Drug Interaction Report

MONITOR: When administered concomitantly, vancomycin and ketorolac may have additive nephrotoxic effects. Ketorolac, like other nonsteroidal anti-inflammatory drugs (NSAIDs), inhibits vasodilatory renal prostaglandin synthesis. Renal dysfunction associated with ketorolac has been reported to be dose-related and reversible following treatment discontinuation. In addition, chronic use of NSAIDs may also be associated with renal toxicities, including renal failure. The mechanism of vancomycin-induced nephrotoxicity is unknown; however, the risk may be increased in patients with preexisting risk factors for nephrotoxicity, high vancomycin blood levels, or prolonged treatment. Data for this interaction are limited to a case report of acute transient renal failure and gastrointestinal bleeding requiring transfusion following uncomplicated surgery and treatment with ketorolac and IV vancomycin in a previously healthy middle-aged man. Data are not available for other NSAIDs.

MANAGEMENT: Caution is recommended in patients receiving ketorolac or other NSAIDs in combination with IV vancomycin, particularly in patients with preexisting risk factors for nephrotoxicity. Renal function and vancomycin therapeutic drug monitoring is recommended according to local policies and protocols. The dose and duration of concomitant NSAID therapy should also be minimized where possible.

MONITOR: Coadministration with celecoxib may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by celecoxib.

MANAGEMENT: Caution is advised if celecoxib must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever celecoxib is added to or withdrawn from therapy.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.