Recently, the government banned 14 fixed dose combination (FDC) drugs, with immediate effect, on the recommendations of expert committee and the Drugs Technical Advisory Board (DTAB), who said that there was "no therapeutic justification" for these medicines and that they may pose "risk" to the patients.

These combination drugs mainly include those that have been used for the treatment of cough, fever as well as common infections.

As per the gazette notification of the Union Health Ministry, dated June 2, 2023, the manufacture for sale, sale and distribution for human use of the following fixed dose combinations have been banned: 

1. Nimesulide+ Paracetamol dispersible tablets
2. Amoxicillin+ Bromhexine
3. Pholcodine+ Promethazine
4. Chlorpheniramine maleate + Dextromethorphan + Guaiphenesin + Ammonium Chloride + Menthol
5. Chlopheniramine Maleate + Codeine Syrup
6. Ammomium Chloride + Bromhexine + Dextromethorphan
7. Bromhexine + Dextromethorphan + Ammonium Chloride + Menthol
8. Dextromethorphan + Chlorpheniramine + Guaiphenesin + Ammonium Chloride
9. Paracetamol + Bromhexine + Phenylephrine + Chlorpheniramine + Guaiphenesin
10. Salbutamol + Bromhexine
11. Chlorpheniramine + Codeine Phosphate + Menthol Syrup
12. Ammonium Chloride + Sodium Citrate + Chlorpheniramine Maleate + Menthol (100mg + 40mg + 2.5mg + 0.9mg), (125mg + 55mg + 4mg + 1mg), (110mg + 46mg + 3mg + 0.9mg) & (130mg + 55mg + 3mg + 0.5mg) per 5ml syrup
13. Salbutamol + Hydroxyethyltheophylline (Etofylline) + Bromhexine.

In addition, the FDC of Phenytoin + Phenobarbitone sodium has also been banned.

FDCs or Fixed Dose Combinations combine two or more active pharmaceutical ingredients (APIs) into a single formulation in a fixed ratio of their doses. FDCs should combine drugs with different but complementary mechanisms of action and comparable or almost similar pharmacokinetic and pharmacodynamic properties. Moreover, their toxicities should not be super additive. FDCs that fulfil these criteria are considered “rational” FDCs. This rationality is decided by the Drugs Technical Advisory Board (DTAB), the technical advisory body, which advises the Drug Controller General of India (DCGI), the regulatory body.

Co-packaged products are also FDCs, according to the policy guidelines for approval of fixed dose combinations (FDCs) in India. FDCs are generally not included in the National List of Essential Medicines (NLEM) “unless the combination has unequivocally proven advantage over individual ingredients administered separately, in terms of increasing efficacy, reducing adverse effects and/or improving compliance”.

The FDCs are justified when they demonstrate clear benefits, which include enhanced efficacy by the synergistic or additive effects of the constituent drugs and better safety profile as the adverse effects of one drug can be reduced by combining it with another drug. The resulting simplified dosing is convenient to the patient and improves compliance to prescribed treatment. The production cost is reduced and therefore they are more affordable to the patients as they have to buy only one product. By reducing polypharmacy, FDCs can reduce the chances of medication errors and also treatment costs.

Many antitubercular (TB) drugs are FDCs; they are also allowed for treatment of HIV and hypertension. Some FDCs are also allowed for treatment of diabetes.

However, their use also has potential downsides. If the individual APIs and the various excipients in the FDC are pharmacologically incompatible with each other, the result is either increased toxicity or diminished efficacy contrary to their use as single drugs. The drugs may peak at different times. Drug-drug interactions may occur. And it is difficult to pinpoint which API in the FDC has caused the adverse effect. Addition of unnecessary drugs increases cost. FDCs restrict flexibility in dosing, especially in patients with hepatic or renal impairment. Another disadvantage of FDCs is development of multidrug resistance.

Earlier in 2016 also, the government had banned 344 FDC drugs. This ban was challenged in courts and the conflicting judgements only muddied the waters. While the Delhi High Court stayed the ban, in 2017, the Hon’ble Supreme Court set aside the High Court order and asked the DTAB to re-examine this ban and said “We say so because we find that the Kokate Committee did deliberate on the 344 FDCs plus 5 FDCs and did come to a conclusion that the aforesaid FDCs be banned, but we are not clear as to what exactly the reasons for such conclusions are, and whether it was necessary in the public interest to take the extreme step of prohibiting such FDCs, instead of restricting or regulating their manufacture and supply. In order that an analysis be made in greater depth, we, therefore, feel that these cases should go to the DTAB and/or a Sub-Committee formed by the DTAB for the purpose of having a relook into these cases.” (https://cdsco.gov.in/opencms/export/sites/CDSCO_WEB/Pdf-documents/Committee/dtab_sub_report.pdf)

Accordingly, the Sub-Committee, which was constituted by the DTAB in 2018 to examine the FDCs in its report upheld the prohibition of 15 FDCs in public interest. But on September 8, 2018, the Supreme Court allowed these 15 drugs stating the technical advisory body’s report was not enough to ban these combination medicines that were being manufactured in India since before 1988. It also said that the government was free to carry out fresh investigations examining the safety of these 15 drugs if it still wants to ban them (Economic Times, Sept. 8, 2018).

Will the latest ban on 14 FDCs be challenged again in a court of law? Only time will tell.