My medicine: Monitoring medicines after licensing

It is impossible to know everything about all the side effects and benefits of a medicine when it is first licensed. A new drug is tested on thousands of people, but can end up being used by many millions.

Different people react to the same medicine differently, depending on their age and sex, and what other treatments they might be taking. And some rare and unexpected side effects may only emerge after a medicine has been in use for several years.

At other times, manufacturing problems may arise, which affect the quality and effectiveness of a medicine. And sometimes fake (counterfeit) medicines may enter the supply chain as a result of criminal activity.

Regulators and pharmaceutical companies know this and work together to continuously monitor the safety and quality of medicines after they have been licensed, so that swift and appropriate action can be taken to protect patients, should the need arise.

Who is involved?
There are several routes through which potential problems can be flagged up:

• Information supplied by manufacturers, including from research carried out during Phase IV clinical trials
• Reports on side effects associated with taking a medicine or herbal remedy made by healthcare professionals and the public to the Yellow Card Scheme
• Alerts raised by healthcare professionals on newly marketed drugs through the Black Triangle Scheme
• Research carried out using records from which patients’ names have been removed and stored in the General Practice Research Database (external link)
• Quality checks on products, including labelling and packaging carried out by MHRA inspectors. Every year they sample around 3000 medicines at manufacturers’ premises, wholesalers, and pharmacies
• Tip-offs about criminal activity, such as the sale of fake (counterfeit) medicines

What action is taken?
The regulators are committed to acting promptly and responsibly to protect patients from potential harm.

They warn healthcare professionals and wholesalers about quality or safety concerns by issuing alerts, which are graded according to the seriousness of their threat to the public’s health.

Healthcare professionals will in turn pass on this information to their patients in cases where continuing to take the medicine poses a serious risk.

• Class 1 life threatening: immediate recall required, for example, fake supplies of blood thinner drug Plavix 75 mg, in June 2007
• Class 2 harmful: recall is required within 48 hours, for example, quality concerns over the effectiveness of the active ingredient in the antibiotic amoxicillin in June 2007
• Class 3 unlikely to harm patients: action required within 5 days, for example, certain batches of a cream/pessary, used to treat fungal infections, such as thrush (Gyno-Pevaryl), because of errors in the patient information leaflet in August 2006
• Class 4 no threat to patient safety: caution advised, for example, fake batches of Sensodyne toothpaste in July 2007

The regulator can also:

• Set up expert panels to review concerns
• Commission further research to look into issues
• Suspend production or sale of a medicine
• Withdraw a medicine from use
• Take legal action against manufacturers and wholesalers when regulations have been breached

New medicines “on probation” (Black Triangle Scheme)
All new and existing medicines being used in a new way are put “on probation” after they are licensed to make extra sure that they work as intended and are acceptably safe.

An upside down black triangle symbol appears in prescribing manuals and adverts, to prompt healthcare professionals to be extra careful when prescribing them and to report any potential side effects.

There is no set time for this probationary period, but the performance of a new medicine will usually be assessed after two years.

Manufacturers also keep a close watch on their newly marketed products, and by law must inform the regulators of any unexpected side effects or quality concerns as soon as reliable information becomes available.

If you want to check on whether a medicine you are taking carries this symbol, you can look under Black Triangle Scheme on the MHRA website.

Using research to check on safety
Researchers, pharmaceutical companies, and drugs regulators can tap into the General Practice Research Database (external link) to carry out research on licensed medicines.

This contains the treatment records of patients, registered at more than 450 GP practices across the UK, and is a rich source of information on the safety and effectiveness of licensed medicines. All names are removed from these records to protect patients’ identity.

More than 500 studies have been published using the information the database contains. And it has been used to assess the safety of the Pill, MMR vaccine, antidepressants and hormone replacement therapy (HRT).

What to do about side effects associated with a medicine

• If you have new or worsening symptoms while taking a medicine always tell the healthcare professional who is treating you
• Speak to your local pharmacist
• You may also find it helpful to call NHS Direct (external link) for advice on 0845 4647 in England and Wales, or NHS24 if you live in Scotland on 08454 242 424
• Use the Yellow Card Scheme to report them to the regulator

Tackling fake (counterfeit) medicines
Sometimes fake versions of a medicine enter the supply chain, as a result of criminal activity by counterfeiters. Fake medicines may contain no active ingredient, so don’t work, or may even contain harmful substances.

The production of counterfeit medicines is a growing problem, and has shifted from lifestyle drugs, such as those for weight loss and erectile dysfunction, to life saving medicines, such as those for cancer and heart disease.

Between 2004 and 2006, the Medicines and Healthcare products Regulatory Agency (MHRA) dealt with 14 cases of fake medicines. This compares with just one case in the previous decade.

Fake medicines can also come from internet pharmacies. The World Health Organization estimates that half of all sales made through internet sites without a return address are for fake medicines.

You can help stamp out the problem by using a dedicated hotline if you have been offered, bought, or have seen for sale, what you suspect might be fake medicines. Call: (0) 207 084 2701 or e-mail: counterfeit@mhra.gsi.gov.uk