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Dr. Mamta Gupta,
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Aug 2018

Dr. Rajendra Kumar Ghritlaharey

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Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
On May 11,2011

Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
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Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."

Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
On April 2011

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.

Dr. Anuradha
On Jan 2020

Important Notice

Year : 2010 | Month : October | Volume : 4 | Issue : 5 | Page : 3255 - 3260 Full Version

Fixed Dose Combination Antimicrobials Practices In Nepal – Review Of Literature

Published: October 1, 2010 | DOI:
Kadir Alam1,2,3, Arjun Poudel1,4, Subish Palaian 1,2,4

1Department of Hospital and Clinical Pharmacy, Manipal Teaching Hospital, Pokhara, Nepal; 2Department of Pharmacology, Manipal College of Medical Sciences, Pokhara, Nepal; 3Department of Social and Administrative Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand; 4Discipline of Social and Administrative Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia.

Correspondence Address :
Kadir Alam
Assistant Professor,
Department of Pharmacology
Manipal College of Medical Sciences
Pokhara, Nepal.
Phone: 061-526420/526416 (Extn 221)


Antibacterial drugs are one used commonly as fixed dose combination. The use of fixed dose combination antimicrobials is more common in developing countries. There are several studies which suggest extensive use of fixed dose combination antimicrobials drugs in Nepal. Although thousands of fixed dose combination are available in world market, WHO has approved only 25 fixed dose combination in 15th edition of WHO essential drug list. Even if some of the fixed dose antimicrobial offer some benefit in treatment of disease like Tuberculosis, Leprosy etc., majority of irrational fixed dose antimicrobials has major contribution in resistance development, decrease the flexibility of prescriber and increase the misuse by self-medication. To minimize the extensive use of fixed dose combination of antimicrobials certain measure like developing guideline for preparing of combination product, evaluation of product before registration, banning of irrational IFDC antimicrobials, strict monitoring, strict antibiotic policy, hospital antibiotic policy etc., will be helpful. In the developing world where resistance to antimicrobials is increasing, minimizing the use of irrational fixed dose combination antimicrobials can be better tool to combat with the resistance.

Rational drug use means patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements, for an adequate period of time and at the lowest cost to them and their community (1). Some of the common irrational drug use problems are polypharmacy, overuse of injections, self medication, misuse of antibiotics, use of irrational fixed dose combinations (IFDCs) etc. A fixed dose combination refers to the combination of two or more drugs in a single pharmaceutical formulation (2). The use of FDCs is common worldwide. Antibacterial drugs are one used commonly as fixed dose combination. Some of the commonly used irrational drug combinations include antibiotics combined with other antibiotics e.g. ampicillin + cloxacillin, antibiotic combination with antiamoebic e.g. ciprofloxacin + tinidazole etc. Irrational fixed dose combination in general and the need of intervention is already been described in a review article by Poudel A et al. (3) This article focuses mainly about the fixed dose combinations of antimicrobials in Nepal.
Fixed dose combination of antimicrobials practices in Nepal
Antimicrobials are grouped in class of drugs which can be dispensed only after the valid prescription from the registered medical practitioner. The relation between the use of antimicrobials and development of resistance is well established. Despite the established relation, the self-medication with the antibiotic is common in developing as well as developed countries (4), (5). The risk of resistance development is increased several fold by the use of irrational fixed dose combination. The use of fixed dose combination antimicrobials is more common in developing countries. There are several studies which suggest the extensive use of fixed dose combination antimicrobials drugs in Nepal. Some of studies showing extensive use of fixed dose of antimicrobials in Nepal are listed in (Table/Fig 1).
(Table/Fig 1): Studies suggesting the use of Fixed Dose Combination of Antimicrobials in Nepal

Fixed dose combination antimicrobials practice in developing countries
Studies showing extensive use of fixed dose of antimicrobials in developing countries are listed in (Table/Fig 2).
(Table/Fig 2): Studies suggesting the use of fixed dose combination of antimicrobials in developing countries

Fixed dose combination antimicrobials suggested by World Health Organization
Although there are thousands of fixed dose combinations that are available in world market. WHO has approved only 25 fixed dose combination in the 15th edition of WHO essential drug list. Fixed dose combination of antimicrobials approved in 15th edition of WHO essential drug list are mentioned in (Table/Fig 3).
(Table/Fig 3): FDC antimicrobials approved in WHO essential drug list 15th Edition (March 2007)

Fixed Dose Combination antimicrobials registered in Nepal
In Nepal, monitoring and evaluation of drugs starting from the production, marketing, distribution, export-import, storage to use of safe and efficacious drug is done by the Department of Drug Administration (DDA). Manufacturer has to register their individual product to the DDA before marketing their product. The list of registered antimicrobials in the DDA of Nepal is given in (Table/Fig 4).
(Table/Fig 4): List of fixed dose combination antimicrobials registered in the DDA of Nepal

