What are fixed dose combination drugs and why are many of them banned?

The union government has banned certain fixed-dose combination drugs due to concerns over safety, efficacy, and potential misuse.

In Short

• Fixed-dose combination drugs contain two or more active pharmaceutical ingredients
• They are used to reduce the number of medicines a person takes
• Some combinations are incompatible, they can lead to serious side effects

The government banned as many as 156 fixed-dose combination drugs in August this year that were administered as painkillers, multivitamins and antibiotics for fever, cold and others.

In 2016, the health ministry prohibited the sale of 344 fixed-dose combination drugs. However, after the move was challenged in the Delhi High Court by drug manufacturers, only 14 drugs were banned.

Countless fixed-dose combination drugs have been circulating the market and are gradually known to be come unscientific and harmful to patients.

Once known to be on top of their game, fixed-dose combination drugs are a major threat to India's public health system.

WHAT ARE FIXED-DOSE COMBINATION DRUGS?

Fixed-Dose Combination (FDC) drugs are formulations that contain two or more active pharmaceutical ingredients (APIs) in a single dose.

The Central Drugs Standard Control Organisation (CDSCO) defines FDC drugs as “products containing two or more active ingredients used for a particular indication(s).”

FDCs are often used to simplify treatment regimens, improve patient compliance, and address multiple health conditions simultaneously, such as in the treatment of HIV, tuberculosis, and hypertension.

By reducing the number of pills a patient needs to take, FDCs help ensure better adherence to the prescribed therapy.

When used rationally, fixed-dose combination drugs allow the medicines to work synergistically, boosting each other's effects while lowering the overall dosage compared to when taken separately.

For instance, a combination of metformin and glyburide has been shown to manage diabetes more effectively at reduced doses in an FDC form than when administered as individual tablets. This can enhance patient outcomes and minimize potential side effects.

However, the Indian government has banned certain FDCs due to concerns over safety, efficacy, and potential misuse. Many of these combinations have not undergone rigorous clinical trials to establish their effectiveness or safety.

WHY HAS THE GOVERNMENT BANNED CERTAIN FDCs?

Some combinations may combine drugs that are incompatible or have conflicting actions, leading to side effects or ineffective treatment.

In response, the government has scrutinised thousands of FDCs, leading to bans on those considered irrational or unsafe.

"These combinations may lead to adverse effects which may have a serious impact on health. This may be arrythmia, tacypnea, hypotension or allergic reactions to life-threatening conditions like hypersensitivity reactions. These may be temporary or long lasting," said Dr Pawan Gupta, Senior Consultant in Pulmonary Medicine at BLK-MAX Super Speciality Hospital, New Delhi.

Dr Narender Saini, Former Honorary President of Indian Medical Association, said that most of the banned fixed dose combination drugs are antibiotics, painkillers and anti-allergic cocktails. They are banned over "no therapeutic advantage and increase side effects."

In India, fixed-dose drug combinations became more popular due to affordability and ease of administration. However, concerns about their irrational use have been raised, particularly since many of these medicines were approved at the state level without proper oversight by central regulatory authorities.

This led to the 2018 Supreme Court order banning 328 FDCs, citing public health risks.

While fixed-dose combination pills may have lowered the ease for patients to consume excessive medicines, they have increasingly posed health threats as well.

"If a patient requires a different dose of one component, they may have to adjust the entire combination, potentially leading to under-treatment or over-treatment. Combining multiple active ingredients can lead to an increased risk of adverse effects, making it harder to identify which component is causing them," said Dr Vibhu Kawatra, Pulmonologist Pediatrician and Allergy Specialist, New Delhi.

In cases like antibiotics, using FDCs can sometimes contribute to resistance if not all components are effective against the target pathogen.

Given that India is increasingly facing the threat of antimicrobial resistance, banning several fixed-dose combination drugs could be a step towards unsolicited sale of these medicines.