Betaxolol

Betaxolol is a cardio-selective beta-adrenergic blocking agent belonging to the beta-blocker class.

Betaxolol is approved for the treatment of essential hypertension, post-myocardial infarction, and chronic stable angina. It is also used to treat tremors, migraine prophylaxis, certain cardiac arrhythmias, anxiety disorders, and relapsing paronychia.

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 concomitant ingestion of food or alcohol. It crosses the placenta and is distributed into breast milk. The plasma protein binding is approximate up to 50%. It undergoes minimal first-pass metabolism and gets excreted through urine.

The common side effects associated with Betaxolol are Eye discomfort (stinging and burning), bradycardia, palpitation, chest pain, edema, insomnia, fatigue, lethargy, nausea, dyspepsia, diarrhea, arthralgia, paraesthesia, dyspnoea, pharyngitis, antinuclear antibody positive, cold extremities.

Betaxolol is available in the form of dosage forms as tablets

Betaxolol is available in Europe, Italy, Australia, Nigeria, and India

Betaxolol, belonging to the beta blocker, acts as a cardio-selective beta-1-adrenergic blocker. Betaxolol works by relaxing blood vessels and slowing heart rate to improve blood flow and decrease blood pressure.

It works by blocking catecholamine stimulation of beta-adrenergic receptors in the heart and vascular smooth muscle. This results in a reduction of the heart rate, cardiac output, systolic and diastolic blood pressure, and possibly reflex orthostatic hypotension.

The onset of action of Betaxolol occurs within 30 minutes of its administration.

The Duration of Action for Betaxolol can be detected 2 hours after topical administration.

The Tmax was found within 2-4 hours following the administration of betaxolol. Cmax was about 1.4 ± 0.41 ng/mL.

Betaxolol is available in the form of tablets and ophthalmic solutions.

Tablets:

Tablets are to be swallowed whole with water. Betaxolol comes as a tablet to be taken by mouth. It is usually taken two times a day.

Ophthalmic solution:

• Shake the medicine well just before each use.
• First, wash your hands. Tilt the head back and press the finger gently on the skin just beneath the lower eyelid, and pull the lower eyelid away from the eye to make a space. Drop the medicine into this space. Let go of the eyelid and gently close the eyes. Do not blink. Keep the eyes closed and apply pressure to the inner corner of the eye with your finger for 1 or 2 minutes to allow the medicine to be absorbed by the eye.
• Immediately after using the medicine, wash your hands to remove any medicine that may be on them.
• To keep the medicine as germ-free as possible, do not touch the applicator tip on any surface (including the eye). Also, keep the container tightly closed. Serious damage to the eye and possible loss of vision may result from using contaminated eye drops.

Betaxolol is a cardio-selective beta-1-adrenergic blocker belonging to the beta-blocker class.

Betaxolol is approved for the treatment of essential hypertension, post-myocardial infarction, and chronic stable angina. It is also used to treat reduction, migraine prophylaxis, certain cardiac arrhythmias, anxiety disorders, and relapsing paronychia.

Betaxolol is used to treat increased pressure in the eye in conditions such as glaucoma (damage to the optic nerve) and ocular hypertension (high fluid pressure inside the eye). Betaxolol works by decreasing the secretion of aqueous humour (a liquid that maintains normal pressure in the eyeball) by the ciliary body into the eyeball. Thereby lowering the pressure in the eye by reducing aqueous humour entry into the eyeball. 

Betaxolol is approved for use in the following clinical indications which include essential hypertension, post-myocardial infarction, and chronic stable angina. :-

• Administration of Betaxolol can be either via topical or systemic routes.
• Topical betaxolol is used for patients with ocular hypertension and chronic open-angle glaucoma.
• In the systemic form, it is used to treat essential hypertension, post-myocardial infarction, and chronic stable angina.
• Similar to the other beta selective beta-blockers, betaxolol is associated with a decreased risk of stroke, congestive heart failure, and coronary artery disease. It also demonstrates decreased mortality and morbidity post-myocardial infarction.
• Although not approved, there have been certain off-label uses documented for Betaxolol. These include tremors, migraine prophylaxis, certain cardiac arrhythmias, and anxiety disorders. The topical betaxolol is used in the treatment of relapsing paronychia, also known as a skin infection around a fingernail.

Betaxolol is available in the form of tablets and ophthalmic solutions.

