nodular acne is 0.5 to 2.0 mg/kg/day given with food in two divided doses. The
dosage of AC used in the clinical trial in this application was 1 mg/kg with food.
According to the Sponsor, it is likely that patients who received AC in the
therapeutic study had approximately 240% higher exposure to isotretinoin than
the subjects who received NF. Since therapeutic equivalence was demonstrated
in the adequately powered total trial population, it would appear that the currently
recommended dosing range for AccutaneÂ® may be too high. This is of
considerable clinical importance because many of the side effects of isotretinoin
are dose-dependent. Even those that would appear to be â€œnon-seriousâ€? (e.g.
mucocutaneous effects, transient moderate hypertriglyceridemia) can lead to
treatment discontinuation for patients who might otherwise greatly benefit by
completing a course. Available dose-ranging studies for AccutaneÂ® do not
definitively establish that even the lower end of the currently labeled dosage is
the minimum effective dose.