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

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.