• Hypertension

The initial dose of Betaxolol in hypertension is ordinarily 10 mg once daily either alone or added to diuretic therapy. The full antihypertensive effect is usually seen within 7 to 14 days. If the desired response is not achieved the dose can be doubled after 7 to 14 days. Increasing doses beyond 20 mg has not been shown to produce statistically significant additional antihypertensive effects, but the 40-mg dose has been studied and is well tolerated. An increased effect (reduction) on heart rate should be anticipated with the increasing dosage.

• Open-Angle Glaucoma and Ocular Hypertension

The recommended dose is one to two drops of Betaxolol Hydrochloride Ophthalmic Solution as 0.25%- 0.5% in the affected eye(s) twice daily. In some patients, the intraocular pressure lowering responses to Betaxolol Hydrochloride Ophthalmic Solution may require a few weeks to stabilize. As with any new medication, careful monitoring of patients is advised.

Betaxolol can be administered orally before/ after meals. The dosage and the duration of treatment should be as per the clinical judgment of the treating physician

Betaxolol is available in various dosage strengths as 0.5% w/v, 0.25%w/v, 10 mg, 20 mg.

Betaxolol is available in the form of tablets and ophthalmic solutions.

Betaxolol is approved for the treatment of essential hypertension, post-myocardial infarction, and chronic stable angina. It is also used to treat tremors, migraine prophylaxis, certain cardiac arrhythmias, anxiety disorders, and relapsing paronychia.

• Hypertension: It has been observed that the low-salt Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure. Sometimes after a few weeks, its effects on blood pressure become noticeable.

• Myocardial infarction: No more than 25 to 35 percent of your daily calories should come from total fat (including saturated fat). Less than 7 % of your daily calories should come from saturated fat. Avoid trans fats and Consume less than 200 milligrams a day of dietary cholesterol.

• Angina Pectoris:  Avoid foods that are high in saturated fat and hydrogenated or partially hydrogenated fats. Reduce your intake of dairy products including cheese, cream, and eggs.

• Open-angle glaucoma:  Avoid caffeine, saturated fats, trans fatty acids, and salt in their daily diet, glaucoma patients should also consider avoiding any foods they’re allergic to.

• Migraine Prophylaxis: Some commonly triggered diets include: Baked food with yeast, such as sourdough bread, bagels, doughnuts, coffee cake, Chocolate, Cultured dairy products (like yogurt and 0kefir), Tomatoes, Vegetables like onions, pea pods, some beans, corn, and sauerkraut, Vinegar and Alcohol must be avoided.

Betaxolol may be contraindicated in the following:

• 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. Lastly, in patients with a recent history of fluid retention, betaxolol is contraindicated without the concomitant addition of a diuretic.
• 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

The treating physician must closely monitor the patient and keep pharmacovigilance as follows:

• General

As with many topically applied ophthalmic drugs, this drug is absorbed systemically. The same adverse reactions found with the systemic administration of beta-adrenergic receptor inhibitors may occur with the topical administration. For example, severe respiratory reactions and cardiac reactions, including death due to bronchospasm in patients with asthma, and death due to cardiac failure, have been reported with topical application of beta-adrenergic receptor inhibitors.

• Cardiac Failure

Betaxolol has been shown to have a minor effect on heart rate and blood pressure in clinical studies. Caution should be used in treating patients with a history of cardiac failure or heart block. Treatment with Betaxolol should be discontinued at the first signs of cardiac failure.

• Diabetes Mellitus

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

• Thyrotoxicosis

Beta-adrenergic receptor inhibitors 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-adrenergic receptor inhibitors, which might precipitate a thyroid storm.

• Muscle Weakness

Beta-adrenergic receptor inhibitors have been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, and generalized weakness).

• Surgical Anesthesia

The necessity or desirability of withdrawal of beta-adrenergic receptor inhibitors prior to major surgery is controversial. Beta-adrenergic receptor inhibitors impair 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 inhibitors have experienced protracted, severe hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has also been reported. In patients undergoing elective surgery, consider gradual withdrawal of beta-adrenergic receptor inhibitors. If necessary during surgery, the effects of beta-adrenergic receptor inhibitors may be reversed by sufficient doses of adrenergic agonists.

