Ciprofloxacin and Dolasetron: Interaction Details

a) In a postmarketing study that evaluated the effect of concomitant administration of alfuzosin with another QT interval-prolonging drug of similar effect size, the observed QT interval prolongation was greater than that seen with either drug alone, but was not more than additive. The corrected (Fridericia) QT interval (QTcF) increased by 5.9 milliseconds (upper bound of 95% confidence interval (CI), 9.4 milliseconds). The QTcF increase observed with moxifloxacin 400 mg (positive control) was 10.2 milliseconds (upper bound 95% CI, 13.8 milliseconds). The mean placebo-subtracted QTcF increase following administration of alfuzosin 10 mg alone was 1.9 milliseconds (upper bound 95% CI, 5.5 milliseconds) ².

b) Concomitant use of amiodarone and ciprofloxacin was one of the most common drug interaction combinations associated with torsade de pointes (TdP) in a retrospective pharmacovigilance study including 4313 cases of TdP (involving 721 drugs and 4230 drug combinations reported in at least 3 cases) from the FDA Adverse Event Reporting System (FAERS) database. Patients were mostly female (55.7%) and a mean of 55.5 years, however the range was 0 to 97 years. TdP led to initial or prolonged hospitalization in 30.4%, life-threatening events in 39.5%, and death in 8.4% of cases in the overall population. Drug interactions were involved in 513 TdP events. The most frequently interacting drug combinations were citalopram and QUEtiapine (86 cases), amiodarone and ciprofloxacin (49 cases), amiodarone and escitalopram (34 cases), amiodarone and FLUoxetine (33 cases), ciprofloxacin and sotalol (31 cases), and amiodarone and citalopram (30 cases). This study was limited by the lack of clinical details within the FAERS database which did not allows comorbidities to be excluded as possible contributing factors to TdP cases ⁵.

c) In a single-center, prospective study, concomitant use of chloroquine and ciprofloxacin significantly increased the rate of ciprofloxacin excretion and cumulative urine ciprofloxacin compared with ciprofloxacin alone in healthy male volunteers (n=8). During phase one, subjects (between 19 and 31 years of age) each received one dose of oral ciprofloxacin 500 mg followed by a 2-week washout period. In the second phase, patients were given oral chloroquine 600 mg together with oral ciprofloxacin 500 mg. Urine samples were collected 0, 1, 2, 4, 8, 12, and 24 hours after administration during both phases. Analysis showed that at 0.5 hours, the urinary excretion of ciprofloxacin increased from 0.09 mg/mL in phase 1 to 5.2 mg/mL in phase 2. Ciprofloxacin urinary recovery also increased from 0.1% when ciprofloxacin was administered alone to 1.1% during concomitant administration with chloroquine ⁶.

d) Concomitant administration of ciprofloxacin and itraconazole increased exposure of itraconazole but did not affect pharmacokinetics of ciprofloxacin in a study of 10 healthy men. All volunteers received ciprofloxacin 500 mg orally every 12 hours for 7 days (after a standard meal), itraconazole 200 mg orally every 12 hours for 7 days, and ciprofloxacin 500 mg in combination with itraconazole 200 mg orally every 12 hours for 7 days (after a standard meal), with 14-day washout periods between each phase of drug administration. Concomitant administration of ciprofloxacin and itraconazole compared with itraconazole administration alone produced significant increases in itraconazole Cmax (53% increase; p less than 0.05), AUC (0 to 96 hours; 49% increase; p less than 0.05) and AUC (0 to infinity; 82% increase; p less than 0.01). No adverse reactions were reported after ciprofloxacin or itraconazole alone. Adverse reactions reported after concomitant administration included nausea (60%), dry mouth (40%), diarrhea (10%), and headache (10%) ⁷.

e) In 3 clinical trials, QTc prolongation greater than 60 msec was observed in 1.5% (15 of 2062) of patients treated with telavancin 10 mg/kg compared with 0.6% (6 of 2062) patients treated with vancomycin. In these studies, 21% (214 of 1029) of telavancin-treated patients and 16% (164 of 1033) of vancomycin-treated patients received concomitant medications known to prolong QTc. Of the patients experiencing QTc prolongation of greater than 60 msec, 9 telavancin-treated patients and 1 vancomycin-treated patient received concomitant medications known to prolong the QTc interval, and less than 1% in each group did not receive a concomitant medication known to prolong the QTc interval. A separate analysis revealed that 1 telavancin-treated patient and 2 vancomycin-treated patients experienced a QTc greater than 500 msec. No patients experienced a cardiac adverse event attributed to QTc prolongation ¹.

f) In a randomized, double-blind, multiple-dose, positive- and placebo-controlled, parallel study, maximum QTc prolongation of 11.6 msec (upper 90% confidence limit (CL), 16 msec) and 15.1 msec (upper 90% CL, 20 msec) was observed in patients treated with telavancin 7.5 mg/kg and 15 mg/kg, respectively, compared with 21.6 msec (upper 90% CL 26 msec) in the positive-control group. Healthy subjects (n=160) were randomized to telavancin 7.5 mg/kg, telavancin 15 mg/kg, positive control, or placebo infused over 60 minutes once daily for 3 days. At the end of the infusion, the mean maximum baseline-corrected, placebo-corrected QTc prolongation estimate for telavancin 10 mg/kg (based on interpolation of the data from patients treated with telavancin 7.5 mg/kg and 15 mg/kg) was 12 to 15 msec compared with 22 msec for the positive control. One hour after infusion, the maximum QTc prolongation for telavancin-treated patients was 6 to 9 msec compared with 15 msec for the positive control ¹.