Fixed dose combination drugs are:
• Medicines containing two or more active components (Active Pharmaceutical Ingredients) in fixed proportions in a single dosage form. Eg: Corex, cough syrup sold by Pfizer Inc, contains two active ingredients namely chlorpheniramine maleate and codeine phosphate.
• Several medications in fixed combination to be taken together, presented in composite packaging i.e., individual dosage forms in a co-pack. Eg: NexiumHp7 is a antibiotic containing clarithromycin, amoxicillin co-packed with esomeprazole.
They have been in news recently as government banned a list of FDCs stating public interest based on ChandrakantKokate committee recommendation. Later the ban was stayed by Delhi high court.
The rationale behind banning some FDCs:
• Not following the criteria: Eg: A combination of Nimesulide + paracetamol is banned as it has no therapeutic justification and also there are studies stating that the combination may produce increased hepatocyte. Thus, as the combination doesn’t have a proven advantage and also as it produces added toxicity it is banned.
• Containing banned drugs: A study published in journal PLOS Medicine has reported that 12% of analgesic FDCs contain either banned or withdrawn drugs.
• Unsafe and lethal at times: These unauthorized FDCs pose risk to patients and communities. Eg: Most FDCs available in India are analgesics, anti-depressants, and anti-psychotics. Few of anti-psychotic FDCs have proved to be lethal.
• Irrational combinations: There have many unapproved combinations. Eg: NSAIDFDCs containing muscle relaxants have no proven therapeutic justification. In countries as U.S., U.K they are never given as FDC.
• Unapproved andIrrational production: State Licensing Authorities had issued manufacturing licences for a very large number of FDCs without prior clearance from Central authorities and this had resulted in the availability of many FDCs in the market which have not been tested for efficacy and safety. Also irrational use of antibiotic FDCs might lead to antibiotic resistance.
• Pose health risk: As pharmacovigilance is at a nascent stage, would make the study of adverse effects even more difficult, thus posing risk to patients health.
Though FDCs are popular in India for its increased efficacy, better compliance, reduced cost and simpler logistics proper regulation is needed for the approval of FDC for sale as the stakes of public health are high.
Note: (Ref) A combination is considered rational, only if it fulfills the following criteria:
• The combination has a proven advantage over single compounds administered separately in therapeutic effect, safety or compliance
• The drugs in the combination should act by different mechanisms.
• The combination should not have any additive toxicity
• The pharmacokinetics (the absorption, metabolism, distribution, elimination of drug in the body) must not be widely different.