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Reader's forum

Indian Pediatrics 1998; 35:941-942

Fixed Drug Combination for Treatment of Diarrhea


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.
 

Reply

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.

References

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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