Prescribing unlicensed and off-label medicines

Introduction

Prescribing unlicensed and off-label medicines remains a common practice across both paediatric and adult clinical settings. Study results, published by the European Medicines Agency (EMA), have revealed that up to 60% of paediatric hospital prescriptions and approximately 10% in primary care are for unlicensed or off-label use^​1,2​. In adults, unlicensed and off-label prescribing is prevalent in areas, such as oncology, psychiatry and palliative care^​3–5​. This widespread practice reflects gaps in the availability of suitable licensed products, particularly for children and patients with rare diseases, as well as the need for flexibility in complex clinical care.

An unlicensed medicine lacks a UK marketing authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA). These medicines include ‘specials’, extemporaneously prepared products, imported medicines, investigational medicinal products (IMPs) and items supplied through the early access to medicines scheme (EAMS)^​6​. In contrast, off-label use involves the use of a licensed medicine outside its authorised indication, route, dose or patient group^​7​. While often clinically justified, such prescribing carries additional legal, ethical and safety considerations for the prescriber.

In adults, off-label use may become established by emerging evidence, clinical guidelines or expert consensus^​7,8​. In recent years, this practice has increased further owing to supply disruptions of licensed products, with the need to find alternatives for continuity of care but still carries legal and ethical implications.

For pharmacist prescribers, understanding the definitions, responsibilities and governance principles underpinning unlicensed and off-label medicines is critical. This article provides practical guidance for safe and effective prescribing, highlighting risk assessment, communication and monitoring responsibilities within multidisciplinary care.

Legal and professional responsibilities

The legal framework governing the use of unlicensed medicines is outlined in the Human Medicines Regulations 2012^​9​. Regulation 167 allows the supply of unlicensed medicines, where no suitable licensed alternative can meet an individual patient’s clinical need^​9​. In addition, the section 10 exemption under the Medicines Act 1968 permits the preparation and supply of unlicensed products within a registered pharmacy by or under the supervision of a pharmacist^​10​.

Pharmacist prescribers must be satisfied that a licensed alternative would not meet the patient’s needs and that there is sufficient evidence or experience to demonstrate safety and efficacy^​11​. They must accept responsibility for the medicine’s use, monitoring and any follow-up required. The General Medical Council (GMC) and MHRA emphasise that prescribing unlicensed medicines carries increased accountability^​7,12​.

Shared decision-making and informed consent are fundamental to good medical practice^​13​. Patients or carers should be given information about the proposed treatment, including the rationale for using an unlicensed or off-label medicine, known side effects and any suitable alternatives. Documentation should clearly record the justification for use, the discussion held and any agreed monitoring arrangements^​13​. While this may be seen as a lot of additional work, much of this is the same as what we should be doing when initiating any new treatment with a patient.

Some medicines are routinely used outside the terms of their licence — for example, in paediatric practice or established specialist areas such as palliative care. When this occurs within accepted clinical standards or authoritative guidance, it may not always be necessary to draw explicit attention to the licensing status, particularly where this might cause distress or confusion and would not change the clinical decision^​11​. In these situations, a general explanation of the rationale for use is often sufficient; however, prescribers must always be ready to answer questions from patients, parents or carers fully and honestly, ensuring open, proportionate and respectful communication. This is particularly true if the licensed patient information leaflet (PIL) states that the medicine may not be recommended in a particular cohort of patients.

Pharmaceutical quality and formulation

‘Specials’ are unlicensed medicines manufactured or imported to meet the specific clinical needs of individual patients when licensed alternatives are unsuitable^​14​. The quality and bioavailability of specials may vary between manufacturers, even when the product name appears identical, as specifications for each manufacturer may differ, while assessment and reassurance of the certificate of analysis and conformality may be required. Prescribers should confirm that the selected formulation is appropriate for the intended route, strength and excipient profile.

Different batches or suppliers may differ in stability, concentration and excipients, potentially affecting bioavailability or tolerability^​13​. Poor product quality can also result in inconsistent dosing (e.g. where suspensions are not uniformly mixed), leading to each dose withdrawn from a container that holds differing amounts of active ingredient^​15​. To minimise these risks, manufacturers should provide a stability statement outlining the evidence supporting the assigned shelf life. Pharmacists should also record batch numbers of the unlicensed products and maintain consistency in supply wherever possible.

