It is known that drug disposition is altered by concurrent administration of different drugs. Drug-drug interaction may also enhance a side effect that is linked to either drug. The purpose of this report is to demonstrate the usefulness of therapeutic drug monitoring (TDM) in the early detection of side effects induced by drug-drug interaction and its treatment.
The combined use of rifampicin and mexiletine may require an increase in the dose of mexdletin by about 50% due to increased clearance resulting from enzyme induction. In addition, three days after discontinuation of the rifampicin therapy, the serum mexiletine level increased from 0.83 mcg/ml to 2.44 mcg/ml. The patient has developed a tremor. After discontinuation of mexiletine medica-tion, the symptom disappeared in two days.
On the other hand, the patient who took theophylline and mexiletine together developed nausea, vomiting and tachycardia. Four days after initiation of the combination therapy, the serum theophyl-line level was in the toxic range of 27.3 mcg/ml. The patient's theophylline dose was decreased 25%, and side effects completely resolved. The serum theophylline concentration became normal (18.8 mcg/ml) seven days later.
Whatever the mechanism, these drug interactions may be sufficient to necessitate the adjustment of drug dosage, preferabily in accordance with serum drug concentration levels. These results suggest that TDM is useful for the suppression of incidence of side effects by drug interactions.