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Brimonidine and timolol: Drug information

Brimonidine and timolol: Drug information
(For additional information see "Brimonidine and timolol: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Combigan
Brand Names: Canada
  • APO-Brimonidine-Timop;
  • Combigan;
  • JAMP-Brimonidine-Timolol
Pharmacologic Category
  • Alpha2 Agonist, Ophthalmic;
  • Beta-Blocker, Nonselective;
  • Ophthalmic Agent, Antiglaucoma
Dosing: Adult
Elevated intraocular pressure

Elevated intraocular pressure: Ophthalmic: Instill 1 drop into 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.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric
Elevated intraocular pressure

Elevated intraocular pressure: Children ≥2 years: Ophthalmic: Instill 1 drop into affected eye(s) twice daily

Note: In the Canadian labeling, use in children (at any age) is not recommended

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Also see individual agents.

>10%: Ophthalmic: Allergic conjunctivitis (5% to 15%), burning sensation of eyes (5% to 15%), conjunctival hyperemia (5% to 15%), eye pruritus (5% to 15%), follicular conjunctivitis (5% to 15%), stinging of eyes (5% to 15%)

1% to 10%:

Cardiovascular: Hypertension (1% to 5%)

Gastrointestinal: Xerostomia (1% to 5%)

Nervous system: Asthenia (1% to 5%), depression (1% to 5%), drowsiness (1% to 5%), headache (1% to 5%)

Ophthalmic: Blepharitis (1% to 5%), corneal erosion (1% to 5%), dry eye syndrome (1% to 5%), epiphora (1% to 5%), erythema of eyelid (1% to 5%), eye discharge (1% to 5%), eye irritation (1% to 5%), eye pain (1% to 5%), eyelid edema (1% to 5%), eyelid pruritus (1% to 5%), foreign body sensation of eye (1% to 5%), superficial punctate keratitis (1% to 5%), visual disturbance (1% to 5%)

Contraindications

Reactive airway disease, including bronchial asthma; history of bronchial asthma; severe chronic obstructive pulmonary disease (COPD); sinus bradycardia, second- or third-degree atrioventricular block, overt cardiac failure, cardiogenic shock; known hypersensitivity to brimonidine/timolol or any component of the formulation; neonates, infants, and children younger than 2 years.

Canadian labeling: Additional contraindications (not in US labeling): Monoamine oxidase (MAO) inhibitor therapy (concurrent or within 14 days); sick sinus syndrome; sinoatrial nodal block

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactic reactions: Use caution with history of atopy or history of severe anaphylaxis to a variety of 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 the potential to cause bacterial keratitis.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Hypersensitivity: Ocular hypersensitivity reactions have been reported with brimonidine; reactions may cause an increase in intraocular pressure.

• Ocular effects: Use of agents that reduce/suppress aqueous humor production has been associated with choroidal detachment after filtration procedures.

Disease-related concerns:

• Angle-closure glaucoma: Appropriate use: Not for use alone to treat acute angle-closure glaucoma (has no effect on papillary constriction).

• Heart failure: Use with caution in patients with compensated heart failure, and monitor for a worsening of the condition; may lead to heart failure in patients without a history of heart failure. Use is contraindicated in overt heart failure. In a scientific statement from the American Heart Association, timolol has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).

• Cerebrovascular disease: Use with caution in cerebrovascular insufficiency; consider alternative therapy for patients with signs/symptoms of decreased cerebral blood flow after therapy initiation.

• Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.

• Myasthenia gravis: Use with caution in patients with myasthenia gravis; may worsen disease or other myasthenic symptoms (diplopia, ptosis, and generalized weakness).

• Respiratory disease: In general, patients with mild to moderate chronic obstructive pulmonary disease (COPD) or bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring.

• 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.

• Vascular insufficiency: Can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease, Raynaud disease, and thromboangiitis obliterans. Use with caution and monitor for progression of arterial obstruction.

Special populations:

• Contact lens wearers: Product contains 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.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Ophthalmic:

Combigan: Brimonidine tartrate 0.2% and timolol 0.5% (5 mL, 10 mL, 15 mL) [contains benzalkonium chloride]

Generic: Brimonidine tartrate 0.2% and timolol 0.5% (5 mL, 10 mL, 15 mL)

Generic Equivalent Available: US

Yes

Pricing: US

Solution (Brimonidine Tartrate-Timolol Ophthalmic)

0.2-0.5% (per mL): $43.74 - $46.54

Solution (Combigan Ophthalmic)

0.2-0.5% (per mL): $48.99

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.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Ophthalmic:

Combigan: Brimonidine tartrate 0.2% and timolol 0.5% (2.5 mL, 10 mL) [contains benzalkonium chloride]

Generic: Brimonidine tartrate 0.2% and timolol 0.5% (5 mL, 10 mL)

Administration: Adult

Ophthalmic: Administer approximately every 12 hours. Remove contact lenses prior to administration; wait 15 minutes before reinserting if using products containing benzalkonium chloride. Separate administration of other ophthalmic agents by ≥5 minutes.

