‘Off-label’ or ‘off-licence’ medicines use

When a licensed medicine is used in a manner that is not described in the medicine’s MA or SPC (eg. a different dose, indication, patient group or route of administration) it is being prescribed outside its approved terms of use. This is often known as a medicine being used ‘off-label’ or ‘off-licence’. In this instance, the medicine is now considered to be ‘unlicensed’ and the protection previously afforded to either the patient or the healthcare professional by both regulatory safeguards and the Consumer Protection Act 1987 is removed.

Main categories of unlicensed medicines’ use:

  • Licensed medicine used ‘off-label’ or ‘off-licence’
  • ‘Specials’, in which a designated manufacturer produces medicines under a licence from the regulatory authorities
  • Imports of medicines that have been licensed by a regulatory authority in another country
  • Extemporaneous products formulated by a pharmacist for an individual patient
  • Manipulated products such as crushed tablets or opened capsules

The MHRA and GMC advise that an unlicensed product should not be used where a product available and licensed within the UK could be used to meet the patient's special need. The MHRA61 cites examples of ‘special needs’ including an intolerance or allergy to a particular ingredient, or an inability to ingest solid oral dosage forms (not exhaustive). It goes on to clarify that the requirement for a ‘special need’ relates to the special clinical needs of the individual patient and does not include reasons of cost, convenience or operational needs. The MHRA59 61 and GMC58 do acknowledge that there are certain clinical situations when the use of unlicensed medicines or the use of licensed medicines outside the terms of their licence may be judged by the prescriber to be in the best interest of the patient on the basis of available evidence and experience.

When prescribing an ‘off-label’ or unlicensed medicine, healthcare professionals assume greater clinical responsibility and potential liability. They have to pay particular attention to the particular risks associated with using unlicensed medicines such as: adverse reactions; product quality; or discrepant product information or labelling (eg. absence of information for some unlicensed medicines, information in a foreign language for unlicensed imports, and potential confusion for patients or carers when the Patient Information Leaflet is inconsistent with a medicine’s off-label use).

Off-label use or unlicensed medicines: prescribers’ responsibilities

Advice for prescribers59 - Consider...

  • Before prescribing an unlicensed medicine, be satisfied that an alternative, licensed medicine would not meet the patient’s needs
  • Before prescribing a medicine off-label, be satisfied that such use would better serve the patient’s needs than an appropriately licensed alternative
  • Before prescribing an unlicensed medicine or using a medicine off-label:

    · Be satisfied that there is a sufficient evidence base and/or experience of using the medicine to show its safety and efficacy
    · Take responsibility for prescribing the medicine and for overseeing the patient’s care, including monitoring and follow-up
    · Record the medicine prescribed and, where common practice is not being followed, the reasons for prescribing this medicine; you may wish to record that you have discussed the issue with the patient

Advice for prescribers59 - Communicate...

  • You give patients, or those authorising treatment on their behalf, sufficient information about the proposed treatment, including known serious or common adverse reactions, to enable them to make an informed decision
  • Where current practice supports the use of a medicine outside the terms of its licence, it may not be necessary to draw attention to the licence when seeking consent. However, it is good practice to give as much information as patients or carers require or which they may see as relevant
  • You explain the reasons for prescribing a medicine off-label or prescribing an unlicensed medicine where there is little evidence to support its use, or where the use of a medicine is innovative

Pharmacists have a professional obligation to supply medicinal products with marketing authorisation where such a product exists in preference to an unlicensed medicinal product or a food supplement. As a result, pharmacists also have specific responsibilities when they receive a prescription for an unlicensed medicine60.

In particular, pharmacists should first make the prescriber fully aware whenever a prescription is received where a prescribed medicine is unlicensed or is being used ‘off-licence’61. Having done this however, they are not absolved of any responsibility of any adverse events even if the prescriber accepts full responsibility of any adverse events arising. The pharmacist would share any potential liability with the prescriber in any event.

Pharmacists should also inform the patient that a medicine is being supplied without marketing authorisation or is being used outside of its marketing authorisation without undermining their confidence in either the prescriber or the medicine. Where appropriate, they should discuss the reasoning behind the prescribing decision and advise the patient to report any adverse effects to their prescriber.

Guidance for pharmacists60

  • 1. Check if there is a suitably licensed alternative available.
  • 2. Contact prescriber to check indication, dose, reason for prescribing it – ascertain you have appropriate information to dispense the medicine with confidence.
  • 3. Inform patient regarding unlicensed status.
  • 4. Ascertain patient consent to have the medicine dispensed.
  • 5. Place order with a ‘Specials’ supplier – you can order the unlicensed medicine from your usual ‘Specials’ supplier with who you have an account. (Please note: Category E items are now deleted from the Drug Tariff following the introduction of the ‘Specials’ tariff (Part VIIIB of the Drug Tariff). Unlicensed medicines can still be prepared in a pharmacy under Section 10 exemption – however, please refer to the NHS Business Services Authority for reimbursement details and requirements for endorsing unlicensed ‘Specials’.)
  • 6. On receipt of medicine, prepare/assemble the prescription and supply patient as per SOPs.
  • 7. Keep appropriate records – PMR, NPA ‘Specials’ procurement record book.

NICE evidence summaries

NICE produces evidence summaries for selected unlicensed or off-label medicines which summarise the best available evidence.

The summaries are the first nationally-available source of information for healthcare professionals and patients. Whilst they do not constitute formal NICE guidance they allow evidence-based prioritisation, treatment and funding decisions to be made where there are no clinically-appropriate licensed alternatives.