Drug Interactions between chloroquine and cholera vaccine, live

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: Coadministration of oral cholera vaccine with food or an oral beverage may impair its efficacy. The formulations of both the inactivated and live, attenuated oral cholera vaccines (Dukoral and Vaxchora, respectively) are acid-labile, and must be administered with a buffer. According to the manufacturer, eating and drinking may interfere with the protective effect of the buffer. However, clinical data are not available.

MANAGEMENT: It is recommended that patients avoid eating or drinking for 60 minutes before and after administration of either Dukoral or Vaxchora oral cholera vaccines.