Download Meeting dated 06.03.2014

Recommendations of Expert Committee Meeting held on 6.03.2014
The expert committee deliberated the following proposals on 06.03.14 and recommended the
following:
Agenda
No.
Name of FDC
1
Amoxicillin Trihydrate IP eq. to
Amoxicillin 125mg +Cloxacillin
Sodium IP eq. to Cloxacillin 125mg
Dispersible Tablets
Although the firm claimed that the proposed FDC
is superior than individual drugs, it could not
produce any data in this regard. The committee
opined that superiority of FDC over individual
drugs needs to be proven in current scenario and
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.
Amoxicillin trihydrate 250 mg +
cloxacillin sodium 250 mg capsule
Firm could not produce any data in respect of
superiority of FDC over individual drugs. The
committee opined that superiority of FDC over
individual drugs needs to be proven in current
scenario and accordingly, protocol shall be
submitted within 3 months and data shall be
generated within next one and half year. Noncompliance of this instruction may lead to
suspension/cancellation of license.
Amoxicillin Trihydrate IP 250mg
+Cloxacillin Sodium 250mg
+Saccharomyces Boulardii 40
million spores Hard Gelatin
Capsules
Firm did not produce any data with respect to use
of Saccharomyces Boulardii in the treatment of
antibiotic associated diarrhea. The committee
opined that currently there is no data/ evidence to
suggest the rationality of the FDC. However, if
the firm generates safety and efficacy data, same
may be re-examined. Accordingly, protocol shall
be submitted within 3 months and data shall be
generated within next one and half year. Noncompliance of this instruction may lead to
suspension/cancellation of license.
2
3
4
Recommendations
Amoxicillin Trihydrate IP Eq. to
Amoxicillin 125mg/500mg
+Dicloxacillin Sodium USP Eq. to
Dicloxacillin
125mg/500mgTablets/Sachet
The committee reviewed following FDC
(i) Amoxicillin 250mg + Dicloxacillin 250mg
(ii)Amoxicillin 125mg + Dicloxacillin 125mg
(iii)Amoxicillin 500mg + Dicloxacillin 500mg
It was noted that Amoxicillin 250mg +
Dicloxacillin 250mg was approved by CDSCO in
2006 and the FDC at (ii) and (iii) are
nowbeingrequested by the company. Committee
opined that :
(a) Since, 2006 the scenario of antimicrobial
resistance pattern has changed
significantly, majority of isolates of Staph.
aureus have become resistance to the
amoxicillin &cloxacillin including
dicloxacillin
(b) Better efficacious antibiotic andare 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 andneed to be proven in current
scenario. Accordingly, Protocol should be
submitted within 3 months and data shall be
generated within next one and half year. Noncompliance of this instruction may lead to
suspension/cancellation of license.
5
6
AmoxycillinTrihydrate IP 250mg
+Dicloxacillin Sodium IP 250mg
+Serratiopeptidase IP 10mg Hard
gelatin capsules
Committee opined that combination of
serratiopeptidase with antibiotics has no rationale.
Hence Committee didn’t recommend for
manufacturing and marketing of the proposed
FDC
Regarding amoxicillin 200 mg + Clavulanic acid
(i) Amoxycillin 875mg + Clavulanic 28.5mg Tablet/dispersible tablet, committee
observed that original data needs to be generated
acid 125 mg Film coated tablets
on their own formulation of the firms in respect of
(ii) Amoxycillin 250 mg+
Bioavailability, Acceptability/ palatability, in
Clavulanic acid 125 Film coated
pediatric population. Accordingly, protocol shall
tablets
be submitted within 3 months and data shall be
generated within next one and half year. Non(iii) Amoxycillin 200mg +
compliance of this instruction may lead to
Clavulanic acid 28.5 mg dispersible suspension/cancellation of license.
tablets
Committee noted that other strengths apart from
the above mentioned strengths are approved by
DCG(I) as claimed by the firm. DCG(I) may take
action accordingly with respect to these strengths.
7
(i) Amoxicillin trihydrate IP 80mg
+ Potassium Clavulanate IP
11.4mg Oral Suspension
(ii) Amoxicillin
80mg/200mg/400mg +
Clavulanic Acid
11.4mg/28.4mg/28.5mg/ 57mg
Suspension
(iii)Amoxicillin
875mg/200mg/400mg/200 mg +
Potassium Clavulanic Acid
125mg/28.5mg/57mg /28.5mg
per 5ml-Suspension
(i) The firm presented that FDC of Amoxycillin
200mg + potassium Clavulanate 28.5mg per 5ml
is already approved by US FDA. The committee
recommended that the combination of
amoxicillin 200 mg+ clavulanic Acid 28.5mg in
children less that 20 kg body weight and 400mg
+ clavulanate potassium57.5 mg per 5 ml in
children more than 20 kg body weight may be
approved for manufacturing and marketing as
there have been no safety concerns with respect to
these strength.
(ii) 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
(iv) Amoxicillin trihydrate 400mg + Bioavailability, acceptability/palatability, in
potassium clavulanate diluted
paediatric population. Accordingly, protocol shall
57 mg- reconstituted suspension be submitted within 3 months and data shall be
generated within next one and half year. Non(v) Amoxycillin Trihydrate
compliance of this instruction may lead to
875/200mg/400 mg/200mg30ml suspension/cancellation of license.
+Potassium Clavulanate
125mg/28.5mg/57.7mg+28.5mg
(iii) As regard to Combipack, it was noted by the
Tablet/ Dispersible tablet/Oral
committee that mentioning of Sterile water for
Suspension/
injection on the label for the purpose of
reconstitution is not appropriate as it could lead to
(vi) Amoxicillin
other confusions. Firm should revise the label and
400mg/200mg/250mg +
other promotional literature appropriately and
Potassium Clavulanate Diluted
should submit the same to the office of DCG(I)
57mg/28.5mg/62.5mg Dry
for further approval.
Syrup
(vii) Amoxycillin Trihydrate
400mg + Potassium
clavulanate diluted 57mg Oral
suspension
(viii) Amoxicillin trihydrate
200mg + clavulanate potassium
28.5mg dry syrup
8
(i)
(iv) 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
The committee noted that the pharmacokinetics of
A Amoxicillin require dosing frequency 6-8 hourly.
moxycillintrihydrate 500 In contradiction Tinidazole dosing is twice a day.
mg + tinidazole 300 mg- Further the proposed indications are not as per the
film coated tablet
(ii)
moxycillin
500mg
+
300mg)
clinical indication of these two individual drugs
A such as Amoebiasis. Tinidazole is good enough
Trihydrate for the treatment of amoebiasis and Amoxicillin
tinidazole does not have any role and therefore the FDC
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.
9
Amoxicillin Trihydrate IP Eq. to
Amoxicillin 500mg + Cefixime IP
as Trihydrate Eq. to Anhydrous
Cefixime 200mg +Potassium
Clavulanic Acid 125mg Tablets
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