- Email: [email protected]
Medical therapy cost considerations for glaucoma
Medical Therapy Cost Considerations for Glaucoma RICHARD G. FISCELLA, RPH, MPH, AMY GREEN, PHARMD, DANIEL H. PATUSZYNSKI, AND JACOB WILENSKY, MD
● PURPOSE: To determine the calculated daily patient cost (cost minimization) of medical glaucoma therapy and review cost trends. ● DESIGN: Experimental, controlled, prospective study. ● METHODS: The actual volume of various glaucoma medications or glaucoma medications with redesigned bottles was determined for most commercially available sizes of the tested products. The drops per milliliter based on the actual volume and the daily costs of the dosage schedules recommended by the manufacturers were compared. The cost of each bottle of medication was determined from the average wholesale price (AWP) in the United States. A comparison to 1999 prices where applicable will be analyzed to review costing trends. ● RESULTS: The generic timolol products (range, $0.38 – $0.46 per day) were similar on a cost per day basis vs Betimol (Santen, Napa Valley, California, USA), Optipranolol (Bausch and Lomb Pharmaceuticals, Tampa, Florida, USA) and Timoptic (Merck, West Point, Pennsylvania, USA). Their percentage cost increase ranged from 5% to 22% since 1999, except for generic timolol XE gel-forming solution (48%). Betagan (Allergan, Irvine, California, USA), Betoptic S (Alcon Laboratories, Fort Worth, Texas, USA), and Ocupress (Novartis, Duluth, Georgia, USA) ranged from $0.88 to $1.11 per day, and their percentage cost increase ranged from 33% to 53%. Some brand-only products have raised their AWPs a greater percentage, including Betoptic S (37%), Iopidine (Alcon, Fort Worth, Texas, USA) (50%), Ocupress (Novartis Ophthalmics, Duluth, Georgia, USA) (53%), and Pilopine gel (Alcon, Fort Worth, Texas, USA) (32%). The mean cost per day for the topical carbonic anhydrase inhibitors Azopt (Alcon Laboratories; $1.33 per day) and Trusopt (Merck; $1.05 per day) differed from 1999 when prices were almost identical. Cosopt (Merck; timolol 0.5% plus dorzolamide 2%, $1.04 per day) was less than the cost Accepted for publication Jan 13, 2003. From the Departments of Pharmacy Practice (R.G.F., D.H.P.) and Ophthalmology (R.G.F., J.W.), University of Illinois at Chicago, Chicago, Illinois, and the Department of Pharmacy, University of Kentucky, Lexington, Kentucky (A.G.). Inquiries to: Richard G. Fiscella, RPh, MPH, 833 South Wood Street, Chicago, IL 60612; fax: (312) 996-0379; e-mail: [email protected]
18
©
2003 BY
of separate bottles of a topical carbonic anhydrase inhibitor and a -blocker. The selective ␣-2 agonist brimonidine 0.15% with Purite (Alphagan-P, Allergan, 5 ml) twice daily was $1.29 per day. The prostaglandin analogs were comparably priced with Lumigan (Allergan) $0.95 per day, Xalatan (Pharmacia and Upjohn, Kalamazoo, Michigan, USA) $1.25 per day, Travatan (Alcon Laboratories) $1.01 per day, and Rescula (Novartis) $0.90 per day. ● CONCLUSIONS: All generic timolol, Betimol, Optipranolol, Timoptic, and Timoptic XE (Merck) ranged from $0.38 to $0.50 per day. Other -blocker products were about twice as costly, ranging from $0.88 to $1.11 per day. Cosopt ($1.05 per day) was less costly than separate bottles of a topical -blocker and a topical carbonic anhydrase inhibitor dosed three times daily or twice daily. The prostaglandin analogs ranged from $0.90 per day (Rescula) to $1.25 per day (Xalatan). Newer glaucoma medications exhibit similar costs per day in many cases, compared with more traditional medications, especially with greater price increases in older brand-only products. (Am J Ophthalmol 2003;136:18 –25. © 2003 by Elsevier Inc. All rights reserved.)
N
EW GLAUCOMA MEDICATIONS HAVE INCREASED
efficacy, reduced dosing frequency, and improved side effect profiles.1,2 Although the average wholesale price (AWP) in the United States is readily accessible for each medication, true cost-effectiveness studies still need to be completed. The price of medication itself does not take into account other variables contributing to the overall cost of treatment, such as extra office visits, ocular side effects, surgeries, and so forth.1 The calculated daily patient cost (cost minimization) of medical glaucoma therapy is one way of starting at a baseline for comparison and has been studied by other investigators.3–7 In the last few years, new products and more ergonomic and efficient ophthalmic bottles have required reexamination of the cost per day. We determined the daily cost of the new prostaglandin analogs, bimatoprost 0.03% (Lumigan; Allergan, Irvine, California, USA) and travoprost 0.004% (Travatan; Al-
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0002-9394/03/$30.00 doi:10.1016/S0002-9394(03)00102-8
con Laboratories, Fort Worth, Texas, USA). Latanoprost 0.005% (Xalatan; Pharmacia and Upjohn, Kalamazoo, Michigan, USA) was also recalculated because of a new dropper tip design. We determined the cost of brinzolamide suspension 1% (Azopt; Alcon Laboratories), dorzolamide 2% (Trusopt, Ocumeter Plus; Merck, West Point, Pennsylvania, USA), the dorzolamide 2% and timolol 0.5% combination (Cosopt, Ocumeter Plus; Merck) because of a bottle redesign (Ocumeter Plus) for Trusopt and Cosopt. Brimonidine with Purite (Alphagan-P; Allergan) is a reformulated brimonidine 0.2% (Alphagan) with a lower concentration of brimonidine (0.15%), comparable efficacy, fewer side effects, and a nontoxic preservative (Purite, a stabilized oxychloro complex).8,9 A comparison of various generic timolol and levobunolol products (including Timoptic [Merck] also in the Ocumeter Plus) against brand name products was also evaluated to determine the percentage price increase since 1999. All commercial sizes were used to determine whether any bottle size variation would be more cost advantageous on a cost per day basis. We also wanted to determine whether generic products provide a cost savings over brand name products on a cost per day basis and quantify the difference where it exists.
METHODS ALL MEDICATIONS WERE ORDERED FROM A WHOLESALER
and not from the manufacturer. The medication national drug codes (NDC number) and each lot number were recorded. The actual, not labeled, volume was determined for each bottle at 25 C. The bottles were held at approximately 135 degrees as the drops were collected, as described previously.3 After the drops ceased to flow, the bottle was inverted to 180 degrees to try to obtain every last complete drop. The entire content of each 2.5-ml bottle was counted and measured in a 5-ml graduated cylinder calibrated in increments of 0.1 ml. The 5-ml, 7.5-ml, 10-ml, and 15-ml bottles were counted and measured into 10-ml (calibrated in increments of 0.2 ml) and/or 5-ml graduated cylinders. After each measurement was made, the cylinders were thoroughly washed using a scrub brush, rinsed with isopropyl alcohol 70%, and towel dried. Sufficient time was allowed for the cylinders to air dry completely after they were towel dried, and each graduated cylinder was inspected to ensure no fluid or moisture remained before each measurement. The numbers of drops per milliliter were determined by counting the number of drops in one bottle and dividing by the total actual volume measured. For the new products and redesigned products, 15 bottles of each commercially available size were averaged to determine the overfill and number of drops per bottle. Previously, five bottles per product and size were used for an average. We recalculated the products previously studied and updated their cost per day based on VOL. 136, NO. 1
2002 pricing. In this current analysis, a greater number of bottles were used to determine a more accurate average drop and milliliter assessment. Certain medications were recalculated from a few years ago, because bottles and/or dropper tips have changed. Industry has improved some bottles so that there is less wastage by producing smaller drop sizes. Another modification allows for less streaming or inadvertent loss of multiple drops, by designing bottles that will allow a drop at the end of the dropper tip to retract back into the bottle once the pressure required to squeeze the bottle is released. Cosopt, Trusopt, and Timoptic are now in the Ocumeter Plus bottles. Xalatan has modified the dropper tip so that it is more efficient and less “streaming” occurs. Alphagan is not available, and Alphagan-P, a product with a different concentration, preservative, and vehicle, has taken its place. As reported previously, Alphagan and Alphagan-P are quoted for twice daily dosing even though the insert states three times daily, because more than 90% of patient usage is twice daily (personal communication with Allergan, Irvine, California, USA, September 16, 2002).3 Newer products, such as Lumigan, Rescula (Novartis, Duluth, Georgia, USA), and Travatan, are in new bottles with more drops per milliliter and were also evaluated. Although a true cost minimization study assumes all compared therapies have the same efficacy, this is obviously not the case in this instance. Assuming use in both eyes for each medication, the cost per day was calculated. This was determined by using the manufacturer’s recommended daily dosing regimen and calculating the numbers of drops required daily. The AWP was obtained from the Red Book 2002.10 Although the true wholesale price of a prescription may vary, especially with generic products, the AWP is a common baseline wholesale price that is the same throughout the United States and often employed for price comparisons in such publications as the Medical Letter (published by The Medical Letter, Inc., New Rochelle, New York, USA). The cost per day was calculated for each bottle by dividing the AWP by the actual number of drops in a bottle and multiplying by the number of drops required daily. The average milliliters per bottle for each size container was also calculated.
