Antimicrobial resistance (AMR) has emerged as a major global public health concern, driven by the inappropriate and excessive use of antibiotics. [1] To address AMR, the World Health Organization (WHO) introduced the AWaRe (Access, Watch, and Reserve) classification system as a stewardship tool to monitor antibiotic consumption and promote rational use of antibiotics. [2] This framework encourages the preferential use of ‘Access’ antibiotics for common infections and recommends judicious use of Watch and Reserve agents for specific, well-defined indications. [3] Treatment decisions in countries such as India where healthcare spending is predominantly out-of-pocket are guided not only by clinical efficacy and resistance patterns but economic considerations as well. The financial aspects play a crucial role in real-world prescribing and patient adherence. [4]

India is one of the largest pharmaceutical markets globally. The Indian market is characterized by widespread availability of branded generics for most antibiotics. [4] Along with enhanced availability, this also leads to substantial price variation between different brands of the same drug. Such variability may influence prescribing decisions, contribute to irrational antibiotic use, and can impose an unwarranted financial burden on patients. [5,6] The cost per Defined Daily Dose (DDD) is a standardized measure developed by the WHO. It offers a useful approach for comparison of the economic burden of antibiotics across different drugs and formulations, independent of dosing schedules. [7,8]

Although several studies from India have explored price variation among antibiotics, relatively few have examined these costs within the context of the WHO AWaRe classification, and even fewer have assessed cost per DDD. [9,10] Evaluating these economic dimensions is crucial in bridging the gap between principles of antimicrobial stewardship and routine clinical practice. Against this background, the present study aimed to assess cost variation and cost per DDD of WHO AWaRe category oral antibiotics available in the Indian market and to explore their implications for rational antimicrobial therapy.

MATERIALS AND METHODS

A cross-sectional, descriptive cost analysis was conducted to evaluate oral antibiotics available in the Indian pharmaceutical market.Antibiotics were included in the study if they met the following criteria:availability in oral solid dosage forms (tablets or capsules), classification under the World Health Organization (WHO) AWaRe framework, assignment of an Anatomical Therapeutic Chemical (ATC) code and a Defined Daily Dose (DDD) by the WHO and marketing in India at the time of data collection.The following were excluded from the analysis: fixed-dose combinations (FDCs), oral syrups or suspensions, parenteral formulations, and antibiotics without an assigned WHO DDD. These exclusions were applied to ensure methodological uniformity and to enable accurate and comparable cost per DDD calculations.

A total of 19 oral antibiotics were included in the analysis, comprising 9 ‘Access’, 9 ‘Watch’, and 1 ‘Reserve’ category antibiotics. The selected agents represent commonly prescribed oral antimicrobials in outpatient clinical practice in India. [3-6]Price data were obtained from the Current Index of Medical Specialties (CIMS), a widely used and publicly accessible Indian drug price database and pharmaceutical compendium. [11] For each antibiotic, multiple marketed brands were identified. As a large number of brands were available, the analysis was restricted to the first ten listed brands to ensure feasibility and consistency. For antibiotics with fewer than ten available brands, all listed brands were included.

Each antibiotic was categorized as Access, Watch, or Reserve according to the WHO AWaRe classification. Classification was applied at the drug level and not at the formulation level. [2]The cost per Defined Daily Dose (DDD) was calculated by multiplying Cost per unit with Number of units required to meet the WHO-defined DDD [7]Unit cost was derived from the retail price of each brand. For each antibiotic, the minimum and maximum cost per DDD across brands were identified.Cost variation for each antibiotic was assessed using the maximum-minimum price ratio, by dividing Maximum cost per DDD by Minimum cost per DDD.

The data was entered in MS excel and was analyzed using the SPSS version 16. Continuous variables were summarized as means with standard deviations or medians, while categorical variables were expressed as proportions with 95% confidence intervals.

