Off label Use

I came across an interesting example of off-label use this week.  'Off label' use is where a product with a marketing authorisation is being used outside of it's licensed indication, administration route or dosage requirements.  Off label use is frequently used within both human and veterinary medicine where there is a need to meet specific requirements of  a patient where existing treatment is unsuitable or ineffective. 

There are numerous examples of off-label use within the UK.  A recent, well publicised example is the use of Avastin in the treatment of wet macular degeneration in place of the more expensive Leucentis that is actually licensed for this indication.  Another common example is the use of Viagra in the treatment of pulmonary hypotension in young children.  Rare examples include the use of Pridel (lithium) in the treatment of thyrotoxicosis.

The example uncovered this week was the use of a drug licensed for IV use but actually administered via the intrathecal route (IT).  The vial was reconstituted within an aseptic facility to produce the final IT syringe ready for administration.  One of the first things that came to my mind was the risk of endotoxin.  From your microbiology revision you should be aware that the BP endotoxin limits for IV and IT administration is different.  Products licensed for IV administration have a limit of 5 EU/kg/hr whereas IT products have a limit of 0.2 EU/kg/hr. 

Therefore using a product licensed for IV administration for IT administration may mean that the patient is at a potential risk of receiving upto 25 times the amount of endotoxin normally expected via this route.  The risks are mitigated some degree by the fact that the volumes administered via the IT route are very small, typically in the region of 1-3ml and patients are often closely supervised following administration. 

The other question is who is responsible for this off label use?  Within the GPC prescribing guidelines it states that doctors are responsible for the prescribing and to ensure the efficacy & safety of the unlicensed use.  Presribers are require to understand the risks associated with off label use.  Would the prescribers actually be aware of the different endotoxin limits for IT vs IV administration?  Would the pharmacist taking responsibility of the quality of the product know about this?  In my experience I would hazard a guess that in most instances neither professional would take this into account. 

A QP's perspective

As a QP are you aware of how & why your products are used off label within your markets?  Having this knowledge should help you respond to any potential PV complaints surrounding off label use.  Another point worth considering is the update to the PV requirements following 2010/84/EU which came into force in the UK last year via SI 2012/1916.  These requirements now stipulate that any unlicensed, off label, abuse or overdose of your product needs to be captured within your PV system.