RESULTS MOST PRODUCTS ACHIEVED THE MINIMAL VOLUME ON THE
label (that is, 5 ml, 10 ml, and so forth). Overfill needs to be considered when determining baseline costs, because some products contain less volume and some contain more volume than the stated label amount on each bottle. The average number of drops per milliliter varied widely from 19.7 drops per milliliter (levobunolol) to 39.3 drops per milliliter for Rescula (Novartis; Table 1). The newer medications were more efficient in regard to number of drops per milliliter. Travatan delivered approximately 34.5
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TABLE 1. Glaucoma Medication Average Drops and Milliliters per Bottle Size
Generic Name Manufacturer/Trade Name
-Blockers Betaxolol 0.25% Alcon, Betoptic S
Carteolol 1% Novartis, Ocupress
Levobunolol 0.5% Allergan, Betagan
Levobunolol 0.5% Bausch & Lomb
Metipranolol 0.3% Bausch & Lomb, Optipranolol
Timolol Hemihydate 0.5% Santen, Betimol
Timolol Maleate 0.5% Akorn
Bausch & Lomb
Falcon gel-forming
Price, Red Book, Jan 1999
Price, Red Book, Sep 2002
Dose/Day OU
Mean Number of Days/Bottle
29.4 25.9 30.3 28.5 2.32
$24.75 $46.00 $68.75
$33.84 $63.18 $94.26
4 4 4
129.2 265.6 388.4
24.8 26.2 25.4 25.5 0.7
$19.44 $36.68 $55.02
$29.77 $56.11 $84.18
5.9 10.0 15.0 Mean SD
119.8 205.6 308
22.2 20.7 20.5 21.1 .92
$21.99 $44.04 $64.19
5 10 15
5.4 10.4 15.3 Mean SD
103.6 207.6 303.6
19.2 20 19.8 19.7 0.42
5 10
5.2 10.1 Mean SD
137.0 253.8
5 10 15
5.3 10.5 15.3 Mean SD
5 10 15
5.2 10.0 15.2 Mean SD 5.4 10.4 15.3 Mean SD 2.5 4.6 Mean SD
Bottle Size (ml)
Cost/Day 1999 $0.00
Cost/Day 2002 $0.00
38.4 66.4 115
0.65 0.69 0.60 0.65 0.05
0.88 0.95 0.82 0.88 0.07
4 4 4
32.3 66.4 97.1
0.60 0.55 0.57 0.57 0.03
0.92 0.85 0.87 0.87 0.04
$29.96 $61.05 $88.98
4 4 4
30 50.2 77
0.73 0.88 0.83 0.81 0.07
0.98 1.19 1.16 1.08 0.11
$16.27 $31.51 $45.80
$16.64 $32.29 $48.32
4 4 4
25.9 51.9 75.9
0.63 0.61 0.60 0.61 0.01
0.64 0.62 0.64 0.64 0.01
26.3 25.1 25.7 0.86
$15.68 $25.35
$18.45 $29.83
4 4
34.3 63.5
0.46 0.40 0.43 0.04
0.54 0.47 0.50 0.05
157.4 317.4 483.4
29.8 30.2 31.6 30.5 0.93
$15.05 $29.16 $43.68
$18.15 $35.10 $52.50
4 4 4
39.4 79.4 121
0.38 0.37 0.36 0.37 0.01
0.46 0.44 0.43 0.45 0.01
159.2 312.6 483.6
30.6 31.3 31.8 31.2 0.6 31.9 34.5 32.5 33 1.38 31.4 33.4 32.3 1.65
$15.76 $30.55 $45.72
$16.64 $32.29 $48.32
4 4 4
39.8 78.2 121
$16.58 $32.15 $48.12
$17.00 $32.29 $48.75
4 4 4
43.4 90.2 124
$11.83 $20.96
$17.42 $30.90
2 2
38.8 70.1
0.40 0.39 0.38 0.39 0.01 0.38 0.36 0.39 0.38 0.02 0.30 0.30 0.30 0.00
0.42 0.41 0.40 0.41 0.01 0.39 0.36 0.39 0.38 0.02 0.45 0.41 0.43 0.03
Average ml
Average Drops
Average Drops/ml
5 10 15
5.2 10.3 15.2 Mean SD
153.4 265.6 460.1
5 10 15
5.2 10.1 15.3 Mean SD
5 10 15
5 10 15
2.5 5
173.6 360.6 495.8
77.0 152.1
Continued on next page.
20
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TABLE 1. Glaucoma Medication Average Drops and Milliliters per Bottle Size (Continued)
Manufacturer/Trade Name Generic Name
Bottle Size (ml)
Falcon
5 10 15
Fougera
10 15
Watson (Schein)
5 10 15
Merck, Timoptic (Ocumeter Plus)*
Merck, Timoptic XE
Carbonic anhydrase inhibitors Brinzolamide 1% Alcon, Azopt
Dorzolamide 2% Merck, Trusopt (Ocumeter Plus)*
Dorzolamide 2% ⫹ timolol 0.5% Merck, Cosopt (Ocumeter Plus)*
Average ml
35.5 75.5 110
$30.55 $45.72
$32.35 $48.46
4 4
79.3 113
$16.50 $32.00 $48.00
$N/A $N/A $N/A
4 4 4
34.4 73 102
164.4 (207.1) 29.8 (33.3) 355.4 (358.7) 32.6 (31.2) 508.6 31.6 31.5 (32.5) 1.2 (1.2) 81.8 23.8 156.8 26.1 24.9 1.61
$19.79 $38.40 $57.48
$22.10 $42.88 $64.19
4 4 4
41.1 (51.8) 88.9 (89.7) 127
$16.29 $28.88
$19.35 $34.33
2 2
40.9 78.4
124.6 263.6 383.4
$20.38 $40.75 $61.13
$28.44 $56.88 $85.32
6 6 6
$23.29 $46.60
$26.94 $53.91
5
5.4 (5.9) 138.0 (154.8) 25.7 (26.3) 10.6 (11.1) 274.4 (308.8) 25.8 (27.7) Mean 25.8 (27.1) SD 0.06 (1.0) 5.4 (5.9) 144.4 (175.1) 26.7 (29.8)
$39.69
10
10.7 (11.2) 277.4 (321.0) 25.9 (28.6)
$79.38
2.5 5
5 10 15
5 10
5.0 10.4 15.2 Mean SD
317.2 453.2
137.6 291.8 408.6
28.4 30.8 29.5 29.5 1.2 29.7 29.3 29.5 0.3 26.5 29.6 27.2 27.8 1.65
Mean Number of Days/Bottle
4 4 4
Mean SD ␣-2 Agonists Brimonidine 2%† Allergan, Alphagan, Alphagan P (2002) Alphagan P (2002)
Price, Price, Red Book, Red Book, Dose/Day Jan 1999 Sep 2002 OU
$17.00 $32.35 $48.75
5.5 (6.2) 10.9 (11.3) 16.1 Mean SD 3.4 6.0 Mean SD
142 301.8 441.8
Average Drops/ml
$16.58 $32.15 $48.12
5 10 15
5.0 9.8 15.0 Mean SD 10.7 15.5 Mean SD 5.2 9.9 15.0 Mean SD
Average Drops
24.6 25.4 25.2 25.1 0.4
Cost/Day Cost/Day 1999 2002 $0.00 $0.00
0.48 0.43 0.44 0.45 0.03 0.39 0.40 0.39 0.01 0.48 0.44 0.47 0.46 0.02
0.48 0.43 0.44 0.45 0.03 0.42 0.42 0.42 0.01 NA NA NA
0.48 0.43 0.45 0.46 0.02 0.40 0.37 0.38 0.02
(0.43) (0.48) NA (0.45) (0.04) 0.47 0.44 0.46 0.02
20.8 43.9 63.9
0.98 0.93 0.96 0.96 0.03
1.37 1.29 1.34 1.33 0.04
6 6
23.0 (25.8) 45.7 (51.5)
$43.85
4
36.1 (43.8)
1.01 1.02 1.02 0 1.10
(1.04) (1.05) 1.05 0 (1.00)
$87.71
4
69.4 (80.3)
1.14
(1.09)
1.12 0.03
1.05 0.06
26.3 (29.2) 0.6 (0.8)
5
5.4
114.0
21.1
$25.94
$36.28
4
28.5
0.91
1.29
10 15
10.1 15.3 Mean SD
238.6 333.4
23.6 21.8 22.2 1.3
$51.84 $77.80
$72.49 $108.80
4 4
59.7 83.4
0.87 0.93 0.90 0.03
1.30 1.30 1.30 0.01
Continued on next page.
