Bupropion to be made available in the UK again from December 2023, says manufacturer

Smoking cessation therapy bupropion will resume supplies to the UK from December 2023, its manufacturer GSK has said, after the product was withdrawn from the market following concerns over potential nitrosamine impurities.

The return of bupropion supplies follows updated guidance from the European Medicines Agency (EMA) on nitrosamine impurities, published in July 2023, which sets out a 1500 nanogram/day limit for acceptable daily intake of n-nitroso-bupropion.

In a statement to The Pharmaceutical Journal on 29 August 2023, a spokesperson for GSK, which markets bupropion as Zyban, said that, as a result of the updated guidance, supplies of “Zyban tablets will be resumed across the EU and Europe on or before the end of December 2023”.

In 2019, the EMA, along with other medicines regulators around the world, asked marketing authorisation holders to carry out a comprehensive review of all chemical and biological human medicines for the possible presence of nitrosamines, which are probable human carcinogens.

Following its review, GSK said it had placed an immediate hold on batch release and distribution of bupropion 150mg tablets in November 2022, having found the potential for the presence of nitrosamine N-nitroso-bupropion at levels above the EMA’s temporary acceptable intake limit.

GSK confirmed that supplies of bupropion would return to the UK as part of its plans to resume distribution across Europe.

On 24 August 2023, the Medicines and Healthcare products Regulatory Agency published a statement announcing that it would look to align its guidance on nitrosamine impurities in medicines “with regulatory authorities like the EMA”.

It added: “We review European Union (EU) decisions on nitrosamine AIs [acceptable intake levels], either recognising EU assessments or conducting national reviews based on product specifics. If AIs are exceeded, we conduct a national assessment for necessary market actions.”

Bupropion is a selective re-uptake inhibitor of noradrenaline and dopamine, which sits under the class of antidepressant drugs. However, in the UK, bupropion is only licensed for smoking cessation.

Since the withdrawal of bupropion — in addition to varenicline, which was withdrawn from use in 2021 also owing to potential nitrosamine impurities — nicotine replacement therapy (NRT) has been the only licensed medicine for smoking cessation in the UK.

Darush Attah-Zadeh, clinical fellow respiratory pharmacist at North West London Integrated Care Board, and co-chair of the Taskforce for Lung Health medicines optimisation working group, said the forthcoming resupply of bupropion was “good news indeed”.

“Bupropion has been available in the UK since 2000 and a good option for many to stop smoking,” he said.

“It’s not as effective as varenicline or combination NRT … [but] I’d like to see it being made more readily available in community pharmacies (under a patient group directive) alongside evidence-based behavioural support,” he added.

Under the NHS smoking cessation service, community pharmacies can supply one of 30 NRTs, including lozenges, gum and patches along with behavioural support. There are no other medicines currently listed under the service.

Since its launch in March 2022, The Pharmaceutical Journal reported that 2,200 pharmacies had signed up to provide the service in the first two months of it going live.

Commenting on the resupply of bupropion, Robert West, professor of health psychology and director of tobacco studies at University College London, said: “Prior to its withdrawal, Zyban was hardly used at all in the UK — [it is] much more popular in the United States, where, of course, the same drug is also widely used for depression, so I would be surprised if it made much of an impact.”

In August 2023, a spokesperson for Pfizer, the manufacturer of varenicline, told The Pharmaceutical Journal that the company was unable to “speculate on resupply timing at this time”.