Management of Side‐Effects of Antiepileptic Drugs

Zaccara, Gaetano; Balestrieri, F.; Ragazzoni, Roberto

doi:10.1002/9781444316667.ch22

Cited by 6 publications

(2 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The clearance of perampanel has also been reported to be increased threefold and twofold by carbamazepine and phenytoin, respectively (Fycompa, 2013), suggesting that its dose requirements may also be impacted by type of co-medication. For some AEDs such as carbamazepine and tiagabine, which exhibit considerably shorter half-lives in the presence of enzyme inducers, enzyme induction also increases fluctuations in serum drug concentrations during a dosing interval, potentially leading to intermittent adverse effects at the time of peak concentration and breakthrough seizures at the time of trough (Riva et al, 1985;Zaccara et al, 2004;Tothfalusi et al, 2008). In these cases, more frequent daily dosing, or the use of extended release formulations, can improve clinical response (Canger et al, 1990).…”

Section: Interactions Resulting In Decreased Serum Concentration Of T...mentioning

confidence: 99%

Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs

Zaccara¹,

Perucca

2014

Epileptic Disorders

Self Cite

241

200

View full text Add to dashboard Cite

Interactions between antiepileptic drugs, or between antiepileptic drugs and other drugs, can be pharmacokinetic or pharmacodynamic in nature. Pharmacokinetic interactions involve changes in absorption, distribution or elimination, whereas pharmacodynamic interactions involve synergism and antagonism at the site of action. Most clinically important interactions of antiepileptic drugs result from induction or inhibition of drug metabolism. Carbamazepine, phenytoin, phenobarbital and primidone are strong inducers of cytochrome P450 and glucuronizing enzymes (as well as P‐glycoprotein) and can reduce the efficacy of co‐administered medications such as oral anticoagulants, calcium antagonists, steroids, antimicrobial and antineoplastic drugs through this mechanism. Oxcarbazepine, eslicarbazepine acetate, felbamate, rufinamide, topiramate (at doses ≥200 mg/day) and perampanel (at doses ≥8 mg/day) have weaker inducing properties, and a lower propensity to cause interactions mediated by enzyme induction. Unlike enzyme induction, enzyme inhibition results in decreased metabolic clearance of the affected drug, the serum concentration of which may increase leading to toxic effects. Examples of important interactions mediated by enzyme inhibition include the increase in the serum concentration of phenobarbital and lamotrigine caused by valproic acid. There are also interactions whereby other drugs induce or inhibit the metabolism of antiepileptic drugs, examples being the increase in serum carbamazepine concentration by erythromycin, and the decrease in serum lamotrigine concentration by oestrogen‐containing contraceptives. Pharmacodynamic interactions between antiepileptic drugs may also be clinically important. These interactions can have potentially beneficial effects, such as the therapeutic synergism of valproic acid combined with lamotrigine, or adverse effects, such as the reciprocal potentiation of neurotoxicity observed in patients treated with a combination of sodium channel blocking antiepileptic drugs.

show abstract

Section: Interactions Resulting In Decreased Serum Concentration Of T...mentioning

confidence: 99%

Interactions between antiepileptic drugs, and between antiepileptic drugs and other drugs

Zaccara¹,

Perucca

2014

Epileptic Disorders

Self Cite

241

200

View full text Add to dashboard Cite

show abstract

“…Habituation to central nervous system (CNS) side effects is common for CNS-active drugs, but the time course is not well understood. Many adverse CNS effects can be minimized by gradual titration, owing to occurrence of pharmacodynamic tolerance [6]. Even some idiosyncratic reactions can also be diminished by use of low starting doses and gradual titration [7].…”

Section: Introductionmentioning

confidence: 99%