Tratamento do glaucoma com medicação genérica: nem sempre igual em segurança e eficácia.

Generic glaucoma eye drops not always equal in terms of safety and efficacy

Generic eye drops should not be considered identical to branded versions due to differences in composition and possibly efficacy. Therefore, the re-evaluation of IOP reduction when switching to generic drugs seems reasonable, Jean-Philippe Nordmann MD, PhD, University Paris V, Paris, France told a Glaucoma Day session of the XXXI Congress of the ESCRS in Amsterdam. He noted that when the patents expire for popular branded IOP-lowering eye drops, generic alternatives quickly account for a greater market share than the original product.
For example, in the case of latanoprost (Xalatan, Pfizer), which lost its patent in 2011, the generic versions already accounted for 82 per cent of the agent sold in France and 66 per cent of latanoprost sold in Italy. “To third-party payers, generics offer the potential for saving money. For pharmacists it provides the potential for generic substitution. Government regulators can legislate for the routine prescription of generic alternatives where possible in order to save money, as has happened in France and Spain. But for physicians, generic-first substitution policies may present the possibility of less control over their prescribing practices. As for patients, the change in the drug’s appearance can influence compliance with medication,” he said.
Dr Nordmann noted that for a new drug preparation to obtain FDA approval as a generic equivalent of a branded product, it must have the same quality and performance as the original branded preparation. In the case of systemically administered agents, that means that the candidate generic agent must achieve the same blood concentration levels of the active ingredients within a specified period and using the same route of administration.

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However, there is no such requirement for agents that have local rather than systemic activity, such as eye drops. Moreover, although the candidate generic agent must have the same active ingredients at the same concentration, there is no prohibition against using different concentrations of inactive ingredients, which include the preservatives, pH adjusters, antioxidants, buffers and thickening agents. Moreover, differences of up to 10 per cent in the concentration of the active ingredients are considered acceptable and added compounds can be present in generics to improve stability.
Physical characteristics
As a result, generic eye drops may differ from the original product in their physical characteristics. For example, a study comparing two generic latanoprost eye drops with Xalatan showed that an increase in temperature lowered the concentration of latanoprost in both of the generic preparations but not in the branded product. The same study showed that there were significantly higher levels of particulate matter in the generic products compared to Xalatan (Kahook et al. Curr Eye Res 2011;epub).
Another study comparing a branded version of timolol eye drops (Timoptic XE, Merck) to two generic versions showed that the branded and generic versions differed in terms of viscosity by a factor of 100. Furthermore, the size of the drop the generic bottle dispensed was lower by 25 per cent than that of the branded timolol preparation (Mammo et al, Can J Ophthalmol, 2012;47(1):55–61). The ultimate test of a generic drug’s bioequivalence is its efficacy, but generic preparations do not need to undergo the same type of clinical evaluation as the original branded product. Furthermore, the results of studies comparing generic preparations with branded products suggest that some generics are better than others in terms of efficacy, he noted.
For example, a generic latanoprost preparation was not inferior to Xalatan in IOP-lowering efficacy in a six-week multicentre, randomised, investigator masked study involving 260 patients with primary open angle glaucoma or ocular hypertension. That is, the generic preparation reduced IOP by 7.29 mmHg, compared to a 7.29 mmHg reduction with Xalatan (Allaire et al. Eur J Ophthalmol 2012;22:19–27).
However, in another randomised open-label crossover study of 30 patients with glaucoma reported a significant difference between Xalatan and a generic product, with the respective IOP reductions of 9.35 mmHG and 5.76 mmHg (Narayanaswamy et al. Indian J Ophthalmol 2007;55:127–31.
There are also safety issues to be considered. There have already been anecdotal reports of unexpected adverse events occurring to patients when they switch to a generic formulation. For example, there was a case reported of an 88-year-old Japanese patient who developed corneal ulceration after each of two attempts to switch to generic latanoprost but whose symptoms resolved upon returning to the branded product. The adverse reaction may have resulted from the preparation including stearic acid polyester, a surfactant agent, as a stabiliser (Takada et al., Case Rep. Ophthalmol. Med., 2012).
On the other hand, given their current widespread use of and the relative rarity of adverse events reported with them, most generic glaucoma eye drop formulations provide an acceptable alternative to branded products for most glaucoma patients, Dr Nordmann said.
Jean-Philippe Nordmann: jpnordmann@quinze-vingts.fr