Advances with extended and controlled release formulations of antiepileptics in the elderly

ABSTRACT

Introduction: As a matter of course, elderly people are more sensitive to both the pharmacological and toxicological effects of pharmacotherapy. A senior’s treatment, therefore, requires more attention compared to younger adults. Extended release (ER) formulations of anti-epileptic drugs (AEDs) have been developed to improve safety, efficacy and long-term adherence. In senior patients, ER AEDs are used to treat epilepsy, psychiatric conditions, and neuropathic pain. However, very limited clinical evidence is available on the use of these ER AEDs in these populations.

Areas covered: The authors of this paper have identified clinical studies of ER AED formulations used in elderly populations through literature searches looking, both, at their use in epileptic and non-epileptic indications. Additionally, immediate release (IR) and ER formulations of AEDs were compared whenever possible.

Expert opinion: The broad use of ER AED formulations in elderly patients with swallowing problems is limited by the fact that ER AED tablets (or capsules) must not be cut, crushed or chewed. The only exception is the ER formulation of valproate or topiramate which can be mixed with soft food. Although, the ER formulations of AEDs seem better tolerated than the IR equivalents, a possibility of numerous interactions with drugs prescribed for other reasons must be carefully considered.

KEYWORDS:

• Extended release formulation
• antiepileptic drugs
• epilepsy
• the elderly

Article highlights

• Extended release (ER) formulations of antiepileptic drugs assume delayed and prolonged drug delivery allowing to reduce the number of daily doses.

• For conventional antiepileptics, carbamazepine, phenytoin, and valproate in ER formulations are available. As regards newer antiepileptic drugs, these are: gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, and topiramate.

• ER formulations have shown effectiveness and they are generally better tolerated compared to classical formulations in elderly patients. However, ER drugs may differ in their bioavailability in comparison to immediate release formulations, so their dosages have to be carefully tailored.

• Due to a great number of drugs taken for other than epilepsy reasons by elderly patients, a possibility of various pharmacokinetic or pharmacodynamics interactions with antiepileptic drugs must be considered.

• Because senior patients may be exposed to a higher risk of osteoporosis-associated fractures, antiepileptic drugs exerting negative effects on mineral bone density need to be avoided or their use at least limited.

• Crushing or cutting ER formulations may disturb their desired properties. The only exceptions are valproate and topiramate and this makes these drugs easy for taking in elderly patients with swallowing difficulties.

This box summarizes key points contained in the article.

Declaration of interest

SJ Czuczwar has received financial support from Bayer Healthcare, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and Sanofi for lecturing. He is also the recipient of an unrestricted grant from GlaxoSmithKline. 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This article is supported by the Medical University of Lublin, Poland (grant #DS 475).