What does off-label use of a medicine mean for me?

What is off-label use of a medicine?

Off-label prescribing means using a medicine outside the conditions of its marketing authorisation – for example a different indication, dosage, age group or route of administration than the ones approved. By law, each medicine's Summary of Product Characteristics (SmPC) contains all the agreed conditions under which it is authorised^[1].

Unlicensed medicines are a separate category: these are medicines that hold no marketing authorisation in the national register of medicinal products. This group includes magistral or "special" preparations, whose formulation is modified on the doctor's prescription and made up by a pharmacist^[1]. A medicine can therefore be licensed overall and still be used off-label, while an unlicensed product has no assessed indication at all.

Off-label practice was first formally recognised in the European Union through Directive 2010/84/EU. That directive made marketing authorisation holders responsible for monitoring their medicines and providing all available information, including information on uses beyond the marketing authorisation^[1].

Which patients are most often treated off-label?

Off-label prescribing is concentrated in groups where organising clinical trials is legally or logistically difficult – paediatrics, oncology, psychiatry and rare diseases – which makes it a common practice in those areas. Off-label prescribing is therefore usually linked to unmet needs for treatment in particular populations or conditions^[1].

Paediatric drugs are frequently used outside the SmPC because many manufacturers do not run the trials needed to secure a licensed paediatric use^[2]. In a study of about 289,000 children and adolescents aged 0–16 covered by a German statutory health insurer, 87.4% of prescribed packages (66.1% of active substances) matched their licence, while 3.2% (15.7% of active substances) were prescribed off-label; for 9.4% of prescriptions the licensing status could not be established. For neonates and infants the share of licensed prescriptions fell below average, at 42.5% and 82.8% of prescribed packages respectively^[3].

In palliative care, medicines are often unlicensed or used off-label – through an unapproved route, indication or dose – when the clinical need cannot be met by licensed medicines^[4]. Paediatric atopic dermatitis illustrates the age dimension: it affects up to 20% of paediatric patients, and in 60% of them it starts before the age of one; most systemic and topical treatments for the condition will need to be used off-label during that period^[1].

How common is off-label use in children and in cancer care?

A retrospective study of discharge letters from children hospitalised for atopic dermatitis in a paediatric dermatology ward in 2019 examined how often off-label prescribing occurred and which medicines were involved, in relation to indication and age^[1].

Off-label use also appears in paediatric oncology. A single-institution retrospective cohort study looked at the prevalence, characteristics and clinical outcomes of off-label prescribing of 108 FDA-approved targeted anticancer drugs in patients under 30 years old treated for cancer between 2007 and 2017. The overall prevalence of off-label use of targeted therapies was 9.2% (374 patients), and it increased significantly over the study period. Of the 108 potential agents, 38 (35%) were used by at least one patient, and patients treated off-label were more likely to have neuro-oncology diagnoses (46% vs 29%)^[5].

Setting	What was measured	Result
Children and adolescents aged 0–16, Germany (outpatient prescriptions, 2002)[3]	Share of prescribed packages matching the licence	87.4% licensed; 3.2% off-label; 9.4% licensing status not established
Neonates and infants, same analysis[3]	Share of licensed prescriptions	42.5% (neonates) and 82.8% (infants) of prescribed packages
Patients under 30 treated for cancer, single US centre, 2007–2017[5]	Prevalence of off-label use of targeted anticancer drugs	9.2% (374 patients); rose significantly over the study period
Paediatric atopic dermatitis[1]	Age at onset, and treatment implications	Up to 20% of paediatric patients; onset before age 1 in 60%

When should a licensed medicine be used off-label rather than an unlicensed one?

Guidance sets out a hierarchy for choosing between a licensed product, an off-label use of a licensed product, and an unlicensed product. An unlicensed product should not be used where a product available and licensed in the UK could meet the patient's special need. Although off-label use of products is not recommended, if a licensed product can meet the clinical need – even off-label – it should be used instead of an unlicensed product^[6].

The reasoning behind that order is the assessment already carried out: licensed products available in the UK have been assessed for quality, safety and efficacy, and while some of that assessment may not apply to an off-label use, much of it will still be valid. The fact that the intended use falls outside the licensed indications is therefore not a reason to switch to an unlicensed product. If the product cannot meet the special need, an imported medicinal product licensed in its country of origin should be considered next^[6].