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TABLE 1. Glaucoma Medication Average Drops and Milliliters per Bottle Size (Continued)
Manufacturer/Trade Name Generic Name
Prostaglandins/prostamides Bimatoprost 0.03% Allergan, Lumigan
Latanoprost 0.005% Pharmacia, Xalatan (new bottle)‡ Travoprost 0.004% Alcon, Travatan§ Unoprostone 0.15% Novartis, Rescula
Price, Red Book, Jan 1999
Price, Red Book, Sep 2002
Dose/Day OU
Mean Number of Days/Bottle
Cost/Day 1999 $0.00
Cost/Day 2002 $0.00
37.4 34.1 34.1 35.2 1.9
NA NA NA
$53.13 $106.25 $159.38
2 2 2
55.7 95.2 129.7
NA NA NA
0.95 1.12 1.23 1.10 0.14
97.6 (85.1) 102.9
32 (28) 34.5
$45.03 NA
$53.00 $52.00 $103.00
2 2 2
48.8 (42.5) 51.5
NA
209
39.3
NA
46.81
4
52.2
NA
Bottle Size (ml)
Average ml
Average Drops
Average Drops/ml
2.5 5.0 7.5
3.3 5.6 7.6 Mean SD
111.3 190.5 259.4
2.5 2.5
3.05 3.01 3.0
5.0
5.3
1.11 1.25 1.01 7.0 0.90
NA ⫽ not available; OU ⫽ both eyes. *The new Ocumeter Plus bottle results are in parenthesis vs the original Ocumeter bottle. † More than 90% of brimonidine usage is twice daily. Brimonidine and brimonidine-P overfill and number of drops per milliliter are approximately the same. ‡ The original latanoprost bottle had some streaming problems. The newer bottle has a larger drop size but causes less streaming. § Travoprost is available as a twin pack containing two bottles of 2.5 ml.
drops per milliliter and Lumigan approximately 35.2 drops per milliliter. The cost of -adrenergic antagonists per day ranged from a low of $0.38 per day to $0.50 per day. Again, the generic timolol products (range, $0.38 –$0.46 per day) were similar on a cost per day basis vs the brand name metipranolol (Optipranolol; Bausch and Lomb Pharmaceuticals, Tampa, Florida, USA; $0.50 per day), timolol hemihydrate (Betimol; Santen, Napa Valley, California, USA; $0.45), Timoptic ($0.51 per day), and Timoptic XE ($0.46 per day). The gap has narrowed between the average prices of both sizes of generic timolol gel ($0.43 per day) vs Timoptic XE ($0.46 per day). One company (Schein, now Watson) discontinued their generic ophthalmic timolol solution. Other -blockers including Betagan (Allergan; $1.11 per day), Betoptic S (Alcon Laboratories; $0.88 per day), generic levobunolol ($0.63 per day) and Ocupress (Novartis; $0.88 per day) were generally still found to be more expensive on a per day basis. The cost of topical carbonic anhydrase inhibitors dosed two and three times daily averaged $0.88 per day and $1.33 per day for Azopt and $0.70 per day and $1.04 per day for Trusopt, respectively. The labeled dose of both topical products is three times daily, although some twice daily dosing, especially as adjunctive therapy, is often done. The combination product Cosopt (timolol 0.5% plus dorzolamide 2%; $1.05 per day) was less costly than two separate bottles of a topical carbonic anhydrase inhibitor (three times daily dosing) and approximately the same daily cost with twice daily dorzolamide dosing and a -blocker. The 22
AMERICAN JOURNAL
new Merck bottle (Ocumeter Plus) contains more overfill than the previous bottle (Ocumeter) and has a slightly smaller drop size. However, there was more variability in the number of drops counted (5-ml bottle; 175 drops ⫾ 8.4), even though the bottle delivered approximately the same amount of overfill each time (5.9 ml; range, 5.8 – 6.0 ml). The viscosity of the methylcellulose vehicle may account for some of the variation in drop size. Other costs per day for glaucoma products included Alphagan-P ($1.29 per day; twice daily dosing, 5 ml), Lumigan ($0.95 per day, 2.5 ml), Travatan ($1.01 per day), and Xalatan ($1.25 per day).
DISCUSSION WE HAD PREVIOUSLY REPORTED ON THE GLAUCOMA MED-
ications on a cost per day basis.3 The number of drops per milliliter, the actual volume, and the cost per bottle are helpful in determining the daily treatment costs for patients with glaucoma. Using a general average (that is, 20 drops per milliliter) to estimate the number of drops per milliliter of a given ophthalmic medication is not accurate. This variability in overfill and drops per milliliter has been demonstrated by others.4 –7 Two different timolol manufacturers’ 10-ml bottles had mean fills of 9.85 ml (Falcon and Schein).3 Timolol gel-forming solution (Falcon) had less than the stated label volume (2.45 ml for 2.5 ml and 4.5 ml for 5 ml).3 The timolol gel-forming solution (Falcon) was clear but appeared more viscous, and thereOF
OPHTHALMOLOGY
JULY 2003
fore the total volume was not available unless the bottle was stored upside down. Therefore, when one compares two products with the same stated volume, the assumption that the one with the higher per bottle price has the higher daily cost may not be correct. The product with the smaller drop size may in reality cost less because it may last longer, and therefore the cost per day may be less to the patient. This study was completed to update the price changes since 1999 to examine new products recently released and to determine whether new bottle designs made any difference. The cost per day of generic timolol was similar to the brand product (Timoptic and Timoptic XE), Betimol, and Optipranolol. These products ranged from $0.38 to $0.51 per day. Betaxolol, Ocupress, and Betagan ranged from $0.88 to $1.11 per day. Generic levobunolol was about $0.64 per day. Older products, such as pilocarpine, are priced from $0.27 to $0.36 per day, although the branded Pilopine HS (Alcon, Fort Worth, Texas, USA) is more costly at $1.13 per day. Propine ($0.61 per day) is more costly than the generic dipivefrin ($0.34 per day). The branded products Diamox and Neptazane, have been discontinued by the manufacturer, and only generic products remain. However, even the generic products range from $0.84 to $1.74 (acetazolamide) and $0.96 to $2.60 (methazolamide) per day. The Ocumeter Plus is a more ergonomic bottle for the patient. The bottle is oversized as is the cap, so the patient who has difficulty grasping a small bottle or bottle cap can grip the bottle more easily. There is also an indentation on the bottle that allows the patient to squeeze the bottle with one finger so that only a single drop is used. The overfill in the bottle helps to offset the cost increase that occurred in the last year. Patient compliance, ease of administration, and drug efficacy should be improved with a single bottle.11 A single bottle of combination eye drops (Cosopt) vs two separate bottles may help to reduce the potential for loss of another drugs’ pharmacologic effect. This is believed to be related to a dilutional effect that occurs when the second medication is administered before complete absorption of the first medication.11 However, there is some loss in dose titration and occasional product confusion when there are fixed-dose combination products. The latanoprost bottle and tip has also been redesigned so that “streaming” of the drops does not occur from the bottle. If pressure is released off the bottle, the remaining fluid will be drawn back into the bottle, which prevents the patient from wasting medication. The newer dropper tip produces a larger drop (therefore less drops per milliliter), but the patient probably wastes less medication than with the previously designed bottle. Bimatoprost, travoprost, and unoprostone are more efficient bottles than those previously manufactured. Each bottle produces more drops per milliliter than previous bottles made by these same companies in the past. However, the travoprost bottle design was difficult to squeeze, VOL. 136, NO. 1
especially when only a small amount of medication is remaining in the bottle. The bottle is not very pliable, and some patients with dexterity problems may encounter difficulty with drop administration. All sizes commercially available were studied to determine if any differences or cost advantages were obtained for the various sizes. The bimatoprost 2.5-ml bottle would be the most cost beneficial on a cost per day basis compared with other once daily prostaglandin analogs. There is more overfill in the 2.5-ml than the 5-ml or 7.5-ml size. However, bimatoprost is the only prostaglandin analog with a larger bottle size that may benefit some managed care patients who pay only one copay. Some patients may also prefer the larger 5-ml bottle (average, 197 drops per bottle or possibly 90 days) or the 7.5-ml bottle (259 drops per bottle or possibly up to 129 days of treatment), the use of which can result in fewer pharmacy trips and potentially provide 3 to 4 months of therapy from one bottle with careful use. Travatan is also available in a dual pack containing two separate 2.5-ml bottles. Although there is no cost advantage, the patient should open only one bottle at a time, because there is a 6-week expiration after a bottle is opened. Brimonidine is a first- or second-line therapeutic option because of minimal ocular and systemic side effects and effective intraocular pressure (IOP)–lowering ability.12 Brimonidine-P is in a carboxymethycellulose vehicle with Purite as the preservative and comparable IOP lowering to brimonidine 