Moxifloxacin (Avelox®, Bayer HealthCare and Vigamox®, Alcon) is a broad-spectrum antibacterial that is available locally in the form of an oral tablet, infusion solution and ophthalmic solution. Avelox® tablet and infusion solution have been registered in Singapore since July 2000 and May 2002 respectively while Vigamox® ophthalmic solution was licensed in November 2004.
Recent safety concerns
In February 2008, Bayer HealthCare issued a Dear Healthcare Professional Letter (DHCPL) in Europe to inform healthcare professionals of very rare liver injuries and serious skin reactions associated with moxifloxacin. This was in response to a worldwide review of serious, including fatal cases of hepatotoxicity and bullous skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) reported for moxifloxacin. In this review, there were eight reports of fatal hepatic injuries considered as possibly related to moxifloxacin therapy. Thirty-five cases of SJS were reported, of which, three had fatal outcomes and seven were considered life threatening. TEN was reported in several cases where a causal relationship was considered possible. Healthcare professionals were reminded that moxifloxacin is contraindicated in patients with impaired liver function (Child Pugh C) and in patients with transaminases elevations greater than 5 fold the upper limit normal (ULN).
In July 2008, the European Medicines Agency (EMEA) finalised their safety review of oral moxifloxacin-containing medicines. The review concluded that the benefits of oral moxifloxacin-containing medicines continue to outweigh the risks. However, in view of the increased risk of adverse hepatic reactions associated with moxifloxacin, it was recommended to restrict oral moxifloxacin-containing medicines to second-line therapy in the EMEA approved indications of treatment of acute bacterial sinusitis, acute exacerbations of chronic bronchitis and community-acquired pneumonia. In addition, the warnings concerning the risk of diarrhoea, heart failure in women and older patients, severe skin reactions and fatal liver injuries were also strengthened in the products' labelling.
Local situation
To date, HSA has received 22 local spontaneous adverse drug reaction reports associated with oral moxifloxacin. Patient exposure to moxifloxacin to date is estimated to be 230,577*, according to local figures provided by Bayer Healthcare. In the interpretation of the above figures, there is a need to consider the significant degree of under-reporting of adverse reactions as is the case with all spontaneous adverse drug reaction reporting programmes.
A majority of the 22 reports were concerning skin reactions, of which, there was one report of SJS, one report of urticaria, four reports of rashes, two reports of anaphylaxis and five reports of anaphylactic shock. In addition, there were two reports of hepatobiliary disorders, of which, one of the patient developed jaundice on the ninth day of moxifloxacin therapy while the other patient developed elevated liver enzymes.
Moxifloxacin is indicated locally for the treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, community acquired pneumonia, and uncomplicated skin and skin structure infections. These indications are similar to those approved by the US Food and Drug Administration (FDA).
The package inserts for moxifloxacin tablets and infusion solution will be updated with safety information on fulminant hepatic failure and bullous skin reactions, in addition to the existing warnings on anaphylactic reaction and abnormal liver function. Although moxifloxacin-containing products are not restricted to second-line therapy locally, physicians are advised to be aware of the development in Europe. Physicians are also advised to be vigilant for early signs and symptoms of severe liver injury and bullous skin reactions such as SJS or TEN in patients taking moxifloxacin.
Healthcare professionals are encouraged to report suspected adverse drug reactions associated with moxifloxacin to the Pharmacovigilance Branch of HSA.
* For tablets, patient exposure is estimated on defined daily dose3 (DDD) of moxifloxacin of 400mg and assuming an average 7-day treatment course per patient. For injections, patient exposure is estimated on DDD of 400mg and assuming an average 4-day treatment course per patient.
References:
- EMEA Press Release: European Medicines Agency recommends restricting the use of oral moxifloxacin-containing medicines. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2010/08/news_detail_001068.jsp&mid=WC0b01ac058004d5c1
- Direct Healthcare Professional Communication regarding moxifloxacin (Avelox®) and serious hepatic and bullous skin reactions. http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName=CON014103&RevisionSelectionMethod=Latest
- WHO Collaborating Center for Drug Statistics Methodology (Oslo).