Approaches to reducing the incidence of lamotrigine-induced rash

Lamotrigine has been used to treat over a million patients worldwide, including about 4000 adults and over 1000 children in clinical trials. It is a valuable broad spectrum drug that is well tolerated and has few adverse effects apart from skin rash. Most of the rashes are mild but some severe, life-threatening skin reactions have been reported. The available evidence does not indicate that either the mild or the severe skin rashes are any more common with lamotrigine than with carbamazepine, phenytoin or phenobarbital (phenobarbitone). In vitro lymphocyte transformation tests suggest that an immune mechanism is involved. The incidence of rash with lamotrigine can be reduced by using starting doses and dose-escalation rates that are no higher than those recommended, especially in patients who are receiving comedication with valproic acid (sodium valproate), which prolongs the half-life of lamotrigine. Consideration might be given to using even lower dose schedules than those currently recommended to reduce the incidence of rash further. Any patient who develops a rash or who becomes unwell in the first few weeks of treatment should be evaluated promptly by a physician. Lamotrigine should be stopped immediately if the rash or illness could be attributed to the drug. Reintroduction after initial rash has been achieved but is not recommended without close specialist supervision and should not be undertaken if the initial reaction was serious. Details of serious reactions should be reported to the appropriate national drug safety agency to provide information that will allow further improvements in the risk/benefit ratio. Extensive data have shown that lamotrigine is a valuable anticonvulsant drug that has few adverse effects if it is used correctly.