Class: beta-Adrenergic Blocking Agents
VA Class: OP101
CAS Number: 91524-16-2
Brands: Betimol, Cosopt Ocumeter Plus, Timoptic Ocudose, Timoptic Ocumeter Plus, Timoptic-XE Ocumeter
Introduction
Nonselective β-adrenergic blocking agent.104 105 106 107
Uses for Timolol
Ocular Hypertension and Glaucoma
Reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension.104 105 106 107 Used alone or in conjunction with another IOP-lowering drug (e.g., latanoprost, a carbonic anhydrase inhibitor).104 105 106 107 108
Fixed-combination preparation containing timolol maleate and dorzolamide hydrochloride used to reduce elevated IOP in patients with open-angle glaucoma or ocular hypertension who have not responded adequately (i.e., failed to achieve target IOP as determined after multiple measurements over time) to a topical β-adrenergic blocking agent.108
Fixed-combination preparation associated with slightly smaller decrease in IOP than combination therapy with timolol (administered twice daily) and dorzolamide (administered 3 times daily).108
Timolol Dosage and Administration
Administration
Ocular Administration
Applied topically to the eye as an ophthalmic solution.104 105 106 107 108
Avoid contamination of the solution container.a
If more than one ophthalmic drug is used, administer the drugs at least 10 minutes apart.104 106
Invert and shake containers of timolol ophthalmic gel-forming solution once just prior to administration of each dose.106
Dosage
Available as timolol maleate or timolol (as the hemihydrate); dosage is expressed in terms of timolol.104 105 107
Adults
Ocular Hypertension and Glaucoma
Ocular Administration
Timolol ophthalmic solution: initially, 1 drop of a 0.25% solution in the affected eye(s) twice daily.104 105 107 May increase dosage to 1 drop of a 0.5% solution in the affected eye(s) twice daily if necessary.104 105 107 May then reduce dosage to 1 drop of the effective strength in the affected eye(s) once daily if satisfactory IOP is maintained.104 105 107
Timolol ophthalmic gel-forming solution: 1 drop of a 0.25 or 0.5% solution in the affected eye(s) once daily.106
Fixed-combination timolol/dorzolamide solution: 1 drop in the affected eye(s) twice daily.108
Prescribing Limits
Adults
Ocular Hypertension and Glaucoma
Ocular Administration
Timolol ophthalmic solution: Dosages >1 drop of a 0.5% solution in the affected eye(s) twice daily generally do not produce further reduction in IOP.104 105 107
Timolol ophthalmic gel-forming solution: Dosages >1 drop of a 0.5% solution in the affected eye(s) once daily not studied.106
Cautions for Timolol
Contraindications
Known hypersensitivity to timolol or any ingredient in the formulation.104 105 106 107
Bronchial asthma or a history of bronchial asthma, severe COPD, sinus bradycardia, AV block greater than first degree, overt cardiac failure, or cardiogenic shock.104 105 106 107
Warnings/Precautions
Warnings
Cardiovascular Effects
Severe cardiac reactions, including death associated with cardiac failure, have been reported in patients receiving systemic or topical (ocular) timolol.104 105 106 107 Discontinue therapy at the first sign or symptom of cardiac failure.104 105 106 107
Respiratory Effects
Severe respiratory reactions, including death resulting from bronchospasm, have been reported in patients receiving systemic or topical (ocular) timolol.104 105 106 107
Patients with mild or moderately severe COPD (e.g., chronic bronchitis, emphysema), bronchospastic disease, or a history of bronchospastic disease (other than bronchial asthma or a history of bronchial asthma, in which condition timolol is contraindicated) generally should not receive β-adrenergic blocking agents.104 105 106 107
Major Surgery
Possible increased risks associated with general anesthesia (e.g., severe hypotension, difficulty restarting or maintaining heart beat) due to decreased ability of the heart to respond to reflex β-adrenergic stimuli.104 105 106 107 Some clinicians recommend gradual withdrawal of β-adrenergic blocking agents prior to elective surgery.104 105 106 107
Diabetes Mellitus
β-Adrenergic blocking agents may mask signs and symptoms of acute hypoglycemia; administer with caution in patients subject to spontaneous hypoglycemia and in diabetic patients (especially those with labile diabetes) who are receiving hypoglycemic agents.104 105 106 107
Thyrotoxicosis
β-Adrenergic blocking agents may mask signs of hyperthyroidism (e.g., tachycardia).104 105 106 107
Possible thyroid storm if β-adrenergic blocking agent is abruptly withdrawn; carefully monitor patients having or suspected of developing thyrotoxicosis.104 105 106 107
Sensitivity Reactions
Patients with a history of atopy or of a severe anaphylactic reaction to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenges with such allergens while taking β-adrenergic blocking agents; such patients may be unresponsive to usual doses of epinephrine used to treat anaphylactic reactions.104 105 106 107
General Precautions
Dorzolamide Component
When using fixed-combination preparation containing dorzolamide hydrochloride, consider the warnings, cautions, precautions, and contraindications associated with dorzolamide.108
Bacterial Keratitis
Bacterial keratitis reported after inadvertent contamination of multiple dose containers for topical ophthalmic use, principally in patients with concurrent corneal disease or disruption of ocular epithelial surface.104 105 106 107 Avoid contamination of solution container.104 105 106 107 (See Advice to Patients.)
