Elevated IOP in open-angle glaucoma or ocular hypertension inadequately controlled on a beta-blocker
1 drop in the affected eye(s) BID
Lowers IOP a further 14 to 20% over timolol alone, matching its components given separately.
OFF-LABELNot in the FDA label for this product
IOP spike prophylaxis before intravitreal anti-VEGF injection
1 drop 1 hour before the injection; a 2-drop regimen of 1 drop at 1 hour and 1 drop at 5 minutes before was also studied
Trial · n=89 · not indexed RCT
Randomized, double-masked trial, 308 patients contributing one eye each, of which 89 received this product by brand name: mean IOP at 30 minutes post-injection stayed within 21 mmHg and was back to baseline at 1 hour, while the untreated group rose 7.84 mmHg at 30 minutes and remained 4.05 mmHg above baseline at 1 hour. Premedication blunted rather than abolished the spike (still up 2.31 mmHg with one drop and 1.71 mmHg with two at 30 minutes), the 32 controls were not randomized but were patients excluded from the drug arms for allergy or contraindication, and the three fixed combinations tested performed comparably.
Bronchial asthma or a history of bronchial asthma.
Severe chronic obstructive pulmonary disease.
Sinus bradycardia, second or third degree atrioventricular block, overt cardiac failure, or cardiogenic shock.
Hypersensitivity to any component of this product.
Available Forms
Dorzolamide 2% (20 mg/mL) and timolol 0.5% (5 mg/mL) ophthalmic solution, benzalkonium chloride preserved, 10 mL bottle
Mechanism of Action
Fixed combination of dorzolamide, a human carbonic anhydrase II inhibitor, and timolol, a nonselective beta-1 and beta-2 adrenergic blocker without significant intrinsic sympathomimetic, myocardial depressant, or membrane-stabilizing activity; each component reduces aqueous humor secretion. Given BID the pair lowers IOP more than either component alone, but not as much as dorzolamide TID plus timolol BID administered concomitantly.
Warnings & Precautions
Systemic beta-blockade: Timolol is absorbed systemically from topical dosing, so reactions attributable to systemic beta-blockers can occur. Severe respiratory reactions including death due to bronchospasm in patients with asthma, and rarely death associated with cardiac failure, have been reported after systemic or ophthalmic timolol.
Cardiac failure: Beta-blockade may precipitate more severe failure where sympathetic stimulation supports the circulation, and in patients with no history of cardiac failure, continued myocardial depression over time can itself lead to failure. Discontinue at the first sign or symptom.
Sulfonamide hypersensitivity: Dorzolamide is a sulfonamide that is absorbed systemically despite topical dosing, so the reactions attributable to sulfonamides can occur, rarely fatal, 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 by any route; discontinue if a serious reaction or hypersensitivity occurs.
Obstructive pulmonary disease: Patients with mild or moderate COPD or bronchospastic disease should in general not receive beta-blockers; asthma, a history of asthma, and severe COPD are contraindications.
Increased reactivity to allergens: Patients with a history of atopy or of severe anaphylaxis may be more reactive to allergen challenge while on a beta-blocker and may be unresponsive to the usual doses of epinephrine.
Potentiation of muscle weakness: Beta-blockade can potentiate myasthenic symptoms such as diplopia, ptosis, and generalized weakness, and timolol has rarely increased weakness in myasthenia gravis.
Masking of hypoglycemic symptoms: Beta-blockers may mask the signs and symptoms of acute hypoglycemia; caution in spontaneous hypoglycemia and in diabetic patients on insulin or oral hypoglycemics.
Masking of thyrotoxicosis: Beta-blockers may mask tachycardia and other signs of hyperthyroidism, and abrupt withdrawal may precipitate thyroid storm.
Common Side Effects
Ocular, up to 30%: Burning and/or stinging on instillation.
Systemic, up to 30%: Taste perversion (bitter, sour, or unusual taste).
Renal and hepatic impairment: Not recommended at CrCl below 30 mL/min, since dorzolamide and its metabolite are renally excreted; not studied in hepatic impairment, so use with caution there.
Beta-adrenergic reflexes during surgery: Blockade impairs the heart's response to reflex adrenergic stimuli; protracted severe hypotension during anesthesia and difficulty restarting the heartbeat have been reported.
Corneal endothelium: Carbonic anhydrase activity is present in the corneal endothelium, and patients with low endothelial cell counts have an increased potential for corneal edema.
Bacterial keratitis: Reported with inadvertently contaminated multi-dose containers, in most cases in patients with a concurrent corneal disease or a disruption of the ocular epithelium.
Contact lens wear: The benzalkonium chloride preservative may be absorbed by soft lenses; remove lenses before instillation and reinsert 15 minutes after.
Oral carbonic anhydrase inhibitors: Concomitant use is not recommended; the systemic effects of carbonic anhydrase inhibition are potentially additive.
High-dose salicylate therapy: Acid-base and electrolyte disturbances were not reported in the dorzolamide trials, but have been reported with oral carbonic anhydrase inhibitors and have in some instances produced drug interactions such as salicylate toxicity; consider the same potential here.
Beta-blocker drug interactions: Additive systemic and IOP beta-blockade with an oral beta-blocker, and two topical beta-blockers are not recommended. Potentiated blockade with CYP2D6 inhibitors (quinidine, SSRIs); atrioventricular conduction disturbance, left ventricular failure, and hypotension with oral or IV calcium antagonists; prolonged AV conduction with digitalis; hypotension and marked bradycardia with catecholamine-depleting drugs such as reserpine.
Pregnancy: No adequate and well-controlled studies in pregnant women; use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Oral dorzolamide in rabbits at 2.5 mg/kg/day and above (37 times the recommended human ophthalmic dose) caused vertebral body malformations at doses that also caused maternal metabolic acidosis and decreased fetal weights, with no treatment-related malformations at 1 mg/kg/day (15 times); timolol showed no fetal malformations in mice, rats, or rabbits at oral doses up to 50 mg/kg/day.
Lactation: Timolol is detected in human milk after oral and ophthalmic dosing, and whether dorzolamide is excreted in human milk is unknown; decide between discontinuing nursing and discontinuing the drug.
Pediatric Use
Safety and effectiveness of the individual components are established at 2 years and older; not established below 2 years.
Available Forms
Mechanism of Action
Pregnancy & Lactation
Pediatric Use