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 Navamedic, Ciprofloxacin Orion, Ciprofloxacin Ranbaxy, Ciprofloxacin Sandoz, Ciprofloxacin STADA®, Ciprofloxacin SUN, Ciproxin, Ciproxin®
ATC code: J01MA02
Substances: ciprofloxacin, ciprofloxacin hydrochloride, ciprofloxacin hydrochloride monohydrate, ciprofloxacin hydrogensulfate, ciprofloxacin lactate
Ciprofloxacin is associated with QT-prolongation on ECG and thus a risk of potentially fatal arrhythmias of the type Torsade de Pointes ventricular tachycardia. No sex difference in risk has been shown for ciprofloxacin but a known risk factor for Torsade de Pointes is female sex.
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 sex difference disappears after weight adjustment. For quinolones, AUC/MIC is the best predictor of therapeutic response.
Pharmacokinetics and dosing
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 patient’s 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 . This may bring a risk for subtherapeutic concentrations in men and an increased risk for dose related adverse events in women.
For quinolones, AUC/MIC correlates best to therapeutic response, both in animal and in vitro kinetic models .Resistance patterns for pathogens often differ between populations. A Dutch study comparing resistance in urinary samples (917 from women, 560 from men) found no difference between men and women in E.coli susceptibility to ciproflocaxin [10, 11]. An American study of urinary E. coli isolates (2274 men, 32 265 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 studied 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 . In contrast to this a Portuguese retrospective analysis of urinary samples (34 898 (22%) from men and 120 691 (78%) from women) ciprofloxacin resistance was more common in male urinary samples positive for E. coli, P. mirabilis, Klebsiella spp, P. vulgaris, Enterobacter spp, and Providencia spp . An Iranian study report higher ciprofloxacin sensitivity in urine samples from girls/women with urinary tract infection caused by E. coli, K. pneumonia, Enterococcus spp., or Staphylococcus spp. .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 .
Fluoroquinolones has been associated with prolonged QT-interval and a risk of Torsade de Pointes ventricular tachycardia. Ciprofloxacin appears to be associated with the lowest risk for QT prolongation and the lowest TdP rate . Risk factors of drug-induced ventricular arrhythmias are female sex, hypokalemia, bradycardia, and base line QT-prolongation .
Reproductive health issues
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2022-06-16
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- van Zanten AR, Polderman KH, van Geijlswijk IM, van der Meer GY, Schouten MA, Girbes AR. Ciprofloxacin pharmacokinetics in critically ill patients: a prospective cohort study. J Crit Care. 2008;23:422-30. PubMed
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- Gallicano K, Sahai J. Lack of gender effect on ciprofloxacin pharmacokinetics in humans. Br J Clin Pharmacol. 1996;42:632-4. PubMed
- Shah A, Lettieri J, Nix D, Wilton J, Heller AH. Pharmacokinetics of high-dose intravenous ciprofloxacin in young and elderly and in male and female subjects. Antimicrob Agents Chemother. 1995;39:1003-6. PubMed
- Ciproxin (ciprofloxacin). Summary of Product Characteristics. Swedish Medical Products Agency (MPA) [updated 2022-02-01, cited 2022-06-16]
- Gunderson BW, Ross GH, Ibrahim KH, Rotschafer JC. What do we really know about antibiotic pharmacodynamics?. Pharmacotherapy. 2001;21:302S-318S. PubMed
- den Heijer CD, Donker GA, Maes J, Stobberingh EE. Antibiotic susceptibility of unselected uropathogenic Escherichia coli from female Dutch general practice patients: a comparison of two surveys with a 5 year interval. J Antimicrob Chemother. 2010;65:2128-33. PubMed
- den Heijer CD, Penders J, Donker GA, Bruggeman CA, Stobberingh EE. The importance of gender-stratified antibiotic resistance surveillance of unselected uropathogens: a Dutch Nationwide Extramural Surveillance study. PLoS One. 2013;8:e60497. PubMed
- McGregor JC, Elman MR, Bearden DT, Smith DH. Sex- and age-specific trends in antibiotic resistance patterns of Escherichia coli urinary isolates from outpatients. BMC Fam Pract. 2013;14:25. PubMed
- Linhares I, Raposo T, Rodrigues A, Almeida A. Frequency and antimicrobial resistance patterns of bacteria implicated in community urinary tract infections: a ten-year surveillance study (2000-2009). BMC Infect Dis. 2013;13:19. PubMed
- Mostafavi SN, Rostami S, Rezaee Nejad Y, Ataei B, Mobasherizadeh S, Cheraghi A et al. Antimicrobial Resistance in Hospitalized Patients with Community Acquired Urinary Tract Infection in Isfahan, Iran. Arch Iran Med. 2021;24(3):187-192. PubMed
- Briasoulis A, Agarwal V, Pierce WJ. QT prolongation and torsade de pointes induced by fluoroquinolones: infrequent side effects from commonly used medications. Cardiology. 2011;120(2):103-10. PubMed
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- Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2021 [cited 2022-03-15.] länk
Reviewed by: Diana Rydberg, Carl-Olav Stiller, Pauline Raaschou
Approved by: Karin Schenck-Gustafsson