Drug Interactions between dexamethasone / ketorolac / moxifloxacin and Fluzone Preservative-Free Pediatric Quadrivalent

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.

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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.

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MONITOR: The administration of inactivated, killed, or otherwise noninfectious vaccines to immunosuppressed patients is generally safe but may be associated with a diminished or suboptimal immunologic response due to antibody inhibition. Such patients may include those who have recently received or are receiving immunosuppressive agents, antilymphocyte globulins, 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.

MANAGEMENT: In general, the U.S. Department of Public Health Advisory Committee on Immunization Practices (ACIP) recommends that inactivated or killed vaccines be administered to non-HIV immunosuppressed patients according to the same guidelines as for healthy patients. However, higher dosages, more frequent boosters, and/or serological testing may be required in some cases. Local guidelines and prescribing information for individual vaccines should be consulted. For Haemophilus influenzae b vaccine, some experts recommend that it be administered at least 2 weeks before starting or 3 months after discontinuing chemotherapy when used in patients with Hodgkin's disease. For rabies vaccine, some authorities suggest that immunosuppressive agents should generally be avoided during postexposure therapy except when absolutely necessary for the treatment of other conditions. For SARS-CoV-2 (COVID-19) vaccines, vaccination should generally be completed at least 2 weeks before initiation or resumption of immunosuppressive therapies; however, decisions to delay or temporarily withhold immunosuppressive therapy to complete COVID-19 vaccination should consider the individual's risks relative to their underlying condition. Some authorities recommend administering the COVID-19 vaccine approximately 4 weeks prior to the next scheduled therapy for those on B-cell-depleting therapies on a continuing basis. Additional shots, boosters, and even revaccination may be appropriate depending on age, prior COVID-19 vaccine formulation(s) received, current or planned immunosuppressive therapy, and other factors in individuals with moderate to severe immune compromise due to medical conditions or immunosuppressive medications or treatments (e.g., solid organ transplant recipients on immunosuppressive therapy; patients on active treatment for solid tumor and hematologic malignancies). Vaccines may generally be administered to patients receiving corticosteroids as replacement therapy (e.g., for Addison's disease).

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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.

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