Drug Interactions between mycophenolic acid and Plaquenil

GENERALLY AVOID: Theoretically, grapefruit and grapefruit juice may increase the plasma concentrations of hydroxychloroquine or chloroquine and the risk of toxicities such as QT interval prolongation and ventricular arrhythmias. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. Following coadministration with cimetidine, a weak to moderate CYP450 3A4 inhibitor, a 2-fold increase in chloroquine exposure occurred. Since chloroquine and hydroxychloroquine have similar structures and metabolic elimination pathways, a similar interaction may be observed with hydroxychloroquine. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

ADJUST DOSING INTERVAL: Administration with food or milk may reduce the incidence of hydroxychloroquine-related gastrointestinal adverse effects.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid the consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract during hydroxychloroquine or chloroquine therapy. Hydroxychloroquine should be administered with food or milk to reduce the occurrence of gastrointestinal upset.

ADJUST DOSING INTERVAL: Administration of enteric coated mycophenolic acid with meals may alter its pharmacokinetics relative to administration in the fasting state. When mycophenolic acid 720 mg was administered with a high-fat meal, there was a 33% decrease in the peak plasma concentration (Cmax); a 3.5-hour increase in delay time for the rise of plasma mycophenolic acid; and a 5-hour delay in the time to reach peak plasma concentration (Tmax). However, no effect was observed on the systemic exposure of mycophenolic acid.

MANAGEMENT: To avoid variability in drug absorption between doses, enteric coated formulations of mycophenolic acid should be taken on an empty stomach, one hour before or two hours after food intake. The tablets should be swallowed whole and not crushed, chewed or divided in order to maintain the integrity of the enteric coating.