Drug Interactions between dexamethasone / ketorolac / moxifloxacin and verteporfin

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.

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.

MONITOR: Drugs that decrease clotting, vasoconstriction, or platelet aggregation may interfere with the therapeutic effect of verteporfin. These agents may antagonize the physiologic responses to local damage of neovascular endothelium induced by activated verteporfin, which include the release of procoagulant and vasoactive factors that result in vessel occlusion. However, the clinical significance is unknown.

MANAGEMENT: If possible, agents such as anticoagulants, thrombolytics, platelet inhibitors, nonsteroidal anti-inflammatory drugs, ginkgo, dong quai, and vasodilators should be discontinued prior to verteporfin therapy. Otherwise, the potential for diminished efficacy of verteporfin should be considered.

MONITOR: Concomitant use of verteporfin with other known photosensitizing agents may increase the risk of photosensitivity reactions. Examples of medicinal products with known phototoxic or photoallergic potential include fluoroquinolones, phenothiazines, retinoids, sulfonamides, sulfonylureas, tetracyclines, thiazide diuretics, griseofulvin, and hypericin extracts (e.g., St John's Wort).

MANAGEMENT: Caution is advised and pharmacologic response to photodynamic therapy should be carefully monitored if concomitant use of other photosensitizing agents cannot be avoided. Patients will become photosensitive, so they should avoid exposure of unprotected skin, eyes, or other body organs to direct sunlight, bright indoor lights (e.g., tanning salons, bright halogen lights, high power lighting in a surgery operating room), and even prolonged exposure from light-emitting medical devices (e.g., pulse oximeter) for 5 days following the infusion of verteporfin. Patients should be counseled to protect their skin and eyes by wearing protective clothing and dark sunglasses if they must go outdoors in daylight during this time, as UV sunscreens are not effective in protecting against photosensitivity reactions. If emergency surgery is necessary within 48 hours of the verteporfin infusion, as much of the patient's internal tissue as possible should be protected from intense light. Patients should be encouraged to expose their skin to ambient indoor light as it is safe and will help eliminate verteporfin through the skin by a process called "photobleaching."