[Clinical survey of tizanidine-induced adverse effects--impact of concomitant drugs providing cytochrome P450 1A2 modification--].
The drug-drug interactions of tizanidine and cytochrome (CYP) P450 1A2 inhibitors, which potentially alter the hepatic metabolism of tizanidine, were investigated by retrospective survey of medical records with regard to prescription. One thousand five hundred sixty-three patients treated with tizanidine at University of Tsukuba Hospital were investigated. Of those, 713 patients (45.6%) were treated with coadministration of tizanidine and CYP1A2 inhibitors (37 drugs). The patients who received a combination of tizanidine and CYP1A2 inhibitors were characterized as elderly, having multiple diseases, and taking a large number of comedications (over 10 drugs) for a long period as compared with the patients who did not receive CYP1A2 inhibitors. Tizanidine-induced adverse effects were examined in 100 patients treated with coadministration of tizanidine and 8 CYP1A2 inhibitors. Adverse effects (e.g., drowsiness: 10 patients; low blood pressure: 9 patients; low heart rate: 9 patients) were observed in 23 patients (23%) 8±10 days after CYP1A2 inhibitors were coadministered. The patients with tizanidine-induced adverse effects were of older age (64.3±9.8 vs. 57.5±18.1 years, p<0.05) and received a higher daily dose of tizanidine (3.00±0.74 vs. 2.56±0.86 mg/day, p<0.05) than the patients without adverse effects. The present results suggest that coadministration of tizanidine and CYP1A2 inhibitors enhances tizanidine-induced adverse effects, especially in elderly patients treated with a higher dose of tizanidine.
Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Kenji
K
Momo
Masato
M
Homma
Sayaka
S
Matsumoto
Tadanori
T
Sasaki
Yukinao
Y
Kohda
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects; D002220:Carbamazepine / Q000008:administration & dosage / Q000009:adverse effects; D003000:Clonidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D013997:Time Factors
D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004791:Enzyme Inhibitors; D004008:Diclofenac; D002220:Carbamazepine; C023754:tizanidine; D009543:Nifedipine; D003000:Clonidine