Class: beta-Adrenergic Blocking Agents
VA Class: CV100
CAS Number: 26921-17-5
Medically reviewed on Jan 1, 2018
Nonselective β-adrenergic blocking agent (β-blocker).111
Uses for Timolol Maleate
β-Blockers generally not preferred for initial management of hypertension, but may be considered in patients who have a compelling indication (e.g., prior MI, ischemic heart disease, heart failure) for their use or as add-on therapy in those who do not respond adequately to the preferred drug classes (ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, or thiazide diuretics).194 501 502 503 504 515 523 524 527 800
Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to β-blockers.176 180 181 500 501 504 However, diminished response to β-blockers is largely eliminated when administered concomitantly with a thiazide diuretic.500
Secondary prevention following acute MI.111
Administration within 7–28 days following MI associated with reductions in cardiovascular mortality and nonfatal reinfarction.a
Experts recommend β-blocker therapy in all patients with left ventricular systolic dysfunction and prior MI; a β-blocker with proven mortality benefit (bisoprolol, carvedilol, or metoprolol succinate) is preferred.525 Although benefits of long-term β-blockade in patients with normal left ventricular function are less well established, experts recommend continuing β-blocker therapy for at least 3 years in such patients.525
Chronic Stable Angina
β-Blockers are recommended as first-line anti-ischemic drugs in most patients with chronic stable angina; despite differences in cardioselectivity, intrinsic sympathomimetic activity, and other clinical factors, all β-blockers appear to be equally effective for this use.1101
Timolol Maleate Dosage and Administration
Monitor reductions in heart rate and BP as a guide for determining optimum dosage.111
If long-term therapy is discontinued, reduce dosage gradually over a period of 1–2 weeks.111 (See Abrupt Withdrawal of Therapy under Cautions.)
BP Monitoring and Treatment Goals
When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501
Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501
Administer orally, usually twice daily.111
For management of hypertension, once-daily dosing may be possible in some patients.a
During maintenance therapy in patients with vascular headaches (migraine), may administer daily dosage as a single rather than divided dose.111
Available as timolol maleate; dosage expressed in terms of the salt.111
Increase dosage gradually at weekly (or longer) intervals until optimum effect is obtained.111
Usual maintenance dosage is 20–40 mg daily, given in 2 divided doses; once-daily dosing may be possible in some patients.111 Increases up to a maximum of 60 mg daily (given in 2 divided doses) may be necessary.111
If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501
Secondary prevention after acute phase of MI: Usual dosage is 10 mg twice daily.111
Optimal duration of therapy for secondary prevention remains to be established.527 802 804 Experts generally recommend long-term therapy in post-MI patients with left ventricular dysfunction, and at least 3 years of therapy in those with normal left ventricular function.525 802 804 1101
Chronic Stable Angina†
Vascular Headaches (Migraine)
Initially, 10 mg twice daily.107 108 110 111 Adjust dosage according to clinical response and patient tolerance; do not exceed 30 mg daily, given in divided doses (e.g., 10 mg in the morning and 20 mg in the evening).108 111
During maintenance therapy, can administer 20-mg daily dosage as a single rather than divided dose; some patients may respond adequately to 10 mg once daily.111
If an adequate response is not achieved after 6–8 weeks at the maximum recommended dosage, discontinue therapy.111
Maximum 60 mg daily.111
Vascular Headaches (Migraine)
Must modify doses and/or frequency of administration in response to degree of hepatic impairment.111
Must modify doses and/or frequency of administration in response to degree of renal impairment.111
Cautions for Timolol Maleate
Known hypersensitivity to timolol or any ingredient in the formulation.111
Bronchial asthma (or a history of bronchial asthma), allergic bronchospasm, or severe COPD.111
Severe bradycardia, heart block greater than first degree, overt cardiac failure, or cardiogenic shock.111
Possible precipitation of heart failure.111
Avoid use in patients with overt heart failure; may use cautiously in patients with inadequate myocardial function and, if necessary, in patients with well-compensated heart failure (e.g., those controlled with cardiac glycosides and/or diuretics).111
Adequate treatment (e.g., with a cardiac glycoside and/or diuretic) and close observation recommended if signs or symptoms of impending heart failure occur; if heart failure continues, discontinue therapy, gradually if possible.111
Abrupt Withdrawal of Therapy
Abrupt withdrawal of therapy is not recommended as it may exacerbate angina symptoms or precipitate MI in patients with coronary artery disease.111
Gradually decrease dosage over a period of 1–2 weeks and monitor patients carefully; advise patients to temporarily limit their physical activity during withdrawal of therapy.111
If exacerbation of angina occurs or acute coronary insufficiency develops, reinstitute therapy promptly, at least temporarily, and initiate appropriate measures for management of unstable angina pectoris.111
Possible inhibition of bronchodilation produced by endogenous catecholamines.111
Generally should not be used in patients with bronchospastic disease, but may use with caution in patients who do not respond to or cannot tolerate alternative treatment.111 a Use with caution in patients with nonallergic bronchospasm (e.g., chronic bronchitis, emphysema) or a history of nonallergic bronchospasm.a (See Contraindications under Cautions.)