0.2%.9 The carboxymethycellulose and the Purite are the same vehicle and preservative system, respectively, as found in Refresh Tears (Allergan). Alphagan-P and Alphagan have an almost identical drop size and count. However, brimonidine-P is more comfortable for the patient and is the only glaucoma medication not containing the preservative benzalkonium chloride or a related sister compound. It is also considered a low-risk preservative or almost preservative-free product available for patients with benzalkonium chloride allergies.8 A generic product that contains brimonidine 0.2% is not a generic equivalent for the brimonidine-P 0.15%, which would have to be taken into consideration for a cost per day comparison. The only preservative-free glaucoma products for commercial use are Timoptic unit dose and 2-ml bottles of pilocarpine in a sterile blister pack. Bimatoprost, latanoprost, and travoprost with their once daily administration and potent IOP-lowering effects are indicated as adjunctive therapy.2 However, because latanoprost has demonstrated very good efficacy and safety since 1996, it has just recently received an indication for the primary treatment of open-angle glaucoma. Older adjunctive therapies may be costly (Table 2). Various adjunctive combinations of new therapeutic agents are less on a cost per day basis than older traditional therapy (Table 2). In fact, an interesting phenomenon occurs when the market share of older brand-only products without generic equivalents decreases. The products will
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23
pharmacies would probably purchase the more reasonably priced generic product, depending on availability. However, should the pharmacy purchase the more expensive generic product, the resulting patient cost may vary. Although a generic medication is purchased at a lower AWP, that total savings would most likely not be passed on to the patient. The pharmacy will purchase the generic product for less than the listed AWP but make more on the markup. The patient will still pay less for the generic product than the brand. Because the price of medications may change often, it may benefit the patient to shop for the best price, because prices among pharmacies may vary significantly even within the same neighborhood. In recent cost surveys of various pharmacies in the Chicago area, prices varied by about $15.00 for the same prostaglandin product and up to $10.00 for Cosopt and Alphagan (R.G.F.). Therefore, it is especially beneficial for the patient without prescription benefits to shop for the best price. The results of the previous study in conjunction with this study, more specifically, the average drops per bottle or average number of days per bottle, were used to determine updated daily costs based on price increases. This study is still based on a best-case scenario for all medicines, assuming no wasted doses by the patient. If a patient misses his or her eye when applying the eye drops, the cost per day will increase with any topical glaucoma medications because of loss of volume in terms of wasted drops. If patients are properly instructed on how to use their eyedrops, and/or have a caregiver to help administer them, wastage will be reduced. The true costs of some of the newer medications may be further decreased by improved compliance and the need for fewer medications to control IOP, fewer patient interventions (for example, office calls, surgeries, lasers), and an improved side effect profile. Poor compliance is one of the most common reasons for treatment failures in glaucoma.14 Limited understanding of the disease state itself may adversely affect compliance. It has been reported that better understanding of disease improved regimen compliance by up to 10 times.14 The cost of a new glaucoma medication is just one of a multitude of factors to consider when choosing a medication for a patient. Recent glaucoma drug developments offer patients more effective products, with less severe ocular side effects and/or less frequent drug administration. New medications are better tolerated, more effective in reducing IOP, dosed less frequently, cause fewer systemic side effects, and are often more reasonable on a cost per day basis.2,3 Improved patient compliance with fewer daily drops is also a benefit of the newer glaucoma medications. The cost of generic timolol, Optipranolol, Timoptic, and Timoptic XE ranged from $0.38 to $0.51 per day. Betaxolol, Betimol, Ocupress, and Betagan ranged from $0.88 to $1.11 per day. Generic levobunolol was about $0.64 per day. Cosopt ($1.05 per day) was less costly than separate bottles of a topical  blocker and a topical carbonic
TABLE 2. Costs of Various Common Glaucoma Medications Medication
Miotics Pilocarpine drops Pilocarpine gel (Pilopine HS, $39.36) Epinephrines Dipivefrin drops (5 ml, $14.07) Propine drops (5 mL, $25.11) Systemic CAIs (prices are per 100 tablets) Acetazolamide (3 or 4 times/day) 125 mg ($33.80, Taro) 250 mg ($28.00, Watson) 250 mg ($43.60, Yaro) Methazolamide (2 or 3 times/day) 25 mg ($48.00, Teva) 25 mg ($57.74, Qualitest) 50 mg ($72.00, Teva) 50 mg ($86.62, Qualitest) -Blockers (5 ml) Timolol, Timoptic, Timoptic XE (daily), Betimol or Optipranolol Ocupress, Betagan, Betoptic S Topical CAIs (5 ml) Dorzolamide (2 or 3 times/day) Brinzolamide (2 or 3 times/day) Combination product (10 ml) Cosopt (timolol 0.5%⫹ dorzolamide 2%) ␣-2 Agonist (5 ml) Alphagan (twice daily) Prostaglandin Lumigan (2.5 ml) Rescula (5.0 ml) Travatan (2.5 ml) Xalatan (2.5 ml)
Cost/Day
$0.27–0.36 $1.13 $0.34 $0.61
$1.02/$1.35 $0.84/$1.12 $1.31/$1.74 $0.96/$1.44 $1.16/$1.73 $1.33/$2.00 $1.73/$2.60 $0.38–$0.50 $0.88–$1.11 $0.69/$1.04 $0.89/$1.33 $1.09 $1.29 $0.95 $0.90 $1.01 $1.25
CAIs ⫽ carbonic anhydrase inhibitors. Adapted in part from Am J Hosp Pharm.13 Average wholesale prices from Red Book 2002.10
have frequent large price increases to “recoup” prescription sales from the product before its use diminishes or it is replaced by a generic. Examples of these products (current AWP; size; percentage increase since 1999) include Betoptic S ($98.19; 15 ml; 37%), Iopidine (Alcon, Fort Worth, Texas, USA) ($123.75; 10 ml; 50% increase), Ocupress ($84.18; 15 ml; 53%), and Pilopine HS ($41.00; 4 g; 32%). The cost per day may be similar for a newer and more effective therapy (that is, Lumigan 2.5 ml at $0.95 per day) than an older brand-only medication losing market share (that is, Betoptic S at $0.88 per day). Another consideration is that the AWPs for some generic products may vary, which may reflect a patient’s cost. For instance, generic acetazolamide tablets are available from a few sources. One source charges an AWP of $28.00 for 100 tablets (Watson) vs $43.60 (Yaro). Most 24
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anhydrase inhibitor dosed three times daily and two times daily. The cost per day of new prostaglandin analog products for similar-size bottles were Lumigan ($0.95 per day), Rescula ($0.90 per day), Travatan ($1.01 per day), and Xalatan ($1.25 per day). New medical glaucoma treatment regimens exhibit similar costs per day compared with more traditional therapies.
REFERENCES 1. Alward WLM. Medical management of glaucoma. N Engl J Med 1998;339:1298 –1307. 2. Novack GD, O’Donnell MJ, Molloy DW. New glaucoma medications in the geriatric population: efficacy and safety. Am Geriat Soc 2002;50:956 –962. 3. Fiscella R, Geller JL, Gryz LL, et al. Costs considerations of medical therapy for glaucoma. Am J Ophthalmol 1999;128: 426 –433. 4. Weiss MA, Hendrickson JR. Information on drop size needs to be eyed closely. Am J Hosp Pharm 1994;51:2969 –2970. 5. Ball SF, Schneider E. Cost of beta-adrenergic receptor blocking agents for ocular hypertension. Arch Ophthalmol 1992;110:654 –657.
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6. Hartenbaum D, Stek M, Haggert B, et al. Quantitative and cost evaluation of three antiglaucoma beta-blocker agents. Timoptic-XE versus two generic levobunolol products. Am J Man Care 1996;2:157–162. 7. Schwartz J, Christensen RE, Lee DA. Comparison of timolol maleate and levobunolol: doses and volume per bottle [Letter]. Arch Ophthalmol 1989;107:17. 8. Noecker R. Effects of common ophthalmic preservatives on ocular health. Adv Ther 2001;18:205–215. 9. Katz LJ. Twelve-month evaluation of brimonidine-purite versus brimonidine in patients with glaucoma or ocular hypertension. J Glaucoma 2002;11:119 –126. 10. Red book 2002. Montvale, NJ. Drug Topics, 2002. 11. Choudhri S, Wand M, Shields MB. A comparison of dorzolamide-timolol combination versus the concomitant drugs. Am J Ophthalmol 2000;130:832–833. 12. Leblanc RP, for the Brimonidine Study Group. Twelvemonth results of an ongoing randomized trial comparing brimonidine tartrate 0.2% and timolol 0.5% given twice daily in patients with glaucoma or ocular hypertension. Ophthalmology 1998;105:1960 –1967. 13. Fiscella R. Cost of glaucoma medications. Am J Hosp Pharm 1998;55:272–275. 14. Zimmerman T. Facilitating patient compliance in glaucoma therapy. Surv Ophthalmol 1983;289(Suppl):S252–S257.
