The expert panel on fixed dose combinations (FDC) has cleared almost all FDCs pertaining to the musculoskeletal system for further marketing on the grounds that the industry should provide satisfactory clinical trial data on them within a year's time, according to the minutes of the meeting.

The minutes of the meeting held on June 4 was released only recently and it would be submitted for clearance by the DTAB, sources said. Out of the total 28 FDCs, the committee had detailed deliberations on 22, while rest of them were either cleared in earlier meeting or duplicated. The FDCs no.120 (as per the DCGI list) and 125 were the same while no.195 and 269 in the list fall outside the purview of the committee as the DTAB had approved them. FDCs (no. 124 and 243) were also found to be duplicates of 106 and 109 respectively.

The committee observed that there was no published data on safety and efficacy of the four FDCs -chlorzoxazone+paracetamol+aceclofenac, chlorzoxazone+paracetamol+diclofenac, chlorzoxazone+ paracetamol+ ibuprofen, chlorzoxazone+ paracetamol+nimesulide. "Further, muscle relaxant like chlorzoxazone is generally given for short term use while paracetamol, diclofenac are administered for longer time period in case of arthritis patients.

The clinical expert opinion by the members were in favour the above three drugs. Based on their experience and information from the companies, it was concluded that documented evidence in support of clinical safety and efficacy is necessary. After detailed discussion, the committee recommended that these FDCs can be considered only for short term use in acute musculoskeletal pain associated with spasm to the condition that satisfactorily powered clinical trials comparing the three drugs with two drug combination of chlorzoxazone+paracetamol is required to be conducted within one year from the date of final decision on marketing of these FDCs. For the fourth FDC, additional study to establish hepatic safety needs to be done within six months, since all these three are potentially hepatotoxic,'' the minutes said.

On the combinations - tizanidine+paracetamol+aceclofenac, tizanidine+ paracetamol+diclofenac, and tizanidine+paracetamol+nimesulide - also the committee felt there was no published data on safety and efficacy. It was also concluded that documental evidence is needed. The committee recommended that these FDCs can be considered for only short term use and satisfactory clinical trials be done within one year from the date of final decision on marketing.

The panel also recommended similar clinical trial data within one year on four combinations consisting serratiopeptidase. They are serratiopeptidase +paracetamol+aceclofenac, serratiopeptidase +paracetamol+diclofenac, serratiopeptidase +paracetamol+ibuprofen, serratiopeptidase +paracetamol+nimesulide. Members like Dr Y K Gupta and Dr Nilima Kshirsagar suggested that for serratiopeptidase, there needs to be data available substantiating its absorption. It can be in the form of documented evidence, or else the industry hast to conduct a study to prove orally administered serratiopeptidase attains blood levels, they suggested.

The committee also recommended clinical trial data to be submitted within one year on the combination of aceclofenac+paracetamol+tramadol. Two other combinations in the category - aceclofenac+tramadol and meloxicam+paracetamol were cleared as not irrational. For acetyl salicylic acid+ethoheptazine, the panel felt that the current status of ethoheptazine needs to be presented as regards the availability and usage in India and globally. This will be taken into consideration before considering the suitability of permitting marketing, the panel said.

"On the combinations of alendronate+calcium carbonate+vitamin and alendronate+calcium citrate+cholecalciferol+magnesium hydroxide, it was unanimously agreed upon to be rational only if available in the form of combi pack," the minutes said. The FDC - diclofenac+famotidine - is apparently not irrational and has similar therapeutic application as a proton pump inhibitor+NSID combination was already permitted for marketing, the meeting noted.

The panel cleared dextropropoxyphene+ibuprofen combination as rational based on the guidelines of the DTAB on dextropropoxyphine combinations in February 2009. The ibuprofen+paracetamol+caffeine was also found by the panel as not irrational. "The role caffeine is well established in providing additional analgesia as well as enhancing absorption of paracetamol. However, the amount of caffeine incorporated must be adequate in the FDC and the clinical data substantiating the same must be made available," the committee noted.

While the panel cleared naproxen+domperidon as not irrational, it wanted to have the details of the availability along with adequate justification for the need of the combination of paracetamol+lignocaine.