Cyclosporin is a potent
immunosuppressant drug commonly used to prevent organ transplant rejection. In recent years, there has been a widening of its
therapeutic use and an increase in the number of patients undergoing
transplantation.
Gingival overgrowth is one of several oral side-effects of
cyclosporin, with a quoted prevalence of between 8% and 100%. There is continued debate over the factors which modify the degree of overgrowth, including individual sensitivity, age, dose of
drug, duration of
drug therapy and the presence of
dental plaque. The exact mechanism of
gingival overgrowth is still being debated, but appears to be caused by a combination of the proliferation of fibroblasts within the gingival tissue, an increase in the deposition of
collagen and extracellular matrix, and a decrease in phagocytosis with a net gain in gingival tissue mass. A number of treatment options are utilized in the treatment of
gingival overgrowth, including
CO2 laser surgery, improved
oral hygiene, the use of
antibiotics such as
metronidazole and
azithromycin, and surgical intervention. In the clinical application of
cyclosporin, there is little correlation between
cyclosporin dose, serum trough levels and total exposure to the
drug, making it difficult to achieve the desired therapeutic response. These problems were previously further complicated by the variability of absorption of the
drug via the gastrointestinal tract. The original
cyclosporin formulation,
Sandimmune, was replaced by a new formulation,
Neoral, which has a more reliable absorption, and gives a closer correlation between trough concentration levels and individual bioavailability. There is a conflict of opinion over whether or not the side-effect profile of
Neoral varies from its precursor
Sandimmune. It has yet to be seen whether the increased bioavailability of
Neoral will result in an increased severity and prevalence of
gingival overgrowth. An alternative
immunosuppressant drug,
tacrolimus, which is a
macrolide antibiotic with a different side-effect profile, has emerged as a substitute for
cyclosporin in
organ transplantation. However, there have been conflicting reports of its side-effects and its capacity to cause
gingival overgrowth.