Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, ophthalmic [drops]:
Cosopt: Dorzolamide 2% [20 mg/mL] and timolol 0.5% [5 mg/mL] (10 mL) [contains benzalkonium chloride]
Generic: Dorzolamide 2% [20 mg/mL] and timolol 0.5% [5 mg/mL] (10 mL)
Solution, ophthalmic [drops, preservative free]:
Cosopt PF: Dorzolamide 2% [20 mg/mL] and timolol 0.5% [5 mg/mL] (0.2 mL)
Generic: Dorzolamide 2% [20 mg/mL] and timolol 0.5% [5 mg/mL] (0.2 mL)
Pharmacology
Mechanism of Action
Dorzolamide: Inhibits carbonic anhydrase in the ciliary processes of the eye resulting decreased bicarbonate ion formation which decreases sodium and fluid transport, thus decreasing aqueous humor secretion and reduces intraocular pressure.
Timolol: Blocks both beta1- and beta2-adrenergic receptors, reduces intraocular pressure by reducing aqueous humor production or possibly increases the outflow of aqueous humor
Use: Labeled Indications
Elevated intraocular pressure: Reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to beta-blockers
Contraindications
Hypersensitivity to dorzolamide, timolol, or any component of the formulation; 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.
Dosage and Administration
Dosing: Adult
Elevated intraocular pressure: Ophthalmic: Instill 1 drop in affected eye(s) twice daily
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Elevated intraocular pressure: Children ≥2 years and Adolescents: Ophthalmic: Refer to adult dosing.
Administration
Ophthalmic:
Cosopt: If using additional topical ophthalmic preparations, separate administration by at least 5 minutes. Remove contact lens prior to administration and wait 15 minutes before reinserting. Instruct patients to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures. Ocular solutions can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may occur from using contaminated solutions.
Cosopt PF: Discard single-use container after initial use. If using additional topical ophthalmic preparations, separate administration by at least 5 minutes.
Storage
Store at 15°C to 30°C (59°F to 86°F). Protect from light.
Cosopt PF: Unused single-use containers may be stored in the opened foil pouch for up to 15 days. Do not freeze.
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Alpha-/Beta-Agonists (Indirect-Acting): Carbonic Anhydrase Inhibitors may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Monitor therapy
Alpha1-Blockers: Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Monitor therapy
Alpha2-Agonists: May enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Exceptions: Apraclonidine. Consider therapy modification
Amantadine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Amantadine. Monitor therapy
Aminoquinolines (Antimalarial): May decrease the metabolism of Beta-Blockers. Monitor therapy
Amiodarone: May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Monitor therapy
Asunaprevir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Consider therapy modification
Barbiturates: May decrease the serum concentration of Beta-Blockers. Monitor therapy
Beta2-Agonists: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy
Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil. Monitor therapy
Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of other Carbonic Anhydrase Inhibitors. The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Management: Avoid concurrent use of different carbonic anhydrase inhibitors if possible. Monitor patients closely for the occurrence of kidney stones and with regards to severity of metabolic acidosis. Avoid combination
Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Exceptions are discussed in separate monographs. Consider therapy modification
Cholinergic Agonists: Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Monitor therapy
CloBAZam: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Cobicistat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
CYP2D6 Inhibitors (Strong): May increase the serum concentration of Timolol (Ophthalmic). Monitor therapy
Dacomitinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. Monitor therapy
Dronedarone: May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Consider therapy modification
EPINEPHrine (Nasal): Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Nasal). Monitor therapy
EPINEPHrine (Oral Inhalation): Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Monitor therapy
Epinephrine (Racemic): Beta-Blockers (Nonselective) may enhance the hypertensive effect of Epinephrine (Racemic). Monitor therapy
EPINEPHrine (Systemic): Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Systemic). Monitor therapy
Ergot Derivatives: Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Exceptions: Nicergoline. Consider therapy modification
Fexinidazole [INT]: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole [INT]. Avoid combination
Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and beta-blockers if possible. If coadministration is necessary, patients should have overnight continuous ECG monitoring conducted after the first dose of fingolimod. Monitor patients for bradycardia. Consider therapy modification
Floctafenine: May enhance the adverse/toxic effect of Beta-Blockers. Avoid combination
Grass Pollen Allergen Extract (5 Grass Extract): Beta-Blockers may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers. Consider therapy modification
Imatinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Insulins: Beta-Blockers may enhance the hypoglycemic effect of Insulins. Monitor therapy
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy
Lidocaine (Systemic): Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). Monitor therapy
Lidocaine (Topical): Beta-Blockers may increase the serum concentration of Lidocaine (Topical). Monitor therapy
Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Monitor therapy
Methoxyflurane: May enhance the hypotensive effect of Beta-Blockers. Monitor therapy
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy
NIFEdipine: May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Monitor therapy
Opioids (Anilidopiperidine): May enhance the bradycardic effect of Beta-Blockers. Opioids (Anilidopiperidine) may enhance the hypotensive effect of Beta-Blockers. Monitor therapy
Panobinostat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Perhexiline: CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Monitor therapy
QuiNINE: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy
Regorafenib: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Reserpine: May enhance the hypotensive effect of Beta-Blockers. Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. Monitor therapy
Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Avoid combination
Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Monitor therapy
Selective Serotonin Reuptake Inhibitors: May increase the serum concentration of Beta-Blockers. Exceptions: Citalopram; Escitalopram; FluvoxaMINE. Monitor therapy
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. Consider therapy modification
Sulfonylureas: Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Monitor therapy
Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy
Theophylline Derivatives: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Monitor therapy
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy
Adverse Reactions
Frequency not always defined. Percentages as reported with combination product. Also see individual agents.
