DORZOLAMIDE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DORZOLAMIDE HYDROCHLORIDE (DORZOLAMIDE HYDROCHLORIDE).
Dorzolamide hydrochloride is a carbonic anhydrase II inhibitor. By inhibiting carbonic anhydrase in the ciliary processes of the eye, it reduces aqueous humor secretion, thereby lowering intraocular pressure.
| Metabolism | Dorzolamide is metabolized primarily by hepatic cytochrome P450 enzymes, specifically CYP2C9, to N-desethyl-dorzolamide. It forms N-acetylated metabolites as well as the N-desethyl metabolite. Minor renal elimination of unchanged drug occurs. |
| Excretion | Renal: approximately 70% of a topically applied dose is excreted unchanged in urine over 120 hours; <2% fecal. |
| Half-life | Terminal elimination half-life is approximately 4 months for red blood cell carbonic anhydrase II binding; systemic half-life of free drug is about 3-4 hours. |
| Protein binding | Approximately 33% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Wide distribution: apparent Vd is approximately 0.53 L/kg; extensive binding to carbonic anhydrase in red blood cells and tissues. |
| Bioavailability | Topical ophthalmic: systemic absorption is minimal (approximately 2-4% of administered dose reaches systemic circulation due to nasolacrimal drainage and ocular absorption). |
| Onset of Action | Topical ophthalmic: intraocular pressure reduction begins within 1-2 hours after instillation. |
| Duration of Action | Topical ophthalmic: intraocular pressure reduction persists for 8-12 hours; clinically dosed three times daily. |
| Molecular Weight | 324.44 |
One drop of 2% solution in the affected eye(s) three times daily.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | Contraindicated in severe renal impairment (CrCl <30 mL/min). No specific dose adjustment for mild to moderate impairment; use with caution. |
| Liver impairment | No specific dose adjustment required based on Child-Pugh classification; however, use with caution in severe hepatic impairment due to potential for systemic accumulation. |
| Pediatric use | Safety and efficacy not established in pediatric patients. No standard weight-based dosing guidelines available. Some sources recommend the same adult dose (one drop of 2% solution three times daily) for children aged ≥2 years; use with caution. |
| Geriatric use | No specific dose adjustment required, but elderly patients may be more susceptible to systemic effects; monitor for ocular irritation and electrolyte imbalance. |
| 1st trimester | Avoid unless clearly needed; limited human data, potential for metabolic acidosis in neonates. |
| 2nd trimester | Use only if benefit outweighs risk; no known teratogenicity in animal studies. |
| 3rd trimester | Avoid near term; risk of neonatal metabolic acidosis due to sulfonamide moiety. |
Clinical note
Comprehensive clinical and safety monograph for DORZOLAMIDE HYDROCHLORIDE (DORZOLAMIDE HYDROCHLORIDE).
| Placental transfer | Limited data; likely crosses placenta due to low molecular weight; sulfonamide moiety may accumulate in fetal tissues. |
| Breastfeeding | Excretion into breast milk unknown; due to potential for sulfonamide-induced kernicterus in neonates, use with caution, especially in infants with G6PD deficiency or jaundice. |
■ FDA Black Box Warning
None
| Common Effects | Dryness in mouth Increased heart rate Orthostatic hypotension sudden lowering of blood pressure on standing Weight gain Difficulty in urination Constipation Blurred vision |
| Serious Effects |
Hypersensitivity to dorzolamide or any componentSevere renal impairment (CrCl <30 mL/min)Hyperchloremic metabolic acidosis
| Precautions | Sulfonamide hypersensitivity: Dorzolamide is a sulfonamide derivative; cross-reactivity may occur. Discontinue if signs of serious hypersensitivity reactions develop., Corneal edema and endothelial decompensation: Use with caution in patients with compromised corneas (e.g., low endothelial cell count)., Ocular effects: Transient blurred vision, burning, stinging, and superficial punctate keratitis may occur., Potential for metabolic acidosis: Carbonic anhydrase inhibitors can cause metabolic acidosis; use with caution in patients with renal impairment or those on concomitant topiramate or acetazolamide., Bacterial keratitis: Risk with contaminated multidose containers. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | Dorzolamide is a carbonic anhydrase inhibitor. No adequate and well-controlled studies in pregnant women. In animal studies, no teratogenic effects at doses up to 2.5 mg/kg/day (rabbit) and 20 mg/kg/day (rat). Low systemic absorption (≈4% of ocular dose) minimizes fetal exposure. FDA Pregnancy Category C. Risk cannot be ruled out; use only if potential benefit justifies potential risk to fetus. No specific trimester risks. |
| Fetal Monitoring | No specific monitoring required beyond routine prenatal care. Monitor intraocular pressure as needed. Observe for systemic side effects (metabolic acidosis, electrolyte disturbances) though unlikely due to low systemic absorption. |
| Fertility Effects | No studies on fertility in humans. In animal studies, no impairment of fertility was observed in rats at doses up to 20 mg/kg/day (240 times the recommended human ophthalmic dose). Based on mechanism and low systemic absorption, unlikely to significantly impact human fertility. |
| Food/Dietary | None known. No dietary restrictions are required with topical dorzolamide use. |
| Clinical Pearls | Dorzolamide is a topical carbonic anhydrase inhibitor used for elevated intraocular pressure. It can cause metabolic acidosis due to systemic absorption, especially in patients with renal impairment. Avoid use with oral carbonic anhydrase inhibitors to prevent additive systemic effects. Monitor for corneal edema in patients with compromised corneas. The drug may cause transient blurred vision; apply pressure over the nasolacrimal duct to minimize systemic absorption. |
| Patient Advice | Instill one drop in the affected eye(s) three times daily, as directed. · Wash hands before and after use. Avoid touching the dropper tip to any surface. · If using other eye drops, wait at least 5 minutes between administrations. · Do not wear contact lenses during treatment; may discolor soft contact lenses. · Report eye pain, redness, vision changes, or signs of allergy (rash, itching). · May cause temporary blurred vision; do not drive or operate machinery until vision clears. · Store at room temperature, tightly closed, and protect from light. |