indication

For the management of hypertension.

pharmacology

Betaxolol is a competitive, beta(1)-selective (cardioselective) adrenergic antagonist. Betaxolol is used to treat hypertension, arrhythmias, coronary heart disease, glaucoma, and is also used to reduce non-fatal cardiac events in patients with heart failure. Activation of beta(1)-receptors (located mainly in the heart) by epinephrine increases the heart rate and the blood pressure, and the heart consumes more oxygen. Drugs such as betaxolol that block these receptors therefore have the reverse effect: they lower the heart rate and blood pressure and hence are used in conditions when the heart itself is deprived of oxygen. They are routinely prescribed in patients with ischemic heart disease. In addition, beta(1)-selective blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels. Betaxolol is lipophilic and exhibits no intrinsic sympathomimetic activity (ISA) or membrane stabilizing activity.

mechanism of action

Betaxolol selectively blocks catecholamine stimulation of beta(1)-adrenergic receptors in the heart and vascular smooth muscle. This results in a reduction of heart rate, cardiac output, systolic and diastolic blood pressure, and possibly reflex orthostatic hypotension. Betaxolol can also competitively block beta(2)-adrenergic responses in the bronchial and vascular smooth muscles, causing bronchospasm.

toxicity

Oral LD₅₀s are 350 to 400 mg betaxolol/kg in mice and 860 to 980 mg/kg in rats. Predicted symptoms of overdose include bradycardia, congestive heart failure, hypotension, bronchospasm, and hypoglycemia.

biotransformation

Primarily hepatic. Approximately 15% of the dose administered is excreted as unchanged drug, the remainder being metabolites whose contribution to the clinical effect is negligible.

absorption

Absorption of an oral dose is complete. There is a small and consistent first-pass effect resulting in an absolute bioavailability of 89% ± 5% that is unaffected by the concomitant ingestion of food or alcohol.

half life

14-22 hours

drug interactions

Acetohexamide: The beta-blocker, betaxolol, may decrease symptoms of hypoglycemia.

Chlorpropamide: The beta-blocker, betaxolol, may decrease symptoms of hypoglycemia.

Clonidine: Increased hypertension when clonidine stopped

Dihydroergotamine: Ischemia with risk of gangrene

Disopyramide: The beta-blocker, betaxolol, may increase the toxicity of disopyramide.

Epinephrine: Beta-Blockers such as betaxolol may enhance the vasopressor effect of epinephrine. Monitor for increases in pressor effects of alpha-/beta-agonists if used in patients receiving beta-blocker therapy (including ophthalmic products). Beta1-selective (i.e., “cardioselective”) agents may confer a more limited risk if used in low enough doses to allow them to retain their selectivity. The amount of epinephrine used in dental procedures as part of local anesthetic administration is not likely to be of clinical concern. Infiltrating larger volumes of local anesthetics for other surgical procedures (e.g., more than 0.06mg epinephrine) may cause clinically-relevant problems. Patients with allergies that require carrying and periodically using subcutaneous epinephrine (e.g., bee sting kits) should probably avoid the use of beta blockers.

Ergotamine: Ischemia with risk of gangrene

Fenoterol: Beta-Blockers (Beta-1 Selective) like betaxolol may diminish the bronchodilatory effect of Beta2-Agonists like fenoterol. Therapy should be monitored.

Formoterol: Beta-Blockers (Beta1 Selective) like betaxolol may diminish the bronchodilatory effect of Beta2-Agonists like formoterol. Therapy should be monitored.

Gliclazide: The beta-blocker, betaxolol, may decrease symptoms of hypoglycemia.

Glyburide: The beta-blocker, betaxolol, may decrease symptoms of hypoglycemia.

Ibuprofen: Nonsteroidal Anti-Inflammatory Agents such as ibuprofen may diminish the antihypertensive effect of Beta-Blockers such as betaxolol. Monitor for increases in blood pressure if a nonsteroidal anti-inflammatory agent (NSAID) is initiated/dose increased, or decreases in blood pressure if a NSAID is discontinued/dose decreased; this is particularly important if NSAID treatment is for extended periods of time. Ophthalmic beta-blockers are likely of little concern.

Indomethacin: Nonsteroidal Anti-Inflammatory Agents such as indomethacin may diminish the antihypertensive effect of Beta-Blockers such as betaxolol. Monitor for increases in blood pressure if a nonsteroidal anti-inflammatory agent (NSAID) is initiated/dose increased, or decreases in blood pressure if a NSAID is discontinued/dose decreased; this is particularly important if NSAID treatment is for extended periods of time. Ophthalmic beta-blockers are likely of little concern.

Insulin Glargine: The beta-blocker, betaxolol, may decrease symptoms of hypoglycemia.

Methacholine: Beta-Blockers like betaxolol may worsen brochoconstriction and decrease the effectiveness of agents used to treat the resulting bronchoconstriction. Use of betaxolol and methacholine concomitantly is contraindicated.

Methysergide: Ischemia with risk of gangrene

Orciprenaline: Beta-Blockers (Beta1 Selective) like betaxolol may diminish the bronchodilatory effect of Beta2-Agonists like orciprenaline. Therapy should be monitored.

Pipobroman: Antagonism

Piroxicam: Nonsteroidal Anti-Inflammatory Agents such as piroxicam may diminish the antihypertensive effect of Beta-Blockers such as betaxolol. Monitor for increases in blood pressure if a nonsteroidal anti-inflammatory agent (NSAID) is initiated/dose increased, or decreases in blood pressure if a NSAID is discontinued/dose decreased; this is particularly important if NSAID treatment is for extended periods of time. Ophthalmic beta-blockers are likely of little concern.

Prazosin: Beta-Blockers such as betaxolol may enhance the orthostatic hypotensive effect of Alpha1-Blockers such as prazosin. The risk associated with ophthalmic products is probably less than systemic products. Exercise caution if an alpha1-blocker is added to existing beta-blocker therapy. Monitor for hypotension during first few days of concomitant therapy. A priori reduction in alpha1-blocker (especially systemic) dose may be warranted. Administering the first dose of systemic agents at bedtime may help minimize risk of severe hypotension. The risk associated with the use of ophthalmic products in either interacting group is probably less than that associated with systemic agents. If the alpha1-blocker is being used to treat BPH, consider using tamsulosin since its alpha1-A selectivity is least likely to cause hypotension.

Repaglinide: The beta-blocker, betaxolol, may decrease symptoms of hypoglycemia.

Rituximab: Antihypertensives like betaxolol may enhance the hypotensive effect of rituximab. Consider temporarily withholding antihypertensive medications for 12 hours prior to rituximab infusion to avoid excessive hypotension during or immediately after infusion.

Terazosin: Increased risk of hypotension. Initiate concomitant therapy cautiously.

Terbutaline: Beta-Blockers (Beta1 Selective) like betaxolol may diminish the bronchodilatory effect of Beta2-Agonists like terbutaline. Therapy should be monitored.

Thiabendazole: The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Betaxolol by decreasing Betaxolol metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Betaxolol if Thiabendazole is initiated, discontinued or dose changed

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.