Moxifloxacin

Moxifloxacin is used as part of a treatment regimen, usually involving 5 medicines, to treat MDR TB. It is part of a group of medicines called fluoroquinolones. Moxifloxacin was discovered in 1996.

 Moxifloxacin is used in South Africa’s standard regimen for the treatment of MDR TB

Dosage:

 How it works:

Moxifloxacin: is a synthetic fluoroquinolone antibacterial agent. It functions by inhibiting enzymes.

 Side effects:

Moxifloxacin is generally well tolerated. Rare side effects can include tendon damage and rupture. Side effects may include diarrhoea, dizziness, headache, nausea, trouble sleeping, vomiting, yeast infections and sensitivity to light.

 It is recommended that moxifloxacin is discontinued during pregnancy and breastfeeding because of the potential for serious adverse events, particularly cartilage damage. Moxifloxacin should only be taken during pregnancy if benefits outweigh the risks.

 Clinical evidence and approval:

Moxiflocacin has been shown to be effective against TB and is included in many guidelines for drug resistant TB. However moxifloxacin does not yet have this indication approved by a stringent regulatory authority and therefore is used “off label” for the treatment of drug resistant TB.¹

Moxifloxacin is an important option for the treatment of MDR TB.² A retrospective analysis showed that levofloxacin and moxifloxacin showed equivalent efficacy for treating MDR-TB.³ Seoul National University Hospital is currently recruiting patients to take part in a phase III clinical trial comparing lexofloxacin and moxifloxacin.

 As well as treating MDR TB, moxifloxacin can be useful in treating drug susceptible TB. A double blind randomised study compared patients receiving isoniazid, rifampicin and pyrazinamide with ethambutol versus isoniazid, rifampicin and pyranzimide with moxifloxacin for 8 weeks.

At 8 weeks, culture conversion to negative had occurred in 59 (80%) of 74 patients in the moxifloxacin group compared with 45 (63%) of 72 in the ethambutol group (difference 17.2%, 95% CI 2.8-31.7; p=0.03). There were 16 adverse events (8 in each group). The researchers concluded that moxifloxacin improved culture conversion in the initial stage of treatment and that further research should be carried out to establish if moxifloxacin can shorten TB treatment duration.⁴

No studies on the interactions with antiretrovirals have been carried out. However, based on the knowledge of the metabolism of moxifloxacin, levels of the drug may be reduced by ritonavir and increased by atazanavir.⁵

Pricing (per lowest unit, i.e. single tablet or injection):

* Private sector prices sourced on 26/07/11. Global Drug Facility prices converted to rands on 26/07/11.

* Private and public sector prices may vary between suppliers. The lowest available prices are shown here.

Advocacy issues:

• SA public sector prices are 2.5 x higher than internationally available prices. Moxifloxacin was included in the 2011 -2013 tender, yet the price at which it will be purchased is not yet available.

• Moxifloxacin is included in the WHO guidelines for the treatment of MDR TB, yet it is used off-label. It is unclear whether liability will fall on doctors if patients experience adverse events. The liability problem would extend to nurses if they began to initiate and manage MDR TB treatment.

• Further research is needed to establish safety and efficacy of paediatric use. There are no paediatric formulations available. [MSF]

• Further research is needed to establish potential interactions with antiretrovirals. [MSF]

 Patents, manufacturers and suppliers:

 Although patents covering the moxifloxacin molecule have now expired in most countries, subsequent patents claiming a crystal monohydrate form of moxifloxacin appear to stand in the way of generic production. Such patents, due to run until 2016, have been granted in several countries including China, Russia, South Africa and Ukraine. In India, where this patent was withdrawn by Bayer, additional patents on other pharmaceutical forms have been granted but do not appear to be blocking generic manufacture.

For many years, Bayer was the only quality-assured source of moxifloxacin available. In November 2010, the first moxifloxacin was prequalified by WHO (Cipla) and a second manufacturer (Macleods) has submitted a dossier that has been accepted for evaluation. The supply of moxifloxacin will therefore be relatively secure in the near future (although price remains a barrier).

In addition, we can expect to see further sources of quality-assured moxifloxacin, because other approved indications of use exist for the drug.

Indeed, there are two generic manufacturers (Dr Reddy's and Teva) that have US FDA tentative approval and are waiting to enter the US market when the patent expires. Additional manufacturers may exist in China, India, the former Soviet Union and other countries, but whether they comply with WHO quality standards is unknown.⁷

Source: MSF