Ocular effects
Choroidal detachment after filtration procedures reported.104 105 106 107
Angle-closure Glaucoma
Timolol has little or no effect on pupil size; do not use alone in patients with angle-closure glaucoma.104 105 106 107
Muscle Weakness
β-Adrenergic blocking agents reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, and generalized weakness).104 105 106 107
Timolol reported rarely to increase muscle weakness in patients with myasthenia gravis or myasthenia symptoms.104 105 106 107
Cerebrovascular Insufficiency
Caution advised in patients with cerebrovascular insufficiency due to the potential effects of β-adrenergic blocking agents on blood pressure and pulse.104 105 106 107
Consider alternative therapy if signs or symptoms suggestive of reduced cerebral blood flow occur.104 105 106 107
Specific Populations
Pregnancy
Category C.104 105 106 107
Lactation
Distributed into milk following topical application to the eye.104 Discontinue nursing or the drug.104 105 106 107
Pediatric Use
Safety and efficacy not established.104 105 106 107
Geriatric Use
Safety and efficacy in those ≥65 years of age similar to those in younger adults; however, possibility exists of greater sensitivity to the drug in some geriatric patients.104 106
Common Adverse Effects
Burning and stinging on instillation.104 105 106 107
Interactions for Timolol
Appears to be metabolized partly by CYP2D6.104 105 106 107 c
Drugs Affecting Hepatic Microsomal Enzymes
CYP2D6 inhibitors: Potential pharmacodynamic (increased β-adrenergic blockade) and pharmacokinetic interaction (increased plasma timolol concentrations).104 105 106 107 c
Specific Drugs
Drug | Interaction | Comments |
|---|---|---|
β-Adrenergic blocking agents, systemic | Additive systemic and ocular effects104 105 106 107 108 | |
Calcium-channel blocking agents | Potential hypotension, AV conduction disturbances, and left ventricular failure101 102 104 105 106 107 | Caution advised104 105 106 107 Avoid concomitant use in patients with impaired cardiac function104 105 106 107 |
Cimetidine | Possible additive reductions in resting heart rate and IOPc | |
Digitalis | Possible additive effect in prolonging AV conduction time when used concomitantly with calcium-channel blocking agents (diltiazem, verapamil)104 105 106 107 | |
Catecholamine-depleting drugs (e.g., reserpine) | Possible additive effects104 105 106 107 | Observe closely for evidence of marked bradycardia or hypotension (may be manifested as vertigo, syncope, or postural hypotension)104 105 106 107 |
Clonidine | Oral β-adrenergic blocking agents may exacerbate rebound hypertension following discontinuance of clonidine104 105 106 107 | Not reported with ophthalmic use of timolol104 105 106 107 |
Epinephrine | Mydriasis possible following concomitant ocular administration104 105 106 107 Atopic individuals and those with a history of severe anaphylactic reactions may not respond to usual doses of epinephrine used in the treatment of anaphylactic reactions104 105 106 107 | |
Ocular hypotensive agents | Additive IOP-lowering effects104 105 106 107 108 | Used to therapeutic advantage104 105 106 107 108 If more than one topical ophthalmic drug is used, administer at least 10 minutes apart104 106 |
Quinidine | Potential increase in plasma timolol concentrations and in β-blockade (bradycardia)103 104 105 106 107 |
Timolol Pharmacokinetics
Absorption
Bioavailability
Absorbed into systemic circulation following topical administration.104 105 106 107
