An overview of the safety of isepamicin in adults.

The safety profile of isepamicin has been assessed from a series of phase II and III clinical trials. A total of 1243 patients were randomised to treatment with isepamicin, mainly administered once daily at a dose of 15 mg/kg or 8 mg/kg depending on the severity of infection. A small proportion of patients were randomised to isepamicin at a dosage of either 7.5 mg/kg twice daily or 4 mg/kg twice daily. In the majority of studies, isepamicin was compared with a standard twice-daily dosing regimen of 7.5 mg/kg amikacin = (n - 552). The clinical studies included patients with a variety of bacterial infections, including lower respiratory tract, urinary tract, intra-abdominal and skin and skin structure infections. The study aminoglycosides were co-administered with other antimicrobial agents in line with normal clinical practice depending on the site, nature and severity of infection. Most patients received isepamicin or amikacin as a 30-minute intravenous infusion and a small proportion of patients with less severe infections received intramuscular injections. The mean duration of treatment was nine days for both the isepamicin and amikacin treatment groups, and was similar for patients with both severe and less severe infections. Overall, the proportion of patients reporting any adverse event was comparable between the isepamicin (13%) and amikacin (11%) groups. No individual adverse event was reported in more than 2% of patients, the most commonly reported events being phlebitis, rash, headache and renal compromise. The frequency of adverse events was not influenced by treatment duration, age or gender. Treatment-related adverse events which were considered severe or life-threatening were reported in 1.8% of patients receiving isepamicin and 2.0% of patients receiving amikacin. Two per cent of patients in each treatment group discontinued the study because of adverse events and 2% of patients in each treatment group died during treating. Four per cent of patients in each treatment group died within 30 days after the end of treatment. Changes in laboratory tests were similar in both treatment groups; few changes were considered by the investigators to be treatment-related. Increases in serum creatinine indicative of possible renal compromise occurred in 4.6% of isepamicin and 5.1% of amikacin patients. The occurrence of ototoxicity as measured by standard frequency pure tone audiometry was low. In summary, isepamicin is a sell-tolerated aminoglycoside with a safety similar to that of amikacin.