• Bronchospasm and Obstructive Pulmonary Disease

Caution should be exercised in the treatment of glaucoma patients with excessive restriction of pulmonary function. There have been reports of asthmatic attacks and pulmonary distress during the betaxolol treatment. Although re-challenges of some such patients with ophthalmic betaxolol have not adversely affected pulmonary function test results, the possibility of adverse pulmonary effects in the patients sensitive to beta-adrenergic receptor inhibitors cannot be ruled out.

• Atopy/Anaphylaxis

While taking beta receptor inhibitors, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenges with such allergens. Such patients may be unresponsive to the usual doses of epinephrine used to treat anaphylactic reactions.

• Angle-Closure Glaucoma

In patients with angle-closure glaucoma, the immediate treatment objective is to reopen the angle. This may require constricting the pupil. Betaxolol has little or no effect on the pupil and should not be used alone in the treatment of angle-closure glaucoma.

• Cerebrovascular Insufficiency

Because of the potential effects of beta-adrenergic receptor inhibitors on 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 develop following initiation of therapy with Betaxolol alternative therapy should be considered.

• Bacterial Keratitis

Bacterial keratitis may occur with the use of multiple-dose containers of topical ophthalmic products when these containers are inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface. Instruct patients on appropriate instillation techniques.

• Choroidal Detachment

Choroidal detachment after filtration procedures has been reported with the administration of aqueous suppressant therapy

PRECAUTIONS:

Bronchospastic disease, cerebrovascular insufficiency, CHF, cardiomegaly, DM, hyperthyroidism/thyrotoxicosis, liver disease, renal impairment, peripheral vascular disease (potential risk of reduced placental perfusion, fetal bradycardia, hypoglycemia), use in pheochromocytoma, IDDM

Surgery/Anesthesia: Chronically administered beta-blockers should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures

Drinking alcohol while taking betaxolol can increase drowsiness and dizziness, which in turn increases the risk of accidental injury.

Betaxolol use in breastfeeding patients is not recommended.

Teratogenic effects

Pregnancy Category C:

Reproduction, teratology, and peri- and postnatal studies have been conducted with orally administered betaxolol HCl in rats and rabbits. There was evidence of drug-related postimplantation loss in rabbits and rats at dose levels above 12 mg/kg and 128 mg/kg, respectively. Betaxolol HCl was not shown to be teratogenic, however, and there were no other adverse effects on the reproduction at the subtoxic dose levels. There are no adequate and well-controlled studies on pregnant women. Betaxolol Ophthalmic Suspension should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

There are some food warnings mentioned below for the drug betaxolol:

• Potassium Rich Foods: Betaxolol is a beta blocker that increases the potassium level in the blood. Potassium-rich foods like bananas and oranges when taken along with betaxolol further increase the potassium level and cause side effects

• Pleurisy Root: Pleurisy roots are not recommended with most heart medications due to the cardiac glycoside content of the root.

The Adverse reactions related to the molecule Betaxolol can be categorized as:

• Common Adverse effects:

Insomnia, Muscle pain, Dizziness, fatigue, etc.

• Less Common adverse effects:

Nervousness, Elevated liver enzymes, joint paint, edema, vivid dreams, abdominal discomfort, nausea, muscle cramps, paresthesias, bradycardia, cold extremities, hypotension, palpitations, syncope, Tachycardia, Anxiety, lethargy, diarrhea, vomiting, Impotence/reduced libido.

• Rare adverse effects:

Heart failure, tachyarrhythmia, bronchospasm, depression, decreased exercise tolerance, Raynaud's phenomenon, etc.

The clinically relevant drug interactions of Betaxolol are briefly summarized here

• Oral Beta-Adrenergic Receptor Inhibitors

Patients who are receiving a beta-adrenergic receptor inhibitor orally and Betaxolol Ophthalmic Suspension 0.25% should be observed for a potential additive effect either on the intraocular pressure or on the known systemic effects of beta-blockade.

• Catecholamine-Depleting Drugs

Close observation of the patient is recommended when a beta-adrenergic receptor inhibitor is administered to patients receiving catecholamine-depleting drugs such as reserpine because of possible additive effects and the production of hypotension and/or bradycardia which may result in vertigo, syncope, or postural hypotension.

• Concomitant Adrenergic Psychotropic Drugs

Betaxolol is an adrenergic receptor inhibitor; therefore, caution should be exercised in patients using concomitant adrenergic psychotropic drugs.

