Ciprofloxacin and Amitriptyline: Interaction Details

a) A postmarketing study assessed what happened when alfuzosin was given together with another QT interval-prolonging drug of comparable effect magnitude, and the QT interval prolongation seen was larger than that produced by either agent by itself, though it did not exceed an additive effect. The Fridericia-corrected QT interval (QTcF) rose by 5.9 milliseconds (upper limit of the 95% confidence interval (CI), 9.4 milliseconds). With moxifloxacin 400 mg, used as the positive control, the QTcF rose by 10.2 milliseconds (upper limit of the 95% CI, 13.8 milliseconds). Administration of alfuzosin 10 mg by itself produced a mean placebo-subtracted QTcF increase of 1.9 milliseconds (upper limit of the 95% CI, 5.5 milliseconds) ³.

b) The combined use of amiodarone and ciprofloxacin ranked among the most frequent drug interaction pairings linked to torsade de pointes (TdP) in a retrospective pharmacovigilance study that included 4313 TdP cases (covering 721 drugs and 4230 drug combinations reported in at least 3 cases) drawn from the FDA Adverse Event Reporting System (FAERS) database. Most patients were female (55.7%) with a mean age of 55.5 years, although ages ranged from 0 to 97 years. Across the whole population, TdP resulted in initial or prolonged hospitalization in 30.4%, life-threatening events in 39.5%, and death in 8.4% of cases. Drug interactions figured in 513 of the TdP events. The drug combinations that interacted most often 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). A limitation of this study was the absence of clinical details in the FAERS database, which meant comorbidities could not be ruled out as potential contributors to the TdP cases ⁴.

c) In a single-center, prospective study, giving chloroquine together with ciprofloxacin significantly raised the rate at which ciprofloxacin was excreted and the cumulative amount of ciprofloxacin in urine when compared with ciprofloxacin given alone in healthy male volunteers (n=8). In the first phase, the subjects (aged 19 to 31 years) each took a single oral dose of ciprofloxacin 500 mg, after which there was a 2-week washout interval. In the second phase, the participants received oral chloroquine 600 mg along with oral ciprofloxacin 500 mg. Urine samples were gathered at 0, 1, 2, 4, 8, 12, and 24 hours following administration in both phases. The analysis demonstrated that at 0.5 hours the urinary excretion of ciprofloxacin rose from 0.09 mg/mL in phase 1 to 5.2 mg/mL in phase 2. Urinary recovery of ciprofloxacin likewise rose from 0.1% when ciprofloxacin was given by itself to 1.1% during concurrent administration with chloroquine ⁵.

d) Giving ciprofloxacin and itraconazole together raised itraconazole exposure but had no effect on the pharmacokinetics of ciprofloxacin in a study involving 10 healthy men. Every volunteer 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 combined with itraconazole 200 mg orally every 12 hours for 7 days (after a standard meal), with 14-day washout intervals separating each drug administration phase. When ciprofloxacin and itraconazole were given together compared with itraconazole given alone, there were significant rises 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 concurrent administration included nausea (60%), dry mouth (40%), diarrhea (10%), and headache (10%) ⁶.

e) Across 3 clinical trials, QTc prolongation exceeding 60 msec occurred in 1.5% (15 of 2062) of patients receiving telavancin 10 mg/kg versus 0.6% (6 of 2062) of patients receiving vancomycin. In these trials, 21% (214 of 1029) of telavancin-treated patients and 16% (164 of 1033) of vancomycin-treated patients were taking concomitant drugs known to prolong QTc. Among the patients who had QTc prolongation greater than 60 msec, 9 telavancin-treated patients and 1 vancomycin-treated patient were receiving concomitant medications known to prolong the QTc interval, and less than 1% in each group were not receiving such a concomitant medication. A separate analysis found that 1 telavancin-treated patient and 2 vancomycin-treated patients had a QTc greater than 500 msec. No patient had a cardiac adverse event attributed to QTc prolongation ⁷.

f) In a randomized, double-blind, multiple-dose, positive- and placebo-controlled, parallel study, the maximum QTc prolongation was 11.6 msec (upper 90% confidence limit (CL), 16 msec) and 15.1 msec (upper 90% CL, 20 msec) in patients given telavancin 7.5 mg/kg and 15 mg/kg, respectively, versus 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 conclusion of the infusion, the mean maximum baseline-corrected, placebo-corrected QTc prolongation estimate for telavancin 10 mg/kg (derived by interpolating 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 following infusion, the maximum QTc prolongation for telavancin-treated patients was 6 to 9 msec compared with 15 msec for the positive control ⁷.