The rise of Fixed-Dose Combinations (FDCs): What it means for pharma players

Fixed-dose combinations (FDCs), which contain two or more active ingredients in a single dosage form, have seen a significant rise in production and usage across the pharmaceutical industry. This increase has been driven by several factors, including the need for simplified treatment regimens, efforts to improve patient adherence, and the demand for cost-effective therapeutic solutions. However, the growing presence of FDCs has also raised concerns about their safety, efficacy, and potential misuse, leading to regulatory crackdowns in recent years.

Factors driving the growth of FDCs

One of the primary reasons for the rise of FDCs has been their role in addressing diseases that require multi-drug therapy, such as tuberculosis, cardiovascular conditions, diabetes, and infectious diseases. Combining multiple active ingredients into a single tablet or capsule is intended to reduce the pill burden for patients, particularly those requiring long-term medication. This approach is believed to improve adherence to treatment, which is critical for managing chronic diseases effectively.

Additionally, pharmaceutical companies have increasingly turned to FDCs as a way to differentiate their products in a highly competitive market. By introducing unique formulations that combine existing drugs, companies can extend product life cycles and maintain exclusivity over certain combinations. This strategy has been particularly prominent in countries like India, which is one of the largest producers of generic medicines and has been a key player in the global FDC market.

Regulatory actions and concerns

Despite their growing adoption, FDCs have been subject to increased regulatory scrutiny due to concerns over irrational combinations. In September 2018, the Indian government banned 328 FDCs after an expert committee found that many lacked therapeutic justification and posed potential health risks. More recently, in August 2024, another 156 FDCs, including widely used cold and fever medications, were prohibited due to safety concerns.

The key reasons for these bans include:

• Lack of therapeutic justification: Many FDCs were found to combine drugs without sufficient evidence that the combination provided added benefits over individual drugs.
• Potential health risks: Some combinations led to reduced efficacy or increased toxicity due to pharmacodynamic or pharmacokinetic mismatches.
• Antimicrobial resistance: The misuse of certain antibiotic combinations contributed to growing concerns about antimicrobial resistance, posing a broader public health risk.

Categories of banned and approved FDCs

The FDCs that have been banned cover multiple therapeutic categories, including analgesics, muscle relaxants, antimicrobials, cough and cold preparations, gastrointestinal treatments, and dermatological formulations. These bans aim to prevent the circulation of medications that lack clinical justification or pose risks to patient safety.

On the other hand, FDCs that continue to be approved and marketed include those with a clear therapeutic need, such as:

• Antitubercular combinations (e.g., Rifampicin + Isoniazid + Ethambutol)
• Antimalarial combinations (e.g., Artemether + Lumefantrine)
• Cardiovascular medications for hypertension and dyslipidemia (e.g., Amlodipine + Telmisartan, Atorvastatin + Ezetimibe)
• Diabetes management formulations for glycemic control (e.g., Metformin + Vildagliptin, Metformin + Glimepiride)

Regulatory bodies have emphasised that approvals will be granted only when supported by strong clinical evidence.

Industry response and future outlook

The pharmaceutical industry has had to adapt to these regulatory shifts by focusing on evidence-based drug formulations and conducting more rigorous clinical trials before seeking approvals. Stricter compliance measures have also prompted companies to reformulate certain medications to align with safety standards.

While the rise of FDCs has been driven by practical medical needs and market dynamics, their future will depend on continued regulatory oversight and scientific validation. As healthcare policies prioritise patient safety, pharmaceutical companies must navigate these challenges carefully to ensure that only well-justified and clinically beneficial FDCs remain in the market.