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25
● PURPOSE: To determine the calculated daily patient cost (cost minimization) of medical glaucoma therapy and review cost trends. ● DESIGN: Experimental, controlled, prospective study. ● METHODS: The actual volume of various glaucoma medications or glaucoma medications with redesigned bottles was determined for most commercially available sizes of the tested products. The drops per milliliter based on the actual volume and the daily costs of the dosage schedules recommended by the manufacturers were compared. The cost of each bottle of medication was determined from the average wholesale price (AWP) in the United States. A comparison to 1999 prices where applicable will be analyzed to review costing trends. ● RESULTS: The generic timolol products (range, $0.38 – $0.46 per day) were similar on a cost per day basis vs Betimol (Santen, Napa Valley, California, USA), Optipranolol (Bausch and Lomb Pharmaceuticals, Tampa, Florida, USA) and Timoptic (Merck, West Point, Pennsylvania, USA). Their percentage cost increase ranged from 5% to 22% since 1999, except for generic timolol XE gel-forming solution (48%). Betagan (Allergan, Irvine, California, USA), Betoptic S (Alcon Laboratories, Fort Worth, Texas, USA), and Ocupress (Novartis, Duluth, Georgia, USA) ranged from $0.88 to $1.11 per day, and their percentage cost increase ranged from 33% to 53%. Some brand-only products have raised their AWPs a greater percentage, including Betoptic S (37%), Iopidine (Alcon, Fort Worth, Texas, USA) (50%), Ocupress (Novartis Ophthalmics, Duluth, Georgia, USA) (53%), and Pilopine gel (Alcon, Fort Worth, Texas, USA) (32%). The mean cost per day for the topical carbonic anhydrase inhibitors Azopt (Alcon Laboratories; $1.33 per day) and Trusopt (Merck; $1.05 per day) differed from 1999 when prices were almost identical. Cosopt (Merck; timolol 0.5% plus dorzolamide 2%, $1.04 per day) was less than the cost Accepted for publication Jan 13, 2003. From the Departments of Pharmacy Practice (R.G.F., D.H.P.) and Ophthalmology (R.G.F., J.W.), University of Illinois at Chicago, Chicago, Illinois, and the Department of Pharmacy, University of Kentucky, Lexington, Kentucky (A.G.). Inquiries to: Richard G. Fiscella, RPh, MPH, 833 South Wood Street, Chicago, IL 60612; fax: (312) 996-0379; e-mail: [email protected]
18
©
2003 BY
of separate bottles of a topical carbonic anhydrase inhibitor and a -blocker. The selective ␣-2 agonist brimonidine 0.15% with Purite (Alphagan-P, Allergan, 5 ml) twice daily was $1.29 per day. The prostaglandin analogs were comparably priced with Lumigan (Allergan) $0.95 per day, Xalatan (Pharmacia and Upjohn, Kalamazoo, Michigan, USA) $1.25 per day, Travatan (Alcon Laboratories) $1.01 per day, and Rescula (Novartis) $0.90 per day. ● CONCLUSIONS: All generic timolol, Betimol, Optipranolol, Timoptic, and Timoptic XE (Merck) ranged from $0.38 to $0.50 per day. Other -blocker products were about twice as costly, ranging from $0.88 to $1.11 per day. Cosopt ($1.05 per day) was less costly than separate bottles of a topical -blocker and a topical carbonic anhydrase inhibitor dosed three times daily or twice daily. The prostaglandin analogs ranged from $0.90 per day (Rescula) to $1.25 per day (Xalatan). Newer glaucoma medications exhibit similar costs per day in many cases, compared with more traditional medications, especially with greater price increases in older brand-only products. (Am J Ophthalmol 2003;136:18 –25. © 2003 by Elsevier Inc. All rights reserved.)
N
EW GLAUCOMA MEDICATIONS HAVE INCREASED
efficacy, reduced dosing frequency, and improved side effect profiles.1,2 Although the average wholesale price (AWP) in the United States is readily accessible for each medication, true cost-effectiveness studies still need to be completed. The price of medication itself does not take into account other variables contributing to the overall cost of treatment, such as extra office visits, ocular side effects, surgeries, and so forth.1 The calculated daily patient cost (cost minimization) of medical glaucoma therapy is one way of starting at a baseline for comparison and has been studied by other investigators.3–7 In the last few years, new products and more ergonomic and efficient ophthalmic bottles have required reexamination of the cost per day. We determined the daily cost of the new prostaglandin analogs, bimatoprost 0.03% (Lumigan; Allergan, Irvine, California, USA) and travoprost 0.004% (Travatan; Al-
ELSEVIER INC. ALL
RIGHTS RESERVED.
0002-9394/03/$30.00 doi:10.1016/S0002-9394(03)00102-8
con Laboratories, Fort Worth, Texas, USA). Latanoprost 0.005% (Xalatan; Pharmacia and Upjohn, Kalamazoo, Michigan, USA) was also recalculated because of a new dropper tip design. We determined the cost of brinzolamide suspension 1% (Azopt; Alcon Laboratories), dorzolamide 2% (Trusopt, Ocumeter Plus; Merck, West Point, Pennsylvania, USA), the dorzolamide 2% and timolol 0.5% combination (Cosopt, Ocumeter Plus; Merck) because of a bottle redesign (Ocumeter Plus) for Trusopt and Cosopt. Brimonidine with Purite (Alphagan-P; Allergan) is a reformulated brimonidine 0.2% (Alphagan) with a lower concentration of brimonidine (0.15%), comparable efficacy, fewer side effects, and a nontoxic preservative (Purite, a stabilized oxychloro complex).8,9 A comparison of various generic timolol and levobunolol products (including Timoptic [Merck] also in the Ocumeter Plus) against brand name products was also evaluated to determine the percentage price increase since 1999. All commercial sizes were used to determine whether any bottle size variation would be more cost advantageous on a cost per day basis. We also wanted to determine whether generic products provide a cost savings over brand name products on a cost per day basis and quantify the difference where it exists.
METHODS ALL MEDICATIONS WERE ORDERED FROM A WHOLESALER
and not from the manufacturer. The medication national drug codes (NDC number) and each lot number were recorded. The actual, not labeled, volume was determined for each bottle at 25 C. The bottles were held at approximately 135 degrees as the drops were collected, as described previously.3 After the drops ceased to flow, the bottle was inverted to 180 degrees to try to obtain every last complete drop. The entire content of each 2.5-ml bottle was counted and measured in a 5-ml graduated cylinder calibrated in increments of 0.1 ml. The 5-ml, 7.5-ml, 10-ml, and 15-ml bottles were counted and measured into 10-ml (calibrated in increments of 0.2 ml) and/or 5-ml graduated cylinders. After each measurement was made, the cylinders were thoroughly washed using a scrub brush, rinsed with isopropyl alcohol 70%, and towel dried. Sufficient time was allowed for the cylinders to air dry completely after they were towel dried, and each graduated cylinder was inspected to ensure no fluid or moisture remained before each measurement. The numbers of drops per milliliter were determined by counting the number of drops in one bottle and dividing by the total actual volume measured. For the new products and redesigned products, 15 bottles of each commercially available size were averaged to determine the overfill and number of drops per bottle. Previously, five bottles per product and size were used for an average. We recalculated the products previously studied and updated their cost per day based on VOL. 136, NO. 1
2002 pricing. In this current analysis, a greater number of bottles were used to determine a more accurate average drop and milliliter assessment. Certain medications were recalculated from a few years ago, because bottles and/or dropper tips have changed. Industry has improved some bottles so that there is less wastage by producing smaller drop sizes. Another modification allows for less streaming or inadvertent loss of multiple drops, by designing bottles that will allow a drop at the end of the dropper tip to retract back into the bottle once the pressure required to squeeze the bottle is released. Cosopt, Trusopt, and Timoptic are now in the Ocumeter Plus bottles. Xalatan has modified the dropper tip so that it is more efficient and less “streaming” occurs. Alphagan is not available, and Alphagan-P, a product with a different concentration, preservative, and vehicle, has taken its place. As reported previously, Alphagan and Alphagan-P are quoted for twice daily dosing even though the insert states three times daily, because more than 90% of patient usage is twice daily (personal communication with Allergan, Irvine, California, USA, September 16, 2002).3 Newer products, such as Lumigan, Rescula (Novartis, Duluth, Georgia, USA), and Travatan, are in new bottles with more drops per milliliter and were also evaluated. Although a true cost minimization study assumes all compared therapies have the same efficacy, this is obviously not the case in this instance. Assuming use in both eyes for each medication, the cost per day was calculated. This was determined by using the manufacturer’s recommended daily dosing regimen and calculating the numbers of drops required daily. The AWP was obtained from the Red Book 2002.10 Although the true wholesale price of a prescription may vary, especially with generic products, the AWP is a common baseline wholesale price that is the same throughout the United States and often employed for price comparisons in such publications as the Medical Letter (published by The Medical Letter, Inc., New Rochelle, New York, USA). The cost per day was calculated for each bottle by dividing the AWP by the actual number of drops in a bottle and multiplying by the number of drops required daily. The average milliliters per bottle for each size container was also calculated.
