Drug Interactions between esketamine and foscarbidopa / foslevodopa

GENERALLY AVOID: Concomitant use of esketamine with central nervous system (CNS) depressants such as alcohol may increase sedation and impairment of attention, judgment, thinking, reaction speed, and psychomotor skills.

ADJUST DOSING INTERVAL: Nausea and vomiting may occur following intranasal administration of esketamine. In clinical studies, nausea and vomiting were reported in approximately 25% and 10% of esketamine-treated patients, respectively.

MANAGEMENT: Patients receiving esketamine should be advised to avoid or limit the consumption of alcohol. In addition, to help prevent nausea and vomiting, patients should be advised not to eat for at least 2 hours before intranasal administration of esketamine and not to drink liquids for at least 30 minutes prior to administration.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of levodopa. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MONITOR: Limited clinical data suggest that high protein content in the diet may reduce or cause fluctuations in the clinical response to oral and enteral formulations of levodopa in patients with Parkinson's disease. Proposed mechanisms include delayed gastric emptying, decreased levodopa absorption when taken with a protein rich diet, and competition with certain amino acids for transport across the gut wall and/or the blood brain barrier. Data have been conflicting. Clinical studies have variously reported no effect, reduced levodopa absorption with low-protein meals, reduced effects of oral and enteral formulations of levodopa with high daily protein intake, and no differences compared to fasting with high-protein meals. Neuroleptic malignant-like symptoms were reported in a patient with Parkinson's disease who was receiving pramipexole, entacapone, and immediate-release levodopa/carbidopa, after the protein content of his enteral feedings via nasogastric tube was increased from 0.88 g/kg/day to 1.8 g/kg/day; symptoms improved after the protein was reduced to 1 g/kg/day and bromocriptine was administered. Another patient receiving immediate-release carbidopa/levodopa, pramipexole, and entacapone experienced severe rigidity after initiation of continuous enteral nutrition via oral gastric tube containing 1.4 g/kg/day of protein; his Parkinsonian symptoms improved after the protein content was reduced to 0.9 g/kg/day, the feeding was changed to bolus feedings, and the levodopa was administered between boluses.

MANAGEMENT: In general, alcohol consumption should be avoided or limited during treatment with CNS-depressant agents. Until more data are available, it is advisable to avoid large fluctuations in daily protein intake and to monitor patients for altered effects of oral and enteral levodopa formulations if the protein content of the diet is increased.