Small Animal/Exotics
PHARM PROFILE
DORZOLAMIDE
Michael G. Davidson, DVM
North Carolina State University
D
orzolamide, a 2-thienothio-
pyran-2-sulfonamide deriva-
tive, is a topical carbonic an-
hydrase inhibitor (CAI) used to treat
glaucoma. Dorzolamide is the first
CAI available in topical form and
thus is an alternative to systemic
CAIs. Because it is applied topically,
limited systemic absorption occurs,1
and the undesirable systemic effects
associated with oral or parenteral
CAI administration are avoided. The
availability of dorzolamide is particu-
larly timely because the manufactur-
ing of dichlorphenamide, the most
widely used systemic CAI in veteri-
nary medicine, has recently been dis-
continued. Acetazolamide, another
oral or parenteral CAI is still avail-
able; its use in dogs may be associat-
ed with moderate hyperchloremic
metabolic acidosis and potassium de-
pletion.2
PHARMACOLOGY
Dorzolamide inhibits carbonic an-
hydrase isoenzyme II in the pigment-
ed and nonpigmented ciliary body
epithelium of the eye. Carbonic an-
hydrase is an essential enzyme in the
production of aqueous humor: It
catalyzes the reaction that is respon-
sible for producing bicarbonate and
Pharm Profile introduces drugs that are new to the veterinary market as well as new indications for existing drugs. If you would like
Pharm Profile to cover a particular agent, please contact column editor GiGi Davidson, BS, RPh, University of North Carolina, 4700
Hillsborough Street, Raleigh, NC 27606; phone 919-821-9500 • fax 919-829-4225 • email gigi_davidson@ncsu.edu.
subsequent entry of water into the
posterior chamber of the eye. Inhibi-
tion of this enzyme decreases aqueous
humor production and intraocular
pressure (IOP). Carbonic anhydrase
is also found in high concentrations
in erythrocytes and in nephrons of
the kidney. Because CAIs typically
inhibit all carbonic anhydrase isoen-
zymes, systemic administration may
cause diuresis and potassium deple-
tion, and interfere with transfer of
carbon dioxide in the lung and subse-
quently result in metabolic acidosis.
After topical administration, dor-
zolamide penetrates the cornea and
sclera. Therapeutic concentrations in
the ciliary processes are comparable
to systemically administered CAI.
Serum concentrations are 100 times
lower than they are after systemic
CAI administration.1 A single appli-
cation of dorzolamide lowers IOP in
normotensive rabbits by approxi-
mately 30% (similar to IOP reduc-
tion after oral administration of the
CAI methazolamide).3 Administered
topically three times daily, 2% dor-
zolamide lowers IOP in humans
with open-angle glaucoma or ocular
hypertension by approximately 4 to
6 mm Hg at peak drug concentra-
tions (2 hours after administration)
Compendium April 2000
and 3 to 4.5 mm Hg at trough con-
centrations (8 hours after administra-
tion).4,5 In long-term studies, the oc-
ular hypotensive efficacy of 2%
dorzolamide administered three times
daily was similar to that of topical β-
blocking agents (IOP reduced ap-
proximately 22%). 6 Although the
specific IOP-lowering effects of dor-
zolamide have not been reported in
dogs and cats to date, administration
of a related compound, MK-907, re-
sulted in a mean reduction in IOP of
approximately 5 mm Hg in both
normotensive and glaucomatous bea-
gles.7 Experimental and clinical stud-
ies of dorzolamide in dogs are cur-
rently being conducted.
INDICATIONS
Dorzolamide can be used to treat
all types of primary and secondary
glaucoma in dogs and cats.
CAUTIONS
The most common ocular side ef-
fect associated with topical 2% dor-
zolamide is a stinging and burning
sensation; this has been reported in
up to 30% of human patients. Con-
junctival hyperemia, superficial
punctate keratitis, or prolonged itch-
ing have been reported in up to 15%
Compendium April 2000 Small Animal/Exotics

is one drop three times daily, al-

Client Counseling Information though, as mentioned, twice-daily
■ The only common side effect reported in humans using dorzolamide is a therapy may be sufficient.
stinging or burning sensation to the eye after topical application. If you
notice repeated and substantial discomfort in your pet after four to five PREPARATIONS
applications, discontinue use and contact your veterinarian. Trusopt® (2% dorzolamide; Merck
■ Dorzolamide should be administered every 8 hours. and Co., Inc., West Point, PA) is avail-
■ If other topical antiglaucoma drugs are being used, wait 5 minutes able in a 15-ml bottle. The combined
between application of the different solutions to prevent one drug from 2% dorzolamide–0.5% timolol maleate
being washed from the eye by the second drug. topical ophthalmic solution (Cosopt®;
■ A follow-up intraocular pressure evaluation is critical to assess the
Merck and Co., Inc., West Point, PA)
effectiveness of the drug and the need for additional therapy.
■ Primary glaucoma is usually a progressive disease, and medical therapy is supplied in a 15-ml bottle.
alone often cannot control the increased intraocular pressure on a long- In addition, clinical trials are cur-
term basis. You should discuss other options with your veterinarian (for rently being conducted on a second
example, a referral to a veterinary ophthalmologist to explore such topical CAI, brinzolamide hydro-
surgical treatments as laser therapy or gonioimplantation). chloride 1% ophthalmic suspension.
■ The drug should be kept out of the reach of children. Available data suggest an equivalent
IOP-lowering effect with fewer topi-
cal side effects compared with dorzo-
of human patients. Taste aversion tensive agents (e.g., osmotic agents, lamide.18,19
(bitter, sour, or unusual taste) has also timolol, 13 pilocarpine, 8 or latano-
been frequently reported in humans.8,9 prost,14) to produce a further but not STORAGE AND HANDLING
Preclinical testing of the drug in totally additive IOP-lowering effect. Dorzolamide should be stored at a
dogs failed to reveal any notable local In humans with glaucoma, concomi- controlled room temperature (15˚C to
side effects.10 In my experience, clini- tant use of 0.5% timolol and 2% dor- 30˚C; 59˚F to 86˚F). The drug should
cally significant ocular irritation in zolamide administered twice daily has be kept out of reach of children.
dogs and cats is uncommon. Although an IOP-lowering effect equivalent to
irreversible corneal decompensation 2% dorzolamide administered three REFERENCES
resulting from an adverse effect on the times daily.9,15,16 When a combined 1. Maren TH, Conroy CW, Wynns GC, et
al: Ocular absorption, blood levels, and
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ported in some humans treated with uct is used, the systemic side effects of tive carbonic anhydrase inhibitor. J Ocul
dorzolamide, 11 another study sug- topically applied β-adrenergic block- Pharmacol Ther 13:23–30, 1997.
gested the drug is well tolerated by ers reported in humans (broncho- 2. Haskins SC, Munger RJ, Helphrey MG,
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by topical and systemic carbonic anhy-
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drase inhibitors in the rabbit. J Ocul Phar-
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DRUG INTERACTIONS DOSAGE AND ADMINISTRATION 122(2):183–194, 1996.
Specific adverse drug interactions The recommended dose of dorzo- 6. Strahlman E, Tipping R, Vogel R: A dou-
between dorzolamide and other topi- lamide is one drop per affected eye ble-masked, randomized 1-year study
comparing dorzolamide (Trusopt), timo-
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Small Animal/Exotics
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Compendium April 2000
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