Onset
Following topical application to the eye of a 0.25 or 0.5% solution, reduction in IOP usually occurs within 15–30 minutes and reaches a maximum within 1–5 hours.b
Duration
Reduction in IOP persists about 24 hours.104 105 106 107
Elimination
Metabolism
Appears to be metabolized in the liver partly by CYP2D6.104 105 106 107 c
Stability
Storage
Ophthalmic
Solution
Timolol maleate or timolol (hemihydrate) solutions: 15–30°C; protect from light.104 105 107 Do not freeze.104 107
Fixed-combination timolol/dorzolamide solution: 15–25°C.108 Protect from light.108
Solution, gel-forming
15–25°C; protect from light.106
ActionsActions
Nonselective β-adrenergic blocking agent that does not have substantial intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic activity.104 105 106 107
Potent ocular hypotensive agent; reduces IOP by about 25–33% in patients with elevated IOP.b
Exact mechanism of action not fully elucidated; tonography and fluorophotometric studies suggest that reduced aqueous humor formation is the principal effect.104 105 106 107 A slight increase in outflow facility observed in some studies.104 105 106 107
Tolerance may develop with prolonged use; however, IOP-lowering effect maintained for at least 3 years of continuous use in some patients.b
Advice to Patients
Importance of learning and adhering to proper administration techniques to avoid contamination of the product.104 105 106 107 If more than one topical ophthalmic drug is used, importance of administering the drugs at least 10 minutes apart.104 106
When an ophthalmic preparation that contains benzalkonium chloride is used, importance of removing soft contact lenses prior to administering a dose and for at least 15 minutes after administration.104
Advise patients to consult a clinician immediately regarding the continued use of ophthalmic preparations if an intercurrent ocular condition (e.g., trauma, infection) occurs.104 105 106 107
Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.104 105 106 107
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.104 105 106 107
Importance of informing patients of other important precautionary information.104 105 106 107 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Ophthalmic | Solution | 0.25% (of anhydrous timolol) | Betimol (with benzalkonium chloride) | Vistakon |
0.5% (of anhydrous timolol) | Betimol (with benzalkonium chloride) | Vistakon |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Ophthalmic | Solution | 0.25% (of timolol)* | Timolol Maleate Ophthalmic Solution | Apotex, Bausch & Lomb, Falcon |
Timoptic Ocumeter Plus (with benzalkonium chloride) | Merck | |||
Timoptic Ocudose (preservative-free) | Merck | |||
0.5% (of timolol)* | Timolol Maleate Ophthalmic Solution | Apotex, Bausch & Lomb, Falcon | ||
Timoptic Ocumeter Plus (with benzalkonium chloride) | Merck | |||
Timoptic Ocudose (preservative-free) | Merck | |||
Solution, gel-forming | 0.25% (of timolol)* | Timolol GFS (with benzalkonium chloride) | Falcon | |
Timoptic-XE Ocumeter (with benzododecinium bromide) | Merck | |||
0.5% (of timolol)* | Timolol GFS (with benzalkonium chloride) | Falcon | ||
Timoptic-XE Ocumeter (with benzododecinium bromide) | Merck |
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Ophthalmic | Solution | 0.5% (of timolol) with Dorzolamide Hydrochloride 2% (of dorzolamide) | Cosopt Ocumeter Plus (with benzalkonium chloride) | Merck |
