DORZOLAMIDE HYDROCHLORIDE AND TIMOLOL MALEATE
Clinical safety rating: safe
Other drugs that lower heart rate or blood pressure can have additive effects Can cause bronchospasm in patients with asthma.
Dorzolamide is a carbonic anhydrase inhibitor that reduces aqueous humor secretion by inhibiting carbonic anhydrase in the ciliary processes. Timolol is a non-selective beta-adrenergic receptor antagonist that reduces aqueous humor production by blocking beta-2 adrenergic receptors in the ciliary epithelium.
| Metabolism | Dorzolamide is metabolized via CYP3A4 and CYP2C9; timolol is metabolized primarily by CYP2D6. |
| Excretion | Dorzolamide: primarily renal (approx. 80% unchanged), with minor biliary/fecal elimination. Timolol: renal (15-20% unchanged) and extensive hepatic metabolism with fecal excretion. |
| Half-life | Dorzolamide: ~4 months but accumulates in RBCs; terminal half-life ~4-5 months due to binding to carbonic anhydrase. Timolol: ~4-6 hours. |
| Protein binding | Dorzolamide: ~33% bound to plasma proteins. Timolol: ~10% bound to plasma proteins. |
| Volume of Distribution | Dorzolamide: high, due to extensive RBC binding; not typically reported in L/kg. Timolol: ~1.3-1.7 L/kg. |
| Bioavailability | Ophthalmic: systemic absorption is low; dorzolamide ~2% of topical dose, timolol ~0.5-1% of topical dose; oral bioavailability not applicable. |
| Onset of Action | Ophthalmic: reduction of IOP within 1-2 hours, peak effect at 2 hours. |
| Duration of Action | Ophthalmic: IOP reduction persists for 8-12 hours, requiring twice-daily dosing. |
One drop of the fixed combination (dorzolamide 22.26 mg/mL, timolol 6.83 mg/mL) in the affected eye(s) every 12 hours.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | Contraindicated if creatinine clearance <30 mL/min. For GFR 30-60 mL/min, use with caution. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment. Severe hepatic impairment not studied; use with caution. |
| Pediatric use | Pediatric use not established for patients <2 years. For children ≥2 years, same dose as adults; one drop every 12 hours. |
| Geriatric use | No dose adjustment required. Monitor for systemic effects of timolol (bronchospasm, bradycardia) in elderly due to potential comorbidities and polypharmacy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other drugs that lower heart rate or blood pressure can have additive effects Can cause bronchospasm in patients with asthma.
| FDA category | Animal |
| Breastfeeding | Timolol is excreted into human milk; dorzolamide is detected in milk in rats but unknown in humans. The milk-to-plasma (M/P) ratio for timolol is approximately 1.1. Potential for β-blockade in infant, including bradycardia, hypotension, and hypoglycemia. Consider risk to benefit; use with caution or consider alternative therapy. |
| Teratogenic Risk |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | hypertension |
| Serious Effects |
["Hypersensitivity to any component of the product","Bronchial asthma or a history of bronchial asthma","Severe chronic obstructive pulmonary disease","Sinus bradycardia","Second- or third-degree atrioventricular block","Overt cardiac failure","Cardiogenic shock"]
| Precautions | ["Sulfonamide allergy: Dorzolamide is a sulfonamide derivative; patients with history of sulfonamide allergy may experience severe hypersensitivity reactions.","Beta-blocker effects: May exacerbate asthma, COPD, sinus bradycardia, heart block, or heart failure. Use with caution in patients with these conditions.","Ocular effects: Corneal edema, conjunctivitis, and eyelid reactions have been reported. Monitoring of corneal endothelial function recommended.","Systemic absorption: Can lead to beta-blocker systemic effects such as bronchospasm and cardiac depression.","Cholinesterase inhibition: Dorzolamide has potential to inhibit cholinesterase; use with caution in patients with myasthenia gravis."] |
Loading safety data…
| Topical ophthalmic administration of dorzolamide/timolol results in minimal systemic absorption. Animal studies with dorzolamide did not show teratogenicity at doses up to 2.5 mg/kg/day; timolol at doses up to 50 mg/kg/day in rabbits and 100 mg/kg/day in mice was not teratogenic but caused delayed fetal ossification and increased resorptions. No adequate human studies in pregnant women. Risk cannot be ruled out; avoid use in pregnancy unless potential benefit outweighs risk. Fetal risk in first trimester is theoretical but low; second and third trimester risk includes potential neonatal β-blockade (bradycardia, hypotension) and respiratory depression if maternal systemic absorption occurs. |
| Fetal Monitoring | Monitor maternal intraocular pressure. Monitor fetal heart rate and growth if prolonged use; newborn should be monitored for signs of β-blockade (bradycardia, hypotension, respiratory depression, hypoglycemia) in the first 24-48 hours if maternal exposure near term. |
| Fertility Effects | No specific human studies on fertility. Animal studies with dorzolamide at high doses showed no adverse effects on male or female fertility. Timolol at high doses in animals caused transient delays in mating but no long-term fertility impairment. Likely minimal clinical effect on human fertility with ophthalmic use. |
| Food/Dietary | No known food interactions. May be taken without regard to meals. |
| Clinical Pearls | Shake the bottle well before use. Wait at least 5 minutes between instilling this combination product and any other ophthalmic medication to prevent washout. Monitor for ocular irritation, blurred vision, and systemic effects of beta-blockade (bradycardia, bronchospasm) especially in patients with asthma, COPD, or heart block. This combination is more effective than either agent alone for lowering intraocular pressure (IOP) by reducing aqueous humor production via carbonic anhydrase inhibition (dorzolamide) and beta-adrenergic blockade (timolol). Contraindicated in patients with sinus bradycardia, second- or third-degree AV block, cardiogenic shock, or severe COPD. |
| Patient Advice | Use exactly as prescribed; do not stop without consulting your doctor. · Wait at least 5 minutes between this and other eye drops. · Remove contact lenses before use; wait 15 minutes before reinserting. · Do not touch the dropper tip to any surface to avoid contamination. · May cause temporary blurred vision; avoid driving until vision clears. · Report signs of allergy (redness, swelling) or systemic effects (slow heart rate, wheezing). · Store at room temperature away from light and moisture. |