There are many drugs & drug combination which found to widely prescribed rampantly in the hospitals of Nepal has got some serious side effects due to which those drugs have been banned in the international market. Such as Nimesulide an anagesic has been banned by European Agency for Evaluation of Medicinal Prodcuts (EMEA) prohibited the use in children belwo 12 years. Earliar countries such as Finland, Portugal & Spain suspended use of Nimesulide. Even countries like Bangladesh banned this drugs for both adult and children.
There are few lists of durgs which has been banned internationally:
- Analgin a Pain-killer causes Bone-marrow depression
- Cisapride used for Acidity, constipation causes Irregular heart beat
- Droperidol used in Anti-depressant causes Irregular heart beat
- Furazolidone used in Anti-diarrhoeal causes Cancer
- Nimesulide a Pain-killer, fever causes Liver failure
- Nitrofurazone used as Anti-bacterial cream found to cause Cancer
- Phenolphthalein a Laxative causes Cancer
- Phenylpropanolamine causes Cold & cough causes Stroke
- Oxyphenbutazone NSAID Bone marrow depression
- Piperazine an Anti-worms causes Nerve damage
- Quiniodochlor an Anti-diarrhoeal causes Damage to sight
If we start adding drugs which is to some extent used in Nepal the list might go long. Manyu Fixed Dose Combinations (FDCs) of Antibiotics and or Antimicrobials has been banned internally for the reasons below
a) FDCs of
Ampicillin and Cloxacillin - Both combinations belong to same class namely penicillins acting at the same site by same mechanism offering no synergism.
- Claims like cloxacillin binds to penicillinase and makes it inactive are false.
- No broader spectrum of action as claimed.
- Fixed ratio of drugs does not allow flexibility of changing one or other antibiotic.
b) FDCs of
Amoxicillin and Cloxacillin - All above arguments for ampicillin and cloxacillin combinations hold in this case also, in addition to the following: dosing pattern of both these antibiotics is different as mentioned in standard medical textbooks: amoxicillin is recommended three times a day whereas cloxacillin is recommended four times a day, thus creating a discrepancy in dosing time schedules.
(c) FDCs of Metronidazole/Tinidazole plus Diloxanide Furoate/Di-iodohydroxyquinoline (DHQ) combinations
- Metronidazole and tinidazole are tissue amoebicides whereas diloxanide furoate and DHQ are luminal amoebicides.
- The standard treatment of invasive amoebiasis is tab. metronidazole (35 to 50 mg/kg/day in the three divided doses) for 7-10 days followed by diloxanide furoate 500 mg three times a day for further 10 days.
- According to Goodman and Gillman (1990) for asymptomatic and non-invasive intestinal amoebiasis, only diloxanide furoate is sufficient. In such patients these combinations will lead to unnecessary intake of metronidazole/tinidazole. In case of invasive intestinal and systemic amoebiasis, including amoebic diseases, metronidazole/tinidazole is given followed by diloxanide furoate (Goodman-Gillman, p.955).
- According to Laurence D.R (Clinical Pharmacology, 1992) treatment with tissue amoebiasis should always be followed by a course of luminal amoebicide to eradicate the source of the infection (p.207).
- The combination is recommended nowhere.
(d) FDCs of Metronidazole/Tinidazole and Furazolidone
- Metronidazole is primarily an antiamoebic whereas furazolidone is an antibacterial effective against colonic gram negative bacteria. Furazolidone is nowhere mentioned for use in the latest editions of Goodman Gillman (1990) and Clinical Pharmacology by D.R. Laurence (1992). They are perhaps replaced by safer and more effective agents.
- All diarrhoeas/dysenteries are not polymicrobial in origin - not always due to concurrent infection by E.histolytica and colonic pathogenic bacteria. Thus a person suffering from amoebiasis is condemned to take furazolidone and a patient suffering from bacterial dysentery has to take metronidazole/tinidazole unnecessarily. This increases cost of therapy and chances of ADR.
- Most diarrhoeal diseases do not need treatment with antibiotics/antibacterials. Many of them are self-limiting and need only supportive therapy like fluids and electrolytes with ORS.
Recommendations: Ban all formulations containing metronidazole/tinidazole and furazolidone combinations. They may be separately formulated and marketed in appropriate conditions.
2. FDCs of Analgesics with Analgesics/Antiinflammatory drugs
FDCs of Ibuprofen/Ketoprofen/Diclofenac with Paracetamol/Analgin
and such others
- i) Ingredients of all these combinations, mainly paracetamol, analgin, ibuprofen, diclofenac, etc., belong to a single category of drugs, i.e., Non-Steroidal Inflammatory Drugs (NSAIDS). Paracetamol and analgin have chiefly analgesic and antipyretic actions. Ibuprofen and diclofenac have mainly anti-inflammatory action in addition to having analgesic and antipyretic effects. All these effects are produced by inhibition of synthesis of prostaglandins. Since the mechanism of action is same, there is no synergism. More over anti-inflammatory action leads to pain relief.
- NSAID combinations are known to cause direct damage to kidney (Clinical Pharmacology, Laurence, 1992, p.469.) Although nephropathy is uncommonly associated with the long-term use of individual aspirin-like drugs, the abuse of analgesic mixtures has been linked to the development of renal injury including papillary necrosis and chronic interstitial nephritis (Goodman-Gillman, 1990, p.643).
Recommendations: All such combinations should be banned. Individual ingredients, except analgin, however may be marketed for use either singly or concurrently in appropriate doses in suitable conditions. - Safer and better alternatives, including injections, for analgin are available. Looking to the dreaded ADR of analgin on bone marrow, its marketing as single agent or combination should be banned.
3) Iron Preparations
a)
Haemoglobin containing iron preparations- The source of haemoglobin is blood of animals killed in slaughter houses. This could be dangerous for human use for the fear of causing allergic reactions (foreign proteins), transmission of infections (zoonosis, because blood is a rich medium for bacterial growth), etc.
- Haemoglobin per se is a poor source of elemental iron absorbed by the body. More than half a bottle of any of above preparations will be required for appropriate response in anaemic conditions
- Because of lack of this knowledge on part of patients, and even doctors, it will result into subtherapeutic use and inadequate treatment.
- A six-month course with such preparations will cost approx. Rs.3,650/- as against Rs.55/- (approx.) of treatment with nearly rational preparations of iron-folic acid (Macrofolin-Iron of Glaxo) available in the market.
- No standard textbooks of medical sciences or medical journals mention the use of haemoglobin as a drug.
Not all but most of this combinations is still prescribed in Nepal. The concern authority might have banned or not but its uses are still rampent. Nimesulide has benn banned in few hospitals of Nepal but I know that Manipal college of Medical Science has banned the use of FDC ampi-clox. But it was surprising for me to know that one of ER doctor prescribed ampi-clox combination for cut injury but the pharmacist at MCOMS pharmacy refuse to give this FDC quoting that they have stopped using this combination, he also said that DDA has banned this combinatin in Nepal.
Ironically MCOMS working doctor are not aware of the fact. I am not talking against MCOMS but I think most of the doctors are not aware in Nepal. As I asked some of my colleagues and they were not aware too and prescribing ampi-clox. It shows that at some points we (doctors) are not update enough about the current literature.
Therefore I thought to start a discussion so that we could let them know those drugs or FDC drugs that has been banned internationally and need to be reviewed according to our system.
Can medical students or doctors update on this issues and start a discussion in their respective hospital. I haven't found any research on this topic so that I could claim few issues but collected informations from the NET. I hope we will have updates by some of the xenoMED users from different places.
Have your say.