>5%:
Gastrointestinal: Dysgeusia (≤30%)
Ophthalmic: Burning sensation of eyes (≤30%), stinging of eyes (≤30%), blurred vision (5% to 15%), conjunctival hyperemia (5% to 15%), eye pruritus (5% to 15%), superficial punctate keratitis (5% to 15%)
1% to 5%:
Cardiovascular: Hypertension
Central nervous system: Dizziness, headache
Dermatologic: Erythema of eyelid
Gastrointestinal: Abdominal pain, dyspepsia, nausea
Genitourinary: Urinary tract infection
Infection: Influenza
Local: Local discoloration (lens nucleus)
Neuromuscular & skeletal: Back pain
Ophthalmic: Blepharitis, cataract (including post-subcapsular), cloudy vision, conjunctival discharge, conjunctival edema, conjunctivitis, corneal erosion, corneal staining, dry eye syndrome, eye discharge (including eyelid), eye disease (debris in eye), eye pain (includes eyelid), eyelid edema, follicular conjunctivitis, foreign body sensation of eye, lacrimation, ocular exudate (eyelid), optic disk cupping (glaucomatous), scaling of eyelid, visual field defect, vitreous detachment
Respiratory: Bronchitis, cough, pharyngitis, sinusitis, upper respiratory tract infection
<1%, postmarketing, and/or case reports: Bradycardia, cardiac failure, cerebrovascular accident, chest pain, choroidal detachment (following filtration procedures), depression, diarrhea, dyspnea, heart block, hypotension, iridocyclitis, myocardial infarction, nasal congestion, paresthesia, photophobia, respiratory failure, skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urolithiasis, vomiting, xerostomia
Warnings/Precautions
Concerns related to adverse effects:
- Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
- Bacterial keratitis: Inadvertent contamination of multiple-dose ophthalmic solutions has caused bacterial keratitis.
- Ocular effects: Local ocular adverse effects (conjunctivitis and lid reactions) were reported with chronic administration; many resolved upon discontinuation of drug therapy. Choroidal detachment has been reported after filtration procedures. Patients with low endothelial cell counts may have increased risk for corneal edema; use caution.
- Sulfonamide (“sulfa”) allergy: Dorzolamide is a sulfonamide; although administered ocularly, systemic absorption may occur and could result in hypersensitivity. Discontinue use if signs of hypersensitivity or a serious reaction occur.
- Systemic effects: Systemic absorption and adverse effects (similar to sulfonamides) including blood dyscrasias, Stevens-Johnson syndrome, toxic epidermal necrolysis, and fulminant hepatic necrosis may occur with ophthalmic use.
Disease-related concerns:
- Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.
- Heart failure (HF): Use with caution in patients with compensated heart failure and monitor for a worsening of the condition; control heart failure prior to initiation of therapy.
- Hepatic impairment: Use with caution in patients with hepatic impairment; not evaluated.
- Myasthenia gravis: Use with caution in patients with myasthenia gravis; may worsen disease or other myasthenic symptoms (diplopia, ptosis, and generalized weakness).
- Narrow-angle glaucoma: Use is not recommended in narrow-angle glaucoma (has not been studied).
- Peripheral vascular disease (PVD) and Raynaud's disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud's disease. Use with caution and monitor for progression of arterial obstruction.
- Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression.
- Renal impairment: Use with caution in patients with renal impairment; not recommended with severe impairment (CrCl <30 mL/minute).
- Respiratory disease: In general, patients with mild-to-moderate COPD or bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring. Use is contraindicated in patients with asthma or severe COPD.
- Thyroid disease: May mask signs of hyperthyroidism (eg, tachycardia). If thyrotoxicosis is suspected, carefully manage and monitor; abrupt withdrawal may exacerbate symptoms of hyperthyroidism or precipitate thyroid storm.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Contact lens wearers: Some products may contain benzalkonium chloride which may be absorbed by soft contact lenses; remove lens prior to administration and wait 15 minutes before reinserting.
Other warnings/precautions:
- Surgery: May block systemic effects of beta agonists (eg, epinephrine, norepinephrine); notify anesthesiologist if patient is receiving ophthalmic beta blocker therapy. Patients undergoing planned major surgery should be gradually tapered off therapy (if possible) prior to procedure. If necessary during surgery, effects of beta blocker therapy may be reversed by adrenergic agonists.
Monitoring Parameters
Ophthalmic exams and IOP periodically
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Reproductive studies have not been conducted with this combination. Refer to individual agents.
Patient Education
What is this drug used for?
- It is used to treat glaucoma.
- It is used to lower high eye pressure.
Frequently reported side effects of this drug
- Blurred vision
- Burning
- Stinging
- Itching
- Eye redness
- Watery eyes
- Change in taste
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Vision changes
- Eye pain
- Severe eye irritation
- Slow heartbeat
- Muscle weakness
- Heart problems like cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out
- Severe sulfonamide reaction like rash; red, swollen, blistered, or peeling skin; red or irritated eyes; mouth, throat, nose, or eye sores; fever, chills, or sore throat; cough that is new or worse; loss of strength and energy; any bruising or bleeding; or signs of liver problems like dark urine, fatigue, lack of appetite, nausea or abdominal pain, light-colored stools, vomiting, or yellow skin
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
