Drug Safety Update

Volume 2, Issue 9 April 2009

Latest advice for medicines users

Off-label or unlicensed use of medicines: prescribers’ responsibilities

Article date: April 2009

A licensed medicine meets acceptable standards of efficacy, safety, and quality

A marketing authorisation or product licence defines a medicine’s terms of use: its Summary of Product Characteristics outlines, among other things, the indication(s), recommended dose(s), contraindications, and special warnings and precautions for use on which the licence is based, and it is in line with such use that the benefits of the medicine have been judged to outweigh the potential risks. Furthermore, a licensed medicine: has been assessed for efficacy, safety, and quality; has been manufactured to appropriate quality standards; and when placed on the market is accompanied by appropriate product information and labelling.

Prescribing in a patient’s best interests

However, there are clinical situations when the use of unlicensed medicines or use of medicines outside the terms of the licence (ie, ‘off-label’) may be judged by the prescriber to be in the best interest of the patient on the basis of available evidence. Such practice is particularly common in certain areas of medicine: for instance, in paediatrics where difficulties in the development of age-appropriate formulations means that many medicines used in children are used off-label or are unlicensed.

Read more about medicines for children on the medicines for childrens section of the website

See also Drug Safety Update January 2009

Healthcare professionals may regard it necessary to prescribe or advise on the use of an unlicensed medicine (ie, through the so-called ‘specials’ regime when no licensed suitable alternative is available, or when a medicine is prepared in a pharmacy by, or under the supervision of, a pharmacist), or the use of a licensed medicine outside the terms defined by the licence (eg, outside defined indications, doses, routes of administration, or contrary to listed warnings).

In practice

At present, the following healthcare professionals can prescribe an unlicensed medicine: doctors; dentists; and, in some circumstances, supplementary prescribers (who can be a pharmacist, nurse, midwife, community nurse, optometrist, physiotherapist, radiographer, or chiropodist/podiatrist). In addition to these health professional groups, the following can prescribe a licensed medicine off-label: nurse independent prescribers, pharmacist independent prescribers, and optometrist independent prescribers. However, all healthcare professionals who can prescribe as outlined above are subject to: their individual clinical competence; the professional codes and ethics of their statutory bodies; and the prescribing policies of their employers.

The responsibility that falls on healthcare professionals when prescribing an unlicensed medicine or a medicine off-label may be greater than when prescribing a licensed medicine within the terms of its licence. Prescribers should pay particular attention to the risks associated with using unlicensed medicines or using a licensed medicine off-label. These risks may include: 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).

Examples of off-label use of medicines

Off-label intravitreal use of bevacizumab (Avastin, licensed for treatment of various solid cancers) has been associated with reports of severe eye inflammation and sterile endophthalmitis. The production methods, formulation, and doses for bevacizumab were developed for use in oncology. Its use in the ophthalmology setting has not been authorised.

Clarification (updated August 2011): The preparation of bevacizumab for intravitreal use involves manipulation of the authorised medicine to produce multiple aliquots, usually in plastic syringes (so-called compounding). Therefore, it is important to note that this process also results in the creation of an unlicensed medicine.

Methylthioninium chloride (methylene blue) is authorised for management of drug-induced methaemoglobinaemia; however, it is sometimes used off-label as a visualising agent during parathyroid surgery. We are aware of 33 reports of a suspected interaction between methylthioninium chloride and recent treatment with serotonergic drugs, leading to CNS toxicity. In all cases, patients were receiving methylthioninium chloride outside its licensed indication.

Example of use of unlicensed medicines

Since June 2008, a licensed formulation of thalidomide has been available for treatment of multiple myeloma. Prescribers should consider use of this licensed thalidomide product first. Use of the licensed thalidomide product is important because pregnancy-prevention measures are linked to the prescription and dispensing of the authorised formulation, but not to those that are unlicensed.

Advice for prescribers:

  • 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

Communicate: best practice is that…

  • 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

Report suspected adverse reactions…

  • Healthcare professionals have a responsibility to help monitor the safety of medicines in clinical use through submission of suspected adverse drug reactions to the MHRA and CHM via the Yellow Card Scheme. Such reporting is equally important for unlicensed medicines or those used off-label as for those that are licensed


General Medical Council Good Practice in Prescribing Medicines (September 2008)

Royal Pharmaceutical Society of Great Britain Pharmacist Prescriber's Pack

Nursing and Midwifery Council standards of proficiency for nurse and midwife prescribers (April 2006)

Health Professions Council

General Dental Council

Department of Health, Medicine Matters (July 2006)

Further information


Drug Safety Update brings you the latest information about changes to prescribing information to support safer use of medicines

Review of unlicensed medicines

Importation of unlicensed medicines


Key documents from the Department of Health

British National Formulary

British National Formulary for Children

Royal College of Paediatrics and Child Health


Article citation: Drug Safety Update April 2009, vol 2 issue 9: 6.


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Page last modified: 08 July 2013