Prescribing unlicensed medicines or off-label

These two terms are often used inter-changeable but to me they are very different and the prescriber should consider their actions carefully. The clinical responsibility lies with the prescriber despite the prescribing often being requested by a specialist.

An unlicensed medicine is one that does not have a licence within the UK. It may be imported (possibly licensed outside the UK) or manufactured as a ‘special’.

An off-label medicine is one that is licensed in the UK, but you are prescribing it either in an indication not included in the license or in a manner not covered by the license.

Medicines undergo a lengthy and expensive development, culminating in phase 3 clinical trials and approval in an initial indication within the granted license. Once the medicine is in use, the company will invest in further clinical studies to add new indications to the licence. At some point nearing loss of exclusivity the company will disinvest and no further indications will be sought.

There are situations where standard treatment includes the prescribing of an unlicensed medicine, but you must recognise that the quality of the product may vary and it may be expensive. Where possible prescribe a licensed medicine even if it is off-label.

A good example of this is prescribing melatonin in children with ADHD. One would say that this is common practice. There are a range of products available, mostly specials (imported or manufactures in the UK) and one product that is licensed but not for this indication. Nice has presented the issues in a new evidence summary for unlicensed and off-label medicines series (USUOM2) which is also available in a format suitable for patients. In my opinion, I would advise the licensed off-label medicine where appropriate.

Considering off-label medicines, the situation needs further exploration as to why a medicine is still not indicated. There are a number of possibilities:
1. It is an older medicine and for economic reasons the studies and application for licence will never be done
2. It is a new medicine and it is just a matter of time for the clinical trials to be completed and the license granted
3. The clinical trials have been completed and the results are not considered strong enough (or have been negative) for the company to make an application
4. An application has been made but an extension to the license has been refused.
5. There is limited or no scientific justification and limited or no clinical evidence supporting the medicine.

These are five interesting possibilities. The last may be called ‘innovation’, but I prefer to use the term experimentation and the prescriber may be hard-pressed to prove that this is appropriate, responsible and in the patient’s best interest.
The worrying part of this is that the answer may not be obvious and the prescriber must do their own research to be sure. Broadly, situation 1 and 2 are more reasonable, but it would be appropriate to check that this prescribing has an evidence and experience base and seen to be reasonable by colleagues. Situation 3 and 4 are less reasonable and prescribing that could be expected to be ineffective should be avoided.

Interestingly there is a sixth category, which is less well known. A medicine that had the application for a license extension rejected in the UK, but it was then approved under European mutual recognition. For this reason, I would tend to recommend Candesartan rather than Losartan when an ARB is required for a patient with heart failure despite both having an indication.

There are medicines information centres that may offer support in making your decision and you may find either NICE or the National Electronic Library for Medicines useful sources in addition to the BNF and cBNF. A wide variety of regional and national organisations exist that produce evidence reviews. The GMC provides guidance on issues of good prescribing and specific advice on gaining consent. In the case do paediatrics, the leaflets produced by the RCPCH/Neonatal and Paediatrics Pharmacists Group may also be helpful.

We are also entering a more difficult time where patients have access to an enormously wide range of information through the Internet. Prescribers will require additional time to deal with patient expectation and understanding and to explain why a treatment used by an individual far away to good effect may not be appropriate in this particular situation.

In conclusion, it is fine to prescribe a medicine that is unlicensed or off-label if there is no appropriate licensed medicine available. But make sure your practice is supported by science, evidence and experience and is in line with current medical opinion. Always discuss the issue with the patient, confirm and document consent. Monitor closely and discontinue if target benefits are not achieved.


One thought on “Prescribing unlicensed medicines or off-label

  1. pharmacists – ensure you get certificate of analysis / quality control document for all unlicensed medicines (ULM). ensures product is safe and fit to give patient.

    in hospitals batch number and expiry date of ULM are recorded against patient names so any problems with batch / pt are traceable
    What happens in community pharmacies?

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