1. Drugs R D. 2012 Jun 1;12(2):71-100. doi: 10.2165/11634300-000000000-00000.

Moxifloxacin safety: an analysis of 14 years of clinical data.

Tulkens PM, Arvis P, Kruesmann F.

Pharmacologie cellulaire et molculaire Centre de Pharmacie clinique, Louvain Drug
Research Institute, Universit catholique de Louvain, Brussels, Belgium.

Background: Moxifloxacin, a fluoroquinolone antibiotic, is used for the treatment
of respiratory tract, pelvic inflammatory disease, skin, and intra-abdominal
infections. Its safety profile is considered favorable in most reviews but has
been challenged with respect to rare but potentially fatal toxicities (e.g.
hepatic, cardiac, or skin reactions). Objective: To analyze and compare the
safety profile of moxifloxacin versus comparators in the entire clinical database
of the manufacturer. Setting: Data on the valid-for-safety population from phase 
II-IV actively controlled studies (performed between 1996 and 2010) were
analyzed. Studies were either double blind (n = 22 369) or open label (n = 7635) 
and included patients with indications that have been approved in at least one
country [acute bacterial sinusitis, acute exacerbation of chronic bronchitis,
community-acquired pneumonia, uncomplicated pelvic inflammatory disease,
complicated and uncomplicated skin and skin structure infections, and complicated
intra-abdominal infections] (n = 27 824) and patients with other indications
(n = 2180), using the recommended daily dose (400 mg) and route of administration
(oral, intravenous/oral, intravenous only). The analysis included patients at
risk (age ≥65 years, diabetes mellitus, renal impairment, hepatic impairment,
cardiac disorders, or body mass index <18 kg/m2). Patients with known
contraindications were excluded from enrollment by study protocol design, but any
patient having entered a study, even if inappropriately, was included in the
analysis. Main Outcome Measure: Crude incidences and relative risk estimates
(Mantel-Haenszel analysis) of patients with any adverse event (AE), adverse drug 
reaction (ADR), serious AE (SAE), serious ADR (SADR), treatment discontinuation
due to an AE or ADR, and fatal outcomes related to an AE or ADR. Results: Overall
incidence rates of AEs were globally similar in the moxifloxacin and comparator
groups. By filtering the data for differences in disfavor of moxifloxacin (i) at 
≥2.5% for events with an incidence ≥2.5% or at ≥2-fold for events with an
incidence <2.5% in one or both groups and (ii) affecting ≥10 patients in either
group, we observed slightly more (i) AEs in double-blind intravenous-only and
open-label oral studies, (ii) SAEs in double-blind intravenous-only studies,
(iii) ADRs and SADRs in open-label oral studies, (iv) SADRs in open-label
intravenous/oral studies, and (v) premature discontinuation due to AEs in
open-label intravenous-only studies. The actual numbers of SADRs (in all studies)
were small, with clinically relevant differences noted only in intravenous/oral
studies and mainly driven by 'gastrointestinal disorders' (15 versus 7 patients) 
and 'changes observed during investigations' (23 versus 7 patients [asymptomatic 
QT prolongation: 11 versus 4 patients in double-blind studies]). Analysis by
comparator (including another fluoroquinolone) did not reveal medically relevant 
differences, even in patients at risk. Incidence rates of hepatic disorders,
tendon disorders, clinical surrogates of QT prolongation, serious cutaneous
reactions, and Clostridium difficile-associated diarrhea were similar with
moxifloxacin and comparators. Conclusion: The safety of moxifloxacin is
essentially comparable to that of standard therapies for patients receiving the
currently registered dosage and for whom contraindications and precautions of use
(as in the product label) are taken into account.

PMID: 22715866  [PubMed - in process]