RESULTS

A total of 19 oral antibiotics were included in this study. Antibiotics were categorized according to the WHO AWaRe classification. (Table 1) ‘Access’ and ‘Watch’ antibiotics were equally represented (9 each), while the ‘Reserve’ category was represented by a single drug. There was substantial variability between the minimum- and maximum-priced brands available for the same antibiotic, demonstrating meaningful dispersion in prices within the market. (Table 2) For ‘Access’ antibiotics, the minimum cost per unit ranged from INR 0.622 to INR 16.33, while the maximum cost per unit ranged from INR 3.30 to INR 46.88. For ‘Watch’ antibiotics, minimum unit costs ranged from INR 3.60 to INR 37.19, and maximum unit costs ranged from INR 5.90 to INR 104.00. The single ‘Reserve’ antibiotic, linezolid, had a minimum unit cost of INR 29.431 and maximum unit cost of INR 80.505.Across all included antibiotics, the lowest observed minimum unit cost was for metronidazole (Access) at INR 0.622, while the highest observed maximum unit cost was for cefuroxime (Watch) at INR 104.00.

When comparing ‘Access’ vs ‘Watch’ antibiotics on minimum cost per unit, ‘Watch’ antibiotics showed higher average minimum unit prices than ‘Access’ antibiotics. This difference was statistically significant. (Mann–Whitney U test p = 0.022). This suggests that ‘Watch’ antibiotics tended to have higher floor prices. For maximum cost per unit, ‘Watch’ antibiotics also had higher mean values than ‘Access’ antibiotics, but the between-group difference was not statistically significant. (Mann–Whitney testing p = 0.14) This indicates that while ‘Watch’ drugs tended to be more expensive, the upper-end brand prices were highly variable across drugs.

When standardized using WHO DDD values, marked cost variability persisted. (Table 3) Among ‘Access’ antibiotics, minimum cost per DDD ranged from INR 0.93 to INR 54.00, and maximum cost per DDD ranged from INR 3.30 to INR 187.52. Among ‘Watch’ antibiotics, minimum cost per DDD ranged from INR 6.54 to INR 37.19, and maximum cost per DDD ranged from INR 10.40 to INR 104.00. For the ‘Reserve’ antibiotic (linezolid), minimum and maximum costs per DDD were INR 58.862 and INR 161.01, respectively.The lowest minimum cost per DDD was for doxycycline (Access) at INR 0.93, whereas the highest maximum cost per DDD was for ampicillin (Access) at INR 187.52. There was no significant difference between ‘Access’ and ‘Watch’ groups for either minimum cost per DDD or maximum cost per DDD. (Mann-Whitney U)

Across antibiotics, price dispersion measures such as the price ratio and percent cost variation indicated substantial within-drug variability between the cheapest and most expensive brands. This pattern was observed across both ‘Access’ and ‘Watch’ groups, consistent with heterogeneous pricing across manufacturers and formulations. The median unit-cost price ratio was 3.55 in the ‘Access’ group, with ratios ranging from 1.64 to 18.03. The largest between-brand price dispersion was observed for ampicillin (Access), which showed a price ratio of 18.03 and percent cost variation of 1703.08 percent, followed by metronidazole (Access) with a price ratio of 12.06 and percent cost variation of 1105.79 percent

Across drugs, there was a strong positive relationship between minimum and maximum prices, both at the unit-cost level and at the DDD-cost level. Pearson and Spearman correlations were high and statistically significant p < 0.001, indicating that antibiotics that were expensive even at their lowest-priced brands also tended to have higher maximum-priced brands. This suggests that pricing tiers move together across the market rather than reflecting isolated extremes.

Table 1. Characteristics of WHO AWaRe Category Oral Antibiotics Included in the Study

NLEM-National List of Essential Medicines 2022

Table 2. Cost Variation among WHO AWaRe Category Oral Antibiotics in India

INR- Indian Rupee ,Max=Maximum ,Min=Minimum

Table 3. Cost per Defined Daily Dose (DDD) of WHO AWaRe Category Oral Antibiotics in India

INR- Indian Rupee , DDD- Defined Daily Dose

DISCUSSION

This study offers a focused assessment of the affordability of oral antibiotics in India by examining cost per defined daily dose (DDD) across WHO Access and Watch categories. By shifting attention from brand-level price differences to molecule-level treatment costs, the analysis provides a practical perspective on the economic burden faced by patients in routine outpatient care. The findings indicate that Access antibiotics are generally associated with lower and more predictable costs per DDD compared with Watch antibiotics, supporting their role as preferred first-line agents.

