In an ideal world medication would only be prescribed within the strict confines as set out in the particular medication’s registration and as briefly documented in the package insert. Patients could rest assured of the proven safety and efficacy of the medication while health professionals could take refuge behind the science and regulation of the registration process.  It will, however, come as no surprise that healthcare practitioners  do not live in an ideal world, and it is not unusual for medication to be prescribed and administered beyond the confines of a medication’s registration.  Two areas where off-label prescribing may indeed dominate are paediatrics and obstetrics.

Given that off-label prescribing is indeed so prevalent it is important that practitioners are aware of the risks involved – to their patients and themselves. When prescribing a medication within the confines of its registration one has the assurance that the safety and the efficacy of the drug have passed the strict review of the regulator.  When prescribing off-label, or contrary to advice given by the manufacturer, a healthcare practitioner does not have that same assurance. While this may place the patient at risk, it definitely also places the practitioner in a more vulnerable medicolegal position.

Medical Protection’s mandate is not to stop you – but a little like informed consent to warn you of the potential risks and how to mitigate against them.  The degree of risk you are willing to bear is your business.  So given a practitioner is at increased risk when prescribing off-label, what is pragmatic advice to help alleviate that medicolegal risk?

1. Prior to prescribing read the package insert carefully to see if you are indeed going to be prescribing off label.  Note that package inserts contain information that may be helpful.  There is often advice that should be carefully read and considered, warnings that one should be aware of, and one must be cognisant of prescriptive directives.  Prescriptive directives such as ‘never’ or ‘always’ should be very carefully considered and breached at one’s peril.

2. Is there an alternative that can and preferably should be used?  In many situations the answer will be a clear no which will be helpful for many practitioners.

3. How would you justify the off-label use of the medication if challenged?  What science is available to support you?  How would you justify the efficacy of the drug and how would you justify your safe use of the drug under the circumstances?  Does the literature support you?  Is the drug widely used by colleagues? Has efficacy and safety data been presented at scientific meetings?  Does your professional society or a similar professional society recommend the drug under the circumstances?

4. With respect to safety it is perhaps important to remember that the absence of evidence does not ensure the evidence of absence.  Just because you or your colleagues have never encountered a problem does not mean that problems do not exist.

5. Do you feel that you can clearly articulate that the advantages to the patient outweighed the risks and disadvantages? Would you be able to satisfy a tribunal or court that you acted as a reasonable doctor would have acted under similar circumstances?  While that may be helpful if you are sued in negligence and perhaps be useful in a criminal setting, it may not protect you regarding consumer protection litigation.

6. You need to ensure that your use is not unusual to the extent that it could be deemed to be experimental in nature. The experimental use of drugs is quite rightly extremely strictly regulated and should only realistically be considered within the realms of a regulated trial with the overview of an acknowledged ethics committee.  You are already placing yourself at some risk by prescribing off label but ask yourself am I prescribing in the realm of experimental medicine?

7. While you may be at medicolegal risk, the patient is the person at risk of complications and the potential protective role of informed consent cannot be overemphasised.  The consent should be documented and retained.

Unsurprisingly off-label prescribing offers a spectrum of risks for patients and healthcare practitioners.  In principle the greater the magnitude of an adverse outcome for a patient the greater the risk a practitioner places themselves at.  For example, as an obstetrician a low-risk use of off-label prescribing includes the administration of corticosteroids to a mother at risk of preterm delivery to enhance fetal lung maturity and therefore to diminish neonatal morbidity and mortality.  The scientific evidence of the advantages have been well documented in meta-analyses and their use is set out in the guidelines of national colleges.  The advantages are legion and well documented while the risks are evidenced to be minimal.  While the importance of informed consent remains relevant, not to offer corticosteroids to a healthy women at risk of preterm delivery, where doing so may enhance lung maturity, would probably open one to criticism.

Sadly we have examples at the opposite end of the spectrum.  It is clear that lipid emulsion agents used by anaesthesiologists are potentially extremely dangerous and need to be administered with caution.  The package inserts of these drugs tend to be voluminous and include information, advice, numerous well-defined warnings and clear prescriptive directives.  The breaching of such warnings clearly places a practitioner at considerable risk should there be an adverse outcome; particularly if a patient dies.  It is of cardinal importance for practitioners to understand what risk they place themselves at should they act in contravention of a well-defined warning or clear prescriptive directive.  How will they justify it?  The authorities may see such conduct as a violation which implies intent and could escalate an extremely uncomfortable situation into an untenable one.  In the absence of pressure it is easy to be blasé about defending one’s position or approach – it has worked well and without problems innumerable times previously.  Practitioners must think very carefully about their potential defence if things go wrong, having breached a clear prescriptive directive.

• Why did you consider the particular medication?  

• What registered alternatives did you consider?  

• What justification can you give for the efficacy of the drug?  

• What evidence can you offer regarding the safety of the drug? 

• What advantage did the particular medication offer the patient and at what additional risk?  

• What did you discuss with the patient and where is it documented?  

• What steps did you take to mitigate risk and where are they documented?

The goal of the article is not to preclude practitioners from prescribing off-label.  The goal is to make practitioners aware of the potential risks, what steps they can take to help mitigate those risks, to reflect on what risks they are willing to take and how they would justify them in the unlikely event of something going wrong.  

Finally, the greater the risk to the patient the greater the medicolegal risk to the practitioner.  When using medication where the documented risks to patients may be dire and include death read the package insert with care, take cognisance of the advice, any warnings and breach any prescriptive directives at your peril – the risk has shifted to you – caveat venditor.