The control of medicines, in general, is based on precise rules relating to Good Manufacturing Practice (GMP) of medicines in order to ensure product quality and safety.
At present, intravitreal corticosteroid drugs for the treatment of diabetic macular oedema (EMD) are:
-a intravitreal implant of dexamethosone 700 micrograms which requires multiple annual administrations, usually every 4-6 months;
-a intravitreal implantation 3.5 mm long and 0.37 mm in diameter - available from 2017 in Italy - capable of releasing fluocinolone acetonide in a controlled and constant manner for 3 years, thus ensuring long-term drug coverage.
However - on 8/10/2018 - in agreement with the Italian Medicines Agency (AIFA), the company holding the Marketing Authorisation for the dexamethasone-based medicinal product 700 micrograms communicated important information and corrective actions to be taken following the detectionduring one of the production checks in-processof a free silicone particle in a sampling of such implants.
The particle, as reported by AIFA itself, is said to have come from the silicone sleeve of the needle, which is an intrinsic part of the medicine and not an external contaminant.
Therefore, as a precautionary measure, batches of dexamethosone 700 micrograms identified as defective have been withdrawn from the European market.
Attached is the Important Information Note of AIFA and the Annex with thelist of lots concerned
This episode, critical in itself, becomes even more severe when one considers that there are only two intravitreal steroid treatment options available on the market, as listed above.
These drugs are used because they are able to inhibit the processes underlying the onset of the disease itself, including inflammatory ones, which become predominant as the disease progresses. Steroids are in fact able to:
-stabilise certain endothelium cells;
-inhibit leukocyte migration, as well as the synthesis of vascular growth factor, cytokines and prostaglandins.
In particular, it is important to emphasise that intravitreal corticosteroid administration is indicated for a specific segment of patients who are not sufficiently responsive to first-line treatmentsnamely grid and focal laser photocoagulation and intravitreal administration of vascular endothelial growth factor (VEGF) receptor antagonists.
Patients presenting with an increase in visual acuity < 5 letters (ETDRS) or a decrease in central foveal thickening < 20% after the Loading Phase ('loading phase', the intended attack dosage for each drug) are considered to be insufficiently responsive to first-line therapy.
Regulatory and clinical aspects ofthe intravitreal fluocinolone acetonide implant
This implant is fully reimbursable in hospital for patients who have already undergone cataract surgery (pseudophakic). The use of this innovative drug delivery results in a significant reduction in the total number of intravitreal injections a patient must undergo over the three-year period (with a reduction in the risk of complications) and a consequent increase in patient adherence to therapy.
Studies conducted on this implant showed that, at the end of three years, about one third of the patients treated with the fluocinolone acetonide-containing implant had experienced a doubling of their visual acuity (equal to a 15-letter increase in BCVA). At the same time, a rapid and significant reduction in the thickness of the central fovea was observed. These data were also confirmed in real-life studies conducted on patients already treated with anti-VEGF drugs.
In general, the risks associated with both implants are those typical of corticosteroids, i.e. occurrence of cataracts and increased intraocular pressure.
Sources
– http://www.aifa.gov.it/content/nota-informativa-importante-su-ozurdex-desametasone-08102018
- Syed YY. Fluocinolone Acetonide Intravitreal Implant 0.19 mg (ILUVIEN): A Review in Diabetic Macular Edema. 2017 Apr;77(5):575-583.
- Veritti D, Sarao V, Diplotti L, Samassa F, Lanzetta P. Fluocinolone acetonide for the treatment of diabetic macular oedema. Expert Opin Pharmacother. 2017Oct;18(14):1507-1516
- Guidelines for the screening, diagnosis and treatment of diabetic retinopathy in Italy, Working Group on Ocular Complications of Diabetes, Italian Society of Diabetology, 2015.
- Schmidt-Erfurth U, Garcia-Arumi J, Bandello F, Berg K, Chakravarthy U,Gerendas BS, Jonas J, Larsen M, Tadayoni R, Loewenstein A. Guidelines for the Management of Diabetic Macular Edema by the European Society of Retina Specialists (EURETINA). Ophthalmologica. 2017;237(4):185-22
Dr. Carmelo Chines
Direttore responsabile
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