Ofloxacin

Ofloxacin (Ofx)

Ofloxacin 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.

Dosage:

How it works:

Ofloxacin is a synthetic fluoroquinoloneantibacterial agent. It functions by inhibiting enzymes which are necessary to separate bacterial DNA, thereby inhibiting cell replication.

Side effects:

Ofloxacin is generally well tolerated. Occasional side effects include nausea, vomiting, headache, malaise, insomnia and dizziness. Rare side effects can include spontaneous rupture of the achilles tendon, peripheral neuropathy, diarrhoea, sensitivity to sunlight and allergic reactions.

Oxfloxacin is not recommended during pregnancy and breastfeeding because of the potential for serious adverse events, particularly cartilage damage and impaired growth.

Clinical trials and approval:

Ofloxacin has demonstrated activity against TB and is included in the WHO guidelines. However ofloxacin has not received approval by any stringent regulatory authority for this use and therefore is used off-label.

In 1990 researchers demonstrated in-vitro activity of ofloxacin against MDR TB. They further demonstrated that ofloxacin is more effective at high doses (800 mg) than low doses (300 mg) in patients. In the study, 10 patients were given 300 mg ofloxacin and 10 patients were given 800 mg ofloxacin. In the 300 mg-ofloxacin group and the 800 mg-ofloxacin group, 5 and 8 patients, respectively, achieved culture conversion.¹

Ofloxacin has been successfully used to treat MDR TB. One paper reports on 10 patients given MDR treatment regimens containing ofloxacin. At 18 months, 8 of 10 patients achieved sputum conversion and achieved therapeutic cure based on improvement of clinical signs and symptoms and chest radiography, weight gain, sputum bacteriology and overall improvement in wellbeing.²

Studies have demonstrated that ofloxacin is less effective than moxifloxacin and levofloxacin in treating drug resistant TB.³

Exposure of rifampicin resistant M. tuberculosis strains to rifampicin can potentially compromise the efficacy of the second-line treatment regimens containing ofloxacin.⁴

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 14.5 x higher than internationally available prices. Tender prices for 2011 -2013 are not yet available.

• Further research is needed to establish safety and efficacy for paediatric use. Paediatric formulations are not available. [MSF]

• Further research is needed to understand potential interactions with antiretrovirals.

• Ofloxacin 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.

Manufacturers and suppliers:

Today there is no ofloxacin approved by WHO PQ, but three manufacturers (including Cipla and Macleods) have dossiers submitted and accepted for evaluation, and an additional manufacturer (Micro Labs) is expected to submit during the course of 2011.

The supply of ofloxacin will therefore be relatively secure in the near future. In addition, there are multiple sources of quality-assured ofloxacin, because other approved indications of use exist for the drug. As the patent for ofloxacin has now expired, there are three generic manufacturers (Ranbaxy, Teva, and Dr. Reddy's) that have products available on the US market and several others on the EU market, but none of them have made their products available to GDF.⁶

Source: MSF