Timolol (tablet)

Timolol (tablet)
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2]

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Black Box Warning

WARNING See full prescribing information for complete Boxed Warning. Exacerbation of Ischemic Heart Disease Following Abrupt Withdrawal: Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy; exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy. When discontinuing chronically administered timolol maleate, particularly in patients with ischemic heart disease, the dosage should be gradually reduced over a period of one to two weeks and the patient should be carefully monitored. If angina markedly worsens or acute coronary insufficiency develops, timolol maleate administration should be reinstituted promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken. Patients should be warned against interruption or discontinuation of therapy without the physician's advice. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue timolol maleate therapy abruptly even in patients treated only for hypertension.

Overview

Timolol (tablet) is a beta-adrenergic blocker that is FDA approved for the treatment of hypertension, myocardial infarction, migraine. There is a Black Box Warning for this drug as shown here. Common adverse reactions include angina, bradyarrhythmia, heart failure, hypotension, pruritus, rash, urticaria, abdominal pain, diarrhea, indigestion, nausea, vomiting, muscle cramps, confusion, dizziness, headache, dry eyes, hallucinations, psychotic disorder, cough, dyspnea, fatigue.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Hypertension

• Dosing Information

• The usual initial dosage of timolol maleate is 10 mg twice a day, whether used alone or added to diuretic therapy. Dosage may be increased or decreased depending on heart rate and blood pressure response. The usual total maintenance dosage is 20 to 40 mg per day. Increases in dosage to a maximum of 60 mg per day divided into two doses may be necessary. There should be an interval of at least 7 days between increases in dosages.

Timolol maleate tablets may be used with a thiazide diuretic or with other antihypertensive agents. Patients should be observed carefully during initiation of such concomitant therapy.

Myocardial Infarction

• Dosing Information

• The recommended dosage for long-term prophylactic use in patients who have survived the acute phase of a myocardial infarction is 10 mg given twice daily.

Migraine

• Dosing information

• The usual initial dosage of timolol maleate is 10 mg twice a day. During maintenance therapy the 20 mg daily dosage may be administered as a single dose. Total daily dosage may be increased to a maximum of 30 mg, given in divided doses, or decreased to 10 mg once per day, depending on clinical response and tolerability. If a satisfactory response is not obtained after 6 to 8 weeks use of the maximum daily dosage, therapy with timolol should be discontinued.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Timolol in adult patients.

Non–Guideline-Supported Use

Angina

• Dosing Information

• 10 to 60 mg/day PO q12-24h.

Anxiety

• Dosing Information

• Outatient surgery: 10 mg (single dose).
• Aerophobia: 20 mg/day.

Essential Tremor

• Dosing Information

• 5 mg PO q12h.

Hyperthyroidism

• Dosing Information

• 10 mg PO q12h.

Supraventricular Arrhythmia

• Dosing Information

• 1 mg IV bolus every 20 minutes up to a total of 3 mg, then 20 mg/day PO.
• Atrial fibrillation: Timolol 20 to 30 mg/day PO + digoxin 0.25 to 0.5 mg/day.
• Premature ventricular beats: 5 to 15 mg PO q12h.
• SVT after coronary artery bypass surgery: 0.5 mg IV 112h, then 10 mg PO q12h.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Timolol (tablet) FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Timolol in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Timolol in pediatric patients.

Contraindications

• Bronchial asthma or with a history of bronchial asthma
• Severe chronic obstructive pulmonary disease
• Sinus bradycardia
• Second-degree atrioventricular block and third-degree atrioventricular block
• Overt cardiac failure
• Cardiogenic shock
• Hypersensitivity to this product.

Warnings

WARNING See full prescribing information for complete Boxed Warning. Exacerbation of Ischemic Heart Disease Following Abrupt Withdrawal: Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy; exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy. When discontinuing chronically administered timolol maleate, particularly in patients with ischemic heart disease, the dosage should be gradually reduced over a period of one to two weeks and the patient should be carefully monitored. If angina markedly worsens or acute coronary insufficiency develops, timolol maleate administration should be reinstituted promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken. Patients should be warned against interruption or discontinuation of therapy without the physician's advice. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue timolol maleate therapy abruptly even in patients treated only for hypertension.

Conidition 1

Cardiac Failure

Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe failure. Although beta-blockers should be avoided in overt congestive heart failure, they can be used, if necessary, with caution in patients with a history of failure who are well compensated, usually with digitalis and diuretics. Both digitalis and timolol maleate slow AV conduction. If cardiac failure persists, therapy with timolol maleate should be withdrawn.

In Patients Without a History of Cardiac Failure

Continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of cardiac failure, patients receiving timolol should be digitalized and/or be given a diuretic, and the response observed closely. If cardiac failure continues, despite adequate digitalization and diuretic therapy, timolol should be withdrawn.

Obstructive Pulmonary Disease

PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (e.g., CHRONIC BRONCHITIS, EMPHYSEMA) OF MILD OR MODERATE SEVERITY, BRONCHOSPASTIC DISEASE OR A HISTORY OF BRONCHOSPASTIC DISEASE, SHOULD IN GENERAL NOT RECEIVE BETA-BLOCKERS, INCLUDING ‘TIMOLOL’. However, if timolol is necessary in such patients, then the drug should be administered with caution since it may block bronchodilation produced by endogenous and exogenous catecholamine stimulation of beta2 receptors.

Major Surgery

The necessity or desirability of withdrawal of beta-blocking therapy prior to major surgery is controversial. Beta-adrenergic receptor blockade impairs the ability of the heart to respond to beta-adrenergically mediated reflex stimuli. This may augment the risk of general anesthesia in surgical procedures. Some patients receiving beta-adrenergic receptor blocking agents have been subject to protracted severe hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has also been reported. For these reasons, in patients undergoing elective surgery, some authorities recommend gradual withdrawal of beta-adrenergic receptor blocking agents.

