Drug Interaction Report

GENERALLY AVOID: Coadministration of topical tacrolimus with other immunosuppressive agents may potentiate the immunosuppressive effects of topical tacrolimus. However, data concerning its safety and efficacy in combination with immunosuppressants are not available. According to the prescribing information, rare cases of skin malignancy and lymphoma have been reported in patients who have received treatment with topical calcineurin inhibitors, including topical tacrolimus. On the other hand, systemic exposure from topical tacrolimus is reported to be less than 1 ng/mL. In addition, the lowest tacrolimus blood concentration from topical application at which systemic effects can be observed is unknown.

MANAGEMENT: According to the manufacturer, use of topical tacrolimus in immunocompromised patients is not recommended. Therefore, until further information is available, it may be advisable to avoid its concomitant use with other immunosuppressants. Screening for the development of malignancy during and after treatment may also be considered.

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.