Trusopt

Carbonic Anhydrase Inhibitors, Ophthalmic

Before the initial use, make sure the safety strip on the front of the bottle is unbroken. Once confirmed, tear off the safety strip to break the seal.
Wash hands before each use.
Unscrew the cap by turning in the direction of the arrows on the top of the cap. DO NOT pull the cap directly up and away from the bottle; doing so will keep the dispenser from working properly.
Care should be taken to avoid contamination. Do not touch the tip of the dropper to the eye, fingertips, or other surfaces.
Tilt the head back slightly and pull the lower eyelid down with the index finger to form a pouch.
Turn dispenser upside down and press lightly with the thumb and index finger over the "Finger Push Area". Squeeze the prescribed number of drops into the pouch and gently close eyes for 1 to 2 minutes. Do not blink.
Replace the cap by turning it until it is firmly touching the dispenser. The arrow on the left side of the cap must be lined up with the arrow on the left side of the dispenser label for it to be closed correctly; DO NOT over tighten.
Remove contact lenses prior to administration. Contact lenses may placed back into the eye 15 minutes post-dose.
The solution may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes apart.

keratitis / Delayed / 10.0-15.0
angioedema / Rapid / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
bronchospasm / Rapid / 0-1.0
aplastic anemia / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
hepatic necrosis / Delayed / Incidence not known

photophobia / Early / 1.0-5.0
conjunctivitis / Delayed / 1.0-5.0
blurred vision / Early / 1.0-5.0
corneal edema / Early / Incidence not known
contact dermatitis / Delayed / Incidence not known
myopia / Delayed / Incidence not known
dyspnea / Early / Incidence not known

ocular irritation / Rapid / 33.0-33.0
dysgeusia / Early / 25.0-25.0
xerophthalmia / Early / 1.0-5.0
lacrimation / Early / 1.0-5.0
urticaria / Rapid / 0-1.0
pruritus / Rapid / 0-1.0
rash / Early / 0-1.0
asthenia / Delayed / Incidence not known
throat irritation / Early / Incidence not known
epistaxis / Delayed / Incidence not known
xerostomia / Early / Incidence not known
nausea / Early / Incidence not known
ocular pain / Early / Incidence not known
paresthesias / Delayed / Incidence not known
dizziness / Early / Incidence not known
headache / Early / Incidence not known

Trusopt

Rx

Ophthalmic carbonic anhydrase inhibitor; used for glaucoma and ocular hypertension; effectively lowers IOP; sulfonamide derivative.

Instill 1 drop of a 2% solution into the affected eye(s) 3 times daily. NOTE: The safety and efficacy of treatment durations longer than 3 months has not been established in pediatric patients.

Specific dosage guidelines are not available; it appears that no dosage adjustment is needed. Dorzolamide should be used with caution in patients with hepatic impairment; data are lacking in these patients.

CrCl >= 30 mL/min: Specific dosage guidelines are not available.
CrCl < 30 mL/min: Dorzolamide has not been studied in these patients. Because dorzolamide and its metabolites are excreted primarily by the kidney, the drug is not recommended in these patients.

There are no drug interactions associated with Dorzolamide products.

Dorzolamide/Trusopt Ophthalmic Sol: 2%

3 drops/day per affected eye.

3 drops/day per affected eye.

3 drops/day per affected eye.

3 drops/day per affected eye.

Dorzolamide is a highly specific inhibitor of an isoenzyme of carbonic anhydrase, CA-II. Many body tissues, including the eye, contain the enzyme carbonic anhydrase (CA). Carbonic anhydrase catalyzes the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. There are a number of isozymes of carbonic anhydrase. The isozyme, CA-II plays a key role in controlling aqueous production and IOP. This isozyme is found in red blood cells and other cells that secrete hydrogen or hydrogen compounds, including the ciliary body of the eye. A decrease in bicarbonate ion concentrations in ocular fluid decreases aqueous humor secretion. Intraocular pressure is subsequently lowered.
 
Following administration of dorzolamide to the eye, intraocular pressure is lowered, reducing the risk of nerve damage and visual field loss in patients with pathologic elevations of intraocular pressure. The plateau of the dosage curve occurred with the 2% concentration. Dorzolamide appears to have no clinically significant biochemical or hematologic effects when administered topically to the eye.

Dorzolamide is administered as an ophthalmic solution. Dorzolamide accumulates in RBCs, where it binds strongly to CA-II, and weakly to CA-I. The metabolite has less affinity for CA-II and is less selective than dorzolamide, but also binds to CA-I. Total carbonic anhydrase activity inhibition is 81—88% (94—96% in RBCs). Steady state concentrations in RBCs were reached after four weeks. Dorzolamide is about 33% bound to plasma protein. Dorzolamide and the metabolite are primarily excreted unchanged in the urine. Systemically-absorbed dorzolamide washes out of RBCs nonlinearly. An initial rapid decline is followed by a slow elimination phase, (i.e., elimination half-life range of about 4 months).
 
A significant lowering of IOP can be detected within 2 hours of first dose dorzolamide, with a significant dose response after 4 hours. Peak reduction is 21% IOP, with mean percent reductions over a one year period of 15% at morning trough and 18% at peak. Dosing three times a day with a 2% solution of dorzolamide maintains a satisfactory response.

Ophthalmic Route
Following topical administration to the eye, there is some systemic absorption of dorzolamide; however, almost no free drug or metabolite is detected in plasma.

There are no adequate and well-controlled studies of dorzolamide use in human pregnancy. Dorzolamide caused fetal vertebral malformations when administered orally to rabbits at 2.5 mg/kg/day (37 times higher than the lower limit of detection in human plasma following ocular administration). Dorzolamide administered during the period of organogenesis was not teratogenic in rabbits dosed up to 1 mg/kg/day (15 times higher than the lower limit of detection in human plasma following ocular administration). Dorzolamide hydrochloride administered orally to rats during late gestation and lactation caused growth delays in offspring at 7.5 mg/kg/day (52 times higher than the lower limit of detection in human plasma following ocular administration). Growth was not delayed at 1 mg/kg/day (8 times higher than the lower limit of detection in human plasma following ocular administration). Systemic absorption of dorzolamide is low following topical administration; plasma concentrations of dorzolamide and metabolite are generally below the assay limit of quantitation (15 nM).

There are no data on the presence of dorzolamide in human milk, the effects on the breastfed infant, or the effects on milk production. Dorzolamide was present in the milk of lactating rats following oral administration. However, systemic absorption of dorzolamide is low following topical administration; plasma concentrations of dorzolamide and metabolite are generally below the assay limit of quantitation (15 nM). The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for dorzolamide and any potential adverse effects on the breast-fed child from dorzolamide.