Only if none of these options will suffice may a completely unlicensed product have to be used – for example UK-manufactured "specials" made in GMP-inspected facilities, which are otherwise unassessed, since GMP inspection of "specials" manufacturers is not product-specific. The least acceptable products are those unlicensed in their country of origin and not classed as medicines there, such as products from countries where they are treated as supplements rather than pharmaceuticals and may not be made to expected standards of pharmaceutical GMP; these should be avoided whenever possible^[6].

What does the approved label – the SmPC – actually cover?

The Summary of Product Characteristics contains all the conditions agreed for a medicine by law, including its licensed indications, dosage, age group and route. Using a medicine outside any of these conditions counts as off-label use^[1].

On the FDA side, the approved product label is the official description of a drug product, covering the indication, who should take it, adverse events, instructions for use in pregnancy and in children, and safety information for the patient; labels are often found inside the product packaging. Off-label or "unlabeled" use is the use of an FDA-approved drug for uses not included in that approved labelling. Many off-label uses are effective, well documented in the peer-reviewed literature and widely used, even though the manufacturer has not pursued the additional indications^[7].

For comparison, in the United States an orphan drug is a product treating a rare disease, defined there as affecting fewer than 200,000 Americans, and orphan designation can be obtained before a marketing application is submitted. Expanded access refers to the use of an investigational new drug^[7].

Why does off-label prescribing change the prescriber's responsibility?

The prescriber's responsibility and potential liability are increased when prescribing off-label^[6]. Prescribing medicines outside the recommendations of their marketing authorisation alters – and probably increases – the prescriber's professional responsibility and potential liability; the prescriber should be able to justify the decision and feel competent in using such medicines^[4].

The same source states that the prescriber should also inform the patient or the patient's carer that the prescribed medicine is unlicensed, and that close collaboration between health professionals in different care settings is essential. Wherever unlicensed or off-label use is necessary because the clinical need cannot be met by licensed medicines, it should be supported by appropriate evidence and experience^[4].

In paediatrics, prescribers take full responsibility for prescribing products outside the licence, but all prescribing should still be carried out in the best interest of the child irrespective of licence status^[2].

How do health services flag off-label and unlicensed prescribing?

Some local formularies mark medicines by traffic-light status to show where off-label or unlicensed use sits. In a paediatric chapter, the red status covers drugs in the BNF for Children but outside the listed indications or dose range, drugs not in the BNF-C, off-label use as defined by that guidance, and unlicensed drugs^[2].

The amber status with a shared care agreement covers drugs within the BNF-C indication and dose range, plus unlicensed or off-label use, and requires specialist initiation and stabilisation, with ongoing division of responsibility for drug and disease monitoring between specialist and GP set out in the agreement. Green status means the drug is within the BNF-C indication and dose range and considered suitable for initiation in both primary and secondary care^[2].

What safety information can emerge once a medicine is in wider use?

Regulators publish safety advice to medicines users as new information accumulates. One bulletin reported increased mortality with bendamustine (Levact) when used in combination treatments outside the approved indications, and warned that post-marketing data suggest the risk of opportunistic infections associated with bendamustine may be greater than previously recognised; patients should be monitored for signs and symptoms of infections throughout treatment, including hepatitis B reactivation^[8].

The same bulletin reported possible organ transplant rejection with nivolumab (Opdivo) or pembrolizumab (Keytruda) when used in transplanted patients, and stated that the benefit of treatment versus the risk of possible organ rejection should be considered in those patients. It also urged healthcare professionals to be clear on their responsibilities when prescribing off-label or unlicensed medicines^[8].

What should you ask before accepting an off-label medicine?

Because the prescriber carries increased responsibility for the decision, the choice of product and its justification are legitimate subjects for a conversation^[6]. The points below follow directly from how the options are ranked and from what the label does and does not cover.

• Is this use inside or outside the approved indications? Off-label use covers a different indication, dose, age group or route than those agreed in the SmPC^[1].
• Is the medicine licensed at all, or is it an unlicensed product? Unlicensed medicines hold no marketing authorisation in the national register; "specials" are made to a modified formulation on the doctor's prescription^[1].
• Why is a licensed option not being used? An unlicensed product should not be used where a licensed product could meet the patient's special need^[6].
• What evidence and experience support this choice? Off-label or unlicensed use should be supported by appropriate evidence and experience when the clinical need cannot be met otherwise^[4].
• Who will monitor you, and where? Close collaboration between health professionals in different care settings is essential, and shared care agreements split monitoring between specialist and GP^[4][2].
• Which side effects should prompt you to contact the team? Monitoring for signs and symptoms of infection throughout treatment, including hepatitis B reactivation, was advised for one off-label combination^[8].

