Generic versus brand-name North American topical glaucoma drops

doi:10.1016/j.jcjo.2011.12.004

Canadian Journal of Ophthalmology

Volume 47, Issue 1, February 2012, Pages 55-61

https://doi.org/10.1016/j.jcjo.2011.12.004 Get rights and content

Abstract

Objective

To determine whether brand-name glaucoma drops differ from generic equivalents in bottle design, viscosity, surface tension, and volume in North America.

Design

Experimental study.

Participants

We studied 5 bottles each of 11 kinds of glaucoma drops.

Methods

Density-based calculations of drop volume were assessed using 0.1 mg analytic balance. Viscosity was measured using rotational rheometery. Bottle tip diameter was measured using 0.05 mm Vernier calipers. Surface tension was measured using a Fisher Scientific (Ottawa, ON) tensiometer.

Results

For the American brand-name Timoptic XE, the average drop volume was 38 ± 3.1 μL versus 24 ± 1.5 μL of Timolol GFS (p < 0.0001). For the Canadian brand-name Timoptic XE, the average drop volume was 42 ± 4.0 μL versus 25 ± 2 μL of timolol maleate EX (p < 0.0001). The Canadian brand-name Timoptic drop volume was 28 ± 1.4 μL versus 35 ± 1.9 μL Apo-Timop (p < 0.01). At a 0.1 per second shear rate, the viscosity of Canadian Timoptic XE was 20 times higher than that of its generic equivalent, whereas the viscosity of American Timoptic XE differed from the generic by a factor of 100. The surface tension of Canadian Timoptic XE was 31% higher than that of the generic (p < 0.001), whereas the surface tension of American Timoptic XE was 21% higher than that of the generic (p < 0.001). The bottle tips of the Canadian and American Timoptic XE measured about 3.5 times larger than those of their generics.

Conclusion

American and Canadian Timoptic XE eye drops vary significantly from the generics in drop volume, viscosity, surface tension, and bottle tip. Canadian brand-name Timoptic delivered significantly smaller drop volumes than generic Apo-Timop. Careful consideration should be given to drop viscosity and bottle design when generic ophthalmic products are evaluated for interchangeability and market entry.

Résumé

Objet

Établir si les gouttes pour le glaucome portant une marque de commerce diffèrent des équivalents génériques quant à la conception des bouteilles, la viscosité, la tension de surface et le volume, en Amérique-du-Nord.

Nature

Étude expérimentale.

Participants

Nous étudions 5 bouteilles de 11 medicaments de glaucome.

Méthodes

Le calcul du volume des gouttes, fondé sur la densité, a été évalué à l'aide d'une balance analytique de 0,1 mg. La viscosité a été mesurée avec le rhéomètre en mode rotation. Le diamètre de l'embout des bouteilles a été mesuré avec un pied à coulisse de 0,05 mm. La tension de surface a été mesurée à l'aide d'un tensiomètre scientifique Fisher.

Résultats

Le volume moyen de la goutte portant la marque de commerce américaine Timoptic CE était de 38 ± 3.1 μL versus celui de 2 ± 1.5 μL du Timolol GFS (p < 0.0001). Le volume moyen de la goutte portant la marque de commerce canadienne Timoptic XE était de 42 ± 4 μL versus celui de 25 ± 2 μL du Timolol Maleate EX (p < 0.0001). Le volume des gouttes de la marque canadienne Timoptic était de 28 ± 1.4 μL versus celui de 35 ± 1.9 μL d'Apo-Timop (p < 0.01). À une vitesse de cisaillement de 0.1 seconde, la viscosité de la Timoptic XE canadienne était vingt fois supérieure à son équivalent générique alors que la viscosité de la Timoptic XE américaine différait du générique par un facteur de 100. La tension de surface de la Timoptic XE canadienne était plus élevée de 31% de celle du générique (p < 0.001) alors que la tension de surface de la Timoptic XE américaine était plus élevée de 21% de celle du générique (p < 0.001). L'embout des bouteilles de Timoptic XE canadiennes et américaines étaient environ 3,5 fois plus grand que celui des génériques.

Conclusion

Les gouttes oculaires Timoptic XE américaines et canadiennes varient grandement des génériques quant au volume des gouttes, à la viscosité, à la tension de surface, et à l'embout des bouteilles. La marque de commerce Timoptic a livré des volumes de goutte beaucoup plus petits que le générique Apo-Timop. Il faudrait examiner attentivement la viscosité des gouttes et la conception des bouteilles lors de l'évaluation des produits ophtalmiques pour l'interchangeabilité et l'entrée sur le marché.

