PORT ELIZABETH OPHTHALMOLOGIST’S

OFF-LABEL INTRAVITREAL INJECTIONS

The most common way to treat retinal eye problems today is by medication injected into the eyeball. This injection is called an intravitreal injection. This procedure is done routinely around the world and is now the most common medical procedure in ophthalmology in the USA with more than 2.5 Million injections done in 2014 alone (USA statistics).

The procedure is simple and safe – information on potential side-effects related to the injection itself is presented elsewhere.

The aim of this pamphlet and consent form is to better inform you what “off-label” injection of medication into your eye implies.

For any medication to be used, it needs to be proven to be effective and safe for the proposed use thereof. Internationally the USA based FDA is the accepted standard as proof that a medication is safe and effective to use. For the medication to receive FDA approval, it has to pass through rigorous testing (trials) before it receives its FDA approval. This process costs billions of dollars at the expense of the company producing the medication – leading to high costs of the medication.

Often medication is registered for a specific use, after passing through the FDA trials. Later it is found that this medication also has beneficial effects on a completely different health problem than that for which it was originally registered for. This medication can then be used as a treatment for the other problem, but as it has not been registered for that specific use, it is seen as off-label use. As such, it is usually not covered by insurers and medical aid because of its off-label status.

In the case of eye injections, the above is of specific importance and cost implications. In the past, it was noted that patients receiving certain cancer medication, could suddenly see better and had improvement of their retinal eye problems during chemotherapy. This led to the discovery of molecules in the eye which controls swelling of the retina. Further research showed that cancer medication such as the FDA approved Avastin contains molecules which improved the eye swelling. Of course, to then use Avastin as an eye injection was off-label, as it was registered as a cancer treatment and not eye treatment. Pharmaceutical companies then paid billions of dollars to have a specific drug made for injection in the eye, which was exactly the same as Avastin – it is called Lucentis, now FDA registered. Due to the cost involved in passing it through FDA trials, this medication is extremely expensive compared to Avastin. Since then developing countries have used the Avastin off-label with great effect and no difference from Lucentis, used in the USA. The same scenario is now playing out again, where a new generation drug called Aflibercept was designed and FDA approved and now sold at great cost as Eyelea. A generic agent Zaltrap is available off-label at a fraction of the cost with the same effect and safety profile.

What does this all mean to you as the patient:

If you need an eye injection, you will have to choose between the off-label drugs and the FDA approved medication. In practice, there are lots of research proving that there is no safety or efficacy difference between the different medication, although the FDA drugs have definitely passed a more rigorous examination. Medical aids, as a rule, do not pay the FDA approved medication due to the extreme costs.

There are currently 5 different medications which are injected into the eye. These are Avastin (Bevacizumab), Lucentis (Ranibizumab), Eyelea (Aflibercept), Zaltrap (Ziv-Aflibrecept) and Kenacort (Triamcinalone).

Lucentis is an FDA approved drug considered to be the gold standard regarding its efficacy and safety profile. Avastin is an off-label generic drug which is molecularly virtually a replica of Lucentis. Avastin has now been injected as the primary agent in Europe and the developing world (and less commonly in the USA) for the last 10 years with many studies now proving that it has the same efficacy and safety profile as Lucentis, but at a fraction of the cost.

Aflibercept is the latest drug now used for intravitreal injection. It has a very favourable efficacy profile, with studies showing it is superior to both Lucentis and Avastin in some patients and specific eye conditions. It is also very attractive because it has a longer duration of action compared to Avastin and Lucentis. This allows us to inject the Aflibercept once every 2 months, compared to Lucentis and Avastin which is injected every month.

Eyelea (Aflibercept) is an FDA approved drug with a very good safety profile. Unfortunately, it is extremely expensive. A generic agent, Zaltrap (Ziv-Aflibercept) which is a molecular mimic, is available at a fraction of the cost – Zaltrap is also used Off-label. It has been used internationally since 2014 with reported good safety and efficacy comparable to that of Eyelea. The manufacturer has not endorsed it for eye injections due to higher osmolarity when compared to other eye injections. This has not been shown in laboratory studies and real-world practice to cause any damage to the eye and reports from sites around the world have shown no complications when injecting Zaltrap.

Kenacort is cortisone which is occasionally injected into the eye. It is used extensively throughout the world with a good safety profile.

We are happy that both Avastin and Zaltrap has been shown in practice to be a safe and effective alternative to Lucentis and Eyelea, and at a fraction of the cost. As such we are confident to reassure you as to the use of Off-label drugs in our practice. The more expensive FDA-approved alternatives are available if you so prefer.

AFLIBERCEPT AND AVASTIN OFF-LABEL USE:

Eylea:

  • This medication is FDA approved meaning it has passed through many phases of intensive studies to ensure it is safe and effective for injection in the eye
  • It is usually injected every 2 months until the retinal problem stabilizes
  • The cost currently is around R13000 per injection per eye – not covered by medical aids in most cases

Zaltrap

  • This medication is a molecular generic of Eyelea, and is registered as cancer medication by the FDA
  • It is used OFF-LABEL for eye injections, meaning it has not been registered for use in the eye
  • The company has not endorsed it for injection in the eye due to uncertainty related to the molecular effect on the eye
  • It has been used internationally for the last 2 years as eye injections with very good reports on safety and efficacy during this time period
  • It has been passed through laboratory tests which demonstrated the same safety and efficacy compared to Eyelea.
  • It is also injected every 2 months
  • The cost currently is around R1500 per injection per eye, covered by medical aid in most cases.

AVASTIN OFF-LABEL USE:

Lucentis:

  • This medication is FDA approved meaning it has passed through many phases of intensive studies to ensure it is safe and effective for injection in the eye
  • It is usually injected every month until the retinal problem stabilizes
  • The cost currently is around R10 000 per injection per eye – not covered by medical aids in most cases

Avastin

  • This medication is a molecular generic of Lucentis, and is registered as cancer medication by the FDA
  • It is used OFF-LABEL for eye injections, meaning it has not been registered for use in the eye
  • It has been used internationally for the last 10 years as eye injections with very good reports on safety and efficacy with many millions of injections performed with no signs of any difference in outcome when compared to Lucentis
  • It has been passed through laboratory tests which demonstrated the same safety and efficacy compared to Lucentis
  • It is also injected every month
  • The cost currently is around R1500 per injection per eye, covered by medical aid in most cases