Drug products: Ciflox, Ciprofloxacin Accord, Ciprofloxacin Actavis, Ciprofloxacin Aristo, Ciprofloxacin Arrow, Ciprofloxacin Bluefish, Ciprofloxacin BMM Pharma, Ciprofloxacin Ebb, Ciprofloxacin Fresenius Kabi, Ciprofloxacin Hexal, Ciprofloxacin Hospira, Ciprofloxacin Kabi, Ciprofloxacin Krka, Ciprofloxacin MDS, Ciprofloxacin Mylan, Ciprofloxacin Orion, Ciprofloxacin Ranbaxy, Ciprofloxacin Sandoz, Ciprofloxacin STADA®, Ciprofloxacin SUN, Ciprofloxacin Villerton, Ciproxin, Ciproxin®
ATC code: J01MA02
Substances: ciprofloxacin, ciprofloxacin hydrochloride, ciprofloxacin hydrochloride monohydrate, ciprofloxacin hydrogensulfate, ciprofloxacin lactate
Pharmacokinetic studies show women to reach a higher plasma concentration than men when taking the same dose. In some, but not all, of these studies the difference between the sexes disappears after weight adjustment. For kinolons, AUC/MIC is the best predictor of therapeutic response.
Studies on sex differences in ciprofloxacin pharmacokinetics show conflicting results. In a Dutch prospective observational cohort study, ciprofloxacin pharmacokinetics was studied in critically ill patients in intensive care (24 men, 8 women). Following intravenous administration of 400 mg ciprofloxacin, exposure was higher in women. The difference in AUC between men and women was not due to variation in body weight or differences in bioavailability and thus a lower clearance in women was suggested . Similar conclusions were drawn in a study in healthy volunteers (8 men, 7 women) where women were found to have increased exposure and slower clearance .Sex differences in ciprofloxacin pharmacokinetics were also investigated in a study where healthy volunteers (12 men, 12 women) received a single oral dose of 100 mg ciprofloxacin. The statistical methods were complex but the results of the study demonstrated that women had higher exposure to ciprofloxacin even after adjustment for body weight .In contrast, results from a multiple-dose pharmacokinetic study in healthy volunteers (12 men, 12 women) suggest that sex has no influence on ciprofloxacin pharmacokinetics after correction for body weight . Two other single-dose pharmacokinetic studies in healthy volunteers (22 men, 18 women) show similar results [6, 7].According to the manufacturer, adult dosing is not based on bodyweight . Theoretically, this may bring a risk for subtherapeutic concentrations in men and an increased risk for dose related adverse events in women.
For quinolons, AUC/MIC correlates best to therapeutic response, both in animal and in vitro kinetic models .In some settings urine cultures to identify pathogens and resistance pattern cannot always be obtained and therapy of urinary tract infections then has to be empirical. A Brazilian study analyzed urine isolates to identify suitable empirical therapy options for cystitis and urinary tract infections in relation to patient’s sex and age (1098 men, 8700 women). Drug classes analyzed was ampicillin, nitrofurantoin, fluoroquinolones (ciprofloxacin and levofloxacin), trimethoprim-sulfamethoxazole, gentamicin, and ceftriazone/cefotaxime, Women exhibited higher susceptibility values for all drug classes studied than men. For women in any age group, only nitrofurantoin and gentamicin provided adequate activity for empirical therapy (> 80% susceptibility). For men in any age group, only gentamicin was suitable for empirical therapy. In women aged over 60 years, few suitable empirical treatment options were identified .Another study of urinary E. coli isolates (2274 men, 32265 women) has described age- and sex-specific antibiotic susceptibility patterns for ampicillin, amoxicillin clavulanate, ciprofloxacin, nitrofurantoin and trimethoprim-sulfamethoxazole. Ciprofloxacin susceptibility was similar in men and women (93.2% vs. 95.9%). Age-specific susceptibilities differed between men and women for all antibiotics studies except trimethoprim-sulfamethoxazole. However, the magnitude of the observed differences was generally less than 5% and the authors suggest that they may not represent clinically meaningful differences .Resistance patterns for pathogens often differ between populations. A Dutch study comparing resistance in urinary samples from 560 men with historic data from urinary samples from 917 women  found no difference between men and women in E.colisusceptibility to ciprofloxacin . In contrast to this a Portuguese retrospective analysis of urinary samples (120,691 (78%) from women and 34,898 (22%) from men) ciprofloxacin resistance was more common in male urinary samples positive for E. coli, P. mirabilis, P. vulgaris, Klebsiella SPP, Enterobacter SPP, Providencia SPP, S. aureus, E. faecalis.
No studies with a clinically relevant sex analysis regarding adverse effects of ciprofloxacin have been found.
In a randomized, multiple-dose, double-blind crossover study (12 men, 12 women) the effect of patient’s sex on the interaction between caffeine and ciprofloxacin (and fleroxacin) was evaluated. Mean plasma concentrations of caffeine alone did not differ significantly between men and women. When adding ciprofloxacin 500 mg twice daily for three days caffeine concentrations were significantly higher in women than in men. Also, in the presence of caffeine, ciprofloxacin AUC was more increased in women while apparent total body clearance was more increased in men. However, these findings could be explained by differences in body weight between men and women . Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2015-02-20
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson