Elevated intraocular pressure: Ophthalmic: Instill 1 drop in affected eye(s) twice daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: Use is not recommended (has not been studied).
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.
Refer to adult dosing.
Elevated intraocular pressure: Children ≥2 years and Adolescents: Ophthalmic: Refer to adult dosing.
Children ≥2 years and Adolescents:
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: Use is not recommended (has not been studied).
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Also see individual agents.
>10%:
Gastrointestinal: Dysgeusia (≤30%)
Ophthalmic: Blurred vision (5% to 15%), burning sensation of eyes (≤30%), conjunctival hyperemia (5% to 15%), eye pruritus (5% to 15%), stinging of eyes (≤30%), superficial punctate keratitis (5% to 15%)
1% to 10%:
Cardiovascular: Hypertension (1% to 5%)
Gastrointestinal: Abdominal pain (1% to 5%), dyspepsia (1% to 5%), nausea (1% to 5%)
Genitourinary: Urinary tract infection (1% to 5%)
Infection: Influenza (1% to 5%)
Nervous system: Dizziness (1% to 5%), headache (1% to 5%)
Neuromuscular & skeletal: Back pain (1% to 5%)
Ophthalmic: Blepharitis (1% to 5%), cataract (including subcapsular posterior cataract) (1% to 5%), cloudy vision (1% to 5%), conjunctival discharge (1% to 5%), conjunctival edema (1% to 5%), conjunctivitis (1% to 5%), corneal erosion (1% to 5%), corneal staining (1% to 5%), dry eye syndrome (1% to 5%), erythema of eyelid (1% to 5%), eye discharge (1% to 5%), eye disease (debris in eye) (1% to 5%), eye pain (includes eyelid) (1% to 5%), eyelid edema (1% to 5%), follicular conjunctivitis (1% to 5%), foreign body sensation of eye (1% to 5%), glaucomatous optic disc cupping (1% to 5%), lacrimation (1% to 5%), ocular discoloration (lens nucleus) (1% to 5%), ocular exudate (eyelid) (1% to 5%), scaling of eyelid (1% to 5%), visual field defect (1% to 5%), vitreous detachment (1% to 5%)
Respiratory: Bronchitis (1% to 5%), cough (1% to 5%), pharyngitis (1% to 5%), sinusitis (1% to 5%), upper respiratory tract infection (1% to 5%)
Postmarketing:
Cardiovascular: Acute myocardial infarction, bradycardia, chest pain, heart block, heart failure, hypotension
Dermatologic: Skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis
Gastrointestinal: Diarrhea, vomiting, xerostomia
Genitourinary: Urolithiasis
Nervous system: Cerebrovascular accident, depression, paresthesia
Ophthalmic: Choroidal detachment (following filtration procedures), iridocyclitis, photophobia
Respiratory: Dyspnea, nasal congestion, respiratory failure
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.
Canadian labeling: Additional contraindications (not in US labeling): Severe renal impairment; sino-atrial block; concomitant use with oral carbonic anhydrase inhibitors.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
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.
Ophthalmic solution contains dorzolamide hydrochloride 2.23% [22.3 mg/mL] and timolol maleate 0.68% [6.8 mg/mL]
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Ophthalmic:
Cosopt: Dorzolamide 2% and timolol 0.5% (10 mL) [contains benzalkonium chloride]
Generic: Dorzolamide 2% and timolol 0.5% (10 mL)
Solution, Ophthalmic [preservative free]:
Cosopt PF: Dorzolamide 2% and timolol 0.5% (15 ea, 60 ea)
Generic: Dorzolamide 2% and timolol 0.5% (15 ea, 60 ea)
Yes
Solution (Cosopt Ophthalmic)
2-0.5% (per mL): $25.15
Solution (Cosopt PF Ophthalmic)
2-0.5% (per each): $3.83
Solution (Dorzolamide HCl-Timolol Mal Ophthalmic)
2-0.5% (per mL): $2.50 - $12.26
Solution (Dorzolamide HCl-Timolol Mal PF Ophthalmic)
2-0.5% (per each): $2.80 - $2.83
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Ophthalmic:
Cosopt Preservative Free: Dorzolamide 2% and timolol 0.5% (0.2 mL)
Cosopt With Preservative: Dorzolamide 2% and timolol 0.5% (10 mL) [contains benzalkonium chloride]
Generic: Dorzolamide 2% and timolol 0.5% (5 mL, 10 mL)
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.
Ophthalmic: Wash hands before use. Pull lower eyelid down slightly to form a pocket for the eye drop and tilt head back; administer 1 drop. Apply gentle pressure to lacrimal sac immediately following instillation (1 minute) or instruct patient to gently close eyelid after administration to decrease systemic absorption of ophthalmic drops (Ref). Avoid contact of bottle tip with skin or eye; 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. Some solutions contain benzalkonium chloride; remove contact lenses prior to administration and wait at least 15 minutes after instillation before reinserting soft contact lenses. Remove contact lens prior to administration (solution contains benzalkonium chloride) and wait 15 minutes before reinserting soft contact lenses. If using additional topical ophthalmic preparations, separate administration by at least 5 minutes.
