Timolol Maleate

Nonselective β-adrenergic blocking agent (β-blocker).111

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).111 500

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

Acute MI

Secondary prevention following acute MI to reduce the risk of reinfarction and mortality.111

Angina

Management of chronic stable angina pectoris†.a

A component of the standard therapeutic measures in the management of unstable angina or non-ST-segment elevation MI†.143 169 172

Vascular Headache

Prophylaxis of common or classic migraine headache.106 107 108 110 111 127 128

Contraindications

• Known hypersensitivity to the timolol or any ingredient in the formulation.111

  Bronchial asthma (or a history of bronchial asthma), allergic bronchospasm, or severe COPD; severe bradycardia, heart block greater than first degree, overt cardiac failure, or cardiogenic shock.111

Warnings/Precautions

Warnings

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 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

Possible decreased signs and symptoms of hypoglycemia (e.g., tachycardia, but not sweating or dizziness).111 Use with caution in patients with diabetes mellitus receiving hypoglycemic drugs.111

May mask signs of hyperthyroidism (e.g., tachycardia).111 Possible thyroid storm if therapy is abruptly withdrawn; carefully monitor patients having or suspected of developing thyrotoxicosis.111

Sensitivity Reactions

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

General Precautions

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

Specific Populations

Category C.111

Distributed into milk.111 Discontinue nursing or the drug.111

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

Absorption

Bioavailability

Absorption from GI tract is rapid; approximately 90% absorbed following oral administration.111 Peak plasma concentration are usually attained within 1–2 hours.111

Distribution

Extent

Distributed into milk.111

Plasma Protein Binding

10–60%, depending on assay method employed.111

Elimination

Metabolism

Approximately 80% metabolized in the liver to inactive metabolites.111 a

Elimination Route

Excreted in urine as unchanged drug and metabolites.111

Half-life

3–4 hours.111 a

Special Populations

Only small amounts of drug are removed by hemodialysis.111 a

• 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

• No intrinsic sympathomimetic activity or membrane-stabilizing effect on the heart.111 a

• Suppresses plasma renin activity and suppresses the renin-aldosterone-angiotensin system.111 a

• Reduces BP by decreasing cardiac output, decreasing sympathetic outflow from the CNS, and/or suppressing renin release.111 a

• Increases airway resistance.111 a