Volume 2, Issue 9 April 2009
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.
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).
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).
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.
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:Consider…
Communicate: best practice is that…
Report suspected adverse reactions…
Drug Safety Update brings you the latest information about changes to prescribing information to support safer use of medicines
Article citation: Drug Safety Update April 2009, vol 2 issue 9: 6.