The Union Ministry of Health and Family Welfare issued a gazette notification prohibiting the manufacture, sale, and distribution of 156 fixed dose combination (FDC) drugs in August 2024. The banned FDC medicines include antibiotics, anti-allergics, painkillers, multivitamins, and combination doses for fever and hypertension. Drugs used for hair treatments, anti-parasitic drugs, and skincare drugs were also included in the banned drugs list. Further, a total of 34 multivitamins are under evaluation based on reviews. The government stated the use of FDCs containing Amylase, Protease, Gluco-amylase, Pectinase, Alpha Galactosidase, Lactase, Beta-Glucanase, Cellulase, Lipase, Bromelain, Xylanase, Hemicellullase, Matt diastase, Invertase, and Papain may pose risk to human health, while safer alternatives to these medicines are accessible. The decision was made on the basis of the recommendations of two expert bodies: the Drug Technical Advisory Board (DTAB) and a central government-formed expert committee.
Fixed dose combinations (FDCs), also referred to as cocktail drugs, are medications that combine two or more active ingredients—chemical substances that impact the body—into a single pill, capsule, or injection. These combinations are designed for patients with conditions like tuberculosis or diabetes, who typically require multiple medications. By consolidating these drugs into one formulation, FDCs reduce the daily pill count, simplify treatment regimens, improve adherence, and potentially reduce costs.
The government has invoked Section 26A of the Drugs and Cosmetics Act, 1940, to impose a ban on the manufacture, sale, and distribution of certain FDCs which have been deemed harmful or unnecessary. The DTAB has stressed that no regulatory measures could justify the use of these FDCs, prompting a complete prohibition to protect public health. According to new regulations, the authority to approve drug combinations has been withdrawn from individual states, and now only the central government has the power to grant approvals for such combinations.
The Indian Pharmaceutical Alliance (IPA) has further endorsed the government’s decision, stating that it was a long-overdue measure that had been under consideration for many years. The IPA believed that the move, which was taken after extensive reviews by expert committees including the Kokate Committee and the committee headed by Nilima Kshirsagar, had prioritised patients’ interests and taken a comprehensive approach to ensuring their safety. Pharmaceutical companies have been given a chance to submit evidence supporting the safety and efficacy of their products. Those companies, that provided sufficient data would be allowed to continue marketing their products, while companies unable to furnish adequate data would be required to discontinue their products.
Banned Combination Drugs
Among the banned drugs are:
- Enzyme combinations for gastrointestinal issues;
- Anti-allergic medicines combined with nasal decongestants, mucus-breakdown syrups, and paracetamol;
- Skin treatment combinations including menthol with aloe vera, aloe vera with vitamin E (medicated soap), silver sulfadiazine with antiseptic aloe extract and vitamin (for burns), and calamine lotion with aloe and natural substances (for skin irritation);
- Migraine medicine combined with nausea prevention;
- Mefenamic acid (menstrual cramps) combined with tranexamic acid (anti-fibrotic); and
- Sildenafil (Viagra) combined with a blood vessel and muscle relaxant.
These combinations have been prohibited due to safety concerns and lack of therapeutic benefits.
Why the Ban
One of the key reasons for the ban was to remove combination antibiotics from the market, as their unnecessary and continued use would lead to the growing issue of antibiotic resistance. This resistance means that increasingly stronger doses or newer antibiotics would be required to treat even minor infections, making antibiotic resistance a significant public health concern.
A 2023 Study had revealed that despite previous bans, the proportion of FDC antibiotics in India’s market increased from 32.9 per cent in 2008 to 37.3 per cent in 2020. India has one of the highest numbers of FDCs globally, with many being potentially inappropriate. Alarmingly, 41.5 per cent of the 4.5 billion standard units of antibiotic FDCs sold in 2020 were combinations which were not recommended by the World Health Organization (WHO).
Another reason for the ban has been to prevent companies from bypassing price controls on essential medicines. The government had set ceiling prices for these medicines based on average market prices. However, companies had been creating FDCs to evade this pricing control mechanism. By banning these FDCs, the government aimed to ensure affordable access to essential medicines and prevent price manipulation.
Further, the government has stated that the FDCs containing multiple enzymes, including amylase, protease, and others pose a potential risk to human health, and therefore, their use is being restricted as safer alternative options are available. Since 2014, a total of 499 FDCs have been banned by the government. The central government has labelled these FDCs as ‘irrational’ and stated that they lack any significant therapeutic value or medical benefit, leading to concerns about their safety and effectiveness. The government has banned the manufacture, sale, and distribution of certain FDCs due to their potential health risks. For example, Cheston Cold combines paracetamol for fever, cetirizine for allergies, and phenylephrine for congestion. This FDC may be suitable for individuals with allergic symptoms; however, it may further result in patients with bacterial infections taking unnecessary medications, such as cetirizine, which is intended for allergy relief rather than bacterial infections.
The government’s move has been aligned with its ongoing efforts to eliminate irrational medicine combinations that have proliferated in the market over time. Notably, the banned drugs were initially cleared by state licencing authorities without requiring clinical trials for the specific combinations, as the individual ingredients had already been approved. This loophole allowed these potentially ineffective or harmful combinations to enter the market, which the government has currently been trying to rectify through the ban.
According to the health and family welfare ministry, the 2019 Rules for new drugs and clinical trials stipulate that FDCs are to be treated as new drugs, requiring approval from the central drug regulator. This regulatory change has been instrumental in reducing the number of irrational FDCs available in the market, as manufacturers could no longer obtain approval for these combinations through state licensing authorities without rigorous testing.
A parliamentary panel highlighted in 2012 the issue of irrational drug combinations being approved in India. A government committee was set up in 2014 to review 3,450 such combinations, and recommended an immediate ban on 963 drugs. So far, 499 have been banned, with more to potentially follow as the review continues.
Availability of FDC Drugs and their Consumption
The health ministry has ordered pharmaceutical manufacturers to halt production, stocking, and sales of the banned FDCs with immediate effect. The drugs may still be available in the market for a short period till their stocks last. The manufacturers may challenge the order in court, potentially obtaining permission to clear existing stock, thereby temporarily delaying the complete removal of these drugs from the market.
Since these medicines have been available for years, many people have likely consumed them without issue. Taking one now might not cause harm, as the risks associated with these medicines are generally related to long-term use or specific individual circumstances, rather than a single dose.
Implications for Stakeholders
For patients, the ban can have both positive and negative effects. On the positive side, the withdrawal of ineffective or unsafe drugs could lead to improved treatment outcomes and reduce the risk of adverse effects. However, it might also cause short-term disruptions in treatment regimens, especially if suitable alternatives are not readily available. Patients currently using these FDCs will need to consult their healthcare providers to transition to other treatments.
Healthcare professionals will need to adjust their treatment protocols and possibly shift to alternative therapies. This could involve additional training or updates on the latest guidelines. The ban also emphasises the need for providers to remain vigilant about the medications they prescribe and the evidence supporting their use.
The ban has significant implications for pharmaceutical companies, especially those that manufactured or marketed the affected FDCs. These companies may face financial losses due to the removal of their products from the market and the associated legal and regulatory challenges.
Conclusion
The ban on 156 FDC drugs by the Indian government represents a significant step towards improving drug safety and efficacy. While the decision has complex implications for various stakeholders, it underscores the importance of regulatory vigilance and evidence-based medicine. As India navigates this regulatory shift, the focus must remain on ensuring that patients receive safe, effective, and high-quality treatments.
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