A new formulation of tacrolimus eye drops, utilizing hydroxypropyl-beta-cyclodextrin (HPβCD) as a solubilizer, demonstrates improved safety and patient compliance compared to previous formulations containing ethanol. The study, published in Journal of Clinical Medicine, evaluated the effectiveness, safety, and compliance of 0.015% tacrolimus eye drops with HPβCD (TCD) against the previously used 0.03% tacrolimus eye drops with ethanol (TE) in managing ocular inflammatory pathologies.
Background and Rationale
Tacrolimus eye drops are commonly compounded in Hospital Pharmacy Departments (HPDs) due to the lack of commercially available options. A limiting factor in their preparation is the low water solubility of tacrolimus. Traditional formulations often use ethanol to solubilize tacrolimus, which can cause ocular irritation, affecting patient adherence and safety. HPβCD, deemed safe for topical ophthalmic applications by the European Medicines Agency (EMA), offers an alternative to ethanol, enhancing tacrolimus solubility and stability while improving ocular biopermanence.
Study Design and Methods
The study involved 56 patients who switched from TE to TCD. Researchers assessed clinical ocular parameters, tear stability, intraocular pressure (IOP), and patient-reported outcomes using Visual Analogue Scale (VAS) and Visual Function Questionnaire-25 (VFQ-25). Objective adherence was measured by comparing the actual and theoretical weight of returned eye drop bottles.
Key Findings
- Symptom Improvement: A significant improvement in burning sensation was reported by 51.6% of patients after switching to TCD, with a statistically significant decrease in burning in both eyes (p = 0.004 for the right eye, p = 0.003 for the left eye). Pain perception also improved in the left eye (p = 0.03).
- Quality of Life: The VFQ-25 total score showed a significant increase with TCD (p = 0.003), with improvements in near vision, distance vision, role, and ocular pain domains. Patients over 65 years old showed a mean increase of almost 10 points in quality of life with TCD eye drops.
- Adherence: Patient adherence, measured using the VAS adherence scale, increased significantly from 100.0% (Q1–Q3: 80–100) for TE to 100.0% (Q1–Q3: 90–100) for TCD (p = 0.003).
- Clinical Parameters: No significant negative changes were observed in most patients after switching to TCD. Corneal staining remained stable, and no corneal rejection symptoms were observed in patients who underwent keratoplasty.
- Tear Stability: Switching from TE to TCD increased the Tear Meniscus Height (TMH) in at least half of the eyes evaluated, indicating improved tear stability.
- Intraocular Pressure: No variations in intraocular pressure were observed between visits, confirming that the 0.015% TCD eye drops do not raise IOP.
Clinical Significance
The study highlights the benefits of using HPβCD in tacrolimus eye drop formulations. The removal of ethanol not only improves patient comfort and adherence but also reduces the potential for ocular surface toxicity. The comparable effectiveness of the lower concentration (0.015%) tacrolimus in TCD, facilitated by increased ocular biopermanence, suggests a safer therapeutic option.
Implications for Practice
The findings support the adoption of HPβCD-based tacrolimus eye drops in HPDs as a safer and more tolerable alternative for managing ocular inflammatory pathologies. The ease of preparation, using readily available raw materials and standard equipment, facilitates the transfer of this formulation to other centers.
Study Limitations
The study acknowledges limitations in objectively measuring adherence due to discrepancies in the weights of returned bottles, which could be attributed to factors beyond compliance. Further research with more precise adherence measurement methods is warranted.
Concluding Remarks
Overall, the study provides compelling evidence for the clinical effectiveness, safety, and improved compliance of tacrolimus eye drops formulated with HPβCD, offering a promising advancement in the management of ocular inflammatory conditions.