Cosopt PF: Administer immediately after opening container; may be used to treat one or both eyes. Discard single-use container immediately after use.
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
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Alpha-/Beta-Agonists (Indirect-Acting): Carbonic Anhydrase Inhibitors may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Risk C: 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. Risk D: Consider therapy modification
Amantadine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Amantadine. Risk C: 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. Risk C: Monitor therapy
Antidiabetic Agents: Beta-Blockers (Nonselective) may enhance the hypoglycemic effect of Antidiabetic Agents. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Antidiabetic Agents. Risk C: 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. Risk C: Monitor therapy
Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Beta2-Agonists: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Risk X: Avoid combination
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy
Cannabis: Beta-Blockers may enhance the adverse/toxic effect of Cannabis. Specifically, the risk of hypoglycemia may be increased. Risk C: 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. Risk X: Avoid combination
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. Risk D: 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. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May increase the serum concentration of Timolol (Ophthalmic). Risk C: Monitor therapy
Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. Risk C: Monitor therapy
DOBUTamine: Beta-Blockers may diminish the therapeutic effect of DOBUTamine. Risk C: 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. Increase monitoring for clinical response and adverse effects. Risk D: Consider therapy modification
EPHEDrine (Systemic): Beta-Blockers may diminish the therapeutic effect of EPHEDrine (Systemic). Risk C: Monitor therapy
EPINEPHrine (Nasal): Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Nasal). Risk C: Monitor therapy
EPINEPHrine (Oral Inhalation): Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Risk C: Monitor therapy
Epinephrine (Racemic): Beta-Blockers (Nonselective) may enhance the hypertensive effect of Epinephrine (Racemic). Risk C: Monitor therapy
EPINEPHrine (Systemic): Beta-Blockers (Nonselective) may enhance the hypertensive effect of EPINEPHrine (Systemic). Risk C: Monitor therapy
Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates): Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives (Vasoconstrictive CYP3A4 Substrates). Risk C: Monitor therapy
Etilefrine: May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may diminish the therapeutic effect of Etilefrine. Risk C: Monitor therapy
Etofylline: Beta-Blockers may diminish the therapeutic effect of Etofylline. Risk X: Avoid combination
Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification
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. Management: Consider alternatives to either grass pollen allergen extract (5 grass extract) or beta-blockers in patients with indications for both agents. Canadian product labeling specifically lists this combination as contraindicated. Risk D: Consider therapy modification
Insulins: Beta-Blockers (Nonselective) may enhance the hypoglycemic effect of Insulins. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Insulins. Risk C: Monitor therapy
Isoproterenol: Beta-Blockers may diminish the therapeutic effect of Isoproterenol. Risk C: Monitor therapy
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Mavacamten: Beta-Blockers may enhance the adverse/toxic effect of Mavacamten. Specifically, negative inotropic effects may be increased. Risk C: Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Risk C: Monitor therapy
Methoxyflurane: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Mivacurium: Beta-Blockers may enhance the therapeutic effect of Mivacurium. Risk C: Monitor therapy
NIFEdipine: May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Risk C: Monitor therapy
Nitrendipine: May enhance the therapeutic effect of Beta-Blockers. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Beta-Blockers. Risk C: Monitor therapy
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: 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). Risk C: Monitor therapy
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification
Reserpine: May enhance the bradycardic effect of Beta-Blockers. Reserpine may enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Risk X: Avoid combination
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification
Succinylcholine: Beta-Blockers may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy
Sulfonylureas: Beta-Blockers (Nonselective) may enhance the hypoglycemic effect of Sulfonylureas. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Sulfonylureas. Risk C: Monitor therapy
Tasimelteon: Beta-Blockers may diminish the therapeutic effect of Tasimelteon. Management: Consider avoiding nighttime administration of beta-blockers during tasimelteon therapy due to the potential for reduced tasimelteon efficacy. Risk D: Consider therapy modification
Theophylline Derivatives: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Risk C: Monitor therapy
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
White Birch Allergen Extract: Beta-Blockers may enhance the adverse/toxic effect of White Birch Allergen Extract. Specifically, beta-blockers may reduce the effectiveness of beta-agonists that may be required to treat systemic reactions to white birch allergen extract. Risk X: Avoid combination
Reproductive studies have not been conducted with this combination. Refer to individual agents.
Timolol is excreted in breast milk following oral and ophthalmic administration; however, it is unknown whether dorzolamide is also excreted. Due to the potential for serious adverse reactions in the nursing infant, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother. Refer to individual agents.
Ophthalmic exams and IOP periodically
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
See individual agents.
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