(TIM oh lol)
Treatment of hypertension and angina; to reduce mortality following myocardial infarction; prophylaxis of migraine
The 2014 guideline for the management of high blood pressure in adults (JNC 8) recommends initiation of pharmacologic treatment to lower blood pressure for the following patients (JNC8 [James, 2013]):
- Patients ≥60 years of age, with systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg. Goal of therapy is SBP <150 mm Hg and DBP <90 mm Hg.
- Patients <60 years of age, with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
- Patients ≥18 years of age with diabetes, with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
- Patients ≥18 years of age with chronic kidney disease (CKD), with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
In patients with chronic kidney disease (CKD), regardless of race or diabetes status, the use of an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) as initial therapy is recommended to improve kidney outcomes. In the general nonblack population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic, calcium channel blocker, ACEI, or ARB. In the general black population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic or a calcium channel blocker instead of an ACEI or ARB.
Hypersensitivity to timolol or any component of the formulation; sinus bradycardia; sinus node dysfunction; heart block greater than first degree (except in patients with a functioning artificial pacemaker); cardiogenic shock; uncompensated cardiac failure; bronchospastic disease
Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy; exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy.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, particularly in patients with ischemic heart disease, gradually reduce the dosage over a period of one to two weeks and carefully monitor the patient. If angina markedly worsens or acute coronary insufficiency develops, reinstitute timolol administration promptly, at least temporarily, and take other measures appropriate for the management of unstable angina. Warn patients against interruption of discontinuation of therapy without the physicians advice. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue timolol therapy abruptly, even in patients treated only for hypertension.
Hypertension: Oral: Initial: 10 mg twice daily, increase gradually every 7 days, usual dosage: 20 to 40 mg/day in 2 divided doses; maximum: 60 mg/day.
Prevention of myocardial infarction: Oral: 10 mg twice daily initiated within 1 to 4 weeks after infarction.
Migraine prophylaxis: Oral: Initial: 10 mg twice daily, increase to maximum of 30 mg/day.
Atrial fibrillation (rate control) (off-label use): Initial: 10 mg twice daily, increase at weekly intervals as tolerated to 20 mg twice daily then to a maximum of 30 mg twice daily; may use in combination with digoxin (Ribeiro, 1986).
Refer to adult dosing.
There are no specific dosage adjustments provided in manufacturer 's labeling. However, timolol is primarily eliminated renally; dosage reduction may be necessary. Significant hypotension has been seen in patients with severe impairment and undergoing dialysis. Use with caution.
There are no specific dosage adjustments provided in manufacturer 's labeling. However, timolol is partially metabolized by the liver; dosage reduction may be necessary.
Should be administered with food at the same time each day.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as maleate:
Generic: 5 mg, 10 mg, 20 mg
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Ajmaline: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Alpha-/Beta-Agonists (Direct-Acting): Beta-Blockers may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Some beta-adrenoceptor mediated effects of Alpha-/Beta-Agonists (Direct-Acting), including anti-anaphylactic effects of epinephrine, may be diminished by Beta-Blockers. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Exceptions: Dipivefrin. Consider therapy modification
Alpha1-Blockers: Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. 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. Exceptions: Apraclonidine. Consider therapy modification
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Aminoquinolines (Antimalarial): May decrease the metabolism of Beta-Blockers. Monitor therapy
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. Monitor therapy
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Anilidopiperidine Opioids: May enhance the bradycardic effect of Beta-Blockers. Anilidopiperidine Opioids may enhance the hypotensive effect of Beta-Blockers. 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. Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Asunaprevir: May increase the serum concentration of CYP2D6 Substrates. Consider therapy modification
Barbiturates: May decrease the serum concentration of Beta-Blockers. Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Beta2-Agonists: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy
Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil. Monitor therapy
Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. 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. Avoid combination
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. Management: Administer these agents in combination with caution, and monitor for conduction disturbances. Avoid methacholine with any beta blocker due to the potential for additive bronchoconstriction. Monitor therapy
Cobicistat: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. 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. Consider therapy modification
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy
Ergot Derivatives: Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Exceptions: Nicergoline. Consider therapy modification
Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and beta-blockers if possible. If coadministration is necessary, patients should have overnight continuous ECG monitoring conducted after the first dose of fingolimod. Monitor patients for bradycardia. Consider therapy modification
Floctafenine: May enhance the adverse/toxic effect of Beta-Blockers. Avoid combination
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. Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Insulin: Beta-Blockers may enhance the hypoglycemic effect of Insulin. Monitor therapy
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy
Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy
Lidocaine (Systemic): Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). Monitor therapy
Lidocaine (Topical): Beta-Blockers may increase the serum concentration of Lidocaine (Topical). Monitor therapy
Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Avoid combination
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Midodrine: Beta-Blockers may enhance the bradycardic effect of Midodrine. Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
NIFEdipine: May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification
