What Nimesulide reveals about drug regulation and patient safety

Recently, the Indian Ministry of Health and Family Welfare issued a government resolution banning the use of Nimesulide above 100 mg dose, citing patient safety concerns at higher doses.
This decision has once again brought attention to the global journey of Nimesulide, making it an important case study to understand:

• How new drugs are introduced worldwide
• How patient safety is evaluated
• Why regulatory standards differ across countries

Nimesulide serves as a classic example of non-uniform global drug regulation, where approval, restriction, or banning depends heavily on the strength and philosophy of regulatory systems rather than universal safety standards.

Brief history of Nimesulide-

Nimesulide is a Non-Steroidal Anti-Inflammatory Drug (NSAID).

• Developed in Italy by Rottapharm (Later became part of Meda Pharmaceuticals)
• Developed in the early 1980s
• First marketed in 1985

Global regulatory status of Nimesulide

1. Countries where Nimesulide is approved (with restrictions)

Due to concerns primarily related to hepatic and nephrotoxic effects, its use is restricted in several countries.

• India
  • Approved in 1995 
  • Banned for children below 12 years (2011)
  • Ban on doses above 100 mg (2025)
• Argentina
  • Approved in 1986, with controlled use

2. Countries where Nimesulide was withdrawn or banned after approval

Withdrawals were mainly due to serious liver toxicity concerns. (Between 2002–2007)

• Finland – Withdrawn
• Spain – Withdrawn
• Ireland – Withdrawn
• Belgium-Withdrawn 
• United Kingdom-Banned in 1985, almost immediately after approval

3. Countries where Nimesulide was never approved

In these countries, regulatory authorities rejected approval outright, citing safety risks.

• United States
  • Not approved by FDA
  • Reason: Severe liver toxicity risks
• Canada
  • Not approved due to safety concerns
• Australia
  • Not approved by TGA
  • Reason: Liver safety concerns
• Japan
  • Not approved by PMDA
• New Zealand
  • Not approved due to safety concerns

Key observations from global data

The regulatory journey of Nimesulide reveals three distinct global patterns:

1. Countries with very strict regulatory systems

• Mostly technologically advanced and highly regulated nations
• No drug is approved unless:
  • Long-term safety data is available
  • Risk–benefit ratio is clearly favourable
• Example: USA, Japan, Australia

2. Countries with moderately developed regulatory systems

• Regulatory processes exist but are:
  • Inconsistently enforced
  • Sometimes reactive rather than preventive
• Drugs may be:
  • Approved first
  • Restricted or banned later based on adverse reports

3. Countries with weak regulatory oversight

• Follow the assumption:

“If a drug is approved in the country of origin, it must be safe for us too.”

• Limited: 
• Independent safety evaluation
• Pharmacovigilance capacity
• Patient safety becomes a secondary consideration

Conclusion: Lessons for Patient Safety-

The story of Nimesulide clearly demonstrates that: There are no uniform global standards for drug safety

• Patient safety varies significantly based on-

• Regulatory strength
• Scientific capability
• Political and economic priorities

• A drug can be:

• Never approved in some countries
• Approved and later banned in others
• Still in use with restrictions elsewhere

Key policy observations:

1. No uniform global drug safety standard exists-
   Regulatory decisions vary widely despite similar scientific evidence.
2. Regulatory strength determines patient safety-
   Countries with strong pharmacovigilance systems reject unsafe drugs early, while others respond after harm is observed.
3. Delayed corrective action increases patient risk-
   Approve–then–ban approaches expose populations to avoidable adverse effects.
4. Developing countries bear disproportionate risk-
   Due to limited independent safety assessment and weaker post-marketing surveillance.

Policy implications for India:

• Reliance on foreign approvals or historical use is insufficient to ensure safety.
• Older drugs approved decades ago require periodic re-evaluation using current scientific standards.
• Paediatric, geriatric, and high-dose safety must receive special regulatory attention.
• Weak pharmacovigilance undermines early detection of adverse drug reactions.

Policy recommendations

It is recommended that the Government may consider:

1. Mandatory periodic safety review of all legacy drugs using updated global evidence
2. Strengthening pharmacovigilance systems at national and state levels
3. Making dose-specific and age-specific safety data compulsory for continued approval
4. Establishing clear, transparent criteria for drug restriction or withdrawal
5. Enhancing regulatory autonomy and technical capacity of drug control authorities
6. Establish uniform national safety benchmarks aligned with global best practices
7. Mandate long-term safety studies before approval of new drugs
8. Periodically review older drugs using updated safety evidence 
9. Testing of old drugs introduced in India but not being used in developed countries 
10. Promote transparency in regulatory decision-making

Key lessons for regulatory governance:

• Drug approval is a public health decision, not merely a technical or commercial one.
• Patient safety must take precedence over market availability.
• Independent, evidence-based regulatory capacity is essential.

Conclusion:

The global regulatory experience of Nimesulide demonstrates that drug safety is not guaranteed by historical use or international availability.

A patient-centric, precautionary, and evidence-driven regulatory framework is essential to prevent avoidable harm and to maintain public trust in the healthcare system.