ch drug interactions should be considered in patients receiving dorzolamide hydrochloride ophthalmic solution.

patient counseling information (17.3) ]. 5.2 bacterial keratitis 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. 5.3 corneal endothelium carbonic anhydrase activity has been observed in both the cytoplasm and around the plasma membranes of the corneal endothelium. there is an increased potential for developing corneal edema in patients with low endothelial cell counts. caution should be used when prescribing dorzolamide hydrochloride ophthalmic solution to this group of patients. 5.4 allergic reactions in clinical studies, local ocular adverse effects, primarily conjunctivitis and lid reactions, were reported with chronic administration of 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, dorzolamide hydrochloride ophthalmic solution should be discontinued and the patient evaluated before considering restarting the drug [ see adverse reactions (6) ]. 5.5 acute angle-closure glaucoma the management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents.

ed with dorzolamide hydrochloride ophthalmic solution were ocular burning, stinging, or discomfort immediately following ocular administration (approximately one-third of patients). approximately one-quarter of patients noted a bitter taste following administration. superficial punctate keratitis occurred in 10 to 15% of patients and signs and symptoms of ocular allergic reaction in approximately 10%. reactions occurring in approximately 1 to 5% of patients were conjunctivitis and lid reactions [ see warnings and precautions (5.5) ], blurred vision, eye redness, tearing, dryness, and photophobia. other ocular reactions and systemic reactions were reported infrequently, including headache, nausea, asthenia/fatigue; and, rarely, skin rashes, urolithiasis, and iridocyclitis. in a 3-month, double-masked, active-treatment-controlled, multicenter study in pediatric patients, the adverse reactions profile of dorzolamide hydrochloride ophthalmic solution was comparable to that seen in adult patients. 6.2 post-marketing experience the following adverse reactions have been identified during post-approval use of dorzolamide hydrochloride ophthalmic solution. because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: signs and symptoms of systemic allergic reactions including angioedema, bronchospasm, pruritus, and urticaria; stevens-johnson syndrome and toxic epidermal necrolysis; dizziness, paresthesia; ocular pain, transient myopia, choroidal detachment following filtration surgery, eyelid crusting; dyspnea; contact dermatitis, epistaxis, dry mouth and throat irritation.

ch drug interactions should be considered in patients receiving dorzolamide hydrochloride ophthalmic solution.

f 7.5 mg/kg/day 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. this dose represents an estimated plasma c max level in rats, 52 times higher than the lower limit of detection in human plasma following ocular administration. 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 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. 8.4 pediatric use safety and effectiveness of dorzolamide hydrochloride ophthalmic solution have been demonstrated in pediatric patients in a 3-month, multicenter, double-masked, active-treatment-controlled trial. 8.5 geriatric use no overall differences in safety or effectiveness have been observed between elderly and younger patients. 8.6 renal and hepatic impairment dorzolamide has not been studied in patients with severe renal impairment (crcl < 30 ml/min). because dorzolamide and its metabolite are excreted predominantly by the kidney, dorzolamide hydrochloride ophthalmic solution is not recommended in such patients. dorzolamide has not been studied in patients with hepatic impairment and should therefore be used with caution in such patients.

is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. 12.3 pharmacokinetics when topically applied, dorzolamide reaches the systemic circulation. to assess the potential for systemic carbonic anhydrase inhibition following topical administration, drug and metabolite concentrations in rbcs and plasma and carbonic anhydrase inhibition in rbcs were measured. dorzolamide accumulates in rbcs during chronic dosing as a result of binding to ca-ii. the parent drug forms a single n-desethyl metabolite, which inhibits ca-ii less potently than the parent drug but also inhibits ca-i. the metabolite also accumulates in rbcs where it binds primarily to ca-i. plasma concentrations of dorzolamide and metabolite are generally below the assay limit of quantitation (15nm). dorzolamide binds moderately to plasma proteins (approximately 33%). dorzolamide is primarily excreted unchanged in the urine; the metabolite also is excreted in urine. after dosing is stopped, dorzolamide washes out of rbcs nonlinearly, resulting in a rapid decline of drug concentration initially, followed by a slower elimination phase with a half-life of about four months. dorzolamide is primarily excreted unchanged in the urine; the metabolite also is excreted in urine. after dosing is stopped, dorzolamide washes out of rbcs nonlinearly, resulting in a rapid decline of drug concentration initially, followed by a slower elimination phase with a half-life of about four months. to simulate the systemic exposure after long-term topical ocular administration, dorzolamide was given orally to eight healthy subjects for up to 20 weeks. the oral dose of 2 mg twice daily closely approximates the amount of drug delivered by topical ocular administration of dorzolamide 2% three times daily. steady state was reached within 8 weeks. the inhibition of ca-ii and total carbonic anhydrase activities was below the degree of inhibition anticipated to be necessary for a pharmacological effect on renal function and respiration in healthy individuals.

