TRUSOPT (dorzolamide hydrochloride ophthalmic solution) is a sulfonamide and, although administered topically, is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration with TRUSOPT (dorzolamide hydrochloride ophthalmic solution) . Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Sensitization may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation.

General

The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. TRUSOPT (dorzolamide hydrochloride ophthalmic solution) has not been studied in patients with acute angle-closure glaucoma.

TRUSOPT (dorzolamide hydrochloride ophthalmic solution) has not been studied in patients with severe renal impairment (CrCl < 30 mL/min). Because TRUSOPT (dorzolamide hydrochloride ophthalmic solution) and its metabolite are excreted predominantly by the kidney, TRUSOPT (dorzolamide hydrochloride ophthalmic solution) is not recommended in such patients.

TRUSOPT (dorzolamide hydrochloride ophthalmic solution) has not been studied in patients with hepatic impairment and should therefore be used with caution in such patients.

In clinical studies, local ocular adverse effects, primarily conjunctivitis and lid reactions, were reported with chronic administration of TRUSOPT (dorzolamide hydrochloride ophthalmic solution) . Many of these reactions had the clinical appearance and course of an allergic-type reaction that resolved upon discontinuation of drug therapy. If such reactions are observed, TRUSOPT (dorzolamide hydrochloride ophthalmic solution) should be discontinued and the patient evaluated before considering restarting the drug. (See ADVERSE REACTIONS.)

There is a potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving an oral carbonic anhydrase inhibitor and TRUSOPT (dorzolamide hydrochloride ophthalmic solution) . The concomitant administration of TRUSOPT (dorzolamide hydrochloride ophthalmic solution) and oral carbonic anhydrase inhibitors is not recommended.

There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface.

Choroidal detachment has been reported with administration of aqueous suppressant therapy (e.g., dorzolamide) after filtration procedures.

There is an increased potential for developing corneal edema in patients with low endothelial cell counts. Precautions should be used when prescribing TRUSOPT (dorzolamide hydrochloride ophthalmic solution) to this group of patients.

Information for Patients

TRUSOPT (dorzolamide hydrochloride ophthalmic solution) is a sulfonamide and although administered topically is absorbed systemically. Therefore the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration. Patients should be advised that if serious or unusual reactions including severe skin reactions or signs of hypersensitivity occur, they should discontinue the use of the product (see WARNINGS).

Patients should be advised that if they develop any ocular reactions, particularly conjunctivitis and lid reactions, they should discontinue use and seek their physician's advice.

Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures.

Patients should also be instructed that ocular solutions, if handled improperly or if the tip of the dispensing container contacts the eye or surrounding structures, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.

Patients also should be advised that if they have ocular surgery or develop an intercurrent ocular condition (e.g., trauma or infection), they should immediately seek their physician's advice concerning the continued use of the present multidose container.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least ten minutes apart.

Patients should be advised that TRUSOPT (dorzolamide hydrochloride ophthalmic solution) contains benzalkonium chloride which may be absorbed by soft contact lenses. Contact lenses should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following TRUSOPT (dorzolamide hydrochloride ophthalmic solution) administration.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a two-year study of dorzolamide hydrochloride administered orally to male and female Sprague-Dawley rats, urinary bladder papillomas were seen in male rats in the highest dosage group of 20 mg/kg/day (250 times the recommended human ophthalmic dose). Papillomas were not seen in rats given oral doses equivalent to approximately 12 times the recommended human ophthalmic dose. No treatment-related tumors were seen in a 21-month study in female and male mice given oral doses up to 75 mg/kg/day (~900 times the recommended human ophthalmic dose).

The increased incidence of urinary bladder papillomas seen in the high-dose male rats is a class-effect of carbonic anhydrase inhibitors in rats. Rats are particularly prone to developing papillomas in response to foreign bodies, compounds causing crystalluria, and diverse sodium salts.

No changes in bladder urothelium were seen in dogs given oral dorzolamide hydrochloride for one year at 2 mg/kg/day (25 times the recommended human ophthalmic dose) or monkeys dosed topically to the eye at 0.4 mg/kg/day (~5 times the recommended human ophthalmic dose) for one year.

The following tests for mutagenic potential were negative: (1) in vivo (mouse) cytogenetic assay; (2) in vitro chromosomal aberration assay; (3) alkaline elution assay; (4) V-79 assay; and (5) Ames test.

In reproduction studies of dorzolamide hydrochloride in rats, there were no adverse effects on the reproductive capacity of males or females at doses up to 188 or 94 times, respectively, the recommended human ophthalmic dose.

Pregnancy

Teratogenic Effects

Pregnancy Category C. Developmental toxicity studies with dorzolamide hydrochloride in rabbits at oral doses of ≥ 2.5 mg/kg/day (31 times the recommended human ophthalmic dose) revealed malformations of the vertebral bodies. These malformations occurred at doses that caused metabolic acidosis with decreased body weight gain in dams and decreased fetal weights. No treatment-related malformations were seen at 1.0 mg/kg/day (13 times the recommended human ophthalmic dose). There are no adequate and well-controlled studies in pregnant women. TRUSOPT (dorzolamide hydrochloride ophthalmic solution) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

In a study of dorzolamide hydrochloride in lactating rats, decreases in body weight gain of 5 to 7% in offspring at an oral dose of 7.5 mg/kg/day (94 times the recommended human ophthalmic dose) were seen during lactation. A slight delay in postnatal development (incisor eruption, vaginal canalization and eye openings), secondary to lower fetal body weight, was noted.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from TRUSOPT (dorzolamide hydrochloride ophthalmic solution) , a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and IOP-lowering effects of TRUSOPT (dorzolamide hydrochloride ophthalmic solution) have been demonstrated in pediatric patients in a 3month, multicenter, double-masked, active-treatment-controlled trial.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Last reviewed on RxList: 7/20/2010
This monograph has been modified to include the generic and brand name in many instances.