Safety and tolerability of quinupristin/dalfopristin: administration guidelines

The safety and tolerability of quinupristin/dalfopristin were assessed in b oth comparative and non-comparative trials (2298 quinupristin/dalfopristin- treated patients). In comparative clinical trials, the most frequent system ic adverse events related to quinupristin/dalfopristin were nausea (4.6%), diarrhoea (2.7%), vomiting (2.7%) and skin rash (2.5%). The comparator grou p showed similar rates, except that nausea was significantly more common (7 .2%; P = 0.01). In non-comparative trials, arthralgia and myalgia were repo rted most frequently but were reversible upon treatment discontinuation. Th e renal, inner ear, cardiovascular and central nervous systems were not imp licated as significant target organs for toxicity. The most frequent local adverse events related to infusion of quinupristin/dalfopristin were inflam mation, pain, oedema, infusion site reaction and thrombophlebitis. Results of laboratory tests while on therapy were comparable for quinupristin/dalfo pristin and comparator groups, except that increases in conjugated bilirubi n of >5 x the upper limit of normal were reported in 5.5% of quinupristin/d alfopristin recipients; increases in total bilirubin of >5 x the upper limi t of normal occurred in 1.5%. Comparator recipients more frequently had inc reases in alanine aminotransferase and alkaline phosphatase. Quinupristin/d alfopristin inhibits the cytochrome P450 3A4-mediated metabolism of drugs i ncluding midazolam, nifedipine, terfenadine and cyclosporin. Therefore, pla sma drug monitoring and/or dosage reduction of these agents is prudent. Con comitant administration of drugs that can prolong the electrocardiographic QTc interval should be avoided. Quinupristin/dalfopristin is visually and c hemically compatible with commonly used drugs of various classes, but it is not compatible with sodium chloride solution and certain other drugs, incl uding some antimicrobials. Therefore, when prescribing quinupristin/dalfopr istin, clinicians should be aware of the potential for peripheral venous in tolerance, arthralgias and myalgias, increases in conjugated bilirubin, int eractions with drugs metabolized by the cytochrome P450 3A4 isoenzyme and c ertain physico-chemical incompatibilities. However, multiple studies have s hown that the safety and tolerability of quinupristin/dalfopristin are gene rally favourable, and that it provides clear benefits to ill patients with severe Gram-positive infections.