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.111 Use with caution in patients undergoing major surgery involving general anesthesia.111
Some clinicians recommend gradual withdrawal before elective surgery.111 b Manufacturers recommend administration of β-agonists (e.g., dopamine, dobutamine, isoproterenol) to reverse β-adrenergic blockade if necessary during surgery.111 a b
Diabetes and Hypoglycemia
Patients with a history of atopy or anaphylactic reactions to a variety of allergens may be more reactive to repeated, accidental, diagnostic, or therapeutic challenges with such allergens while taking β-blocking agents; such patients may be unresponsive to usual doses of epinephrine.111
β-Adrenergic blockade reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, generalized weakness).111 b Increased muscle weakness reported rarely in some patients with myasthenia gravis or myasthenic symptoms.111 b
Possible cardiovascular effects (e.g., hypotension, bradycardia) that can adversely affect cerebral blood flow.111 Use with caution in patients with cerebrovascular insufficiency.111 If signs or symptoms suggestive of reduced cerebral blood flow occur, consider discontinuance.111
Shares the toxic potentials of β-blockers; observe usual precautions of these agents.a
Safety and efficacy not established.111
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.111
Substantially eliminated by the kidneys; assess renal function periodically and adjust dosage since geriatric patients are more likely to have decreased renal function.111 (See Geriatric Patients under Dosage and Administration.)
Use with caution; dosage adjustment may be necessary.111 (See Hepatic Impairment under Dosage and Administration.)
Use with caution; dosage adjustment may be necessary.111 (See Renal Impairment under Dosage and Administration.)
Common Adverse Effects
Fatigue, headache, bradycardia, arrhythmia, pruritus, dizziness, dyspnea, eye irritation.111
Interactions for Timolol Maleate
Drugs Affecting Hepatic Microsomal Enzymes
Calcium-channel blocking agents
Potential hypotension, AV conduction disturbances, and left ventricular failure111
Avoid concomitant use in patients with impaired cardiac function111
Possible additive effect in prolonging AV conduction time when used concomitantly with diltiazem or verapamil111
Hypotensive agents (hydralazine, methyldopa)
Possible increased hypotensive effecta
Careful dosage adjustment is recommendeda
Potential blunting of hypotensive effects111
Monitor patients carefully111
Possible potentiation of β-adrenergic blockade (e.g., decreased heart rate)111
Possible additive effects111
Observe closely for evidence of marked bradycardia or hypotension (may be manifested as vertigo, presyncope or syncope, or orthostatic changes in BP without compensatory tachycardia)111
Timolol Maleate Pharmacokinetics
Distributed into milk.111
Plasma Protein Binding
10–60%, depending on assay method employed.111
Excreted in urine as unchanged drug and metabolites.111
Inhibits response to adrenergic stimuli by competitively blocking β-adrenergic receptors within the myocardium (β1-receptors) and bronchial and vascular smooth muscle (β2-receptors).111
Decreases resting and exercise-stimulated heart rate and reflex orthostatic tachycardia; slows conduction in the AV node; slightly reduces cardiac output, probably secondary to its effect on heart rate.111 a
Advice to Patients
Importance of taking timolol exactly as prescribed.111
Importance of immediately informing clinician at the first sign or symptom of impending heart failure (e.g., weight gain, increased shortness of breath) or if any difficulty in breathing occurs.111
In patients with heart failure, importance of informing clinician of signs or symptoms of exacerbation (e.g., weight gain, difficulty in breathing).111
Importance of patients informing anesthesiologist or dentist that they are receiving timolol therapy prior to undergoing major surgery.111
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.111
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.111
Importance of informing patients of other important precautionary information.111 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Timolol Maleate Tablets
Timolol Maleate Tablets
Timolol Maleate Tablets
AHFS DI Essentials™. © Copyright 2019, Selected Revisions January 1, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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