Several fixed dose combinations currently in the market are set to lose the license and many will be put on lifeline as the expert committees started scrutinising the applications of companies for regularising those combinations, which were permitted by the State licencing authorities without concurrence from the Drug Controller General of India.
The expert panel, which examined the first batch of applications as part of the massive exercise to cover thousands of FDCs, has already recommended cancellation of licenses of some FDCs sold in the market and gave a lifeline of three months to some others to prove the efficacy with additional data.
In the case of amoxycillin trihydrate IP 250mg +dicloxacillin sodium IP 250mg +serratiopeptidase IP 10mg hard gelatin capsules, the committee opined that combination of serratiopeptidase with antibiotics has no rationale. Hence Committee did not recommend for manufacturing and marketing of the proposed FDC.
Regarding amoxycillin 250 mg + clauvulanic acid 62.5 mg per 5 ml, committee opined that the proposed strength is not recommendable as too many strength will lead to confusion in prescribing for the physician. Hence the committee did not recommend for the proposed strength.
Amoxicillin trihydrate IP Eq. to amoxicillin 500mg + cefixime IP as trihydrate Eq. to anhydrous cefixime 200mg +potassium clavulanic acid 125mg tablets also failed to get clearance from the panel. “Committee noted that cefixime requires 12 hourly dosing whereas, amoxicillin dosing schedule is 6-8 hrs. When these two drugs are given in combination, it will have a pharmacokinetic mismatch. As claimed by the firm the dosing of FDC is 12 hourly, which will lead to under dosing of amoxicillin and may increase possibility of drug resistance. Further the FDC is not approved anywhere in the world. The committee did not recommend for the manufacturing and marketing of the FDC,” according to the minutes of the panel set up by the DCGI to go through the huge number of applications.
The committee also reviewed amoxicillin 250mg + dicloxacillin 250mg, amoxicillin 125mg + dicloxacillin 125mg, and amoxicillin 500mg + dicloxacillin 500mg. It was noted that amoxicillin 250mg + dicloxacillin 250mg was approved by CDSCO in 2006 and the two others are being pushed for marketing by the company. Committee opined that since, 2006 the scenario of antimicrobial resistance pattern has changed significantly, majority of isolates of staph. aureus have become resistant to the amoxicillin & cloxacillin including dicloxacillin .
“Better efficacious antibiotic and are now available and used for staph. aureus infections. In light of these, the rationality of combination in current scenario is questionable. It is also noted that this combination is not available anywhere in the world as per information provided by the firm and also the fact that there is only one study presently by the firm showing better efficacy was published in journal “Pharmazie” Sept. 40(9), 650-1, 1984. However after 30 years, this has lost its relevance in today’s scenario of drug resistance. Committee therefore doesn’t recommended the new strengths of the FDC and also recommended that the superiority of such FDC over the individual drug and need to be proven in current scenario. Accordingly, Protocol should be submitted within three months and data shall be generated within next one and half year. Non- compliance of this instruction may lead to suspension/cancellation of license,” the minutes said.
Regarding amoxicillin 200 mg + clavulanic acid 28.5mg tablet/dispersible tablet, committee observed that original data needs to be generated on their own formulation of the firms in respect of bioavailability, acceptability/ palatability, in paediatric population. Accordingly, protocol shall be submitted within 3 months and data shall be generated within next one and half year. Non- compliance of this instruction may lead to suspension/cancellation of license, it said.
As regard to combipack, it was noted by the committee that mentioning of Sterile water for injection on the label for the purpose of reconstitution is not appropriate as it could lead to other confusions. Firm should revise the label and other promotional literature appropriately and should submit the same to the office of DCG(I) for further approval.
“The committee noted that the pharmacokinetics of amoxicillin require dosing frequency six to eight hourly. In contradiction, tinidazole dosing is twice a day. Further the proposed indications are not as per the clinical indication of these two individual drugs. Tinidazole is good enough for the treatment of amoebiasis and amoxicillin does not have any role and therefore the FDC of these two drugs does not have any rationale. Even for H. pylori infection the proposed FDC is not rationale. The proposed FDC is also not approved anywhere in the world. Hence the committee didn’t recommend the FDC for manufacturing and marketing,” it said.