Betaxolol is a lipophilic beta-adrenergic blocker that is selective to the beta-1 adrenergic receptor, with a limited beta-2 blocking effect. This factor is an important distinction compared to topical nonselective beta-blockers.[1][2] Administration of the drug can be either via topical or systemic routes. The FDA primarily indicates topical betaxolol for use in patients with ocular hypertension and chronic open-angle glaucoma.[1][2][3] In the systemic form, the FDA approves its use to treat essential hypertension, post-myocardial infarction, and chronic stable angina. Similar to the other beta-1 selective beta-blockers, betaxolol is associated with a decreased risk of stroke, congestive heart failure, coronary artery disease. It also demonstrates decreased mortality and morbidity post-myocardial infarction. The non-FDA uses for betaxolol include tremor reduction, migraine prophylaxis, certain cardiac arrhythmias, and anxiety disorders.[3] Recently, one study showed the use of topical betaxolol in the treatment of relapsing paronychia, also known as a skin infection around a fingernail.[4] 

Glaucoma is an optic neuropathy, defined by the death of retinal ganglion cells and characteristic changes to the optic nerve head. Intraocular pressure, as well as other factors, are factors for the loss of ganglion cells. While the exact mechanism of glaucoma is not completely known, there are two main independent pathways, the trabecular meshwork and uveoscleral, that contribute to the intraocular pressure.  In primary open-angle glaucoma, there is increased resistance of outflow of aqueous humor, a clear fluid produced by the ciliary bodies, through the trabecular meshwork of the eye. This action increases intraocular pressure, leading to the degeneration of retinal ganglion cells and the optic nerve over time, causing progressive vision loss that typically starts at the periphery and can expand to involve the whole field of vision for that eye.  It is also known that patients with normal intraocular pressure can also develop glaucoma.[5]

Beta-blockers like betaxolol were once first-line treatment for open-angle glaucoma, but now topical prostaglandin analogs, like latanoprost, are often the first drugs of choice.[5][6] This change in prescribing is because even in the topical form, beta-blockers have more systemic side effects in comparison to the prostaglandin analogs.[5][7] Betaxolol and other beta-blockers like timolol are often the drugs of choice when patients cannot tolerate prostaglandins, additional pressure reduction is needed, or there is a rare contraindication to them. Betaxolol’s niche comes when a patient also has mild respiratory comorbidity like asthma or COPD. Betaxolol’s selective beta-1 adrenergic blockade decreases the likelihood of systemic, respiratory side effects in comparison to nonselective beta-blockers like timolol.[2]

Betaxolol selectively antagonizes Beta-1 receptors. The adrenergic receptors are located primarily in the kidney, cardiac myocytes, nodal tissue, and other cardiac conduction tissue.[8] Specifically, beta-1 receptors are G protein-coupled receptors that activate cyclic AMP (cAMP) through a cascade of events. cAMP activation leads to an interaction with cAMP-dependent protein kinases, which increases the calcium ion (Ca2+) concentration. This increase in calcium leads to different physiological changes depending on the location of the receptor. 

For example, in the ciliary body, the increase in calcium leads to an increased aqueous humor production, which can lead to increased intraocular pressure seen in glaucoma. Betaxolol acts to prevent the G protein cascade from increasing intracellular calcium, thus preventing the production of aqueous humor production from the ciliary body.[3][5][8]

Betaxolol is rarely associated with bronchospasm, sometimes seen in nonselective beta-blockers like timolol. Beta-2 receptors are present in bronchial and vascular smooth muscle; this explains betaxolol’s preferred use to nonselective beta-blockers, like timolol, in those with mild comorbid respiratory pathologies when there are contraindications to other therapeutic options.[2][3][8]

For the treatment of ocular hypertension and open-angle glaucoma, betaxolol is administered in its topical form, a 0.5% betaxolol hydrochloride ophthalmic solution. The current guidelines recommend one drop of 0.5% betaxolol hydrochloride ophthalmic solution twice daily in the affected eye(s). This dosing equates to approximately 28 μg per day. Patients should see a stabilization in the decrease in intraocular pressure within a few weeks. If the desired response does not occur, the patient’s physician can consider adding other medications to the treatment regimen.[9]

For the treatment of hypertension, betaxolol is administered in its oral form at a starting dose of 10mg daily. Betaxolol is either used as monotherapy or in combination with a diuretic. If there is not the desired antihypertensive response within 7 to 14 days, the patient’s physician can consider doubling the dose. Although betaxolol is not proven to show a significant increase in its efficacy beyond 20 mg, the dose can safely increase up to a maximum of 40 mg daily.[10]

The adverse effects of betaxolol divide into the local and systemic side effects. The local side effects include transient irritation (25 to 40% of patients), burning, pruritus, punctate keratitis, and blurry vision. When compared to topical timolol (a nonselective beta-blocker), betaxolol showed a higher incidence of ocular side effects.  Compared to nonselective topical beta-adrenergic receptor blockers, betaxolol seems to be less likely to cause adverse effects on pulmonary function. However, betaxolol use still requires caution in patients with underlying pulmonary disease. One study showed that 5, out of 85 patients, with glaucoma and asthma, chronic obstructive pulmonary disease, or timolol-induced bronchoconstriction, developed symptomatic pulmonary obstruction. Another study found 8 cases of asthma exacerbation requiring hospitalization, out of a total of 56 spontaneous adverse effect reports, were reported during the first year of betaxolol marketing in the United States.[2][3][5]

The systemic side effects are more often seen in the oral form but can also occur with the topical administration of betaxolol. Although betaxolol is considered a “selective” beta blocker, at higher doses, it loses its selective binding and starts to antagonize beta-2 and 3 receptors. Some of the systemic adverse effects include bradycardia, hypotension, fatigue, sexual impotence, hair loss, confusion, headache, dizziness, and bronchospasm at higher doses. Other cardiac problems like arrhythmia, bundle branch block, myocardial infarction, sinus arrest, congestive heart failure have also been reported in association with betaxolol use. Additional adverse effects reported are depression, disorientation, vertigo, sleepwalking, rhinitis, dysuria, alopecia, and prolonged prothrombin time.[2]  Also, betaxolol and the other beta-blockers can cause metabolic side effects like an increase in LDL cholesterol levels and, most notably, can dangerously mask the symptoms of hypoglycemia (i.e., tachycardia) in people with diabetes.[3][11] Lastly, although betaxolol and other beta-blockers are highly unlikely to cause muscle weakness in a relatively healthy individual, it can unmask the symptoms and/or exacerbate the muscle weakness seen in patients with Myasthenia Gravis.[12]

The use of betaxolol is contraindicated in patients with underlying heart conditions, including complete heart block, syncope, and bradycardia. Precaution is necessary for patients with second-degree heart block. Especially at higher doses, betaxolol is contraindicated in patients with moderate to severe asthma or chronic obstructive pulmonary disease.[3][5][11] Lastly, in patients with a recent history of fluid retention, betaxolol is contraindicated without the concomitant addition of a diuretic.[3][11] Due to betaxolol's ability to cause a mild neuromuscular blockade, it has the potential to exacerbate muscle weakness in patients with myasthenia gravis. It thus is contraindicated in patients with neuromuscular disease.[12]