The common side effects of Betaxolol include the following:

Insomnia, dizziness, vertigo, headaches, depression, lethargy, depression, dizziness, nausea, etc.

The use of Betaxolol should be prudent in the following group of special populations:

• Pregnancy

Teratogenic effects

Pregnancy Category C:

Reproduction, teratology, and peri- and postnatal studies have been conducted with orally administered betaxolol HCl in rats and rabbits. There was evidence of drug-related postimplantation loss in rabbits and rats at dose levels above 12 mg/kg and 128 mg/kg, respectively. Betaxolol HCl was not shown to be teratogenic, however, and there were no other adverse effects on reproduction at subtoxic dose levels. There are no adequate and well-controlled studies on pregnant women. Betaxolol Ophthalmic Suspension should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Nursing Mothers

It is not known whether betaxolol HCl is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Betaxolol Ophthalmic Suspension 0.25% is administered to nursing women.

• Pediatric Use

Safety and Intraocular pressure-lowering effect of Betaxolol Ophthalmic Suspension 0.25% has been demonstrated in pediatric patients in a 3-month, multicenter, double-masked, active-controlled trial.

• Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

• Symptoms:

Symptomatic bradycardia, bronchospasm, hypotension, and acute cardiac failure.

• Management:

Perform gastric lavage. Administer IV atropine sulfate to induce vagal blockade; dopamine, dobutamine, or norepinephrine for hypotension and glucagon for refractory cases; isoprenaline HCl and aminophylline for bronchospasm; conventional therapy w/ digitalis, diuretics, and oxygen for acute cardiac failure.

Pharmacodynamics:

Betaxolol is a competitive, beta(1)-selective (cardioselective) adrenergic antagonist. Betaxolol is used to treat hypertension, arrhythmias, coronary heart disease, and glaucoma and is also used to reduce non-fatal cardiac events in patients with heart failure. Activation of beta(1)-receptors by epinephrine increase the heart rate and blood pressure, and the heart consumes more oxygen. Drugs such as betaxolol that block these receptors, therefore, have the reverse effect: they lower 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 kidneys that leads to constriction of blood vessels. Betaxolol is lipophilic and exhibits no intrinsic sympathomimetic activity (ISA) or membrane stabilizing activity.

Pharmacokinetics:

• Absorption:

The 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.

• Distribution:

It crosses the placenta and is distributed into breast milk. The plasma protein binding of Betaxolol was found to be approximately 50%.

• Metabolism:

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

• Elimination:

It is eliminated through urine, and about 15% remained as an unchanged drug. The elimination half-life was found to be between 14-22 hours.

1. Goldberg I, Goldberg H. Betaxolol eye drops. A clinical trial of safety and efficacy. Aust N Z J Ophthalmol. 1995 Feb;23(1):17-24. doi: 10.1111/j.1442-9071.1995.tb01640.x. PMID: 7619450.
2. Berry DP Jr, Van Buskirk EM, Shields MB. Betaxolol and timolol. A comparison of efficacy and side effects. Arch Ophthalmol. 1984 Jan;102(1):42-5. doi: 10.1001/archopht.1984.01040030026028. PMID: 6367723.
3. https://clinicaltrials.gov/ct2/show/NCT01660620

1. Beresford R, Heel RC. Betaxolol. Drugs. 1986 Jan;31(1):6-28. Doi: https://doi.org/10.2165/00003495-198631010-00002
2. Goldberg I. Betaxolol. Australian and New Zealand Journal of Ophthalmology. 1989 Feb 1;17(1):9-13. Doi: https://doi.org/10.1111/j.1442-9071.1989.tb00483.x
3. Ramos BP, Colgan L, Nou E, Ovadia S, Wilson SR, Arnsten AF. The beta-1 adrenergic antagonist, betaxolol, improves working memory performance in rats and monkeys. Biological psychiatry. 2005 Dec 1;58(11):894-900. Doi: https://doi.org/10.1016/j.biopsych.2005.05.022
4. https://go.drugbank.com/drugs/DB00195
5. https://www.mims.com/india/drug/info/betaxolol?type=full&mtype=generic
6. https://www.ncbi.nlm.nih.gov/books/NBK557870/
7. https://reference.medscape.com/drug/betaxolol-342366
8. https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/19270s031lbl.pdf