COSOPT PF

Clinical safety rating: caution

Comprehensive clinical and safety monograph for COSOPT PF (COSOPT PF).

How it works

Fixed combination of a carbonic anhydrase inhibitor (dorzolamide) and a beta-adrenergic antagonist (timolol). Dorzolamide inhibits carbonic anhydrase II in the ciliary processes, reducing aqueous humor secretion. Timolol antagonizes beta-2 adrenergic receptors in the ciliary epithelium, decreasing aqueous humor production.

What the body does with it

Metabolism	Dorzolamide undergoes hepatic metabolism via N-deethylation and O-glucuronidation. Timolol is metabolized by CYP2D6 and to a lesser extent by other CYP450 enzymes.
Excretion	Dorzolamide: 70-80% renal elimination as unchanged drug and N-desethyl metabolite; ~20% fecal. Timolol: 20% renal unchanged, rest metabolized in liver with metabolites excreted renally.
Half-life	Dorzolamide: ~4 months (due to RBC binding); Timolol: 3-4 hours for parent drug, but pharmacodynamic effect may persist longer.
Protein binding	Dorzolamide: ~33% bound to plasma proteins; Timolol: ~10-60% bound primarily to albumin.
Volume of Distribution	Dorzolamide: Vd very large (extensive RBC binding, ~9 L/kg); Timolol: Vd ~1.3-1.7 L/kg.
Bioavailability	Topical ophthalmic: Systemic bioavailability is low; dorzolamide: ~2%, timolol: ~7% after ocular administration.
Onset of Action	Topical: Timolol IOP reduction begins within 30 minutes; Dorzolamide IOP reduction begins within 1-2 hours.
Duration of Action	IOP reduction for both agents persists for 8-12 hours; typically dosed twice daily.

Classification & Brands

Dosing & administration

One drop in the affected eye(s) twice daily, approximately 12 hours apart. The combination product contains dorzolamide 2% and timolol 0.5%.

Dosage form	SOLUTION/DROPS
Renal impairment	Contraindicated in severe renal impairment (CrCl < 30 mL/min). For CrCl 30-60 mL/min, no specific dose adjustment is provided; however, use with caution and monitor for systemic effects.
Liver impairment	No specific dose adjustment guidelines are available for hepatic impairment. However, dorzolamide and timolol metabolism may be affected; use with caution in severe hepatic disease.
Pediatric use	Safety and efficacy in pediatric patients <2 years have not been established. For children ≥2 years, the same dose as adults (one drop twice daily) may be used based on clinical judgment and limited data.
Geriatric use	No specific dose adjustment is required in elderly patients. However, due to the potential for increased systemic absorption and comorbidities, monitor intraocular pressure and side effects such as bradycardia and hypotension more frequently.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for COSOPT PF (COSOPT PF).

Breastfeeding	Timolol is excreted into breast milk; dorzolamide is likely excreted. M/P ratio for timolol is approximately 0.8. Monitor infant for bradycardia, hypotension, and respiratory depression. Use with caution in breastfeeding.
Teratogenic Risk	COSOPT PF (dorzolamide/timolol) has limited human data. Based on animal studies and timolol's beta-blocker effects, there is a potential risk of fetal bradycardia and intrauterine growth restriction, especially in the second and third trimesters. Avoid in the first trimester unless necessary; use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None (no FDA black box warning for this product).

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to any component of the product","Reactive airway disease (e.g., bronchial asthma, history of asthma, severe COPD)","Sinus bradycardia, sick sinus syndrome, sinoatrial block, second- or third-degree atrioventricular block (unless pacemaker is present), overt cardiac failure, cardiogenic shock","Severe renal impairment (CrCl <30 mL/min) or hyperchloremic acidosis"]

Clinical Precautions

Precautions

["Sulfonamide allergy: dorzolamide is a sulfonamide derivative; may cause allergic reactions.","Beta-blocker systemic effects: caution in patients with asthma, COPD, bradycardia, heart block, or heart failure.","Corneal effects: dorzolamide may cause corneal edema, especially in patients with compromised corneas.","Ocular irritation and hypersensitivity reactions.","Use in pregnancy and lactation: not recommended unless benefit outweighs risk.","Pediatric use: safety and efficacy not established."]

Clinical Tips & Counseling

Drug interactions

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COSOPT PF

Clinical safety rating: caution

Comprehensive clinical and safety monograph for COSOPT PF (COSOPT PF).

How it works

What the body does with it

Metabolism	Dorzolamide undergoes hepatic metabolism via N-deethylation and O-glucuronidation. Timolol is metabolized by CYP2D6 and to a lesser extent by other CYP450 enzymes.
Excretion	Dorzolamide: 70-80% renal elimination as unchanged drug and N-desethyl metabolite; ~20% fecal. Timolol: 20% renal unchanged, rest metabolized in liver with metabolites excreted renally.
Half-life	Dorzolamide: ~4 months (due to RBC binding); Timolol: 3-4 hours for parent drug, but pharmacodynamic effect may persist longer.
Protein binding	Dorzolamide: ~33% bound to plasma proteins; Timolol: ~10-60% bound primarily to albumin.
Volume of Distribution	Dorzolamide: Vd very large (extensive RBC binding, ~9 L/kg); Timolol: Vd ~1.3-1.7 L/kg.
Bioavailability	Topical ophthalmic: Systemic bioavailability is low; dorzolamide: ~2%, timolol: ~7% after ocular administration.
Onset of Action	Topical: Timolol IOP reduction begins within 30 minutes; Dorzolamide IOP reduction begins within 1-2 hours.
Duration of Action	IOP reduction for both agents persists for 8-12 hours; typically dosed twice daily.

Classification & Brands

Dosing & administration

One drop in the affected eye(s) twice daily, approximately 12 hours apart. The combination product contains dorzolamide 2% and timolol 0.5%.

Dosage form	SOLUTION/DROPS
Renal impairment	Contraindicated in severe renal impairment (CrCl < 30 mL/min). For CrCl 30-60 mL/min, no specific dose adjustment is provided; however, use with caution and monitor for systemic effects.
Liver impairment	No specific dose adjustment guidelines are available for hepatic impairment. However, dorzolamide and timolol metabolism may be affected; use with caution in severe hepatic disease.
Pediatric use	Safety and efficacy in pediatric patients <2 years have not been established. For children ≥2 years, the same dose as adults (one drop twice daily) may be used based on clinical judgment and limited data.
Geriatric use	No specific dose adjustment is required in elderly patients. However, due to the potential for increased systemic absorption and comorbidities, monitor intraocular pressure and side effects such as bradycardia and hypotension more frequently.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for COSOPT PF (COSOPT PF).

Breastfeeding	Timolol is excreted into breast milk; dorzolamide is likely excreted. M/P ratio for timolol is approximately 0.8. Monitor infant for bradycardia, hypotension, and respiratory depression. Use with caution in breastfeeding.
Teratogenic Risk	COSOPT PF (dorzolamide/timolol) has limited human data. Based on animal studies and timolol's beta-blocker effects, there is a potential risk of fetal bradycardia and intrauterine growth restriction, especially in the second and third trimesters. Avoid in the first trimester unless necessary; use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None (no FDA black box warning for this product).

Side Effect Profile

Serious Effects

Absolute Contraindications

Clinical Precautions

Precautions

Clinical Tips & Counseling

Drug interactions

Loading safety data…