India is the largest producer and consumer of antibiotics in absolute volume although the per-capita consumption rate is still lower compared to Europe and America. Yet India consumes a high volume of broad-spectrum (drugs which act against a number of bacterial types) antibiotics which should ideally be used sparingly. These and other findings from our recent study — using one of the largest available dataset on drug sales in India, PharmaTrac — published in Lancet Regional Health Southeast Asia, show the extent of inappropriate use of antibiotics in India.
We used a standard measure— defined daily doses (DDD)— which helped to uniformly quantify drug use irrespective of package size, strength of formulations and dose. We examined inappropriateness levels using a globally acceptable norm — WHO ‘Access-Watch-Reserve’ (AWaRe) grouping. ‘Watch’ antibiotics, as the name indicates, should be used watchfully, as these are mostly broad-spectrum antibiotics to be used in very specific indications. ‘Access’ antibiotics on the other hand should be prioritised whenever an antibiotic is indicated and globally the target is to have at least 60 per cent share of ‘Access’ molecules in total consumption.
Our study reported a total reversal of ‘Access-Watch’ ratio with ‘Watch’ antibiotics constituting 72.7 per cent of total DDDs used in 2019 in India. Azithromycin — a broad-spectrum ‘watch’ group antibiotic — was the most consumed antibiotic in 2019. (640 million DDDs, 12.6 per cent of total antibiotic doses). Using these drugs for even trivial upper respiratory infections, which are mostly viral infections that do not require any antibiotic, is a threat to preserving the potential of available antibiotics. The indiscriminate use of broad-spectrum antibiotics is an important reason for the emergence of drug resistance.
So what are the most commonly miused drugs? Quite a few
Azithromycin — Fever, throat pain, cough in adults and children
Amoxycillin — Common cold, fever, ear pain, throat pain, cough
Amoxycillin — Clavulanic acid combination – fever, throat pain and cough in adults
Ciprofloxacin, ofloxacin — Urinary infection, diarrhoea
Cefixime — Fever, throat pain, cough
We examined the inappropriate use against the prevailing antibiotic market system and licensing and regulatory environment in India. India is among a handful of countries that use a large number of fixed dose combinations (FDCs). Antibiotic FDCs — except a very few that have proven scientific value — are problematic due to reduced efficiency and wrong dose-scheduling, resulting in either under-dosing or over-dosing leading to emergence of antibiotic resistance. Previous reports, including a parliamentary standing committee report and an Indian Council of Medical Research expert committee report, highlighted the growing number of “irrational” FDCs as a public health issue.
In terms of regulation, India has a complicated system with one central regulator (Central Drugs Standard Control Organisation (CDSCO) and 28 state level regulators sharing powers and responsibilities. While all new molecules (drugs) need CDSCO approval, the marketing licences which are specific for products (brands/formulations) can be obtained from state regulators — and these state level agencies have limited human resource and technical capacity to decide on the merit of the formulations in the product. This leads to a large influx of antibiotic FDCs into the market with varying strengths and combinations, which have not gone through systematic clinical trials or studies unlike the individual components of these FDCs.
These FDCs often contain medicines from different antibiotic classes, resulting in inappropriate combinations, fuelling the emergence of anti-microbial resistance. Our study showed that only 45 per cent antibiotic brands and 23 per cent of FDC doses had CDSCO approved formulations.
These findings call for careful policy scrutiny at the highest level of the government considering the serious threat of antibiotic resistance that the world and particularly India face today. As the Indian government is in the process of bringing in a new law to replace the Drugs and Cosmetics Act, 1940, we have a golden opportunity to clean up the drug regulatory environment in India. First, we need to have a single central regulator for drug approval and licensing like the US FDA. Or else the CDSCO should have legal and regulatory powers to overrule decisions of state regulators if state regulators approve inappropriate formulations/products. There should be a process to challenge the approval decisions by state regulators. Second, we need to empower state regulators with adequate funding and human resources to take scientific decisions when it comes to approval of drug products. Third, the new law should expand the list of Schedule H1 medicines to include at least all the ‘Watch’ and ‘Reserve’ antibiotics that require mandatory documented evidence of prescription by a qualified doctor before a pharmacist can dispense these medicines. Lastly, the government initiatives on digital health should be used to facilitate the secure transfer of prescription details between doctors and pharmacists. They should have regular audits of prescription and sales data to ensure that antibiotic prescriptions and sales follow certain standards based on local microbiological and drug sensitivity patterns. These policy measures are important even when we continue to invest in improving access to appropriate antibiotics through the Jan Aushadhi stores and an efficient procurement system.