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Is adherence an issue with generic eye-drops for glaucoma?

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Joseph Halwagy
BPharm FSHP MBA
Medical Manager, Global Established Pharma, Pfizer Australia and New Zealand

A study published in 2011 notes that Australian pharmacists recommended generics for 96.4 per cent of the prescription items which were eligible for substitution.1 The study, which looked at generic substitution across a nationally stratified sample of 500 community pharmacies, revealed that patients with chronic diseases demonstrated a significantly lower rate of acceptance of generic medicines (72.4 per cent) than patients with acute conditions (81.6 per cent).

Challenges to adherence to therapy

Similar substitution rates have been reported in the United Kingdom (UK) with 74 per cent of glaucoma patients having their prescriptions substituted with generic latanoprost.2

The study, published in the British Journal of Ophthalmology in 2013, demonstrated that 35 per cent of patients found the generic latanoprost drops more difficult to use, and 19 per cent of patients were unable to use them afterwards. This would suggest an emerging issue with adherence to therapy for up to one in three previously stabilised glaucoma patients.

Although changes in a medication name and attributes of the physical packaging can be a major source of confusion,3 upwards of 20-27 per cent of glaucoma patients in the UK reported changes in effectiveness and/or side-effects when switched to generic medication.4 Although these were self-reported outcomes, and whether factual or perceived, this may cause certain patients to use their drugs inappropriately or cease their use.

The pharmacological management of primary open angle glaucoma in Australia is similar to that in the UK where latanoprost as monotherapy, or in combination with timolol maleate accounts for =75 per cent of all prescribed prostaglandin analogues.5,6

Given the availability of no less than five generic formulations for latanoprost eye drops in the Australian market,7 glaucoma patients here may also be likely to exhibit similar issues with adherence after generic substitution.

Generic medicines

In general, the clinical effectiveness of a generic medicine is considered to be similar to that of the branded product.

The Therapeutic Goods Administration (TGA) requires generic medicines to contain the same active ingredient as the brand-name drug and to be identical in strength.8 However, a recent US study looking at drug formulations, concentrations and stability of generic latanoprost versus the originator brand (Pfizer Xalatan) found large discrepancies, particularly over time, with up to a 10 per cent increase in drug concentration and more particulate matter in the generic formulations.9 Malik Kahook, one of the authors of this study, is Professor of Ophthalmology and Chief of the Glaucoma Service at the University of Colorado School of Medicine. At the 2013 annual meeting of the American Academy of Ophthalmology, Kahook argued that although the active and non-active ingredients may be similar, other differences may impact the effectiveness and safety of generic use. He noted that changes in bottle shape and size as well as alteration in plastic stiffness may cause installation difficulties in an elderly population even if laboratory testing shows no difference between the generic and branded agent.10

985 Figure 1_final

Figure 1. Changes in the active ingredient concentration for brand name and generic for- mulations of latanoprost at baseline and after exposure to different temperatures for 30 days (Adapted from Kahook et al)

The TGA does not stipulate that generic formulations must be identical to the originator brand product and indeed, side by side comparison of generic versus originator brand product information documents suggests that inactive ingredients can be different from those in the original product.11,12

A recent study comparing North American branded timolol maleate versus 11 other generic preparations showed significant differences in drop volume, viscosity, surface tension, bottle design and bottle tips, with the authors recommending ‘careful consideration should be given to drop viscosity and bottle design when generic ophthalmic products are evaluated for interchangeability and market entry’.12

985 Figure 2_final

Figure 2. Average rheological measurements (log-log scales) of American brand-name Timoptic XE and American generic Timolol GFS (Adapted from Mammo et al)

Beyond the formulation and efficacy factors, originator companies may provide patient aids such as eye-drop instilling devices. These devices may make the administration of eye-drops easier compared with the dropper bottle, especially in the elderly.13 To date, generic glaucoma products have been supplied in the standard round eye-drop bottles that do not fit into originator brand eye-drop aid devices available in Australia.

Conclusion

The switching of glaucoma eye-drop medications to generics is occurring at the pharmacy. Available data suggest compliance with generic glaucoma eye-drops may be an issue in up to one in three glaucoma patients previously stabilised with originator branded medicines. Clinicians’ re-evaluation of intraocular pressures and that control is being maintained may be useful for glaucoma patients switching from originator to generic formulations. Educating patients on the value of brand compliance could be a way forward for maximizing adherence and persistence with therapy.

Due to the increase in generic switching, it is recommended that optometrists and ophthalmologists ask their patients to bring in their medication bottles to each visit. By doing this, clinicians can track each type of generic medication switch and watch for any tolerability issue or intraocular pressure change.

Generic drugs

Generic drugs as defined by the Therapeutic Goods Administration* are medicines that in comparison to the originator product** have the same quantitative composition of therapeutically-active substances, contain substances of similar quality to those in the originator product; have the same pharmaceutical form; are bioequivalent or for topical products, are considered to be therapeutically equivalent; and have the same safety and efficacy properties.

* Therapeutic Goods Administration, ARGOM Appendix 1: Guidelines on efficacy and safety aspects of OTC applications, V1.0; October 2012

** An ‘originator’ product (sometimes referred to as the ‘innovator’ product) is a medicine that has been approved for marketing in Australia on the basis of a full dossier which may include chemical, biological, pharmaceutical, pharmacological-toxicological and clinical data.

  1. Chong et al. A nationwide study on generic medicines substitution practices of Australian community pharmacists and patient acceptance. Health Policy 2011; 99: 2: 139-148.
  2. Connor AJ, Fraser S. Post script letters generic medications in ophthalmology. Br J Ophthalmol 2013; 97: 795.
  3. Emery J, McKenzie A, Bulsara C, Holman D. Controversy over generic substitution. BMJ 2010; 341: c3570.
  4. Harris et al. Authors’ response: Generic medications in ophthalmology. Br J Ophthalmol 2013; 97: 795-796.
  5. IMS Retail and monthly market data to May 2013.
  6. Lafuma et al. Treatment persistence and cost-effectiveness of latanoprost/latanoprost-timolol, bimatoprost/bimatoprost-timolol, and travoprost/travoprost-timolol in glaucoma: an analysis based on the United Kingdom general practitioner research database. Clin Ophthalmol 2011; 5: 361-367.
  7. www.PBS.gov.au.
  8. Therapeutic Goods Administration. Australian regulatory guidelines for prescription medicines, Department of Health and Ageing.
  9. Kahook et al. A comparison of active ingredients and preservatives between brand name and generic topical glaucoma medications using liquid chromatography-tandem mass spectrometry. Curr Eye Res 2012; 37; 2: 101-108.
  10. Kayhook MY. The Great Debate. Glaucoma Subspecialty Day. 117th Annual Meeting of the American Academy of Ophthalmology 2013.
  11. McLachlan et al. Frequently asked questions about generic medicines. Aust Prescr 2007; 30: 41-43.
  12. Mammo et al. Generic versus brand-name North American topical glaucoma drops. Can J Ophthalmol 2012; 47: 1: 55-61.
  13. Nordmann et al. Xal-Ease: impact of an ocular hypotensive delivery device on ease of eyedrop administration, patient compliance, and satisfaction. Eur J Ophthalmol 2009; 19: 6: 949-956.


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