Affordability is a critical determinant of antibiotic use in India, where out-of-pocket expenditure remains substantial. [12,13] Even small increases in daily treatment cost can influence whether patients initiate therapy promptly or complete the prescribed course. [14,15,16] The higher median costs and wider cost dispersion observed among Watch antibiotics suggest that economic factors may unintentionally shape prescribing decisions and patient adherence. From a stewardship standpoint, this raises concerns, as incomplete treatment or cost-driven substitutions can compromise clinical outcomes and potentially contribute to antimicrobial resistance. [17,18]

An important observation from this analysis is that affordability is not uniform within AWaRe categories. Although Access antibiotics were generally less expensive, a small number were associated with relatively higher costs per DDD. This finding highlights that classification within the Access group does not automatically translate into affordability at the point of care. Market forces and pricing structures may influence treatment costs, underscoring the need for continuous monitoring of affordability even among antibiotics recommended for widespread use. [19,20]

The use of cost per DDD as an outcome measure offers several advantages. Unlike unit-based pricing, cost per DDD reflects the actual daily cost of therapy and allows meaningful comparison across antibiotics with different dosing schedules. Incorporating such pharmacoeconomic indicators into clinical decision-making could help prescribers evaluate therapeutic alternatives within the same AWaRe category, balancing effectiveness with affordability. This approach is particularly relevant in resource-constrained settings, where cost considerations strongly influence both prescribing behavior and patient adherence. [21,22]

The findings also have implications for antimicrobial stewardship programs. While stewardship efforts traditionally focus on resistance patterns and appropriateness of use, integrating affordability considerations may strengthen their effectiveness. Promoting the rational use of affordable Access antibiotics, where clinically appropriate, could support adherence, reduce unnecessary reliance on higher-cost Watch antibiotics, and enhance equity in access to essential medicines.

From a broader health system perspective, molecule-level affordability data can inform formulary decisions and guide procurement strategies in public healthcare settings. Identifying antibiotics associated with higher treatment costs may help prioritize cost-effective options without compromising clinical efficacy.

Overall, this study underscores the importance of incorporating economic evaluation into antimicrobial stewardship and policy frameworks. By highlighting differences in affordability between Access and Watch antibiotics, the analysis supports a more holistic approach to rational antibiotic use—one that aligns clinical effectiveness, resistance containment, and patient-centered affordability.

LIMITATIONS

This study has several limitations. The cross-sectional design of this study captured prices at a single time point and thus does not account for temporal price fluctuations. We restricted our analysis to a maximum of ten brands, which may have resulted in underestimation of true market price variability for antibiotics with extensive brand price variability. We excluded fixed dose combinations and parenteral formulations. This was necessary for methodological consistency but can limit generalizability. Also, there might be variability in actual procurement prices and listed retailed prices in CIMS.

CONCLUSION

Significant cost variation exists among WHO AWaRe category oral antibiotics in India, particularly within the ‘Watch’ group. Cost per DDD analysis should be incorporated into antimicrobial stewardship initiatives as it can provide valuable insight into the economic burden of antibiotic therapy. Policy measures should aim at reducing extensive price variation and promoting use of ‘Access’ antibiotics. This can enhance rational antimicrobial use and improve patient outcomes.

DECLARATIONS

Acknowledgments: Nil

Funding source:  Nil

Conflicts of interest/Competing interests: Nil

Ethics Statement: This research did not involve human participants, animal subjects, or any material that requires ethical approval.

Informed Consent Statement: This study did not involve human participants, and therefore, informed consent was not required.

