Practical pearls to improve the efficacy and tolerability of levodopa in Parkinson’s disease

ABSTRACT

Introduction

Levodopa is the most effective medication for the treatment of motor symptoms of Parkinson’s disease (PD). Several factors may affect the efficacy and tolerability of levodopa. These include the timing, dosage and administration of levodopa, concomitant drugs, food, PD-associated non-motor symptoms, and various neurologic and non-neurologic comorbidities. If not appropriately addressed, these issues may limit levodopa efficacy, tolerability, and compliance.

Areas covered

This article reviews the basics of the metabolism of orally administered levodopa, its side effects, and the factors that may affect its tolerability and efficacy. We provide several practical pearls to improve the tolerability and efficacy of levodopa.

Expert opinion

Protein-rich food delays and reduces levodopa absorption. Hence, levodopa should preferably be administered in a relatively empty stomach. Carbidopa dosing is crucial as it not only enhances the entry of levodopa into the central nervous system but also reduces levodopa’s peripheral adverse effects. Patients experiencing the early side effects such as nausea/vomiting should be prescribed with anti-nausea medications that do not block dopamine receptors. Non-oral routes of administration can be used to obviate persistent gastrointestinal side effects. Implementation of these and other tips may help improve the tolerability and efficacy of levodopa.

KEYWORDS:

• Benserazide
• carbidopa
• levodopa
• orthostasis
• parkinson’s disease

Article highlight box

• As levodopa is the most effective medication for treating PD, prescribers should be familiar with the tips and tricks to improve its efficacy and tolerability.

• Interaction with food, dose of carbidopa, suboptimal management of adverse effects, and certain non-motor symptoms impact the efficacy and tolerability of levodopa.

• Gut dysmotility and small intestinal bacterial overgrowth may blunt the levodopa absorption.

• Treatment of patients who cannot take medications orally warrants consideration of alternate routes of medication administration.

• This article comprehensively discusses the aforementioned issues and provide practical pearls to manage each of those.

Declaration of interest

L. Bahroo has served as a consultant for AbbVie Inc, Acadia, Acorda, Amneal, Kyowa Kirin, Neurocrine, Supernus, Sunovion, Revenace Therapeutics and Teva Pharmaceutical Industries Ltd. L. Bahroo is in the speakers bureau of AbbVie Inc, Acadia, acorda, Amneal, Kyowa Kirin, Neurocrine, and Supernus.

J. Jankovic has received research or training grants from AbbVie Inc; CHDI Foundation; Dystonia Coalition; Emalex Biosciences, Inc; Medtronic Neuromodulation; Michael J Fox Foundation for Parkinson Research; Parkinson’s Foundation; Revance Therapeutics, Inc; Teva Pharmaceutical Industries Ltd. J. Jankovic has served as a consultant for AbbVie Inc; Aeon BioPharma; Neurocrine; Revance Therapeutics; Teva Pharmaceutical Industries Ltd.

J. Jankovic has received royalties from Cambridge; Elsevier; Medlink: Neurology; Lippincott Williams and Wilkins; UpToDate; Wiley-Blackwell.

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 paper was not funded.