Administration: Pediatric

Ophthalmic: Wash hands prior to use. Instill into conjunctival sac avoiding contact of bottle tip with skin or eye. Apply gentle pressure to lacrimal sac during and immediately following instillation (1 minute) or instruct patient to gently close eyelid after administration, to decrease systemic absorption of ophthalmic drops (Ref). Separate administration of other ophthalmic agents by ≥5 minutes. Remove contact lenses prior to administration; wait 15 minutes before reinserting if using products containing benzalkonium chloride.

Use: Labeled Indications

Elevated intraocular pressure: For the reduction of elevated intraocular pressure (IOP) in patients with glaucoma or ocular hypertension who require adjunctive or replacement therapy because of inadequately controlled IOP.

Medication Safety Issues
Sound-alike/look-alike issues:

Combigan may be confused with Combivent, Comtan

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

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

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. 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

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

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Beta2-Agonists: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Risk X: Avoid combination

Beta-Blockers: 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

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. 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

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

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

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

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

CYP2D6 Inhibitors (Strong): May increase the serum concentration of Timolol (Ophthalmic). Risk C: Monitor therapy

Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. 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

Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. 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

DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. 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

Esketamine: May enhance the CNS depressant effect of CNS Depressants. 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

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. 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

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. 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

Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. 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

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Methoxyflurane: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Mianserin: May diminish the therapeutic effect of Alpha2-Agonists (Ophthalmic). Risk X: Avoid combination

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirtazapine: May diminish the antihypertensive effect of Alpha2-Agonists. Management: Consider avoiding concurrent use. If the combination cannot be avoided, monitor for decreased effects of alpha2-agonists if mirtazapine is initiated/dose increased, or increased effects if mirtazapine is discontinued/dose decreased. Risk D: Consider therapy modification

Mivacurium: Beta-Blockers may enhance the therapeutic effect of Mivacurium. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Brimonidine (Ophthalmic). Monoamine Oxidase Inhibitors may increase the serum concentration of Brimonidine (Ophthalmic). Risk C: Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

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

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

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

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. 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

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May diminish the therapeutic effect of Alpha2-Agonists. Risk C: Monitor therapy

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

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

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

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

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

Tricyclic Antidepressants: May diminish the therapeutic effect of Alpha2-Agonists (Ophthalmic). Risk C: Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Valerian: May enhance the CNS depressant effect of CNS Depressants. 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

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification

Pregnancy Considerations

There are no adequate and well-controlled studies in pregnant women with the combination product. Also see individual agents.

Breastfeeding Considerations

Timolol has been detected in human breast milk following ophthalmic administration. It is not known if brimonidine is excreted in human milk. Due to the potential for serious adverse reactions in the breast-feeding infant, the manufacturer recommends a decision be made to discontinue breast-feeding or to discontinue the drug, taking into account the importance of treatment to the mother. See individual agents.

Monitoring Parameters

Intraocular pressure; monitor for systemic effect of beta-blockade with ophthalmic administration; blood pressure

Mechanism of Action

Brimonidine: A relatively selective alpha-2 adrenergic agonist; causes reduction of aqueous humor formation and increased uveoscleral outflow

Timolol: Blocks both beta-1 and beta-2 adrenergic receptors, reduces intraocular pressure by reducing aqueous humor production or possibly outflow; reduces blood pressure by blocking adrenergic receptors and decreasing sympathetic outflow, produces a negative chronotropic and inotropic activity by blocking beta-1 adrenergic receptors

Pharmacokinetics (Adult Data Unless Noted)