initially, followed by a slower elimination phase with a half-life of about four months. dorzolamide is primarily excreted unchanged in the urine; the metabolite also is excreted in urine. after dosing is stopped, dorzolamide washes out of rbcs nonlinearly, resulting in a rapid decline of drug concentration initially, followed by a slower elimination phase with a half-life of about four months. to simulate the systemic exposure after long-term topical ocular administration, dorzolamide was given orally to eight healthy subjects for up to 20 weeks. the oral dose of 2 mg twice daily closely approximates the amount of drug delivered by topical ocular administration of dorzolamide 2% three times daily. steady state was reached within 8 weeks. the inhibition of ca-ii and total carbonic anhydrase activities was below the degree of inhibition anticipated to be necessary for a pharmacological effect on renal function and respiration in healthy individuals.

oping 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 or monkeys dosed topically to the eye for one year. an oral dose of 2 mg/kg/day in dogs represents an estimated plasma c max level, 137 times higher than the lower limit of detection in human plasma following ocular administration. the topical ophthalmic dose in monkeys was approximately equivalent to the human topical ophthalmic dose. 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 of 15 and 7.5 mg/kg/day, respectively. these doses represent estimated plasma c max levels in rats, 104 and 52 times higher than the lower limit of detection in human plasma following ocular administration, respectively.

se 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 or monkeys dosed topically to the eye for one year. an oral dose of 2 mg/kg/day in dogs represents an estimated plasma c max level, 137 times higher than the lower limit of detection in human plasma following ocular administration. the topical ophthalmic dose in monkeys was approximately equivalent to the human topical ophthalmic dose. 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 of 15 and 7.5 mg/kg/day, respectively. these doses represent estimated plasma c max levels in rats, 104 and 52 times higher than the lower limit of detection in human plasma following ocular administration, respectively.

eal thickness measurements. there was a mean loss of approximately 4% in the endothelial cell counts for each group over the one year period.

he 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. 17.4 concomitant topical ocular therapy if more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart. 17.5 contact lens use advise patients that 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 dorzolamide hydrochloride ophthalmic solution administration. 17.6 patient instructions advise patients that if they develop any ocular reactions, particularly conjunctivitis and lid reactions, they should discontinue use and seek their physician's advice. instruct patients to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures. instructions for use dorzolamide hydrochloride ophthalmic solution usp, 2% (dor zol a mide) before using your dorzolamide hydrochloride ophthalmic solution before using your dorzolamide hydrochloride ophthalmic solution, for the first time, make sure the tamper evident ring of the bottle is unbroken. a gap between the bottle and the cap is normal for an unopened bottle.see figure a . step 1. wash your hands. step 2. unscrew the cap by turning in the direction as shown in the figure b. giving your dorzolamide hydrochloride ophthalmic solution drops. step 3. tilt your head back and pull your lower eyelid down slightly to form a pocket between your eyelid and your eye. see figure c. step 4 . hold the dorzolamide hydrochloride ophthalmic solution, 2% bottle upside down. place tip as close as possible to the lower eyelid without touching the tip to the eye, and gently squeeze until a single drop is placed in your eye. do not touch your eye or eyelid with the dropper tip. see figure d. step 5.if your doctor has told you to use dorzolamide hydrochloride ophthalmic solution usp, 2% in both eyes, repeat steps 3 and 4. after using your dorzolamide hydrochloride ophthalmic solution step 6. replace the cap by turning it until it is firmly touching your bottle. after you have used all of your dorzolamide hydrochloride ophthalmic solution, 2% doses, there will be some dorzolamide hydrochloride ophthalmic solution, 2% medicine left in the dispenser. do not try to remove the extra medicine from the dorzolamide hydrochloride ophthalmic solution, 2% dispenser. throw away your dorzolamide hydrochloride ophthalmic solution, 2% dispenser in your household trash. how should i store dorzolamide hydrochloride ophthalmic solution? •store dorzolamide hydrochloride ophthalmic solution between 59°f to 86°f (15°c to 30°c) •protect from light •safely throw away medicine that is out of date or no longer needed. keep dorzolamide hydrochloride ophthalmic solution and all medicines out of the reach of children. important information about using dorzolamide hydrochloride ophthalmic solution •if you have any eye or skin reactions, especially conjunctivitis or eyelid reactions to dorzolamide hydrochloride ophthalmic solution, stop using it and call your doctor right away. •if you have eye surgery or have a problem such as trauma or infection of your eye while using dorzolamide hydrochloride ophthalmic solution, call your doctor right away. •if you do not handle eye medicines the right way the medicine can become contaminated. if the tip of the dispenser touches your eye or areas around your eye, the tip can become contaminated with bacteria which can cause an eye infection and other serious problems including loss of eyesight. •if you use other eye medicines dropped onto the eye like dorzolamide hydrochloride ophthalmic solution, use the medicines at least 5 minutes before or after you use dorzolamide hydrochloride ophthalmic solution. •dorzolamide hydrochloride ophthalmic solution contains benzalkonium chloride which may be absorbed by soft contact lenses. if you wear contact lenses, remove them before you use your dorzolamide hydrochloride ophthalmic solution. you can place your contact lenses back into your eyes 15 minutes after using your dorzolamide hydrochloride ophthalmic solution. manufactured for: alembic pharmaceuticals inc. 750 route 202, bridgewater, nj 08807 usa manufactured by: gland pharma limited, d.p. pally, dundigal post, hyderabad - 500043, india. revised 06/2019 dorzolamide-fig-a dorzolamide-fig-b dorzolamide-fig-c dorzolamide-fig-d .