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Q.
In the market a fixed drug combination (FDC) of Norfioxacin and Metronidazole is available for treatment of diarrhea in children. Is the use of this FDC
rational for the management of acute diarrhea in children?
S.K. Shahid,
'8' - Jayanti,
353/21,
R.B. Mehta Road,
Ghatkopar
[E],
Mumbai 400 077.
Dr. Shahid's queries are relevant and raise three important issues of rational therapy, namely,
1. Rationality of Fixed Dose Combination
(FDCs) in general and the said combination in particular.
2. Rational management
of diarrheal disorders.
3. Promotional
practices
of
pharmaceutical
companies and our prescription behavior.
It is widely accepted that most essential drugs should be formulated as single compounds. Fixed ratio combination products
are acceptable only when the dosage
of
each ingredient meets the requirement
of a defined
population group and when the combination
has a proven advantage over
single compound administered separately in therapeutic effect, safety or compliance(1). They must act as
synergistic to
achieve
a
better
therapeutic response than
each drug alone. Most FDCs have following demerits:
1. Dosage alteration
of one
drug is not possible without alteration
of other
drugs.
2. Differing pharmacokinetics
of
constituent drugs pose the problem
of frequency of
administration
of the formulation.
3. By
simple logic there are increased
chances
of adverse
drug effects and
drug interactions.
4.
FDCs cause confusion or delay in the diagnosis and encourage polypharmacy.
Combination
of
Metronidazole
and
Norfloxacin
The recent model list
of essential
drugs prepared by the WHO includes only
340 items and 532 formulations of which only 12 are FDCs(2).
The combination of metronidazole and norflocacin
rightly does not figure in this list. This is an irrational combination. It can not be overemphasized that most diarrheal illnesses in children are self limiting and require only supportive measures like fluid replacement with ORS.
Antimicrobials have a role to play
in few
children who have dysentery (blood in
stool). Empiric therapy
of dysentery
would
involve use of an antibiotic which can cover common pathogenic Gram negative enteric organisms prevalent in a particular community(3,4). Usually Cotrimoxazole or Nalidixic
Acid are effective. Third generation cephalosporins are also reported to be
effective. Routine
use of Flouroquinolones
in children below 12 years is not recommended. However, Norfloxacin can be used only when other alternatives are not effective. Its recommended dose is 20 to 30 mg/kg/ day in 2 divided doses(5).
Amebic dysentery is very uncommon in children. Its treatment should be considered only if the patient with dysentery fails to improve after consecutive treatment with two antibiotics, each given for 2 days. or when trophozoites of E. histolytica
containing red blood cells are seen in fresh stools(3). The recommended treatment is with Metronidazole 35 to 50 mg/kg/ day in 3 divided doses(6).
The available combinations of Norfloxacin and Metronidazole contain Metronidazole 100 mg and Norfloxacin 100 mg in each
5ml. Considering the pharmacokinetics also, this combination is not proper because Metronidazole in to be given in 3 doses whereas Norfloxacin is to be given in 2 doses. Dosage wise also, this combination has the fallacy of underdose or overdose of one of the ingredients.
All dysenteris are not polymicrobial in origin. Resorting to polypharmacy with
the hope to "cover all possible organisms" is not only unscientific but harmful
to the patient. Both the drugs have common gastrointestinal side effects like anorexia, nau-sea, vomiting and abdominal discomfort(4,6). With use of this combination, the patient is unnecessarily exposed to the risk of additional side effects.
Use of such a combination is not recommended in any standard Text Book of Pediatrics or Pharmacology. For obvious reasons there are no studies available to justify this combination. This combination is only one example of many such irrational preparations flooding the Indian markets. Improving our own prescription behavior by resisting to prescribe such irrational preparations can go a long way in weeding them
out.
Satish Pandya,
Convener, lAP Committee
On Protection of Child Consumer
and Secretary,
Society for Rational Therapy, Vadodra,
Varun Children Hospital,
4, Suhas Society, Opposite Shastri School, Harni Road,
Vadodra 390 006,
India.
1.
The Use of Essential Drugs. WHO Technical Report Series 825. Geneva. World Health Organization, 1992.
2.
The Use of Essential Drugs. WHO Technical Report Series 850. Geneva, World Health Organization, 1995.
3.
The Management and Prevention of Diarrhoea - Practical Guidelines, 3rd edn. Geneva. World Health Organization, New Delhi, Jaypee Brothers 1994; pp 23- 49.
4.
Mandell GL, Petri W A. Antimicrobial agents. In: Goodman and Gilman's The
Pharmacological Basis of Therapeutics,
9th edn. Eds. Hardman JG, Limbird LE. New York, Mc Graw-Hill, 1996; pp 1067- 1068.
5.
Santhana Krishnan BR. Newer antimicrobial agents - Uses and abuses. lAP J Pract Pediatr 1994; 2: 424-426.
6.
Tracy JW, Webster LT. Drugs used in the chemotherapy of Protozoal infections. In: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th edn. Eds. Hardman JG, Limbrid LE. New York, McGraw-Hill, 1996; p 997.
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