If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of such agonists as isoproterenol, dopamine, dobutamine or norepinephrine.

Diabetes Mellitus

Timolol should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic receptor blocking agents may mask the signs and symptoms of acute hypoglycemia.

Thyrotoxicosis

Beta-adrenergic blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-blockade which might precipitate a thyroid storm.

Precautions

Muscle Weakness

Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, and generalized weakness). Timolol has been reported rarely to increase muscle weakness in some patients with myasthenia gravis or myasthenic symptoms.

Cerebrovascular Insufficiency

Because of potential effects of beta-adrenergic blocking agents relative to blood pressure and pulse, these agents should be used with caution in patients with cerebrovascular insufficiency. If signs or symptoms suggesting reduced cerebral blood flow are observed, consideration should be given to discontinuing these agents.

Adverse Reactions

Clinical Trials Experience

Timolol maleate tablets are usually well tolerated in properly selected patients. Most adverse effects have been mild and transient.

In a multi-center (12 week) clinical trial comparing timolol maleate and placebo in hypertensive patients, the following adverse reactions were reported spontaneously and considered to be causally related to timolol maleate:

This image is provided by the National Library of Medicine.

These data are representative of the incidence of adverse effects that may be observed in properly selected patients treated with timolol maleate, i.e., excluding patients with bronchospastic disease, congestive heart failure or other contraindications to beta-blocker therapy.

In patients with migraine the incidence of bradycardia was 5 percent.

In a coronary artery disease population studied in the Norwegian multi-center trial, the frequency of the principal adverse reactions and the frequency with which these resulted in discontinuation of therapy in the timolol and placebo groups were:

This image is provided by the National Library of Medicine.

The following additional adverse effects have been reported in clinical experience with the drug:

• Body as a Whole: Anaphylaxis, extremity pain, decreased exercise tolerance, weight loss, fever.
• Cardiovascular: Cardiac arrest, cardiac failure, cerebral vascular accident, worsening of angina pectoris, worsening of arterial insufficiency, Raynaud's phenomenon, palpitations, vasodilatation.
• Digestive: Gastrointestinal pain, hepatomegaly, vomiting, diarrhea, dyspepsia.
• Hematologic: Nonthrombocytopenic purpura.
• Endocrine: Hyperglycemia, [[hypoglycemia].
• Skin: Rash, skin irritation, increased pigmentation, sweating, alopecia.
• Musculoskeletal: Arthralgia.
• Nervous System: Local weakness, increase in signs and symptoms of myasthenia gravis.
• Psychiatric: Depression, nightmares, somnolence, insomnia, nervousness, diminished concentration, hallucinations.
• Respiratory: Cough.
• Special Senses: Visual disturbances, diplopia, ptosis, dry eyes.
• Urogenital: Impotence, urination difficulties.

There have been reports of retroperitoneal fibrosis in patients receiving timolol maleate and in patients receiving other beta-adrenergic blocking agents. A causal relationship between this condition and therapy with beta-adrenergic blocking agents has not been established.

Potential Adverse Effects

In addition, a variety of adverse effects not observed in clinical trials with timolol maleate, but reported with other beta-adrenergic blocking agents, should be considered potential adverse effects of timolol.

• Nervous System: Reversible mental depression progressing to catatonia, an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics.
• Cardiovascular: Intensification of AV block.
• Digestive: Mesenteric arterial thrombosis, ischemic colitis.
• Hematologic: Agranulocytosis, thrombocytopenic purpura.
• Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm with respiratory distress.
• Miscellaneous: Peyronie's disease]].

There have been reports of a syndrome comprising psoriasiform skin rash, conjunctivitis sicca, otitis, and sclerosing serositis attributed to the beta-adrenergic receptor blocking agent, practolol. This syndrome has not been reported with timolol.

Clinical Laboratory Test Findings

Clinically important changes in standard laboratory parameters were rarely associated with the administration of timolol. Slight increases in blood urea nitrogen, serum potassium, uric acid, and triglycerides, and slight decreases in hemoglobin, hematocrit and HDL cholesterol occurred, but were not progressive or associated with clinical manifestations. Increases in liver function tests have been reported.

Postmarketing Experience

There is limited information regarding Timolol (tablet) Postmarketing Experience in the drug label.

Drug Interactions

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Use in Specific Populations

Pregnancy

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Labor and Delivery

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Nursing Mothers

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Pediatric Use

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Geriatic Use

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Race

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Renal Impairment

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Hepatic Impairment

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Females of Reproductive Potential and Males

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Immunocompromised Patients

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Others

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Administration and Monitoring

Administration

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Monitoring

Condition 1

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Condition 2

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IV Compatibility

Solution

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Not Tested

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Variable

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Y-Site

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Incompatible

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Admixture

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Syringe

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TPN/TNA

Compatible

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Incompatible

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Overdosage

Acute Overdose

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Management

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Chronic Overdose

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Pharmacology

Mechanism of Action

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Structure

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Pharmacodynamics

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Pharmacokinetics

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Nonclinical Toxicology

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Clinical Studies

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How Supplied

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Storage

There is limited information regarding Timolol (tablet) Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

(Patient Counseling Information)

Precautions with Alcohol

Alcohol-Timolol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Timolol (tablet) Brand Names in the drug label.

Look-Alike Drug Names

• (Paired Confused Name 1a) — (Paired Confused Name 1b)
• (Paired Confused Name 2a) — (Paired Confused Name 2b)
• (Paired Confused Name 3a) — (Paired Confused Name 3b)

Drug Shortage Status

Drug Shortage

Price

References

The contents of this FDA label are provided by the National Library of Medicine.