RESULTS MOST PRODUCTS ACHIEVED THE MINIMAL VOLUME ON THE
label (that is, 5 ml, 10 ml, and so forth). Overfill needs to be considered when determining baseline costs, because some products contain less volume and some contain more volume than the stated label amount on each bottle. The average number of drops per milliliter varied widely from 19.7 drops per milliliter (levobunolol) to 39.3 drops per milliliter for Rescula (Novartis; Table 1). The newer medications were more efficient in regard to number of drops per milliliter. Travatan delivered approximately 34.5
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TABLE 1. Glaucoma Medication Average Drops and Milliliters per Bottle Size
Generic Name Manufacturer/Trade Name
-Blockers Betaxolol 0.25% Alcon, Betoptic S
Carteolol 1% Novartis, Ocupress
Levobunolol 0.5% Allergan, Betagan
Levobunolol 0.5% Bausch & Lomb
Metipranolol 0.3% Bausch & Lomb, Optipranolol
Timolol Hemihydate 0.5% Santen, Betimol
Timolol Maleate 0.5% Akorn
Bausch & Lomb
Falcon gel-forming
Price, Red Book, Jan 1999
Price, Red Book, Sep 2002
Dose/Day OU
Mean Number of Days/Bottle
29.4 25.9 30.3 28.5 2.32
$24.75 $46.00 $68.75
$33.84 $63.18 $94.26
4 4 4
129.2 265.6 388.4
24.8 26.2 25.4 25.5 0.7
$19.44 $36.68 $55.02
$29.77 $56.11 $84.18
5.9 10.0 15.0 Mean SD
119.8 205.6 308
22.2 20.7 20.5 21.1 .92
$21.99 $44.04 $64.19
5 10 15
5.4 10.4 15.3 Mean SD
103.6 207.6 303.6
19.2 20 19.8 19.7 0.42
5 10
5.2 10.1 Mean SD
137.0 253.8
5 10 15
5.3 10.5 15.3 Mean SD
5 10 15
5.2 10.0 15.2 Mean SD 5.4 10.4 15.3 Mean SD 2.5 4.6 Mean SD
Bottle Size (ml)
Cost/Day 1999 $0.00
Cost/Day 2002 $0.00
38.4 66.4 115
0.65 0.69 0.60 0.65 0.05
0.88 0.95 0.82 0.88 0.07
4 4 4
32.3 66.4 97.1
0.60 0.55 0.57 0.57 0.03
0.92 0.85 0.87 0.87 0.04
$29.96 $61.05 $88.98
4 4 4
30 50.2 77
0.73 0.88 0.83 0.81 0.07
0.98 1.19 1.16 1.08 0.11
$16.27 $31.51 $45.80
$16.64 $32.29 $48.32
4 4 4
25.9 51.9 75.9
0.63 0.61 0.60 0.61 0.01
0.64 0.62 0.64 0.64 0.01
26.3 25.1 25.7 0.86
$15.68 $25.35
$18.45 $29.83
4 4
34.3 63.5
0.46 0.40 0.43 0.04
0.54 0.47 0.50 0.05
157.4 317.4 483.4
29.8 30.2 31.6 30.5 0.93
$15.05 $29.16 $43.68
$18.15 $35.10 $52.50
4 4 4
39.4 79.4 121
0.38 0.37 0.36 0.37 0.01
0.46 0.44 0.43 0.45 0.01
159.2 312.6 483.6
30.6 31.3 31.8 31.2 0.6 31.9 34.5 32.5 33 1.38 31.4 33.4 32.3 1.65
$15.76 $30.55 $45.72
$16.64 $32.29 $48.32
4 4 4
39.8 78.2 121
$16.58 $32.15 $48.12
$17.00 $32.29 $48.75
4 4 4
43.4 90.2 124
$11.83 $20.96
$17.42 $30.90
2 2
38.8 70.1
0.40 0.39 0.38 0.39 0.01 0.38 0.36 0.39 0.38 0.02 0.30 0.30 0.30 0.00
0.42 0.41 0.40 0.41 0.01 0.39 0.36 0.39 0.38 0.02 0.45 0.41 0.43 0.03
Average ml
Average Drops
Average Drops/ml
5 10 15
5.2 10.3 15.2 Mean SD
153.4 265.6 460.1
5 10 15
5.2 10.1 15.3 Mean SD
5 10 15
5 10 15
2.5 5
173.6 360.6 495.8
77.0 152.1
Continued on next page.
20
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TABLE 1. Glaucoma Medication Average Drops and Milliliters per Bottle Size (Continued)
Manufacturer/Trade Name Generic Name
Bottle Size (ml)
Falcon
5 10 15
Fougera
10 15
Watson (Schein)
5 10 15
Merck, Timoptic (Ocumeter Plus)*
Merck, Timoptic XE
Carbonic anhydrase inhibitors Brinzolamide 1% Alcon, Azopt
Dorzolamide 2% Merck, Trusopt (Ocumeter Plus)*
Dorzolamide 2% ⫹ timolol 0.5% Merck, Cosopt (Ocumeter Plus)*
Average ml
35.5 75.5 110
$30.55 $45.72
$32.35 $48.46
4 4
79.3 113
$16.50 $32.00 $48.00
$N/A $N/A $N/A
4 4 4
34.4 73 102
164.4 (207.1) 29.8 (33.3) 355.4 (358.7) 32.6 (31.2) 508.6 31.6 31.5 (32.5) 1.2 (1.2) 81.8 23.8 156.8 26.1 24.9 1.61
$19.79 $38.40 $57.48
$22.10 $42.88 $64.19
4 4 4
41.1 (51.8) 88.9 (89.7) 127
$16.29 $28.88
$19.35 $34.33
2 2
40.9 78.4
124.6 263.6 383.4
$20.38 $40.75 $61.13
$28.44 $56.88 $85.32
6 6 6
$23.29 $46.60
$26.94 $53.91
5
5.4 (5.9) 138.0 (154.8) 25.7 (26.3) 10.6 (11.1) 274.4 (308.8) 25.8 (27.7) Mean 25.8 (27.1) SD 0.06 (1.0) 5.4 (5.9) 144.4 (175.1) 26.7 (29.8)
$39.69
10
10.7 (11.2) 277.4 (321.0) 25.9 (28.6)
$79.38
2.5 5
5 10 15
5 10
5.0 10.4 15.2 Mean SD
317.2 453.2
137.6 291.8 408.6
28.4 30.8 29.5 29.5 1.2 29.7 29.3 29.5 0.3 26.5 29.6 27.2 27.8 1.65
Mean Number of Days/Bottle
4 4 4
Mean SD ␣-2 Agonists Brimonidine 2%† Allergan, Alphagan, Alphagan P (2002) Alphagan P (2002)
Price, Price, Red Book, Red Book, Dose/Day Jan 1999 Sep 2002 OU
$17.00 $32.35 $48.75
5.5 (6.2) 10.9 (11.3) 16.1 Mean SD 3.4 6.0 Mean SD
142 301.8 441.8
Average Drops/ml
$16.58 $32.15 $48.12
5 10 15
5.0 9.8 15.0 Mean SD 10.7 15.5 Mean SD 5.2 9.9 15.0 Mean SD
Average Drops
24.6 25.4 25.2 25.1 0.4
Cost/Day Cost/Day 1999 2002 $0.00 $0.00
0.48 0.43 0.44 0.45 0.03 0.39 0.40 0.39 0.01 0.48 0.44 0.47 0.46 0.02
0.48 0.43 0.44 0.45 0.03 0.42 0.42 0.42 0.01 NA NA NA
0.48 0.43 0.45 0.46 0.02 0.40 0.37 0.38 0.02
(0.43) (0.48) NA (0.45) (0.04) 0.47 0.44 0.46 0.02
20.8 43.9 63.9
0.98 0.93 0.96 0.96 0.03
1.37 1.29 1.34 1.33 0.04
6 6
23.0 (25.8) 45.7 (51.5)
$43.85
4
36.1 (43.8)
1.01 1.02 1.02 0 1.10
(1.04) (1.05) 1.05 0 (1.00)
$87.71
4
69.4 (80.3)
1.14
(1.09)
1.12 0.03
1.05 0.06
26.3 (29.2) 0.6 (0.8)
5
5.4
114.0
21.1
$25.94
$36.28
4
28.5
0.91
1.29
10 15
10.1 15.3 Mean SD
238.6 333.4
23.6 21.8 22.2 1.3
$51.84 $77.80
$72.49 $108.80
4 4
59.7 83.4
0.87 0.93 0.90 0.03
1.30 1.30 1.30 0.01
Continued on next page.
