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Jan-Mar2003-11(1)
EDITORIAL
Irrational fixed-dose drug
combinations: a sordid story of profits before patients
C M Gulhati
Anyone with even an elementary knowledge of
medicine knows that, ideally, drugs should be administered as single molecules
based on the specific requirement of each patient. This enables the prescriber
to select specific drugs in specific doses for specific durations. Only
under exceptional circumstances are fixed dose combinations (FDCs) allowed.
These are when (a) two or more drugs have a synergistic action, i.e. the
combination acts to achieve a better therapeutic response than the individual
drugs alone; (b) there is corrective action, and one drug acts to reduce the
incidence and/or severity of adverse effects caused by the other; (c) two or
more molecules are normally needed and taken by the patient concurrently -
provided the dosage of each drug does not need to be individualised, or (d)
prescribing two or more drugs separately could result in one of them not being
ingested, and this would adversely affect the patient's health.
Even under such situations care has to be taken to
ensure that there are no adverse interactions between the combined drugs, that
the pharmacological behaviour (absorption, duration of action, elimination) is
not grossly different, that the withdrawal of one of the agents does not lead to
withdrawal symptoms and in any event sub-therapeutic doses are never used.
Conversely medicines cannot be mixed if side effects are additive or they belong
to the same group with similar mode of action, such as two NSAIDs.
Are these precise and scientifically sound
guidelines being followed in permitting the combination of drugs in our country?
Certainly not. All sorts of bizarre combinations have flooded the market. Many
of them not only harm the patients, they can also damage the health of entire
communities in the future by promoting the emergence of drug-resistant strains
of micro-organisms. Take the example of combining quinolones (e.g.
ciprofloxacin) with imidazoles (e.g. tinidazole). This combination is widely
used, overused and misused for diarrhoea. Since most cases of diarrhoea are due
to viruses, suboptimal use is giving rise to quinolone-resistant strains of
typhoid germs.
Manufacturers' main motive behind mixing drugs is,
of course, to generate prescriptions and make profits. One can hardly expect
anything else if there are over 17,000 pharmaceutical manufacturers, some 40,000
brands but only around 450 basic medicines. When atenolol does not generate
enough sales, it is mixed with alprazolam to create an expensive 'novel'
product. In the absence of research, the pharmaceutical industry in India has
been reduced to a purely commercial activity in which marketing is the name of
the game. It is no wonder that the basic principles of pharmacology get pushed
to the background.
As a result we have combinations such as nimesulide
with paracetamol (both with hepato-toxic additive adverse effects); diclofenac
(taken three times daily) with famotidine (taken once daily); mebendazole (taken
twice daily for three days) with pyrantel (taken as a single dose), atenolol
(taken once daily) with plain nifedipine (taken two-three times daily), and so
on.
Cisapride is combined with omeprazole so that a
patient who requires just omeprazole, a relatively safe medicine, is also made
to consume cisapride, a far more dangerous drug which is banned in western
countries.
Some of the most absurd fixed drug combinations are
available in India. A few examples: nimesulide, paracetamol and tizanidine;
amoxycillin,probenecid and tinidazole; diazepam, antacids and oxyphenonium. Over
70 dangerous FDCs are being sold in India under more than 1,000 brand
names.
Who is responsible for this mess of mixing
incompatible medicines? We must blame the total lack of accountability of the
drug regulatory apparatus, and the existence of parallel drug control centres in
our country.
All new molecules have to be approved by the Drugs
Controller General, India (DCGI). Once a new molecule is licensed, the state
drug controllers take over and monitor pharmaceutical manufacturing facilities
located in their own jurisdictions.
Legally, when two or more individually approved
drugs are combined, the mixed medicine is deemed to be a 'new' product and hence
requires DCGI approval. In practice, state drug controllers merrily go on
licensing such combinations -- even though they do not have the legal powers to
do so. Once one state drug controller approves a combination, it can be sold all
over the country. The result: a patient in, say, Maharashtra consumes a drug
that is neither approved by the DCGI nor by the Maharashtra drug controller but
by a drug controller in, say, Assam! Unless state drug controllers are made to
obey the law, no improvement can occur.
The DCGI is no less culpable. In a federal set-up
he may hesitate to move against erring state controllers but he has the power to
ban such illegal combinations. He has failed to do so. If the Central Government
does not move quickly, the day is not far off when courts will be compelled to
move in to protect the health of the people.
C M Gulhati, editor,
MIMS India. 90, Nehru Place, New Delhi 110 019. Email:mims@ndb.vsnl.net.in