When Clinical Practice Moves Ahead of the Label: The Real-World Need for Off-Label Use and the Challenge of Updating Drug Information

As precision medicine and evidence-based medicine continue to advance, new clinical evidence is emerging at an unprecedented pace. DengYueMed, which has long been engaged in the global distribution of innovative and specialty medicines, has also observed a widely discussed phenomenon in clinical practice: some medications have already been recommended by authoritative domestic and international clinical guidelines, yet the corresponding indications have not been included in their approved prescribing information.

This situation—where clinical evidence advances faster than label updates—has made off-label drug use an unavoidable topic in modern medical practice.

For patients, this issue not only affects the range of available treatment options but also influences drug accessibility, reimbursement eligibility, and medical decision-making.

What Is Off-Label Drug Use?

Off-label drug use refers to the use of a medication in a manner that falls outside the scope of its regulatory-approved prescribing information, including:

● New indications that have not yet been approved;

● Different dosages or treatment regimens;

● Use in different age groups;

● Alternative routes of administration;

● Use in specific disease conditions.

It is important to emphasize that off-label use does not equate to inappropriate use.

In many countries and regions, off-label prescribing is considered a legitimate and common clinical practice when supported by sufficient scientific evidence and professional medical evaluation.

Off-label use is particularly common in oncology, pediatrics, rare diseases, and neurological disorders.

Why Do Label Updates Often Lag Behind Clinical Practice?

Updating prescribing information requires pharmaceutical companies to submit comprehensive registration data and obtain approval from regulatory authorities.

In reality, however, new clinical evidence often emerges much faster.

The main reasons include:

Rapid Accumulation of New Evidence

Large international clinical studies continuously generate new findings every year.

When a medication demonstrates clear benefits in a new disease area, professional medical societies may incorporate it into clinical guidelines before a formal label expansion is completed.

However, obtaining regulatory approval for a supplemental indication often requires a lengthy process.

Economic Considerations

For drugs approaching patent expiration or those that have been on the market for many years, manufacturers may have limited incentives to invest in costly regulatory submissions for additional indications.

As a result, some evidence-supported uses may remain off-label for extended periods.

Differences in Global Regulatory Timelines

The approval timeline for the same medication often varies across countries and regions.

Certain indications may already be approved by the U.S. FDA or the European Medicines Agency (EMA) but have not yet completed the registration process in other markets.

Which Off-Label Uses Are Supported by Clinical Guidelines?

1. Bevacizumab for Recurrent Glioblastoma

Bevacizumab was initially approved for the treatment of solid tumors such as colorectal cancer and lung cancer.

In recurrent glioblastoma, its role in improving progression-free survival and controlling cerebral edema has been extensively studied.

The National Comprehensive Cancer Network (NCCN) has long included it as a treatment option in this setting.

As a result, there remains a consistent clinical demand for its use in this disease.

2. Rituximab for Multiple Autoimmune Diseases

Rituximab was originally approved for lymphoma and rheumatoid arthritis.

In recent years, substantial evidence has accumulated supporting its use in neuromyelitis optica spectrum disorder (NMOSD), immune-mediated kidney diseases, autoimmune encephalitis, and other autoimmune conditions.

Multiple international guidelines now recommend its use.

Even in regions where these indications have not yet received formal approval, clinical demand continues to grow.

3. Pregabalin for Various Types of Neuropathic Pain

Pregabalin has been approved for certain neuropathic pain conditions.

However, it is also recommended by several professional guidelines for the management of cancer-related neuropathic pain and pain associated with certain rare neurological disorders.

4. Propranolol for Infantile Hemangioma

Propranolol remained an off-label treatment for many years.

With the accumulation of extensive clinical experience and research evidence, its effectiveness in treating infantile hemangioma became widely recognized, eventually leading to formal regulatory approval for this indication.

This case is often regarded as a classic example of an off-label use successfully transitioning into an approved indication.

What Patient Needs Are Reflected by Off-Label Drug Use?

The greatest demand for off-label therapies is concentrated in several key areas:

Oncology

Cancer classification is becoming increasingly molecularly driven.

Patients hope to gain earlier access to therapies targeting new biomarkers and emerging indications.

Rare Diseases

Because patient populations are often very small, conducting large-scale registration studies can be challenging.

As a result, clinical practice frequently relies on guideline recommendations and real-world evidence.

Pediatric Medicine

Many medications were originally studied only in adult populations.

Children have long faced a shortage of label-supported treatment information.

Neurological Disorders

Off-label use is relatively common in areas such as autoimmune encephalitis and rare inherited neurological diseases.

How Should Off-Label Drug Use Be Viewed Rationally?

Off-label use does not necessarily mean that a medication lacks research support or scientific evidence.

The key considerations include:

● Recommendations from authoritative clinical guidelines;

● Support from high-quality clinical studies;

● Careful physician assessment of benefits and risks;

● Informed patient consent;

● Management within compliant healthcare institutions.

For patients, the term “off-label” should not automatically be interpreted as “experimental treatment,” nor should they believe exaggerated claims suggesting that a drug is “proven effective overseas but unavailable domestically.”

The true value of any medication should be assessed based on scientific evidence and professional guideline recommendations.

Conclusion

Overall, clinical evidence continues to evolve rapidly, while updates to prescribing information often require significantly more time. This gap has allowed off-label drug use to remain an important component of modern healthcare, helping address certain unmet medical needs.

Looking ahead, accelerating the transition of high-quality clinical evidence into officially approved indications—while maintaining patient safety—and ensuring that prescribing information keeps pace with clinical practice will remain important priorities for regulators, pharmaceutical companies, and the medical community alike.