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TABLE 1. Glaucoma Medication Average Drops and Milliliters per Bottle Size (Continued)
Manufacturer/Trade Name Generic Name
Prostaglandins/prostamides Bimatoprost 0.03% Allergan, Lumigan
Latanoprost 0.005% Pharmacia, Xalatan (new bottle)‡ Travoprost 0.004% Alcon, Travatan§ Unoprostone 0.15% Novartis, Rescula
Price, Red Book, Jan 1999
Price, Red Book, Sep 2002
Dose/Day OU
Mean Number of Days/Bottle
Cost/Day 1999 $0.00
Cost/Day 2002 $0.00
37.4 34.1 34.1 35.2 1.9
NA NA NA
$53.13 $106.25 $159.38
2 2 2
55.7 95.2 129.7
NA NA NA
0.95 1.12 1.23 1.10 0.14
97.6 (85.1) 102.9
32 (28) 34.5
$45.03 NA
$53.00 $52.00 $103.00
2 2 2
48.8 (42.5) 51.5
NA
209
39.3
NA
46.81
4
52.2
NA
Bottle Size (ml)
Average ml
Average Drops
Average Drops/ml
2.5 5.0 7.5
3.3 5.6 7.6 Mean SD
111.3 190.5 259.4
2.5 2.5
3.05 3.01 3.0
5.0
5.3
1.11 1.25 1.01 7.0 0.90
NA ⫽ not available; OU ⫽ both eyes. *The new Ocumeter Plus bottle results are in parenthesis vs the original Ocumeter bottle. † More than 90% of brimonidine usage is twice daily. Brimonidine and brimonidine-P overfill and number of drops per milliliter are approximately the same. ‡ The original latanoprost bottle had some streaming problems. The newer bottle has a larger drop size but causes less streaming. § Travoprost is available as a twin pack containing two bottles of 2.5 ml.
drops per milliliter and Lumigan approximately 35.2 drops per milliliter. The cost of -adrenergic antagonists per day ranged from a low of $0.38 per day to $0.50 per day. Again, the generic timolol products (range, $0.38 –$0.46 per day) were similar on a cost per day basis vs the brand name metipranolol (Optipranolol; Bausch and Lomb Pharmaceuticals, Tampa, Florida, USA; $0.50 per day), timolol hemihydrate (Betimol; Santen, Napa Valley, California, USA; $0.45), Timoptic ($0.51 per day), and Timoptic XE ($0.46 per day). The gap has narrowed between the average prices of both sizes of generic timolol gel ($0.43 per day) vs Timoptic XE ($0.46 per day). One company (Schein, now Watson) discontinued their generic ophthalmic timolol solution. Other -blockers including Betagan (Allergan; $1.11 per day), Betoptic S (Alcon Laboratories; $0.88 per day), generic levobunolol ($0.63 per day) and Ocupress (Novartis; $0.88 per day) were generally still found to be more expensive on a per day basis. The cost of topical carbonic anhydrase inhibitors dosed two and three times daily averaged $0.88 per day and $1.33 per day for Azopt and $0.70 per day and $1.04 per day for Trusopt, respectively. The labeled dose of both topical products is three times daily, although some twice daily dosing, especially as adjunctive therapy, is often done. The combination product Cosopt (timolol 0.5% plus dorzolamide 2%; $1.05 per day) was less costly than two separate bottles of a topical carbonic anhydrase inhibitor (three times daily dosing) and approximately the same daily cost with twice daily dorzolamide dosing and a -blocker. The 22
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new Merck bottle (Ocumeter Plus) contains more overfill than the previous bottle (Ocumeter) and has a slightly smaller drop size. However, there was more variability in the number of drops counted (5-ml bottle; 175 drops ⫾ 8.4), even though the bottle delivered approximately the same amount of overfill each time (5.9 ml; range, 5.8 – 6.0 ml). The viscosity of the methylcellulose vehicle may account for some of the variation in drop size. Other costs per day for glaucoma products included Alphagan-P ($1.29 per day; twice daily dosing, 5 ml), Lumigan ($0.95 per day, 2.5 ml), Travatan ($1.01 per day), and Xalatan ($1.25 per day).
DISCUSSION WE HAD PREVIOUSLY REPORTED ON THE GLAUCOMA MED-
ications on a cost per day basis.3 The number of drops per milliliter, the actual volume, and the cost per bottle are helpful in determining the daily treatment costs for patients with glaucoma. Using a general average (that is, 20 drops per milliliter) to estimate the number of drops per milliliter of a given ophthalmic medication is not accurate. This variability in overfill and drops per milliliter has been demonstrated by others.4 –7 Two different timolol manufacturers’ 10-ml bottles had mean fills of 9.85 ml (Falcon and Schein).3 Timolol gel-forming solution (Falcon) had less than the stated label volume (2.45 ml for 2.5 ml and 4.5 ml for 5 ml).3 The timolol gel-forming solution (Falcon) was clear but appeared more viscous, and thereOF
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fore the total volume was not available unless the bottle was stored upside down. Therefore, when one compares two products with the same stated volume, the assumption that the one with the higher per bottle price has the higher daily cost may not be correct. The product with the smaller drop size may in reality cost less because it may last longer, and therefore the cost per day may be less to the patient. This study was completed to update the price changes since 1999 to examine new products recently released and to determine whether new bottle designs made any difference. The cost per day of generic timolol was similar to the brand product (Timoptic and Timoptic XE), Betimol, and Optipranolol. These products ranged from $0.38 to $0.51 per day. Betaxolol, Ocupress, and Betagan ranged from $0.88 to $1.11 per day. Generic levobunolol was about $0.64 per day. Older products, such as pilocarpine, are priced from $0.27 to $0.36 per day, although the branded Pilopine HS (Alcon, Fort Worth, Texas, USA) is more costly at $1.13 per day. Propine ($0.61 per day) is more costly than the generic dipivefrin ($0.34 per day). The branded products Diamox and Neptazane, have been discontinued by the manufacturer, and only generic products remain. However, even the generic products range from $0.84 to $1.74 (acetazolamide) and $0.96 to $2.60 (methazolamide) per day. The Ocumeter Plus is a more ergonomic bottle for the patient. The bottle is oversized as is the cap, so the patient who has difficulty grasping a small bottle or bottle cap can grip the bottle more easily. There is also an indentation on the bottle that allows the patient to squeeze the bottle with one finger so that only a single drop is used. The overfill in the bottle helps to offset the cost increase that occurred in the last year. Patient compliance, ease of administration, and drug efficacy should be improved with a single bottle.11 A single bottle of combination eye drops (Cosopt) vs two separate bottles may help to reduce the potential for loss of another drugs’ pharmacologic effect. This is believed to be related to a dilutional effect that occurs when the second medication is administered before complete absorption of the first medication.11 However, there is some loss in dose titration and occasional product confusion when there are fixed-dose combination products. The latanoprost bottle and tip has also been redesigned so that “streaming” of the drops does not occur from the bottle. If pressure is released off the bottle, the remaining fluid will be drawn back into the bottle, which prevents the patient from wasting medication. The newer dropper tip produces a larger drop (therefore less drops per milliliter), but the patient probably wastes less medication than with the previously designed bottle. Bimatoprost, travoprost, and unoprostone are more efficient bottles than those previously manufactured. Each bottle produces more drops per milliliter than previous bottles made by these same companies in the past. However, the travoprost bottle design was difficult to squeeze, VOL. 136, NO. 1
especially when only a small amount of medication is remaining in the bottle. The bottle is not very pliable, and some patients with dexterity problems may encounter difficulty with drop administration. All sizes commercially available were studied to determine if any differences or cost advantages were obtained for the various sizes. The bimatoprost 2.5-ml bottle would be the most cost beneficial on a cost per day basis compared with other once daily prostaglandin analogs. There is more overfill in the 2.5-ml than the 5-ml or 7.5-ml size. However, bimatoprost is the only prostaglandin analog with a larger bottle size that may benefit some managed care patients who pay only one copay. Some patients may also prefer the larger 5-ml bottle (average, 197 drops per bottle or possibly 90 days) or the 7.5-ml bottle (259 drops per bottle or possibly up to 129 days of treatment), the use of which can result in fewer pharmacy trips and potentially provide 3 to 4 months of therapy from one bottle with careful use. Travatan is also available in a dual pack containing two separate 2.5-ml bottles. Although there is no cost advantage, the patient should open only one bottle at a time, because there is a 6-week expiration after a bottle is opened. Brimonidine is a first- or second-line therapeutic option because of minimal ocular and systemic side effects and effective intraocular pressure (IOP)–lowering ability.12 Brimonidine-P is in a carboxymethycellulose vehicle with Purite as the preservative and comparable IOP lowering to