India Bans 16 'Irrational' Drug Combinations: Expert Warns of Antimicrobial Resistance and Unnecessary Exposure

The Indian government has banned 16 fixed-dose combination (FDC) drugs, including certain antibiotic combinations and dermatological products containing aloe vera and other herbal ingredients. The decision was based on a lack of scientific justification for the combined benefits of these products.

Fixed-dose combinations contain two or more active ingredients in a single formulation and are commonly prescribed for conditions ranging from infections to pain and skin ailments. While some combinations are evidence-based and improve patient outcomes, others are considered 'irrational' because there is little or no scientific evidence that the ingredients work better together than when used separately.

'Public health experts have long warned that irrational combinations can expose patients to unnecessary drugs, increase costs and, in the case of antibiotics, contribute to antimicrobial resistance,' said Dr Kamini Walia, senior scientist at the Indian Council of Medical Research (ICMR). Antimicrobial resistance is a growing public health problem because bacteria, viruses, fungi, and parasites no longer respond to the medicines designed to kill them.

One of the banned products combines amoxicillin and serratiopeptidase. Serratiopeptidase is a proteolytic enzyme that breaks down proteins. The evidence supporting its use alongside antibiotics is extremely limited. The enzyme is acid-labile, meaning it can be degraded in the stomach before reaching the bloodstream. No peer-reviewed randomised controlled trial has shown that adding serratiopeptidase improves bacterial clearance, increases cure rates or reduces the amount of antibiotic required.

Another example is the antibiotic combination of norfloxacin and tinidazole, sold under brand names like Norfolk TZ. If a patient has purely bacterial diarrhoea, taking tinidazole is pointless. Conversely, if they have amoebic dysentery, norfloxacin provides zero benefit. Patients rarely suffer from bacterial and protozoal infections simultaneously, but the combination drug unnecessarily exposes them to both drugs, promoting bacterial resistance.

Doctors often caution against the misuse of Augmentin 625, a combination of amoxicillin and clavulanic acid. The clavulanic acid acts as a barrier to block enzymes that certain resilient bacteria produce to destroy amoxicillin. However, if the specific bacteria causing an infection are not resistant, the clavulanic acid is useless.

Such irrational combinations can contribute to antimicrobial resistance. When combinations are marketed as being more effective without sufficient evidence, they may encourage unnecessary or prolonged antibiotic use. This increases antibiotic exposure in the community and creates selective pressure on bacteria, allowing resistant organisms to survive and multiply.

The government's action follows recommendations from the Drugs Technical Advisory Board, which reviewed scientific evidence for these combinations. This is not the first such measure; in 2018, the Supreme Court upheld a ban on 328 FDCs. The latest ban aims to protect public health by removing products that lack scientific validation from the market. Patients are advised to consult doctors for appropriate single-ingredient alternatives and to avoid self-medication with combination drugs.