Panobinostat: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of sensitive CYP2D6 substrates when possible, particularly those substrates with a narrow therapeutic index. Consider therapy modification
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Perhexiline: CYP2D6 Substrates may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Regorafenib: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Reserpine: May enhance the hypotensive effect of Beta-Blockers. Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. Monitor therapy
Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Avoid combination
Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Monitor therapy
Selective Serotonin Reuptake Inhibitors: May increase the serum concentration of Beta-Blockers. Exceptions: Citalopram; Escitalopram; FluvoxaMINE. Monitor therapy
Sulfonylureas: Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Monitor therapy
Theophylline Derivatives: Beta-Blockers (Nonselective) may diminish the bronchodilatory effect of Theophylline Derivatives. Consider therapy modification
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Blood pressure, apical and radial pulses, fluid I & O, daily weight, respirations, mental status, and circulation in extremities before and during therapy; monitor for systemic effect of beta-blockade
1% to 10%:
Cardiovascular: Bradycardia
Central nervous system: Fatigue, dizziness
Respiratory: Dyspnea
Frequency not defined:
Cardiovascular: Angina pectoris, arrhythmia, cardiac arrest, cardiac failure, cerebral ischemia, cerebral vascular accident, edema, heart block, hypotension, palpitation, Raynauds phenomenon
Central nervous system: Anxiety, confusion, depression, disorientation, hallucinations, insomnia, memory loss, nervousness, nightmares, somnolence
Dermatologic: Alopecia, angioedema, pseudopemphigoid, psoriasiform rash, psoriasis exacerbation, rash, urticaria
Endocrine & metabolic: Hypoglycemia masked, libido decreased
Gastrointestinal: Anorexia, diarrhea, dyspepsia, nausea, xerostomia
Genitourinary: Impotence, retoperitoneal fibrosis
Hematologic: Claudication
Neuromuscular & skeletal: Myasthenia gravis exacerbation, paresthesia
Ocular: Corneal sensitivity decreased, cystoid macular edema, diplopia, dry eyes, keratitis, ocular discharge, ocular pain, ptosis, refractive changes, visual disturbances
Otic: Tinnitus
Respiratory: Bronchospasm, cough, nasal congestion, pulmonary edema, respiratory failure
Miscellaneous: Allergic reactions, cold hands/feet, Peyronie's disease, systemic lupus erythematosus
Concerns related to adverse events:
- Anaphylactic reactions: Use caution with history of severe anaphylaxis to 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.
Disease-related concerns:
- Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; if used at all, should be used cautiously with close monitoring.
- Conduction abnormality: Consider pre-existing conditions such as sick sinus syndrome before initiating.
- Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.
- Heart failure: Use with caution in patients with compensated heart failure and monitor for a worsening of the condition.
- Myasthenia gravis: Use with caution in patients with myasthenia gravis; can worsen.
- Peripheral vascular disease (PVD) and Raynauds disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud's disease. Use with caution and monitor for progression of arterial obstruction.
- Pheochromocytoma (untreated): Adequate alpha-blockade is required prior to use of any beta-blocker.
- Prinzmetal variant angina: Beta-blockers without alpha1-adrenergic receptor blocking activity should be avoided in patients with Prinzmetal variant angina since unopposed alpha1-adrenergic receptors mediate coronary vasoconstriction and can worsen anginal symptoms (Mayer, 1998).
- Psoriasis: Beta-blocker use has been associated with induction or exacerbation of psoriasis, but cause and effect have not been firmly established.
- Renal impairment: Use with caution in patients with severe renal impairment; marked hypotension can occur in patients maintained on hemodialysis.
- 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.
Concurrent drug therapy issues:
- Calcium channel blockers: Use with caution in patients on concurrent verapamil or diltiazem; bradycardia or heart block can occur.
- Cardiac glycosides: Use with caution in patients receiving digoxin; bradycardia or heart block can occur.
- Inhaled anesthetic agents: Use with caution in patients receiving inhaled anesthetic agents known to depress myocardial contractility.
Special populations:
- Elderly: Bradycardia may be observed more frequently in elderly patients (>65 years of age); dosage reductions may be necessary.
Other warnings/precautions:
- Abrupt withdrawal: [U.S. Boxed Warning]: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered to avoid acute tachycardia, hypertension, and/or ischemia. Severe exacerbation of angina, ventricular arrhythmias, and myocardial infarction (MI) have been reported following abrupt withdrawal of beta-blocker therapy. Temporary but prompt resumption of beta-blocker therapy may be indicated with worsening of angina or acute coronary insufficiency.
- Major surgery: Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery.
C
Adverse events were not observed in the initial animal reproduction studies. Timolol crosses the placenta (Schneider 1988) and decreased fetal heart rate has been observed following maternal use of timolol during pregnancy (Devoe 1986). Adverse events, such as fetal/neonatal hypoglycemia and reduced birth weight, have been observed following in utero exposure to beta-blockers as a class. Adequate facilities for monitoring infants at birth is generally recommended.
Untreated chronic maternal hypertension and preeclampsia are also associated with adverse events in the fetus, infant, and mother (ACOG 2015; Magee 2014). Although beta-blockers may be used when treatment of hypertension in pregnancy is indicated, agents other than timolol are preferred (ACOG 2013; Magee 2014). In addition, other agents are preferred when migraine prophylaxis is needed in pregnant women (Pringsheim 2012).
Blocks both beta1- and beta2-adrenergic receptors; reduces blood pressure by blocking adrenergic receptors and decreasing sympathetic outflow, produces a negative chronotropic and inotropic activity through an unknown mechanism
Rapid and complete (~90%)
Vd: 1.7 L/kg
Extensively hepatic via CYP2D6; extensive first-pass effect
Urine (15% to 20% as unchanged drug)
Hypotensive: 15-45 minutes; Peak effect: 0.5-2.5 hours
Plasma: 1-2 hours
~4 hours
2-2.7 hours; prolonged with renal impairment
60%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience nausea or loss of strength and energy. Have patient report immediately to prescriber severe dizziness, passing out, shortness of breath, excessive weight gain, swelling of arms or legs, angina, bradycardia, arrhythmia, muscle weakness, or sensation of cold (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.