2016 via an electronic search on PubMed. Articles that reported original data, written in French, Spanish, Portuguese or English, with available individual data for patients with neurological symptoms (such as seizure, disturbed vigilance, confusional state, myoclonia, localising signs, and/or hallucinations) after the introduction of a β-lactam antibiotic were included. The neurological adverse effects of piperacillin and ertapenem are often described as seizures and hallucinations (>50 and 25% of cases, respectively). Antibiotic treatment is often adapted to renal function (>70%), and underlying brain abnormalities are seen in one in four to one in three cases. By contrast, the neurological adverse drug reactions of ceftazidime and cefepime often include abnormal movements but few hallucinations and seizures. These reactions are associated with renal insufficiency (>80%) and doses are rarely adapted to renal function. Otherwise, it appears that monobactams do not have serious neurological adverse drug reactions and that valproic acid and carbapenem combinations should be avoided. The onset of disturbed vigilance, myoclonus, and/or seizure in a patient taking β-lactam antibiotics, especially if associated with renal insufficiency or underlying brain abnormalities, should lead physicians to suspect adverse drug reactions and to consider changes in antibacterial therapy.

Neurological Adverse Effects Attributable to β-Lactam Antibiotics: A Literature Review

Qualitative studies on drug–drug interactions (DDIs) between anticonvulsants and antibiotics report pharmacokinetic changes that may increase the clinical risks in terms of adverse drug reactions (ADRs) and efficacy. However, no studies have provided a systematic and quantitative analysis of anticonvulsant–antibiotic pharmacokinetic DDIs. To provide such indications, we systematically and critically reviewed the literature on anticonvulsant–antibiotic DDIs in terms of quantitative pharmacokinetic changes and related ADRs. We also investigated less-known interactions for the possible occurrence of clinically relevant events. We conducted a systematic review of all reports of DDIs between anticonvulsants and antibiotics assessing pharmacokinetic parameters published until 9 June 2017. We were able to meta-analyse the effect of macrolides on carbamazepine area under the concentration-time curve from time zero to infinity [AUC∞] (+ 34.5 µg/mL*h, p = 0.005, n = 38), clearance (− 2.88 mL/min, p < 0.001, n = 46) and trough plasma concentration [Ct] (+ 8.0 µg/mL, p = 0.002, n = 23), and of carbapenems on valproic acid Ct (− 42.9 µg/mL, p < 0.001, n = 262). Pharmacokinetic parameters with other DDIs were insufficiently reported to allow a statistical analysis. Therapeutic drug monitoring in patients receiving long-term antiepileptic therapies may help, in specific conditions, to improve safety while preserving efficacy. Such a procedure would also increase scientific information on how pharmacokinetic variations are associated with ADR occurrence, and possibly epileptological outcomes for those DDIs for which available information is suggestive of a relevant effect but is not yet sufficient to draw conclusions.

Interactions Between Antiepileptic and Antibiotic Drugs: A Systematic Review and Meta-Analysis with Dosing Implications

Increasing the dose of valproatemay not compensate for the reduction, which puts the patientat risk for recurrent seizures. Therefore, close monitoring of valproate levels is necessary when initiating a carbapenemantibiotic in patients whose condition has been stabilized withvalproate therapy. Several case reports of significant reductions in serum valproate concentrations following initiation of carbapenemantibiotics have been published. To the authors’ knowledge,however, there has been no published systematic review of thecarbapenem–valproate interaction. We report a case of ertapenem-induced reduction in valproate concentration anddescribe the extent, clinical relevance, potential mechanisms,and therapeutic options for management of the carbapenem –valproate interaction.

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Ertapenem-induced reduction in valproate levels: case report and review of the literature.

The Side Effects of Drugs Annuals forms a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: the International Encyclopedia of Adverse Drug Reactions and Interactions. This review of the January 2012 to June 2013 publications on penicillins, cephalosporins, other beta-lactam antibiotics and tetracyclines covers carbapenems (imipenem and meropenem), cephalosporins (cefazolin, cefditoren, cefepime, cefixime, cefoperazone, cefoxitin, ceftobiprole, ceftriaxone and cephalexin), the monobactam aztreonam, penicillins (amoxicillin, ampicillin, phenoxymethylpenicillin and piperacillin + tazobactam), tetracyclines and glycylcyclines (doxycycline, minocycline, tetracycline and tigecycline).

Penicillins, Cephalosporins, Other Beta-Lactam Antibiotics and Tetracyclines

https://revistafarmaciahospitalaria.sefh.es/gdcr/index.php/fh/article/download/994/994

S. Higueruelo Demasón

Papers

Descripción de un caso de interacción farmacocinética entre ácido valproico e imipenem