See individual agents.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Combigan;
  • (AR) Argentina: Brimopress t | Brit | Timobrim;
  • (AT) Austria: Combigan;
  • (BD) Bangladesh: Abpres | Bimolet | Brimodin Plus | Brimolol | Brimopres | Combat | Combigan | Combipres | Locular plus | Ticoma b | Xilol B;
  • (BE) Belgium: Combigan;
  • (BF) Burkina Faso: Brimochek t;
  • (BR) Brazil: Britens | Combigan | Tartarato de brimonidina + maleato de timolol | Tinodin | Visoneo;
  • (CI) Côte d'Ivoire: Brimochek t;
  • (CL) Chile: Brimopress t | Combigan;
  • (CO) Colombia: Alfabrim T | Brimodelt plus | Brimolol | Combigan | Timobrim;
  • (CZ) Czech Republic: Combigan;
  • (DE) Germany: Combigan;
  • (DO) Dominican Republic: Brimogot mol | Brimopress t | Combigan;
  • (EC) Ecuador: Combigan;
  • (EE) Estonia: Combigan;
  • (EG) Egypt: Alphanova Plus | Azgoclatens | Brimodrops | Brimonocond Plus | Combigan | Pharmatimogan | Timobrim | Timomondin;
  • (ES) Spain: Combigan;
  • (FR) France: Brimonidine/timolol biogaran | Brimonidine/timolol eg | Brimonidine/timolol mylan | Combigan;
  • (GB) United Kingdom: Combigan;
  • (GR) Greece: Combigan;
  • (HK) Hong Kong: Combigan;
  • (HR) Croatia: Combigan;
  • (HU) Hungary: Combigan;
  • (IL) Israel: Combigan;
  • (IN) India: Abpress | Albrim t | Alfabet pf | Apbidin Tm | Arobrim t | Betabrim | Bidin ls tm | Brimochek t | Brimocom | Brimolol | Brimonix t | Brimopress t | Brimosoft t | Brimotim | Britiblu | Britiblu bf | Bromostar t | Combigan | Glubrim | Iobrim t | Iotim B | Kaibrim t | Rimoflo T | Timobrim | Vidinorm;
  • (IT) Italy: Brimocomb | Brimonidina e timololo eg | Brimonidina e Timololo Mylan | Combigan;
  • (JO) Jordan: Combigan;
  • (JP) Japan: Aibeta;
  • (KE) Kenya: Brimochek t | Combigan;
  • (KR) Korea, Republic of: Bridin plus | Bridine plus | Combi free | Combigan;
  • (KW) Kuwait: Combigan;
  • (LB) Lebanon: Combigan;
  • (LT) Lithuania: Combigan;
  • (LU) Luxembourg: Combigan;
  • (LV) Latvia: Combigan;
  • (MA) Morocco: Combigan;
  • (MX) Mexico: Combigan d;
  • (MY) Malaysia: Combigan;
  • (NG) Nigeria: Brimocom | Maxiflo;
  • (NL) Netherlands: Combigan;
  • (NO) Norway: Combigan;
  • (NZ) New Zealand: Combigan;
  • (PE) Peru: Brimopress t | Combigan | Oftalmol b+t;
  • (PH) Philippines: Brimochek t | Combigan;
  • (PK) Pakistan: Bremol t | Brimogan | Brimson plus | Brytim | Combigan | Timbro | Timodine;
  • (PL) Poland: Combigan;
  • (PR) Puerto Rico: Brimonidine tartrate/timolol maleate | Combigan;
  • (PT) Portugal: Combigan;
  • (PY) Paraguay: Brimopress t | Brimotim | Oftalmol b+t;
  • (RU) Russian Federation: Combigan;
  • (SA) Saudi Arabia: Combigan;
  • (SE) Sweden: Combigan;
  • (SI) Slovenia: Combigan;
  • (TN) Tunisia: Combigan;
  • (TR) Turkey: Brimo Tim | Combigan | Rimosopt;
  • (UA) Ukraine: Brionit | Combigan;
  • (VE) Venezuela, Bolivarian Republic of: Combigan;
  • (ZA) South Africa: Brimoct co
  1. Combigan (brimonidine/timolol) [prescribing information]. Irvine, CA: Allergan Inc; October 2015.
  2. Combigan (brimonidine and timolol) [product monograph]. St-Laurent, Quebec, Canada: AbbVie Corp; October 2022.
  3. Page RL 2nd, O'Bryant CL, Cheng D, et al; American Heart Association Clinical Pharmacology and Heart Failure and Transplantation Committees of the Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research. Drugs that may cause or exacerbate heart failure: a scientific statement from the American Heart Association. Circulation. 2016;134(6):e32-e69. [PubMed 27400984]
  4. Urtti A, Salminen L. Minimizing systemic absorption of topically administered ophthalmic drugs. Surv Ophthalmol. 1993;37(6):435-456. [PubMed 8100087]
  5. Zimmerman TJ, Kooner KS, Kandarakis AS, Ziegler LP. Improving the therapeutic index of topically applied ocular drugs. Arch Ophthalmol. 1984;102(4):551-553. [PubMed 6704011]
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