Drug Interaction Report

CONTRAINDICATED: The administration of live smallpox virus vaccine during immunosuppressant or intense antineoplastic therapy may be associated with a risk of disseminated infection due to enhanced replication of vaccine virus in the presence of diminished immune competence. Patients may be immunosuppressed if they have recently received or are receiving alkylating agents, antimetabolites, radiation, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents, or long-term topical or inhaled corticosteroids. These patients may also have increased adverse reactions and decreased or suboptimal immunologic response to vaccines. Cases of generalized vaccinia and progressive vaccinia have been reported in HIV patients who received the smallpox vaccine.

MANAGEMENT: Routine, nonemergency smallpox vaccination is contraindicated in patients receiving immunosuppressive therapy or cancer chemotherapy. Vaccination should be deferred until after such therapy is discontinued for at least 3 months in most cases. A longer waiting period may be necessary following treatment with agents that have a prolonged elimination half-life (e.g., leflunomide, teriflunomide). In patients who have recently been vaccinated, such therapy should not be initiated for at least 2 weeks (may be longer in some cases; refer to individual product labeling). Household contacts of immunosuppressed patients should also not be vaccinated. However, there are no absolute contraindications to vaccination if a high-risk exposure has occurred. In an outbreak emergency, smallpox vaccine is recommended for all persons, regardless of medical conditions. The risk for experiencing serious complications from the vaccine should be weighed against the risk of acquiring a potentially fatal smallpox infection.

GENERALLY AVOID: Grapefruit and/or grapefruit juice may reduce the efficacy of ifosfamide, whose anticancer effect is dependent on its activation to the 4-hydroxyifosfamide metabolite via CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4 metabolism by certain compounds present in grapefruit. There are no data available about the effects of grapefruit on ifosfamide. However, in a small study, 8 patients with incurable malignancies received ifosfamide 3 g/m2 by infusion with the potent CYP450 3A4 inhibitor ketoconazole 200 mg orally twice daily for 4 days starting 1 day before the ifosfamide infusion. Ketoconazole decreased the clearance of ifosfamide by 11%, decreased systemic exposure (AUC) of the active metabolite 4-hydroxyifosfamide by 30%, and increased the AUC of the inactive but potentially neurotoxic metabolite 2-dechloroethylifosfamide by 23%, as compared to control. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

GENERALLY AVOID: Alcohol may potentiate the neurotoxic effects of ifosfamide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills. In addition, ifosfamide therapy may cause gastrointestinal disorders and alcohol consumption may increase nausea and vomiting.

MANAGEMENT: Given the potential for reduced efficacy of ifosfamide and increased risk of neurotoxicity and nephrotoxicity it may be advisable for patients to avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with ifosfamide. In addition, patients receiving ifosfamide should be warned of the increased risk of neurotoxicity, nausea and vomiting when used in combination with alcohol. Patients should avoid or limit the consumption of alcohol during treatment with ifosfamide.