Rationale: When patients with epilepsy have some infections, their seizures decrease in some patients and unfavorable symptoms such as somnolence appear in other patients. This may be a result of interaction between antiseizure medications (ASMs) and common pediatric medications (CPMs) for infection. The interaction was studied from metabolic enzymes of ASMs and CPMs.
Methods: Eleven patients showed marked reduction of seizures (Group A) and five patients presented with unfavorable symptoms (Group B) when they took CPMs including antibiotics orally for some infection. The patients in Group A had combination of some of
CBZ, CLB, CZP, perampanel (PER), ZNS, RUF, STP, VPA, LTG and bromide. Five cases took clarithromycin (CAM) (with pranlukast (PK) in one case and with PK and acetaminophen (AA) in one case), four cases had dextromethorphan (DM) (with cyproheptadine (CH), with tipepidine (TP), and with CH and TP in one case each), and two cases had TP (with AA in one case). With these concomitant CPMs, daily to weekly seizures decreased by 80-100% but returned to baseline level after discontinuation of them. All five patients in Group B showed unfavorable symptoms by taking CAM. They had combination of some of CBZ, CLB, PER, ZNS, STP, VPA and LTG. One case showed marked hypotonia and could not stand up by herself. Her CLB and DMCLB levels were increased by 1.3 times than before. One case on ZNS showed somnolence and another case on PER and CZP presented with agitation and violent behavior. All these improved by discontinuation of CAM. Two cases was instituted long-term low dose CAM to prevent aspiration pneumonia, one showed decreased heart rate by 10-20 beats/minutes and sudden drop of SpO2 during sleep two months later. His PER level was 2.1 times than before. Another one showed somnolence and excess bronchial secretion in a few months, and his CLB, DMCLB and PER levels were 1.0, 1.8 and 1.8 times than before. The symptoms ameliorated by reduction of PER or CLB.
Results: CBZ, CLB, CZP, PER, ZNS, RUF, STP and CAM, DM and PK are mainly metabolized by CYP3A4, and VPA, LTG, AA, CH, and TP mainly metabolized by UGTs. CAM inhibits CYP3A4. The level of ASMs metabolized by CYP3A4 increase
with combination of CAM by inhibition of CYP3A4 and with DM and PK by competition of metabolism by CYP3A4, and the level of ASMs metabolized by UGTs increase with combination of TP, AA and CH by competition of metabolism by UGTs.
In Group A, ASMs presumed to be elevated level by combination of CPMs including CBZ, CLB, CZP, PER, ZNS, LTG or VPA, were increased after discontinuation of CPMs and seizures again deceased markedly.
Conclusions: As ASM levels are elevated by concomitant CPMs which metabolizing enzymes inhibit or compete with those of ASM, we must be aware of metabolizing enzymes in both medications. It may lead to detect effective ASMs and to avoid adverse effects, particularly for CPMs which inhibit metabolic enzymes of ASMs. Pediatricians are not aware of interaction of ASMs and CPMs, and we should remind this to patients who take corresponding ASMs and PCMs to avoid adverse events.
Funding: None