Drug Interaction Report

GENERALLY AVOID: The safety and efficacy of live, attenuated cholera vaccine have not been established in patients receiving immunosuppressive therapies, including alkylating agents, antimetabolites, radiation, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents, and long-term topical or inhaled corticosteroids. It is not known whether immunosuppressed patients may have an increased risk of adverse reactions or a decreased or suboptimal immunologic response to the vaccine.

MANAGEMENT: The safety and efficacy of live, attenuated cholera vaccine have not been established in patients receiving immunosuppressive therapies. Some authorities consider coadministration of live, attenuated oral cholera vaccine with immunosuppressant therapies contraindicated. Administration of live attenuated vaccines in severely immunocompromised persons is generally considered a contraindication. The risks of adverse reactions or a decreased or suboptimal immunologic response should be weighed against the benefits of vaccination. Current local immunization guidelines and individual product labeling for the prescribed immunosuppressive therapy should be consulted for further information.

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.

GENERALLY AVOID: Coadministration of protein-bound sirolimus intravenous suspension with grapefruit juice may increase the systemic exposure to sirolimus. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of sirolimus by certain compounds present in grapefruit. However, grapefruit juice primarily inhibits CYP450 3A4-mediated first-pass metabolism in the gut wall and may have limited effects on medications that are not administered orally. No formal studies evaluating the drug interaction potential of protein-bound sirolimus have been conducted. 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.

MANAGEMENT: The manufacturer recommends avoiding grapefruit and grapefruit juice during treatment with protein-bound sirolimus.