Drug Interactions between foscarbidopa / foslevodopa and nisoldipine

GENERALLY AVOID: The consumption of grapefruit juice may be associated with significantly increased plasma concentrations of some calcium channel blockers (CCBs) when they are administered orally. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. The interaction has been reported with the dihydropyridine CCBs (in roughly decreasing order of magnitude) felodipine, nisoldipine, nifedipine, and nimodipine, often with a high degree of interindividual variability. Grapefruit juice caused more than twofold increases in felodipine, nifedipine, and nisoldipine AUCs.

MANAGEMENT: The manufacturers of nifedipine and nisoldipine recommend avoiding grapefruit juice. Patients treated orally with other calcium channel blockers should be advised to avoid consumption of large amounts of grapefruits and grapefruit juice to prevent any undue fluctuations in serum drug levels. Increased effects on blood pressure may persist for up to 4 days after the consumption of grapefruit juice. Monitoring for calcium channel blocker adverse effects (e.g., headache, hypotension, syncope, tachycardia, edema) is recommended.

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.