REFERENCES

1. Laxminarayan R, Chaudhury RR. Antibiotic Resistance in India: Drivers and Opportunities for Action. PLOS Medicine. 2016 Mar 2;13(3):e1001974.
2. AWaRe classification of antibiotics for evaluation and monitoring of use, 2023 [Internet]. Available from: https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2023.04
3. Mudenda S, Daka V, Matafwali SK. World Health Organization AWaRe framework for antibiotic stewardship: Where are we now and where do we need to go? An expert viewpoint. Antimicrob Steward Healthc Epidemiol. 2023 Apr 26;3(1):e84.
4. Regulating the Generic Drugs Market: Eliminating the difference between Branded and Unbranded Generics [Internet]. NLIU CBCL. 2022 . Available from: https://cbcl.nliu.ac.in/competition-law/regulating-the-generic-drugs-market-eliminating-the-difference-between-branded-and-unbranded-generics/
5. Fazaludeen Koya S, Ganesh S, Klemperer K, Yadav P, McDonnell A. Injectable antibiotic use in India: public-private share in volume and cost. Wellcome Open Res. 2024 Feb 19;9:70.
6. Kasse GE, Humphries J, Cosh SM, Islam MS. Factors contributing to the variation in antibiotic prescribing among primary health care physicians: a systematic review. BMC Prim Care. 2024 Jan 2;25:8.
7. DDD Indicators [Internet]. Available from: https://www.who.int/tools/atc-ddd-toolkit/indicators
8. ATCDDD - Guidelines [Internet]. Available from: https://atcddd.fhi.no/atc_ddd_index_and_guidelines/guidelines/
9. Meena DK, Jayanthi M. Cost Analysis of Different Antibiotic Brands Available in Indian Market with Reference to National List of Essential Medicines. Indian J Community Med. 2021;46(1):93–6.
10. Injectable antibiotic use in India: ... | Wellcome Open Research [Internet]. Available from: https://wellcomeopenresearch.org/articles/9-70
11. Drug Website, Directory & Medical Information | CIMS India [Internet]. [cited 2025 Jan 11]. Available from: https://www.mims.com/india
12. Atal S, Mathur A, S B. Cost of Treating Bacterial Infections in India: A Cost Minimization Analysis to Assess Price Variations. Biomedical and Pharmacology Journal. 2020 June 25;13(2):765–78.
13. Kotwani A, Joshi J, Lamkang AS. Over-the-Counter Sale of Antibiotics in India: A Qualitative Study of Providers’ Perspectives across Two States. Antibiotics (Basel). 2021 Sept 17;10(9):1123.
14. Alsan M, Schoemaker L, Eggleston K, Kammili N, Kolli P, Bhattacharya J. Out-of-pocket health expenditures and antimicrobial resistance in low- and middle-income countries. Lancet Infect Dis. 2015 Oct;15(10):1203–10.
15. Bibeau WS, Fu H, Taylor AD, Kwan AYM. Impact of Out-of-Pocket Pharmacy Costs on Branded Medication Adherence Among Patients with Type 2 Diabetes. J Manag Care Spec Pharm. 2016 Nov;22(11):10.18553/jmcp.2016.22.11.1338.
16. Eaddy MT, Cook CL, O’Day K, Burch SP, Cantrell CR. How Patient Cost-Sharing Trends Affect Adherence and Outcomes. P T. 2012 Jan;37(1):45–55.
17. Manning DH, DeBuck E, Simchick M. A Tale of Unequal Substitution. J Pharm Technol. 2014 Apr;30(2):69–72.
18. Salam MdA, Al-Amin MdY, Salam MT, Pawar JS, Akhter N, Rabaan AA, et al. Antimicrobial Resistance: A Growing Serious Threat for Global Public Health. Healthcare (Basel). 2023 July 5;11(13):1946.
19. Pandey AK, Shafiq N, Kakkar AK, Malhotra S, Woods B, Little C, et al. Antimicrobial drug pricing. Commun Med (Lond). 2024 Oct 11;4:198.
20. Gautham M, Miller R, Rego S, Goodman C, Gautham M, Miller R, et al. Availability, Prices and Affordability of Antibiotics Stocked by Informal Providers in Rural India: A Cross-Sectional Survey. Antibiotics [Internet]. 2022 Apr 14 [cited 2025 Jan 14];11(4).
21. Rohatgi KW, Humble S, McQueen A, Hunleth J, Chang SH, Herrick C, et al. Medication adherence and characteristics of patients who spend less on basic needs to afford medications. J Am Board Fam Med. 2021;34(3):561–70.
22. Mishra P, Vamadevan AS, Roy A, Bhatia R, Naik N, Singh S, et al. Exploring Barriers to Medication Adherence Using COM-B Model of Behaviour Among Patients with Cardiovascular Diseases in Low- and Middle-Income Countries: A Qualitative Study. Patient Prefer Adherence. 2021 June 23;15:1359–71.