Rational prescription of drugs within similar therapeutic or structural class for gastrointestinal disease treatment: Drug metabolism and its related interactions

Table 1 Metabolic drug interactions of fluoroquinolones with clinical relevance

Polytherapy regimen	Clinical consequence	Ref
Ciprofloxacin + tizanidine	Oral ciprofloxacin (500 mg twice daily for 3 d) increased AUC (0-infinity) of tizanidine by 10-fold and Cmax by 7-fold and dangerously potentiates its hypotensive and sedative effects, mainly by inhibiting CYP1A2. Care should be exercised when tizanidine is used concomitantly with ciprofloxacin.	70
Ciprofloxacin + clozapine	Ciprofloxacin (250 mg twice daily for 7 d) can moderately increase serum concentrations of clozapine and N-desmethylclozapine in patients with schizophrenia. A probable mechanism of interaction is an inhibition of CYP1A2 by ciprofloxacin.	71
Ciprofloxacin + theophylline	The interaction between oral ciprofloxacin (500 mg twice daily for 60 h) and theophylline can be clinically significant. Inter-individual variability in the magnitude of interaction can be attributed to inter-individual differences in the level of CYP1A2 expression.	72
Ciprofloxacin + olanzapine	Ciprofloxacin treatment (250 mg twice daily for 3 d) doubled olanzapine concentrations in one patient through the inhibition of CYP1A2.	73
Ciprofloxacin + sildenafil	Ciprofloxacin significantly increased sildenafil bioavailability (above 2-fold) in healthy volunteers, mainly by CYP3A4 inhibition. Dose adjustment of sildenafil is thus necessary.	65
Ciprofloxacin + methadone	Ciprofloxacin inhibited metabolism of methadone via CYP1A2 and CYP3A4, and caused profound sedation, confusion, and respiratory depression	66
Ciprofloxacin + cyclosporine	Ciprofloxacin and cyclosporine may be used together safely at the recommended dosage. However, case reports have suggested a possible pharmacokinetic interaction, e.g., ciprofloxacin substantially increased cyclosporine blood levels in a patient with pure red blood cell aplasia. However, levofloxacin therapy (500 mg/d IV) did not interfere with cyclosporine blood levels and thus it could be a therapeutic alternative.	67, 68
Enoxacin + fluvoxamine	Enoxacin (200 mg/d for 11 d) significantly increased the plasma concentrations at 2, 3 h and the Cmax of fluvoxamine in healthy volunteers. Sleepiness produced by fluvoxamine increased when coadministered with enoxacin.	74
Enoxacin + theophylline	A multidose regimen of enoxacin significantly slowed the clearance of theophylline and elevated theophylline concentrations in serum. The careful monitoring of serum theophylline level and modification of theophylline dosage in patients receiving enoxacin and theophylline were recommended.	75
Norfloxacin + cyclosporine	In pediatric patients undergoing renal transplantation norfloxacin impaired cyclosporine disposition by inhibition of CYP3A4, resulting in cyclosporine dose reduction from 7.4 mg/kg per day to 4.5 mg/kg per day.	69