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Dorzolamide is an inhibitor of carbonic anhydrase, a zinc-containing enzyme that catalyzes the rapid conversion of carbon dioxide and water into carbonic acid, protons, and bicarbonate ions. Distributed throughout many cells and tissues, various carbonic anhydrases play important roles in mineral and metabolic homeostasis. (NCI04)
Dorzolamide is 5,6-Dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide in which hydrogens at the 4 and 6 positions are substituted by ethylamino and methyl groups, respectively (4S, trans-configuration). A carbonic anhydrase inhibitor, it is used as the hydrochloride in ophthalmic solutions to lower increased intraocular pressure in the treatment of open-angle glaucoma and ocular hypertension. It has a role as an EC 4.2.1.1 (carbonic anhydrase) inhibitor, an antihypertensive agent, and an antiglaucoma drug. It is a sulfonamide and a member of thiophenes.
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, dorzolamide is available in ophthalmic solutions as monotherapy marketed as Trusopt or in combination with [timolol] as Cosopt PF.
Mechanism of Action
Elevated intraocular pressure is a characteristic manifestation of ocular hypertension or open-angle glaucoma. The level of intraocular pressure (IOP) is governed by the balance between the production of aqueous humor (by ocular ciliary processes) and its outflow from the anterior segment of the eye via trabecular (conventional) or uveoscleral (unconventional) pathways. When there is an increase in the resistance to the trabecular outflow of aqueous humor, the intraocular pressure is elevated. Subsequently, optic nerve damage can occur from blood flow restrictions and mechanical distortion of ocular structures. Optic nerve damage can further result in optic disc cupping and progressive visual field loss (and blindness in some cases).[A1304] Carbonic anhydrase (CA) is a ubiquitous enzyme that catalyzes the reversible hydration of carbon dioxide to bicarbonate ions and dehydration of carbonic acid.[A1304, L11377] In the ocular ciliary processes, the local production of bicarbonate by CAs promotes sodium and fluid transport. CA-II is a key isoenzyme found primarily in red blood cells (RBCs) that regulates aqueous humor production.[A1304] Dorzolamide is a highly specific CA-II inhibitor, where it displays a 4000-fold higher affinity for carbonic anhydrase II than carbonic anhydrase I.[A1304] The inhibition of CA-II in the ciliary process disrupts the formation of bicarbonate ions and reduces sodium and fluid transport, which leads to decreased aqueous humor secretion and reduced intraocular pressure.[A1304, L11377]
Indications of Dorzolamide
- Dorzolamide is indicated for the management of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.[L11377] It can also be used in combination with [timolol] for the same indication in patients who are insufficiently responsive to ophthalmic beta-blockers.[L11380] Its pre-operative use was also investigated to prevent elevated intraocular pressure after neodymium yttrium aluminum garnet laser posterior capsulotomy.
- Intraocular Hypertension
- Glaucoma, Open-Angle
- Treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma
Contraindications Of Dorzolamide
- Hyperchloremic acidosis
- Hypokalemia (low blood potassium)
- Hyponatremia (low blood sodium)
- Adrenal insufficiency
- Impaired kidney function
- Hypersensitivity to acetazolamide or other sulfonamides.
- Marked liver disease or impairment of liver function, including cirrhosis because of the risk of development of hepatic encephalopathy. Acetazolamide decreases ammonia clearance
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- a condition where the adrenal glands produce less hormones called Addison’s disease
- a type of joint disorder due to excess uric acid in the blood called gout
- respiratory acidosis, an acid-base disorder
- a blood disorder
- decreased lung function
- liver problems
- severe liver disease
- renal tubular acidosis
- recurrent calcium-containing kidney stones
- decreased kidney function
- hyperchloremic acidosis
Dosage of Dorzolamide
- Strengths: 2%; 2% preservative-free
Intraocular Hypertension
- One drop in the affected eye(s) three times a day
Glaucoma (Open Angle)
- One drop in the affected eye(s) three times a day
Pediatric Dose for Intraocular Hypertension
- Safety and effectiveness have been demonstrated in pediatric patients in a 3-month, multicenter, double-masked, active-treatment-controlled trial:
- One drop in the affected eye(s) three times a day.
Side Effects of Dorzolamide
The Most Common
- Burning, stinging, or discomfort when the medicine is applied
- itching, redness, swelling, or other sign of eye or eyelid irritation
- Burning, dry, or itching eyes
- discharge from the eye
- excessive tearing
- redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid
- Blood in the urine
- blurred vision
- nausea or vomiting
- pain in the side, back, or abdomen
- skin rash
- tearing
Common
- Blistering, burning, crusting, dryness, or flaking of the skin
- change in vision
- chills
- cough
- diarrhea
- difficult or labored breathing
- flashes of light
- floaters in vision
- hives or welts
- itching skin
- joint or muscle pain
- large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
- noisy breathing
- redness of the skin
- sore throat
- sores, ulcers, or white spots in the mouth or on the lips
- tightness in the chest
- unusual tiredness or weakness
Rare
- Confusion
- irregular heartbeat
- muscle cramps or pain
- numbness, tingling, pain, or weakness in the hands or feet
- seizures
- trembling
- weakness and heaviness of the legs
Drug Interactions of Dorzolamide
- acetazolamide
- aspirin
- bismuth subsalicylate
- choline salicylate
- dichlorphenamide
- diflunisal
- magnesium salicylate
- methazolamide
- salsalate
- sodium salicylate
- sodium thiosalicylate
- topiramate
- zonisamide
Pregnancy Category
US FDA Pregnancy Category – C
Pregnancy
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).
Lactation
There are no data on the presence of Dorzolamide hydrochloride ophthalmic solution in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Dorzolamide hydrochloride ophthalmic solution and any potential adverse effects on the breast-fed child from Dorzolamide hydrochloride ophthalmic solution. Dorzolamide is present in the milk of lactating rats (see Data).
References