How does off-label use connect to clinical trials?

Off-label prescribing is closely linked to gaps in the evidence base. It is a widely accepted view that off-label prescribing, which practically always happens in an intended manner, needs to be made safe and researched further, including from a legal and regulatory viewpoint. More information is needed on the medicines regularly prescribed outside their marketing authorisations^[1].

The European Union has addressed the paediatric evidence gap through a regulation on medicinal products for paediatric use. The analysis of German prescription data notes that this regulation could assume increasing importance and contribute to the development of appropriate and safe medicines for children^[3]. For the clinical side of that picture, a study of off-label targeted anticancer therapy set a composite toxicity endpoint defined as a patient having unplanned clinic visits, emergency department visits or unplanned hospital admissions at least possibly related to the off-label treatment^[5].

When should you seek advice from your doctor or pharmacist?

You should ask for clarification whenever a medicine is offered or continued outside the conditions listed in its SmPC, and whenever you are told a product is unlicensed^[1]. The prescriber should be able to justify the choice and feel competent in it^[4].

Contact your treatment team promptly if you develop signs or symptoms of infection during treatment that includes an off-label combination, since monitoring for these signs and for hepatitis B reactivation has been specifically advised. If you receive a medicine in a transplanted-patient setting, the balance between treatment benefit and the risk of possible organ rejection should be discussed with you^[8]. Where responsibility for monitoring is split between a specialist and a GP under a shared care agreement, confirm with both which side effects each of them should be told about^[2].

Summary

Off-label use is a defined, documented practice rather than an improvised one. It means using a medicine outside the indications, dose, age group or route set out in its marketing authorisation, and it is distinct from an unlicensed product, which has no assessed authorisation^[1].

Three practical points follow. First, when a licensed product can meet the need – even off-label – it is preferred over an unlicensed one, because the licensed product has already been assessed for quality, safety and efficacy^[6]. Second, the prescriber's responsibility and potential liability increase, so the justification and the prescriber's competence are fair questions to raise^[4]. Third, safety information can change after a medicine is in use, so keep monitoring for the signs you were told to watch for^[8].

1. [1] Pełny tekst: Off-label medications in the treatment of hospitalized children with atopic dermatitis, Michał Niedźwiedź - Postępy Dermatologii i Alergologii 1/2023 — termedia.pl (accessed 25.09.2026) — https://www.termedia.pl/Off-label-medications-in-the-treatment-of-hospitalized-children-with-atopic-dermatitis,7,47932,1,1.html
2. [2] NHS Bath and North East Somerset, Swindon and Wiltshire ICB Formulary, Chapter 16: Paediatrics (accessed 02 June 2026) — https://bswformulary.nhs.uk/chaptersSubDetails.asp?FormularySectionID=16&SubSectionRef=16.17&SubSectionID=A100
3. [3] Off-Label Use of Prescription Drugs in Childhood and Adolescence: An Analysis of Prescription Patterns in Germany - PMC — PubMed Central (accessed 25.09.2026) — https://pmc.ncbi.nlm.nih.gov/articles/PMC2695292/
4. [4] NHS Bath and North East Somerset, Swindon and Wiltshire ICB Formulary, Chapter 21: Palliative Care (accessed 02 June 2026) — https://www.bswformulary.nhs.uk/chaptersSubDetails.asp?FormularySectionID=21&SubSectionRef=21.01.01.05&SubSectionID=A100
5. [5] Off‐label prescribing of targeted anticancer therapy at a large pediatric cancer center - PMC — PubMed Central (accessed 25.09.2026) — https://pmc.ncbi.nlm.nih.gov/articles/PMC7520353/
6. [6] MHRA Guidance on the hierarchy for the use of unlicensed medicines (Appendix 4) (accessed 02 June 2026) — https://mg.salisbury.nhs.uk/media/1087/unlicenced-medicines-appendix-4.pdf
7. [7] CareSource Medical Policy Statement: Medical Necessity – Off Label, Approved Orphan and Compassionate Use Drugs (accessed 02 June 2026) — https://www.caresource.com/documents/medical-necessity-off-label-approved-orphan-and-compassionate-use-drugs/
8. [8] Drug Safety Update, Volume 10 Issue 12, July 2017 (accessed 02 June 2026) — https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/632819/DSU-July_PDF.pdf