Off-label prescribing: using an approved medicine in an unapproved way

Every registered medicine carries a "label" — the formal product information that a medicines regulator has authorised. This label sets out the specific indications, doses, routes of administration, and patient groups (such as age ranges) for which the manufacturer presented evidence and the regulator granted approval. When a prescriber uses that same medicine in a way that falls outside those approved terms, the use is described as "off-label". Off-label prescribing is common across many health systems and, in most jurisdictions, is legal — but it occupies a distinct regulatory space that limits what manufacturers may say about it.

What the "label" actually is

The label goes by different names in different countries: the package insert in South Africa, the Summary of Product Characteristics (SmPC) in the European Union, and the prescribing information or physician labelling in the United States. Whichever name is used, it is the document a regulator such as SAHPRA, the EMA, or the FDA has assessed and approved alongside the medicine itself. It reflects the body of evidence the manufacturer submitted — typically from controlled clinical trials — and the specific conditions under which the regulator concluded the benefits outweigh the risks.

The label is therefore not a complete inventory of everything a medicine can do, but rather a record of what has been formally evaluated and accepted. A medicine might carry a single approved indication, or several, each with its own dose range and population. Anything beyond those approved terms — a different condition, a different dose, a different route, or a different age group — is off-label.

Why off-label use is legal

Medicines regulators approve products for marketing; they do not generally regulate the individual clinical decisions of qualified prescribers. Once a medicine is registered, a licensed prescriber may, using professional judgement, prescribe it for a patient in a manner not described on the label. This principle is recognised across many jurisdictions and underpins clinical flexibility.

The distinction matters because the rules governing manufacturers differ from those governing prescribers. A company may only promote a medicine for its approved (on-label) uses. Actively advertising or promoting an off-label use is generally prohibited, and regulators have taken enforcement action against companies that cross this line. The rationale is that promotional claims should be backed by the kind of evidence a regulator has reviewed, rather than by marketing alone.

Where off-label use commonly arises

Off-label prescribing tends to cluster in areas where formal evidence and regulatory approval lag behind clinical practice. Paediatrics is the classic example: many medicines are studied and approved primarily in adults, and treating children often requires adapting those medicines in ways that fall outside the label. Oncology is another common setting, where established regimens combine medicines in sequences and doses that individual regulators may not have approved as a single package. Rare diseases, psychiatry, chronic pain, and dermatology also see substantial off-label use.

Well-known historical examples include low-dose aspirin for cardiovascular risk reduction, which was used off-label for years before dedicated approvals in some countries, and propranolol — first approved for heart conditions — later used for migraine prevention. None of this is a recommendation; the examples simply illustrate how off-label use can precede, run alongside, or never receive formal label expansion. The World Health Organization's Essential Medicines List occasionally notes uses that are off-label in some jurisdictions, reflecting their public-health importance even where regulatory approval has not kept pace.

Regulatory boundaries and manufacturer conduct

The central boundary in off-label use sits not on prescribers but on manufacturers. Companies may respond to unsolicited requests for information, distribute scientific reprints under certain conditions, and support genuine medical education — but they may not actively promote off-label uses through advertising, sales representatives, or sponsored materials that frame an unapproved use as recommended.

Some jurisdictions have created formal pathways that touch the edges of off-label practice. These include compassionate-use or expanded-access programmes for serious conditions without satisfactory alternatives, and paediatric regulations that incentivise or require companies to generate evidence in children. In South Africa, SAHPRA's registration documents and the Single Exit Price framework apply to the registered product as marketed; whether a prescriber uses that product off-label is a clinical decision that sits outside price regulation but remains subject to professional and ethical oversight.

Practical implications

Off-label prescribing is neither inherently good nor bad — it is a consequence of the gap between a formal, evidence-based approval process and the messier reality of individual patients. It can be clinically appropriate and well supported by professional guidelines, or it can rest on thinner evidence. What changes is the context: the strength of evidence, the expectations around informed consent, and the allocation of professional responsibility.

Patients who are unsure why a medicine has been prescribed can ask whether the use is on-label or off-label, and what evidence supports it. Checking the registration status and approved product information — for example, through SAHPRA records, a medicine's package insert, or a search on HealthSA — can clarify what a medicine is formally approved for, even when clinical practice extends further.