Usefulness of Fixed Dose Combination antimicrobials
When two or more drugs are given together as like fixed dose combination, they may either be indifference to each other or produce synergism or antagonism. When the action of one drug is increased by another drug given concomitantly, it is said to be synergism and when one drug inhibit or decreases the action of another said to be antagonism. The synergistic actions produced by the fixed dose combination drug many remains beneficial for the treatment. Some of the synergistic action of fixed dose combination antibiotics is very much beneficial role in the treatment of infectious disease especially when resistant to single drug treatment is high. In addition, clinically the use of combinations of antimicrobials is advocated for empirical therapy when cause of infection is unknown, for treatment of multiple microbial infections, for synergistic action and to prevent the resistance (18). Examples of some of synergistic FDC antibiotics are listed in the (Table/Fig 5).
Moreover, the resistant to the treatment of disease like Tuberculosis, Leprosy is very high and is recommended to treat such disease with the multi-drug. In such condition, FDC antibiotics can decrease the complexity of dosage regimen, cost of therapy, incidence of ADR and increase the compliance of therapy.19 Thus decreases the resistance to the treatment.
(Table/Fig 5): Examples of some of synergistic FDC antimicrobials
Harmfulness of IFDC antimicrobials
Although some of the fixed dose antimicrobials offer some benefit in treatment of disease like Tuberculosis, Leprosy etc. The majority of irrational fixed antimicrobials have major contribution in resistance development. In addition, IFDC antimicrobials increase the toxicity and identification of causative drug in the combination (19). Moreover, the combination drug decreases the flexibility of prescriber and increase the misuse by self-medication.
Are all FDC antibiotics rational?
Rationality of fixed dose combination is always remains questionable. When it comes to antimicrobial, it may be rational sometimes but not always. Many irrational fixed dose combinations of antimicrobials are available. One of the examples is Ampicillin + Cloxacillin. None of the evidence supports the combination of these two drugs combinations (26). Moreover, there are so many other irrational combinations are available in the market. Some of them are Metronidazole + Tinidazole, Metronidazole + Diloxanate furate + Diphenhydramine, Doxycycline + Neomycine sulphate, Furazolidone + Metronidazole, Ofloxacin + Tinidazole, Ciprofloxacin + Metronidazole, Norfloxacin + Ornidazole, Tinidazole + Ciprofloxacin etc.
Strategies to minimize IFDC antimicrobials
The various strategies to minimize the IFDC antimicrobials are
1. Developing guidelines for preparing of combination product: Many irrational drugs get registered because of lack of guideline for combination products. Hence developing guideline for preparing fixed dose combination will be effective in minimizing irrational fixed dose combination of antimicrobials.
2. Evaluation of product before registration: The complete evaluation of fixed dose antimicrobials before registration will be helpful in minimizing irrational fixed dose combination antimicrobial.
3. Banning of irrational FDC antimicrobial: Banning of irrational fixed dose combination antimicrobials will be helpful in minimizing irrational fixed dose combination antimicrobial.
4. Strict monitoring of use of antimicrobial: Strict monitoring of specially fixed dose combination antimicrobials use can decrease the irrational fixed dose combination.
5. Strict antibiotic policy: Many countries have their antibiotic policy and the strict implementation of it has minimized the use of not only irrational fixed dose combination antimicrobials but also the use of antimicrobial and there was decrease in resistance.
6. Hospital antibiotic policy: In addition to antibiotic policy of the countries, many hospitals have their own antibiotic policy which monitors the use of antimicrobials at the hospital level. Hence the formation of hospital antibiotic policy to individual hospital may be helpful to minimize not only the use of IFDC antimicrobials also the excessive use of antimicrobial.
Initiatives to minimize the IFDC antibiotics in Nepal
In Nepal, some of the initiatives taken in the past to minimize the IFDC antimicrobials are
1. Banning of Irrational fixed dose combination antimicrobials: in the past DDA has banned several irrational fixed dose antimicrobial periodically (27). Some of them are
o Combinations of antihistamines with antidiarrhoeals or with antiamoebic
o Combinations of penicillin with sulfonamides
o Combinations of vitamins C with tetracycline
o Combinations of chloramphenicol except in combination with streptomycin
o Combinations of vitamins with antitubercular drugs except in combinations of antitubercular drug isoniazide with vitamin B6.
o Combination of Antidiarrhoeal/Antibacterial with Electrolytes
o Combination of Two or More Antibacterials Except the Following
o Combination Used for the Treatment of Tuberculosis
o Combination Used for the Treatment of Leprosy
o Combination of Two Antibiotics of the Penicillin Group
o Combination of Two or More Therapeutic Agents as Recognized by Standard Pharmacopoeia
o Combination of anti-amoebic or anti-diarrhoeal drug except the following
o Combination of Metronidazole or Tinidazole with Diloxanide furoate
o Combination of diphenoxylate 2.5mg with Atropine 0.025mg in a tablet
2. Re-evaluation of registered products: DDA re-evaluate the registered product time to time to find the harmful registered drugs, irrational combinations and drugs/combinations of doubtful therapeutic value (28). The evaluation is done by some of the NGO. Base on their recommendation DDA ban the harmful and irrational drugs. First time the drug was banned in 1983 followed by banning items in 1986, 1990, 1992 and 1997.
3. Incorporation of prudent use of antimicrobials in National Drug Policy (NDP): Although there is no separate antibiotic policy, Govt. of Nepal has added prudent use of antimicrobials in NDP as a one of the component under rational drug use which suggest about the supervision and monitoring of antimicrobial use to control the misuse of antimicrobial.
4.Drug Act 1978:Drug Act 1978 was brought into action which prohibits the misuse of drugs and also has categorized the antimicrobial into class of drug which can be sold only with prescription from the registered medical practitioner.


The misuse or over use of antimicrobial can lead to antimicrobial resistance. The use of irrational fixed dose combination antimicrobials can increase the antimicrobial resistance. To minimize the extensive use of fixed dose combination of antimicrobials certain measures like developing guidelines for manufacturing of combination products, evaluation of new products before registration, banning of IFDC antimicrobials, strict monitoring, strict antibiotic policy, hospital antibiotic policies etc., will be helpful. In the developing world where resistance to antimicrobial is increasing, minimizing the use of irrational fixed dose combination antimicrobials can be a better tool to combat antimicrobial resistance.


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