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Betimol 0.25% Solution (VISTAKON PHARMACEUTICALS): 5/$55.56 or 15/$146.03
Betimol 0.5% Solution (VISTAKON PHARMACEUTICALS): 10/$106.88 or 30/$293.53
Betimol 0.5% Solution (VISTAKON PHARMACEUTICALS): 15/$152.23 or 45/$434.07
Betimol 0.5% Solution (VISTAKON PHARMACEUTICALS): 5/$63.43 or 15/$158.57
Combigan 0.2-0.5% Solution (ALLERGAN): 5/$87.36 or 15/$245.43
Cosopt 2-0.5% Solution (MERCK SHARP & DOHME): 10/$134.67 or 30/$391.19
Dorzolamide-Timolol 2-0.5% Solution (HI-TECH): 10/$99.99 or 30/$279.97
Istalol 0.5% Solution (ISTA PHARMACEUTICALS): 5/$160 or 15/$443.94
Timolol Maleate 0.25% Solution (APOTEX): 15/$19.99 or 45/$49.97
Timolol Maleate 0.25% Solution (FALCON PHARMACEUTICALS): 10/$16.99 or 30/$40.98
Timolol Maleate 0.25% Solution (FALCON PHARMACEUTICALS): 5/$12.99 or 15/$30.99
Timolol Maleate 0.25% Solution (FALCON PHARMACEUTICALS): 5/$59.71 or 15/$126.86
Timolol Maleate 0.5% Solution (FALCON PHARMACEUTICALS): 15/$20.99 or 45/$53.98
Timolol Maleate 0.5% Solution (FALCON PHARMACEUTICALS): 5/$15.99 or 15/$34.99
Timolol Maleate 0.5% Solution (BAUSCH & LOMB): 10/$19.99 or 30/$44.97
Timolol Maleate 0.5% Solution (FALCON PHARMACEUTICALS): 5/$55.99 or 15/$145.96
Timoptic 0.5% Solution (ATON PHARMA): 10/$79.99 or 30/$221.98
Timoptic 0.5% Solution (VALEANT): 5/$59.99 or 10/$107.96
Timoptic Ocudose 0.5% Solution (ATON PHARMA): 60/$233.98 or 180/$677.95
Timoptic-XE 0.5% Solution (VALEANT): 5/$89.99 or 15/$243.98
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References
100. Knoll Pharmaceuticals. Isoptin SR (verapamil HCl) sustained release oral tablets prescribing information. Whippany, NJ; 1992 Aug.
101. Pringle SD, MacEwen CJ. Severe bradycardia due to interaction of timolol eye drops and verapamil. BMJ. 1987; 294:155-6. [IDIS 225511] [PubMed 3109547]
102. Sinclair NI, Benzie JL. Timolol eye drops and verapamil–a dangerous combination. Med J Aust. 1983; 1:548. [IDIS 175967] [PubMed 6343813]
103. Dinai Y, Sharir M, Naveh N et al. Bradycardia induced by interaction between quinidine and ophthalmic timolol. Ann Intern Med. 1985; 103:890-1. [IDIS 208000] [PubMed 4062090]
104. Merck and Co. Timoptic 0.25% and 0.5% (timolol maleate) ophthalmic solution, prescribing information. West Point, PA; 2001 Apr.
105. Merck and Co. Timoptic 0.25% and 0.5% (timolol maleate) ophthalmic solution in OCUDOSE (dispenser), prescribing information. West Point, PA; 2000 Mar.
106. Merck and Co. Timoptic-XE 0.25% and 0.5% (timolol maleate) ophthalmic gel forming solution prescribing information. West Point, PA; 2001 Mar.
107. Ciba Vision Ophthalmics. Betimol (timolol) ophthalmic solution 0.25%, 0.5% prescribing information. In: Physician’s desk reference for ophthalmology. 24th ed. Montvale, NJ: Medical Economics Company, Inc; 1996:261-3.
108. Merck & Company. Cosopt (dorzolamide hydrochloride and timolol maleate) sterile ophthalmic solution prescribing information. West Point, PA; 2000 Aug.
a. AHFS drug information 2003. McEvoy GK, ed. Timolol Maleate. Bethesda, MD: American Society of Health-System Pharmacists; 2003: page 1793-7.
b. AHFS drug information 2003. McEvoy GK, ed. Timolol. Bethesda, MD: American Society of Health-System Pharmacists; 2003: page 2720-3.
c. Ishii Y, Nakamura K, Tsutsumi K et al. Drug interaction between cimetidine and timolol ophthalmic solution: effect on heart rate and intraocular pressure in healthy Japanese volunteers. J Clin Pharmacol. 2000; 40:193-9. [PubMed 10664926]
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