See Table 1 for more information on how location can affect the quality, consistency and bioavailability of specials^​14​.

Risks, safety and monitoring

The use of unlicensed medicines carries inherent risks, including variable bioavailability, limited stability data and the potential for increased adverse drug reactions^{​1,16,17​}. Quality assurance and robust clinical governance are therefore essential. Pharmacists and prescribers should evaluate risks using a structured risk–benefit framework, considering the product’s formulation, labelling, packaging and information quality^​18​. They should ensure that documentation, communication and patient counselling reflect any known limitations and that prescribers and dispensers use the same product specification for repeat supplies.

Monitoring requirements should be proportionate to the risks identified. Regular review of continued need, therapeutic response and tolerability is essential^​14​. Adverse reactions must be reported through the MHRA Yellow Card system, which plays a crucial role in pharmacovigilance for both licensed and unlicensed medicines^​19​.

Clinical decision-making in practice

Prescribers should only consider unlicensed medicines when — after thorough assessment — no licensed alternative meets the patient’s needs. Decision-making should be collaborative, involving pharmacists, prescribers and, where appropriate, the patient or carer. Each decision should be guided by evidence, clinical experience and patient preference, supported by clear documentation^​7,11​. When assessing a product for unlicensed or off-label use, prescribers must evaluate not only the clinical rationale but also the pharmaceutical and governance aspects of the proposed treatment. Table 2 conceptualises the main considerations when using such medicines in practice, illustrating common examples and the factors that should inform safe prescribing decisions^{​20–23​}.

The following scenario explores the clinical reasoning and risk management process used when prescribing an off-label medicine in practice.

Managing transitions of care

When unlicensed or off-label medicines have been prescribed, clear and accurate communication between care settings is vital to avoid medication errors and interruptions in supply. The results of research, published in 2017, showed frequent issues during transitions from secondary to primary care, including general practitioners refusing to prescribe, differences in formulations or doses and delays in obtaining medicines^​24​. To mitigate these issues, strategies should include better communication among healthcare professionals — with the prescribing rationale clearly explained — greater support for community pharmacists and improved information for parents and carers to ensure safe, consistent treatment continuity^​24​. In efforts to improve communication, the NHS Discharge Medicines Service (DMS) was launched in 2021, as an essential service to be provided by all community contractors^​25​. The service allows communication to bridge between hospital care and community pharmacies, ensuring patients receive necessary support and information to manage discharge medicines effectively. The platform also allows specialist pharmacists to provide details on unlicensed and off-label medicines used for a particular patient. 

Pharmacists play a pivotal role in specifying and sourcing appropriate products, confirming pharmaceutical suitability and advising on administration. Prescribers should liaise with pharmacy colleagues to confirm formulation characteristics, such as stability, concentration and excipients, and ensure reliable supply for ongoing therapy.

Governance and best practice

Safe prescribing of unlicensed and off-label medicines depends on strong clinical governance frameworks. The findings of an Canadian population-based study, published in 2016, demonstrated that off-label prescribing without supporting evidence was associated with a 50% higher risk of adverse drug reactions, whereas evidence-supported off-label use did not differ significantly from on-label prescribing^​26​. In adults, polypharmacy is also common, raising the potential for adverse drug reactions and increasing prescribing safety risks^​27,28​. The study findings highlight that risk is not inherent to off-label or unlicensed use itself but to the absence of robust clinical evidence guiding practice. Organisations should have policies for approval, documentation, review and audit of unlicensed medicine use^​20​. Regular review ensures that continued use remains clinically justified and that emerging licensed options are considered.

Five governance principles for safe unlicensed medicine use include: 

1. Establishing optimal treatment; 
2. Understanding patient experience; 
3. Identifying appropriate preparations; 
4. Adequate monitoring and review;
5. Ensuring governance oversight^​14​. 

These principles provide a practical framework for pharmacist prescribers to manage clinical risk while ensuring patient-centred care. Ultimately, unlicensed and off-label prescribing reflects the complexity of real-world medicine use. Pharmacist prescribers must balance evidence, ethics and regulation to ensure decisions are made transparently and collaboratively in the best interest of patients.

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