COSOPT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for COSOPT (COSOPT).
Cosopt is a combination of dorzolamide, a carbonic anhydrase inhibitor, and timolol, a beta-adrenergic receptor antagonist. Dorzolamide inhibits carbonic anhydrase II in the ciliary processes, decreasing aqueous humor secretion. Timolol reduces aqueous humor production by blocking beta-2 adrenergic receptors in the ciliary epithelium.
| Metabolism | Dorzolamide is primarily metabolized via hepatic CYP450 enzymes forming N-desethyl dorzolamide. Timolol is metabolized by CYP2D6 and to a lesser extent CYP2C19 and other enzymes. |
| Excretion | Dorzolamide: renal excretion of unchanged drug and N-desethyl metabolite accounts for approximately 70% of the dose, with ~20% as unchanged drug. Timolol: ~20% renal excretion unchanged, remainder as metabolites in urine |
| Half-life | Dorzolamide: terminal half-life ~4 months due to carbonic anhydrase binding in RBCs (slow dissociation); timolol: 4 hours, prolonged in renal impairment |
| Protein binding | Dorzolamide: ~33% (primarily to carbonic anhydrase in RBCs and plasma); timolol: ~10% (plasma proteins, mainly albumin) |
| Volume of Distribution | Dorzolamide: Vd ~0.23 L/kg; timolol: Vd ~2 L/kg (extensive tissue distribution) |
| Bioavailability | Topical: low systemic absorption; plasma concentrations near limit of quantification after ocular dosing |
| Onset of Action | Topical: dorzolamide reduces IOP within 1 hour, timolol within 30 minutes; peak effect at 2 hours |
| Duration of Action | IOP reduction persists for 8-12 hours; twice-daily dosing maintains effect for 24 hours |
One drop in the affected eye(s) twice daily.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | Contraindicated in severe renal impairment (CrCl < 30 mL/min). No dosage adjustment required for mild to moderate impairment (CrCl 30-89 mL/min). |
| Liver impairment | No specific dose adjustment guidelines; use caution in severe hepatic impairment due to potential systemic effects. |
| Pediatric use | Not recommended for use in pediatric patients due to lack of safety and efficacy data. |
| Geriatric use | No specific dose adjustment required, but monitor for increased systemic effects due to age-related renal function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for COSOPT (COSOPT).
| Breastfeeding | Timolol: excreted in human breast milk; M/P ratio approximately 0.8. Dorzolamide: unknown if excreted in milk, but systemically absorbed (low). Potential for infant bradycardia, hypotension, and metabolic acidosis. Limited data; use with caution, monitor infant for signs of beta-blockade. American Academy of Pediatrics considers timolol compatible with breastfeeding. |
| Teratogenic Risk | Teratogenic risk not established in humans; animal studies show no teratogenicity at ophthalmic doses. Timolol: increased fetal resorption and delayed skeletal ossification in rabbits at high doses. Dorzolamide: no teratogenic effects in rats or rabbits at doses up to 2.5 mg/kg/day. Risk of fetal bradycardia and metabolic acidosis with systemic beta-blockade; limit use in pregnancy to cases where benefit outweighs risk. No adequate human studies; first trimester use may be associated with beta-blocker effects. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to any component of the product","Bronchial asthma, history of bronchial asthma, or severe chronic obstructive pulmonary disease","Sinus bradycardia, sick sinus syndrome, sinoatrial block, second- or third-degree AV block (unless pacemaker is present), overt cardiac failure, cardiogenic shock","Severe renal impairment (CrCl <30 mL/min) due to dorzolamide accumulation"]
| Precautions | ["Beta-blocker effects may mask signs of hypoglycemia or hyperthyroidism","May cause bronchospasm in patients with asthma or COPD","Caution in patients with sinus bradycardia, heart block, or heart failure","Sulfonamide allergy: dorzolamide is a sulfonamide derivative; may cause hypersensitivity reactions","Ocular effects: corneal edema, conjunctivitis, blurred vision","Potential for additive effects with oral carbonic anhydrase inhibitors"] |
Loading safety data…
| Fetal Monitoring | Maternal: Monitor heart rate, blood pressure, and signs of bronchospasm; assess for electrolyte and metabolic acidosis (dorzolamide). Fetal/neonatal: Assess heart rate and glucose in neonates; monitor for respiratory depression, bradycardia, and metabolic acidosis. Periodic fetal ultrasound for growth if prolonged use. |
| Fertility Effects | No specific human studies on fertility with ophthalmic COSOPT. Systemic beta-blockers (timolol) may reduce sperm motility and testosterone levels in men; animal studies show no effect on female fertility. Dorzolamide: no adverse effects on fertility in rats. Clinical relevance for ophthalmic use negligible due to low systemic absorption. |