DAROMED

Dorzolamide is a non-bacteriostatic sulfonamide derivative and topical carbonic anhydrase (CA) inhibitor that treats elevated intraocular pressure (IOP) associated with open-angle glaucoma and ocular hypertension.

It works by blocking an enzyme in the ciliary process that regulates ion balance and fluid pressure in the eyes.

Unlike oral

CA inhibitors, dorzolamide has negligible effects of acid-base or electrolyte disturbances and other systemic adverse effects.

First marketed in 1995, 5 dorzolamide is available in ophthalmic solutions as monotherapy marketed as Trusopt 6 or in combination with timolol as Cosopt PF.

Dorzolamide is indicated for the management of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.

It can also be used in combination with timolol for the same indication in patients who are insufficiently responsive to ophthalmic beta-blockers.

Its pre-operative use was also investigated to prevent elevated intraocular pressure after neodynium yttrium aluminum garnet laser posterior capsulotomy.

Dorzolamide is a carbonic anhydrase inhibitor that reduces elevated intraocular pressure in open-angle glaucoma or ocular hypertension.

When used in combination with topic beta-adrenergic antagonists, dorzolamide has an additive effect of lowering intraocular pressure.

The peak ocular hypotensive effect of dorzolamide is observed at about 2 hours following ophthalmic administration.

Carbonic anhydrase 2 Inhibitor Carbonic anhydrase 4 Inhibitor Carbonic anhydrase 1 Inhibitor.

Dorzolamide readily penetrated into the eye in animal studies.

Upon ophthalmic administration, dorzolamide is absorbed via the cornea and stroma.

Dorzolamide is reported to be absorbed systematically following topical administration.

The systemic exposure of dorzolamide following long-term administration was assessed in healthy subjects receiving an oral dose of 2 mg dorzolamide twice daily, which equates to the ophthalmic dose of 2% dorzolamide three times daily.

In these subjects receiving the treatment for 20 weeks, the steady-state was reached within 8 weeks.

There is limited information on the volume of distribution of dorzolamide; however, the plasma concentrations of dorzolamide and its main metabolite are generally below the assay limit of quantitation, which is 15nM.

Dorzolamide accumulates in red blood cells following chronic administration as a result of binding to CA-II, which is contained in peripheral red blood cells (RBCs).

Dorzolamide is slowly metabolised to

N-desethyldorzolamide, which has a less potent pharmacological activity on CA-II and some inhibitory effect on CA-I.

Like the parent drug, N-desethyldorzolamide is also stored in RBCs, where it binds to CA-I. 1, 6 The findings of an in vitro study using liver microsomes from Sprague-Dawley rats suggest the involvement of CYP2B1, CYP2E1, and CYP3A2 in the metabolism of dorzolamide in rat liver.

Hover over products below to view reaction partners Dorzolamide N-desethyldorzolamide.

Dorzolamide is primarily excreted unchanged in the urine; however, N-desethyldorzolamide is also detected in the urine.

As the drug administration is stopped, dorzolamide stored in RBCs is washed out of RBCs in a non-linear fashion, 6 with the terminal elimination half-life of ≥120 days in RBCs.

This initial rapid decline in drug concentrations is followed by the slow elimination phase, where the elimination half-life of the drug is about >4 months.

There is limited information on the clearance rate of dorzolamide.

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The oral

LD of dorzolamide is 1927 mg/kg in rats and 1320 mg/kg in mice.

The subcutaneous

LD is >2 g/kg in both rats and mice.

Overdose may result in electrolyte imbalance, acidosis, and possibly central nervous system effects; these symptoms should be responded with appropriate supportive treatment.

It is advised that the patient's serum electrolyte (particularly potassium) levels and blood pH levels are monitored in the case of a suspected overdose.

Solution is contraindicated in patients who are hypersensitive to any component of this product.

The dose is one drop of Dorzolamide Hydrochloride Ophthalmic Solution in the affected eye(s) three times daily.

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 five minutes apart.

Solution, USP 2% is supplied in 10 mL ratchet modified screw neck white LDPE bottle with LDPE nozzle having white Opaque pump with a dip tube and Orange color ring modified HDPE screw cap as follows: NDC Dorzolamide Hydrochloride Ophthalmic Solution, USP 2% Package Factor 25021-006-10 10 mL fill 1 bottle per carton Storage Conditions Store at 15° to 30°C (59° to 86°F).

After opening, Dorzolamide Hydrochloride Ophthalmic Solution, USP 2% can be used until the expiration date on the bottle.

Protect from light.

The container closure is not made with natural rubber latex.

Store at 15° to 30°C (59° to 86°F).

After opening, Dorzolamide Hydrochloride Ophthalmic Solution, USP 2% can be used until the expiration date on the bottle.

Protect from light.

The container closure is not made with natural rubber latex.

There are no adequate and well-controlled studies in pregnant women with Dorzolamide Hydrochloride Ophthalmic Solution.

Dorzolamide caused fetal vertebral malformations when administered orally to rabbits at 2.5 mg/kg/day (37 times the clinical exposure).

Dorzolamide administered during the period of organogenesis was not teratogenic in rabbits dosed up to 1 mg/kg/day (15 times the clinical exposure).

Dorzolamide hydrochloride administered orally to rats during late gestation and lactation caused growth delays in offspring at 7.5 mg/kg/day (52 times the clinical exposure).

Growth was not delayed at 1 mg/kg/day (8.0 times the clinical exposure).

The background risk of major birth defects and miscarriage for the indicated population is unknown.

In the

U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is to 4% and to 20%, respectively.

Developmental toxicity studies were conducted in pregnant rabbits administered dorzolamide hydrochloride orally during the period of organogenesis from gestation days 6 through at doses of 0.2, 1, 2.5, 5, and 10 mg/kg/day. The developmental lowest observed adverse effect level (LOAEL) was 2.5 mg/kg/day, based on vertebral malformations and decreased fetal body weight.

The maternal

LOAEL was 2.5 mg/kg/day, based on metabolic acidosis and reduced weight gain.

The maternal and developmental no adverse effect levels (NOAELs) were 1 mg/kg/day. The rabbit doses of and 2.5 mg/kg/day represent estimated plasma C max levels in rabbits and 37 times higher than the lower limit of detection in human plasma following ocular administration, respectively.

Dorzolamide hydrochloride was administered orally to rats during late gestation and lactation (gestation day 17 through postpartum day 20) at doses of 0.1, 1, or 7.5 mg/kg/day. The developmental LOAEL was 7.5 mg/kg/day, based on reduced birth weight, reduced weight gain, and a slight delay in postnatal development (incisor eruption, vaginal canalization and eye openings) secondary to lower offspring body weight.

This 7.5 mg/kg/day 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.

The developmental

NOAEL was 1 mg/kg/day. The maternal LOAEL was 1 mg/kg/day, based on reduced body weight gain.

NOAEL was 0.1 mg/kg/day. The rat doses of and 0.1 mg/kg/day represent estimated plasma C max levels in rats approximately 8.0 times and approximately equal (1x), respectively to the lower limit of detection in human plasma following ocular administration.

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.

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