Variation in Number of Doses, Bottle Volume, and Calculated Yearly Cost of Generic and Branded Latanoprost for Glaucoma


To evaluate discrepancies in doses per bottle, bottle fill volume, and cost among branded and generic formulations of latanoprost.


Comparative economic analysis.


This study was conducted at the Ruiz Department of Ophthalmology and Visual Science at The University of Texas Health Science Center at Houston (UTHealth). Four regionally available latanoprost formulations were measured. Number of drops per bottle and actual bottle fill volume were measured for a calculated sample size (10 bottles). Annual cost (using average wholesale price), days use per bottle, drops per milliliter, and number of bottles used per year were calculated. Data were summarized using mean and standard deviation; 1-way analysis of variance and post hoc Tukey’s studentized range test were used for comparing means among manufacturers.


Pfizer’s branded lantanoprost, Xalatan (New York, New York, USA), had the largest fill volume ( P < .001). Pfizer had the highest yearly cost at $1198 ( P < .001), whereas Akorn (Lake Forest, Illinois, USA) and Bausch & Lomb (Rochester, New York, USA) had the lowest ($184 and $201, respectively). Pfizer and Bausch & Lomb had the most drops per bottle (87.3 and 88.7, respectively), which was statistically more ( P < .001) than either Akorn or Sandoz (Princeton, New Jersey, USA) (77.6 and 76.6, respectively), but there was no statistical difference among the standard deviation of drops per bottle (Levene 0.14).


Annual cost and number of doses per bottle, factors important to patients, vary significantly depending on the manufacturer of latanoprost. Practitioners can better advise patients by being aware of these differences.

Prostaglandin analogue topical intraocular pressure (IOP)-lowering medications (PGAs) are a class of IOP-lowering medications that work via uveal and scleral collagen breakdown to effectively increase outflow of aqueous humor via the uveoscleral pathway. The once-daily dosing, efficacy, and minimal systemic safety issues of PGAs have made them a mainstay in the treatment of primary open-angle glaucoma and ocular hypertension. Seven generic formulations of latanoprost entered the market after the termination of branded Xalatan’s (Pfizer, New York, New York) patent in March 2011.

Variations in drop size and number of doses per bottle have been noted as potential inconsistencies between branded and generic medications. Issues such as bottle streaming and large drop size are also concerns with regard to medication waste, increased cost, and a patient finishing a bottle prior to the allotted time frame. Potential variability in how long a bottle lasts and the influence of cost of a particular generic may affect patient adherence to the prescribed regimen.

Previous studies have examined similar characteristics of branded and generic topical IOP-lowering medications, including a recent study of branded PGAs.


This comparative economic analysis was conducted at the Ruiz Department of Ophthalmology and Visual Science at The University of Texas Health Science Center at Houston (UTHealth) McGovern Medical School. Four regionally (Southeast United States) available latanoprost formulations (branded Xalatan, as well as generic latanoprost from Akorn, Lake Forest, Illinois, USA; Bausch & Lomb, Rochester, New York, USA; and Sandoz, Princeton, New Jersey, USA) were investigated. All medications were purchased from a wholesaler, not from the manufacturer of the product. All purchased medications from a given manufacturer came from the same lot.

Medications were stored at 25–27°C prior to the experiment. The bottles were held at 135° as the drops were collected and counted, as outlined by Fiscella and associates. In an effort to avoid streaming, the bottles were squeezed with sufficient pressure to expel drops, then pressure was released between each complete drop. After the drops ceased to flow, the bottle was inverted to 180° to obtain every last complete drop. The fill volume was measured in a graduated cylinder calibrated in increments of 0.1 mL. After each measurement, the cylinders were thoroughly washed using a scrub brush, rinsed with isopropyl alcohol 70%, and allowed sufficient time to air dry.

Sample Size

Rylander and Vold investigated the number of drops in branded lantoprost and reported that the standard deviation (SD) ranged from 2 to 6 drops per bottle. In investigating efficacy of PGA drop instillation, Fiscella and associates reported the SD of branded latanoprost as roughly 5 drops per bottle. Since glaucoma is a bilateral disease and patients apply PGA drops once a day to both eyes, on average, a 2.5 mL size of PGA can last for 45 days (8.1 bottles of medication per year). If the number of drops/bottle differs by 8 drops (4 daily dosages) among medications, then the yearly difference is 32 daily dosages (4 daily doses for each of the 8.1 bottles per year) or approximately 1 month’s worth of medication. Ten bottles per drug is required to detect an 8-drop difference among the drugs, assuming the SD is 5 drops and 5% significance and 80% power.

Data Analysis

The numbers of drops per milliliter were determined by dividing the fill volume measured by the number of drops in the bottle. Assuming both eyes receive the medication once daily, as per prescribing guidelines, the number of bottles per year was calculated by dividing the number of drops per bottle by 2, then multiplying by 365.20 days (accounting for leap years). The yearly cost was calculated by multiplying the average wholesale price (AWP) by the number of bottles per year. Although the true wholesale price of a prescription may vary, especially with generic products, and the price to the patient varies greatly owing to specific insurance coverage, the AWP is a common baseline wholesale price that is the same throughout the United States and has been used previously for price comparisons.

Data were summarized using mean and SD for each manufacturer. One-way analysis of variance (1-way ANOVA) and post hoc Tukey studentized range test for comparison were used for comparing means among manufacturers. However, Levene’s test for homogeneity was conducted first to compare variances among manufacturers. If heterogeneous variances were found, variance-weighted 1-way ANOVA was performed using the Welch method.

All statistical analyses were performed using SAS for Windows v9.3 (SAS, Inc, Cary, North Carolina, USA). P < .05 was considered statistically significant for all comparisons.


Fill Volume

The Table denotes the fill volume, number of drops per bottle, number of drops per milliliter, and costs for each manufacturer’s product, assuming no drops were wasted. The Figure demonstrates the differences among mean values and SD of these data. Kolmogorov-Smirnov testing was used to examine the normality distribution assumption for each study variable for each brand. All P values were >.05.


Mean (±Standard Deviation) [Range] of Fill Volume, Drops per Bottle, Drops per mL, and Yearly Cost of Lantanoprost for Each Manufacturer

Variable Manufacturer P Value
Pfizer Akorn Bausch & Lomb Sandoz
Fill volume (mL) 2.91 (±0.03) a
2.50 (±0.11) c
2.68 (±0.04) a
2.56 (±0.04) a
Levene: .002
Welch: <.001
Drops/bottle 87.3 (±3.9) a
77.6 (±4.1) b
88.7 (±2.3) a
76.6 (±2.07) b
Levene: .14
F: <.001
Drops/mL 30.0 (±1.4) b
31.0 (±1.2) b
33.1 (±0.6) a
30.0 (±0.9) b
Levene: .10
F: <.001
Yearly cost ($) 1198 (±54) a
184 (±10) c
201 (±5) c
907 (±25) b
Levene: .003
Welch: <.001

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Jan 6, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Variation in Number of Doses, Bottle Volume, and Calculated Yearly Cost of Generic and Branded Latanoprost for Glaucoma

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