Section snippets

Methods

We purchased 11 representative ocular medications (5 brand-name and 6 generic) that were created to lower elevated IOP. They were purchased from 1 hospital pharmacy in Canada and 4 community pharmacies in the United States. The products were stored at room temperature, per the manufacturers' recommendations, in a locked and secured area in the research laboratory facility at Toronto Western Hospital. All products were at least 9 months away from their expiry date during the testing phase of the

Results

Figure 1 shows the average drop volumes of the brand-name and generic products. Most notably, the Canadian brand-name Timoptic XE drop volume was 42 ± 4.0 μL versus 25 ± 2.0 μL for the Canadian generic timolol maleate EX (p < 0.0001). The American brand-name Timoptic XE average drop volume was 38 ± 3.1 μL versus 24 ± 1.5 μL for the American generic Timolol GFS (p < 0.0001). The Canadian brand-name Timoptic drop volume was 28 ± 1.4 μL versus 35 ± 1.9 μL for the generic Canadian Apo-Timop (p <

Discussion

In this study, we report that brand-name versus generic drop volume variability was found among a limited subset of the investigated eye drops. The most notable difference was observed between the gel-based beta-blocker formulations in both Canadian and American products. Generic Timolol GFS (Falcon Pharmaceuticals) delivered approximately 37% less drop volume than brand-name Timoptic XE (Merck U.S.). Generic Timolol Maleate EX (Pharmascience) delivered approximately 40% less drop volume than

Conclusions

American- and Canadian-produced brand-name Timoptic XE drops vary significantly from their country-specific generic equivalents in drop volume, viscosity, surface tension, and bottle orifice diameter. Generic Timolol Maleate EX (Pharmascience) delivered 40% less drop volume, and the daily prescribed dosage compared with that of brand-name Timoptic XE (Merck, Canada). Similarly, generic Timolol GFS (Falcon Pharmaceuticals) delivered 37% less drop volume and daily therapeutic dosage compared to

Disclosure

The authors have no proprietary or commercial interest in any materials discussed in this article.

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Glaucoma being an irreversible and progressive optic neuropathy necessitates early detection and life-long therapy. Intraocular pressure (IOP) is the only known modifiable risk factor for glaucoma progression, and all known glaucoma therapies aim to effectively reduce IOP. Topical glaucoma medications are the preferred first line of therapy of glaucoma, which could be used as a long-term therapy or as a temporalizing measure until surgical intervention. Glaucoma medications can be broadly classified as aqueous suppressants or outflow enhancing agents. The choice of medication depends on the type and severity of glaucoma, presence of co-morbid factors and patient preferences. Each class of drugs with a specific mechanism of action presents with unique side-effect profile and list of contraindications. It is prudent to consider the efficacy and tolerability of glaucoma medications prior to initiating therapy. Fixed combination glaucoma medications are preferred over prescribing individual drugs, as they improve adherence and tolerability. The problem of missed drops and drug discontinuation with lost to follow-up worsen the severity of glaucoma and patient counselling needs to be an integral part of medical therapy.
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There are several companies that produce generics of travoprost; the version from Sandoz was randomly chosen as the generic drop for the study. It was decided not to use masked bottles and instead retain the original bottles in order to avoid the introduction of biases by influencing ease of use, drop size, and drug concentration, all of which can be influenced by the characteristics of the bottle.6 The inclusion criteria were patients over the age of 18 years, able to consent, and diagnosed with primary open-angle glaucoma (POAG), OHT, or normotensive glaucoma (NTG) requiring pharmacological treatment.
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The intraocular pressure lowering effect of generic Sandoz travoprost was equivalent to that of Travatan Z (18.20 ± 3.41 mmHg and 18.44 ± 3.48 mmHg respectively, p < 0.0001). Tolerability, as measured with a questionnaire, was similar between the two formulations of travoprost.
This study is the first to compare a brand-name travoprost with one of its generic forms and adds to the body of evidence that generic glaucoma eye drops are as effective and well-tolerated as their brand name counterparts. The intraocular pressure lowering effect of generic Sandoz travoprost is equivalent to that of Travatan Z. Patient tolerance of generic and brand-name travoprost is similar.
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Cette étude prospective randomisée et en chassé-croisé comptait 76 patients atteints de glaucome primitif à angle ouvert, de glaucome normotensif ou d’hypertension oculaire qui ont d’abord reçu l’un ou l’autre médicament (Sandoz Travoprost ou Travatan Z) dans un rapport 1:1. Le chassé-croisé a eu lieu 3 semaines plus tard. La pression intraoculaire (paramètre principal) a été mesurée dans les 2 yeux au départ, à la semaine 3 et à la semaine 6. La tolérabilité des 2 médicaments (paramètre secondaire) a été évaluée au moyen d’un questionnaire aux semaines 3 et 6.
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Given limited published data, assumptions needed to be made about the measured volume and drops per milliliter of included preparations in many cases. It has been noted that these values may be dependent on the manufacturer, even for the same medication.30 We have tried to standardize bottle volumes for solutions and dosages for oral preparations within individual medication classes; however, this was not possible for all analyses.
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Original articleGeneric versus brand-name North American topical glaucoma drops

Abstract

Objective

Design

Participants

Methods

Results

Conclusion

Résumé

Objet

Nature

Participants

Méthodes

Résultats

Conclusion

Section snippets

Methods

Results

Discussion

Conclusions

Disclosure

Surv Ophthalmol

Clin Ther

Int J Pharm

J Pharm Sci

Am J Ophthalmol

Global Data on Visual Impairment in the Year 2002

Primary open-angle glaucoma

N Engl J Med

Dosage variability of topical ocular hypotensive products: a densitometric assessment

J Glaucoma

Barriers to glaucoma drug delivery

J Glaucoma

Equivalence of generic and brand-name ophthalmic products

Am J Health Syst Pharm

Original article
Generic versus brand-name North American topical glaucoma drops