Drug Interactions between dexamethasone / ketorolac / moxifloxacin and ganciclovir

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 use of ganciclovir or its prodrug, valganciclovir, with other drugs associated with myelosuppression and/or nephrotoxicity may increase the risk and severity of these adverse reactions due to additive effects on the kidney and bone marrow. Valganciclovir is rapidly and extensively converted to ganciclovir, which has had the following adverse reactions observed with its treatment when used alone: severe leucopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow depression, aplastic anemia, increased serum creatinine levels, and acute renal failure. Additionally, ganciclovir is primarily renally excreted; therefore, patients with impaired renal function will have increased concentrations of ganciclovir and may be at an even greater risk of experiencing adverse reactions from treatment. Theoretically when two or more medications with similar side effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased.

MANAGEMENT: Ganciclovir or its prodrug, valganciclovir, should generally not be combined with other drugs associated with myelosuppression and/or nephrotoxicity unless the benefits are anticipated to outweigh the potential risks. Extreme caution is advised if they are used in patients who have recently received or are receiving treatment with myelotoxic and/or nephrotoxic drugs, and vice versa. If coadministration is required, reduced dosages of one or more of the drugs may be required, and the patient should be monitored for the development of hematologic and/or renal adverse effects both during and after discontinuation of therapy.

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.