Drug Interactions between dexamethasone / ketorolac / moxifloxacin and influenza virus vaccine, h1n1, live

MONITOR CLOSELY: Concomitant administration of corticosteroids may potentiate the risk of tendinitis and tendon rupture associated with fluoroquinolone treatment. The mechanism is unknown. Tendinitis and tendon rupture have most frequently involved the Achilles tendon, although cases involving the rotator cuff (the shoulder), the hand, the biceps, and the thumb have also been reported. Some have required surgical repair or resulted in prolonged disability. Tendon rupture can occur during or up to several months after completion of fluoroquinolone therapy.

MANAGEMENT: Caution is recommended if fluoroquinolones are prescribed in combination with corticosteroids, particularly in patients with other concomitant risk factors (e.g., age over 60 years; recipient of kidney, heart, and/or lung transplant). Patients should be advised to stop taking the fluoroquinolone, avoid exercise and use of the affected area, and promptly contact their physician if they experience pain, swelling, or inflammation of a tendon. In general, fluoroquinolones should only be used to treat conditions that are proven or strongly suspected to be caused by bacteria and only if the benefits outweigh the risks.

GENERALLY AVOID: The administration of live, attenuated virus or bacterial vaccines during immunosuppressant or intense antineoplastic therapy may be associated with a risk of disseminated infection due to enhanced replication of vaccine virus or bacteria 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 (e.g., greater than or equal to 2 mg/kg/day or 20 mg/day of prednisone or equivalent for 14 consecutive days or more), or long-term topical or inhaled corticosteroids. These patients may also have increased adverse reactions and decreased or suboptimal immunologic response to vaccines. Data concerning the use of live influenza virus vaccines in immunosuppressed patients are limited. In a study consisting of 57 HIV-infected subjects with a median CD4 cell count of 541 cells/mm3 and 54 HIV-negative adults aged 18 to 58 years, no serious adverse events were reported during the one-month follow-up period after administration of a live influenza virus vaccine (FluMist intranasal spray). Vaccine strain (type B) virus was detected in 1 of 28 HIV-infected subjects on day 5 only and none of the HIV-negative vaccine recipients. No adverse effects on HIV viral load or CD4 counts were identified following vaccine administration. The effectiveness of live influenza virus vaccines in preventing influenza illness in HIV-infected individuals has not been evaluated.

MANAGEMENT: Administration of live influenza virus vaccines to immunocompromised persons should be based on careful consideration of potential benefits and risks. In general, live attenuated vaccines should preferably not be used in patients receiving immunosuppressive therapy or cancer chemotherapy. Vaccination should be deferred until after such therapy is discontinued and immune function has been restored, usually 4 to 12 weeks after stopping immunosuppressive therapy. A longer waiting period may be necessary following treatment with agents that have a prolonged elimination half-life (e.g., leflunomide, teriflunomide). Current local immunization guidelines should be consulted for recommendations. 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). However, the decision to vaccinate with a live influenza virus vaccine should be considered on an individual basis. Use of the inactivated form of the vaccine may be a safer alternative in some patients. Vaccines may generally be administered to patients receiving corticosteroids as replacement therapy (e.g., for Addison's disease).

MONITOR: The combined use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the potential for serious gastrointestinal (GI) toxicity, including inflammation, bleeding, ulceration, and perforation. In a large, case-control study of elderly patients, those who used corticosteroids and NSAIDs concurrently had an estimated relative risk (RR) for peptic ulcer disease and GI hemorrhage of 14.6 compared to those who used neither. Corticosteroid use was associated with a doubling of the risk (estimated RR = 2.0), but the risk was confined to those who also used NSAIDs. It is possible that both categories of agents are ulcerogenic and have additive effects on the GI mucosa during coadministration. Some investigators have also suggested that the primary effect of corticosteroids in this interaction is to delay healing of erosions caused by NSAIDs rather than cause de novo ulcerations.

MANAGEMENT: Caution is advised if corticosteroids and NSAIDs are used together, especially in patients with a prior history of peptic ulcer disease or GI bleeding and in elderly and debilitated patients. During concomitant therapy, patients should be advised to take the medications with food and to immediately report signs and symptoms of GI ulceration and bleeding such as severe abdominal pain, dizziness, lightheadedness, and the appearance of black, tarry stools. The selective use of prophylactic anti-ulcer therapy (e.g., antacids, H2-antagonists) may be considered.

MONITOR: Coadministration with nonsteroidal anti-inflammatory drugs (NSAIDs) may potentiate the risk of central nervous system toxicity sometimes associated with fluoroquinolone use. The interaction has been reported most often with enoxacin. It may occur with other fluoroquinolones as well, but is poorly documented. The exact mechanism of interaction is unknown. Some investigators suggest that the piperazine ring of fluoroquinolones may inhibit the binding of gamma-aminobutyric acid (GABA) to brain receptors and that NSAIDs may synergistically add to this effect. Patients with a history of seizures may be at greater risk.

MANAGEMENT: Clinical monitoring for signs of CNS stimulation such as tremors, involuntary muscle movements, hallucinations, or seizures is recommended if fluoroquinolone antibiotics are prescribed in combination with NSAIDs.