AZT Twice-Daily Tablets Approved; Dosing Concerns

On October 25 the FDA approved a 300 mg AZT tablet, intended for twice-daily dosing. (AZT is commonly taken as 200 mg three times a day in the U.S.) The new dose is intended to be more convenient by reducing the three daily doses to two -- hopefully improving patients' compliance with their physicians' instructions.

There are concerns that twice-daily dosing may not work as well as giving the same amount of drug at more frequent intervals, because of the greater variation in blood levels throughout the day. These concerns are (1) that low trough levels could allow viral resistance to develop faster, and (2) that higher peak levels after each dose could increase side effects. In defense of twice-daily dosing, Glaxo-Wellcome notes that 250 mg twice daily is the standard AZT dose in Europe, that most clinical trials using AZT today use twice-daily dosing, and that no differences in safety or efficacy was seen in a trial of 320 volunteers which compared 100 mg every four hours vs. 300 mg every 12 hours for 48 weeks (the trial was not powered to find differences in efficacy, however, and it did not measure viral resistance). Glaxo also notes that the new dose is only an option, since the previous formulation remains available, and that trials to measure the development of viral resistance are now in progress or being planned.