brimonidine 0.2%.9 The carboxymethycellulose and the Purite are the same vehicle and preservative system, respectively, as found in Refresh Tears (Allergan). Alphagan-P and Alphagan have an almost identical drop size and count. However, brimonidine-P is more comfortable for the patient and is the only glaucoma medication not containing the preservative benzalkonium chloride or a related sister compound. It is also considered a low-risk preservative or almost preservative-free product available for patients with benzalkonium chloride allergies.8 A generic product that contains brimonidine 0.2% is not a generic equivalent for the brimonidine-P 0.15%, which would have to be taken into consideration for a cost per day comparison. The only preservative-free glaucoma products for commercial use are Timoptic unit dose and 2-ml bottles of pilocarpine in a sterile blister pack. Bimatoprost, latanoprost, and travoprost with their once daily administration and potent IOP-lowering effects are indicated as adjunctive therapy.2 However, because latanoprost has demonstrated very good efficacy and safety since 1996, it has just recently received an indication for the primary treatment of open-angle glaucoma. Older adjunctive therapies may be costly (Table 2). Various adjunctive combinations of new therapeutic agents are less on a cost per day basis than older traditional therapy (Table 2). In fact, an interesting phenomenon occurs when the market share of older brand-only products without generic equivalents decreases. The products will
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pharmacies would probably purchase the more reasonably priced generic product, depending on availability. However, should the pharmacy purchase the more expensive generic product, the resulting patient cost may vary. Although a generic medication is purchased at a lower AWP, that total savings would most likely not be passed on to the patient. The pharmacy will purchase the generic product for less than the listed AWP but make more on the markup. The patient will still pay less for the generic product than the brand. Because the price of medications may change often, it may benefit the patient to shop for the best price, because prices among pharmacies may vary significantly even within the same neighborhood. In recent cost surveys of various pharmacies in the Chicago area, prices varied by about $15.00 for the same prostaglandin product and up to $10.00 for Cosopt and Alphagan (R.G.F.). Therefore, it is especially beneficial for the patient without prescription benefits to shop for the best price. The results of the previous study in conjunction with this study, more specifically, the average drops per bottle or average number of days per bottle, were used to determine updated daily costs based on price increases. This study is still based on a best-case scenario for all medicines, assuming no wasted doses by the patient. If a patient misses his or her eye when applying the eye drops, the cost per day will increase with any topical glaucoma medications because of loss of volume in terms of wasted drops. If patients are properly instructed on how to use their eyedrops, and/or have a caregiver to help administer them, wastage will be reduced. The true costs of some of the newer medications may be further decreased by improved compliance and the need for fewer medications to control IOP, fewer patient interventions (for example, office calls, surgeries, lasers), and an improved side effect profile. Poor compliance is one of the most common reasons for treatment failures in glaucoma.14 Limited understanding of the disease state itself may adversely affect compliance. It has been reported that better understanding of disease improved regimen compliance by up to 10 times.14 The cost of a new glaucoma medication is just one of a multitude of factors to consider when choosing a medication for a patient. Recent glaucoma drug developments offer patients more effective products, with less severe ocular side effects and/or less frequent drug administration. New medications are better tolerated, more effective in reducing IOP, dosed less frequently, cause fewer systemic side effects, and are often more reasonable on a cost per day basis.2,3 Improved patient compliance with fewer daily drops is also a benefit of the newer glaucoma medications. The cost of generic timolol, Optipranolol, Timoptic, and Timoptic XE ranged from $0.38 to $0.51 per day. Betaxolol, Betimol, Ocupress, and Betagan ranged from $0.88 to $1.11 per day. Generic levobunolol was about $0.64 per day. Cosopt ($1.05 per day) was less costly than separate bottles of a topical  blocker and a topical carbonic
TABLE 2. Costs of Various Common Glaucoma Medications Medication
Miotics Pilocarpine drops Pilocarpine gel (Pilopine HS, $39.36) Epinephrines Dipivefrin drops (5 ml, $14.07) Propine drops (5 mL, $25.11) Systemic CAIs (prices are per 100 tablets) Acetazolamide (3 or 4 times/day) 125 mg ($33.80, Taro) 250 mg ($28.00, Watson) 250 mg ($43.60, Yaro) Methazolamide (2 or 3 times/day) 25 mg ($48.00, Teva) 25 mg ($57.74, Qualitest) 50 mg ($72.00, Teva) 50 mg ($86.62, Qualitest) -Blockers (5 ml) Timolol, Timoptic, Timoptic XE (daily), Betimol or Optipranolol Ocupress, Betagan, Betoptic S Topical CAIs (5 ml) Dorzolamide (2 or 3 times/day) Brinzolamide (2 or 3 times/day) Combination product (10 ml) Cosopt (timolol 0.5%⫹ dorzolamide 2%) ␣-2 Agonist (5 ml) Alphagan (twice daily) Prostaglandin Lumigan (2.5 ml) Rescula (5.0 ml) Travatan (2.5 ml) Xalatan (2.5 ml)
Cost/Day
$0.27–0.36 $1.13 $0.34 $0.61
$1.02/$1.35 $0.84/$1.12 $1.31/$1.74 $0.96/$1.44 $1.16/$1.73 $1.33/$2.00 $1.73/$2.60 $0.38–$0.50 $0.88–$1.11 $0.69/$1.04 $0.89/$1.33 $1.09 $1.29 $0.95 $0.90 $1.01 $1.25
CAIs ⫽ carbonic anhydrase inhibitors. Adapted in part from Am J Hosp Pharm.13 Average wholesale prices from Red Book 2002.10
have frequent large price increases to “recoup” prescription sales from the product before its use diminishes or it is replaced by a generic. Examples of these products (current AWP; size; percentage increase since 1999) include Betoptic S ($98.19; 15 ml; 37%), Iopidine (Alcon, Fort Worth, Texas, USA) ($123.75; 10 ml; 50% increase), Ocupress ($84.18; 15 ml; 53%), and Pilopine HS ($41.00; 4 g; 32%). The cost per day may be similar for a newer and more effective therapy (that is, Lumigan 2.5 ml at $0.95 per day) than an older brand-only medication losing market share (that is, Betoptic S at $0.88 per day). Another consideration is that the AWPs for some generic products may vary, which may reflect a patient’s cost. For instance, generic acetazolamide tablets are available from a few sources. One source charges an AWP of $28.00 for 100 tablets (Watson) vs $43.60 (Yaro). Most 24
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anhydrase inhibitor dosed three times daily and two times daily. The cost per day of new prostaglandin analog products for similar-size bottles were Lumigan ($0.95 per day), Rescula ($0.90 per day), Travatan ($1.01 per day), and Xalatan ($1.25 per day). New medical glaucoma treatment regimens exhibit similar costs per day compared with more traditional therapies.
REFERENCES 1. Alward WLM. Medical management of glaucoma. N Engl J Med 1998;339:1298 –1307. 2. Novack GD, O’Donnell MJ, Molloy DW. New glaucoma medications in the geriatric population: efficacy and safety. Am Geriat Soc 2002;50:956 –962. 3. Fiscella R, Geller JL, Gryz LL, et al. Costs considerations of medical therapy for glaucoma. Am J Ophthalmol 1999;128: 426 –433. 4. Weiss MA, Hendrickson JR. Information on drop size needs to be eyed closely. Am J Hosp Pharm 1994;51:2969 –2970. 5. Ball SF, Schneider E. Cost of beta-adrenergic receptor blocking agents for ocular hypertension. Arch Ophthalmol 1992;110:654 –657.
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6. Hartenbaum D, Stek M, Haggert B, et al. Quantitative and cost evaluation of three antiglaucoma beta-blocker agents. Timoptic-XE versus two generic levobunolol products. Am J Man Care 1996;2:157–162. 7. Schwartz J, Christensen RE, Lee DA. Comparison of timolol maleate and levobunolol: doses and volume per bottle [Letter]. Arch Ophthalmol 1989;107:17. 8. Noecker R. Effects of common ophthalmic preservatives on ocular health. Adv Ther 2001;18:205–215. 9. Katz LJ. Twelve-month evaluation of brimonidine-purite versus brimonidine in patients with glaucoma or ocular hypertension. J Glaucoma 2002;11:119 –126. 10. Red book 2002. Montvale, NJ. Drug Topics, 2002. 11. Choudhri S, Wand M, Shields MB. A comparison of dorzolamide-timolol combination versus the concomitant drugs. Am J Ophthalmol 2000;130:832–833. 12. Leblanc RP, for the Brimonidine Study Group. Twelvemonth results of an ongoing randomized trial comparing brimonidine tartrate 0.2% and timolol 0.5% given twice daily in patients with glaucoma or ocular hypertension. Ophthalmology 1998;105:1960 –1967. 13. Fiscella R. Cost of glaucoma medications. Am J Hosp Pharm 1998;55:272–275. 14. Zimmerman T. Facilitating patient compliance in glaucoma therapy. Surv Ophthalmol 1983;289(Suppl):S252–S257.
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