Pharmacokinetic considerations about antiseizure medications in the elderly

ABSTRACT

Introduction

Epilepsy represents the third most common neurological disorder in the elderly. Antiseizure medications (ASMs) are often used not only to treat epilepsy but also other disorders in this age group. Many physio-pathological changes occur in body composition and organ or system functions with aging. Furthermore, drug–drug interactions (DDIs) represent a major risk considering the prevalence of polytherapy in the elderly.

Areas covered

Relevant studies on the pharmacokinetics of ASMs in the elderly were identified through a literature search. We have reviewed all available data on known alterations in pharmacokinetic parameters of ASMs in elderly also considering pathophysiological alterations such as renal function impairment. Finally, we have highlighted the potential risk of DDIs with some drug classes.

Expert opinion

Large interindividual variability also due to co-morbidities and related co-therapies makes elderly patients a not homogeneous group. Overall, a reduction in loading and maintenance doses of almost all ASMs should be considered to avoid adverse events (AEs) as well as a slow titration, following the rule ‘start low and go slow’. Therapeutic drug monitoring should be performed to apply the ‘individual therapeutic concentration’ and implemented to overcome the age-related differences between dose and plasma concentrations, to monitor DDIs and guide dosage adjustments.

KEYWORDS:

• Metabolism
• renal function
• plasma proteins
• antiseizure medications
• antiepileptic drugs
• drug-drug interactions
• distribution

Article highlights

• Antiseizure medications (ASMs) are often used in the elderly, not only to treat epilepsy but also other diseases.

• Age-related physiological and pathological changes occur in body composition and organ or system functions with a substantial inter- and intra-individual variability, affecting all pharmacokinetic (PK) processes.

• Clearance of almost all ASMs (with the exception of brivaracetam, eslicarbazepine, perampanel, tiagabine and zonisamide) is reduced by about 20–50% in elderly patients; other PK modifications include a reduction in plasma protein binding and a subsequent increase in unbound fraction.

• A reduction in loading and maintenance doses as well as a slow titration of almost all ASMs should be considered in order to avoid adverse events; therapeutic drug monitoring should be implemented.

• ASMs can act as inducers or inhibitors of drug-metabolizing enzymes, leading to a high potential risk of drug–drug interactions (DDIs) with other medications used to treat common comorbidities (e.g. antihypertensive drugs, anticoagulants, statins, antibiotics, antidepressants and anti-inflammatory drugs).

• Second and third-generation ASMs seem to be well tolerated with low potential of DDIs although more specific studies are needed and safety concerns should be considered.

Declaration of interest

C. Di Bonaventura has received speaker fees from Eisai, UCB Pharma, FB Health and Sandoz. E. Russo has received speaker fees or fundings or has participated in advisory boards for Eisai, Pfizer, GW Pharmaceuticals, UCB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Articles of special interest have been highlighted as either of interest (*) or of considerable interest (**) to readers.

Additional information

Funding

This paper was not funded.