Betaxolol

Usage

Betaxolol is primarily prescribed for:

• Hypertension (High Blood Pressure): It is used to lower blood pressure, either alone or in combination with other antihypertensive medications.
• Glaucoma: Betaxolol ophthalmic solution is used to reduce intraocular pressure.
• Post-Myocardial Infarction: In some cases, it may be used to reduce the risk of subsequent cardiac events after a heart attack.

Pharmacological Classification:

Betaxolol is classified as a cardioselective beta-1 adrenergic receptor blocker, also known as a beta-blocker.

Mechanism of Action:

Betaxolol primarily blocks beta-1 adrenergic receptors in the heart. This action reduces heart rate, myocardial contractility, and cardiac output, leading to a decrease in blood pressure. It also reduces renin release from the kidneys. While primarily beta-1 selective, at higher doses, some beta-2 blocking activity can occur.

Alternate Names

International or Regional Variations: Betaxolol hydrochloride.

Brand Names: Kerlone (oral), Betoptic, Betoptic S (ophthalmic).

How It Works

Pharmacodynamics:

• Betaxolol lowers blood pressure by decreasing heart rate, myocardial contractility, cardiac output, and renin release.
• It has minimal effect on peripheral vascular resistance.
• It may increase airway resistance, especially at higher doses or in susceptible individuals.

Pharmacokinetics:

• Absorption: Well-absorbed orally, reaching peak plasma concentration in 1.5 to 6 hours.
• Distribution: Distributes widely, including into breast milk. Approximately 50% protein bound.
• Metabolism: Primarily metabolized in the liver to inactive metabolites.
• Elimination: Excreted primarily in the urine as metabolites and unchanged drug. Elimination half-life is 14-22 hours, prolonged in renal impairment.

Mode of Action:

Betaxolol competitively binds to beta-1 adrenergic receptors in the heart, blocking the binding of catecholamines (such as norepinephrine and epinephrine). This inhibition reduces sympathetic stimulation of the heart, leading to decreased heart rate and contractility.

Receptor Binding: Primarily binds to beta-1 adrenergic receptors with high selectivity at lower doses. At higher doses, some beta-2 receptor blockade may occur.

Elimination Pathways: Primarily renal excretion of inactive metabolites and unchanged drug. Hepatic metabolism plays a role but hepatic impairment does not significantly alter clearance.

Dosage

Standard Dosage

Adults:

• Hypertension: Initial dose: 5-10 mg orally once daily. Maintenance dose: 10-20 mg orally once daily. Maximum dose: Up to 40 mg/day has been studied but doses above 20mg provide little additional antihypertensive effect.
• Glaucoma: 1 drop of 0.25% or 0.5% ophthalmic solution in the affected eye(s) twice daily.

Children:

Safety and efficacy in children for oral betaxolol have not been established. Betaxolol ophthalmic solution 0.25% can be used in children over 2 years.

Special Cases:

• Elderly Patients: Initial dose: 5 mg orally once daily. Increased risk of bradycardia requires careful monitoring.
• Patients with Renal Impairment: Severe impairment: initial dose 5 mg orally once daily, increasing by 5 mg every 2 weeks to a maximum of 20 mg daily. Hemodialysis requires a starting dose of 5 mg/day, titratable as above.
• Patients with Hepatic Dysfunction: No routine dosage adjustments are needed, but careful monitoring is recommended.
• Patients with Comorbid Conditions: Use with caution in patients with asthma, COPD, diabetes, and peripheral vascular disease. Close monitoring is necessary.

Clinical Use Cases

Betaxolol is not typically indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like status epilepticus or cardiac arrest. Other medications are preferred in these clinical settings.

Dosage Adjustments

Dosage adjustments are required for renal impairment, and should be considered for elderly patients. Consider dividing the dose for patients with bronchospastic diseases if doses above 10mg are necessary. Monitor renal function, blood pressure, and heart rate, and adjust accordingly. Patients with hepatic disease usually do not need changes to their dosage, however these patients should be observed.

Side Effects

Common Side Effects:

• Ophthalmic: Eye discomfort, burning, stinging, blurred vision, tearing, dry eyes.
• Oral: Fatigue, dizziness, bradycardia, cold hands and feet, nausea, dysgeusia.

Rare but Serious Side Effects:

• Ophthalmic: Keratitis
• Oral: Hypotension, heart block, bronchospasm, heart failure, masking of hypoglycemia symptoms, allergic reactions.

Long-Term Effects:

Chronic complications from prolonged use of oral betaxolol are rare but can include worsening of heart failure or bronchospastic disease.

Adverse Drug Reactions (ADR):

Severe bradycardia, heart block, bronchospasm, and anaphylaxis require immediate intervention.

Contraindications

• Absolute: Sinus bradycardia, second- or third-degree heart block (without a pacemaker), cardiogenic shock, overt cardiac failure, hypersensitivity to betaxolol.
• Relative: Severe bronchospastic disease (COPD, asthma), Prinzmetal’s angina, untreated pheochromocytoma.

Drug Interactions

• Calcium channel blockers (e.g., diltiazem, verapamil): Increased risk of bradycardia and hypotension.
• Clonidine: Exacerbated rebound hypertension upon clonidine withdrawal.
• Digoxin: Increased risk of bradycardia.
• Other beta-blockers: Additive effects on heart rate and blood pressure.
• CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): May increase betaxolol levels.
• Insulin, oral hypoglycemics: May mask signs of hypoglycemia.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C. Use with caution only if the benefits outweigh the risks. Fetal risks include bradycardia, hypoglycemia, and intrauterine growth restriction.
• Breastfeeding: Betaxolol is excreted in breast milk and may cause adverse effects in nursing infants. Use with caution. Consider safer alternative medications.

Drug Profile Summary

• Mechanism of Action: Cardioselective beta-1 adrenergic receptor blocker.
• Side Effects: Fatigue, dizziness, bradycardia, cold extremities (oral), eye irritation, blurred vision (ophthalmic).
• Contraindications: Sinus bradycardia, heart block, cardiogenic shock, overt cardiac failure.
• Drug Interactions: Calcium channel blockers, clonidine, digoxin.
• Pregnancy & Breastfeeding: Category C; use with caution. Excreted in breast milk.
• Dosage: Hypertension: 5-20 mg orally once daily. Glaucoma: 1 drop 0.25% or 0.5% solution twice daily.
• Monitoring Parameters: Heart rate, blood pressure, renal function, intraocular pressure (ophthalmic), blood glucose (in diabetics).

Popular Combinations

Betaxolol is often combined with thiazide diuretics for synergistic antihypertensive effects.

Precautions

• General Precautions: Assess cardiac, respiratory, and renal function before initiating therapy. Monitor for adverse effects.
• Specific Populations:
  • Pregnant Women: Use with caution if benefits outweigh risks.
  • Breastfeeding Mothers: Use with caution. Monitor infant for bradycardia and hypoglycemia.
  • Children & Elderly: Safety and efficacy not established for oral use in children. Reduced initial dose for elderly.
  • Lifestyle Considerations: May impair ability to operate machinery or drive. Limit alcohol intake.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Betaxolol?

A: For hypertension in adults, the initial dose is 5-10 mg once daily, which can be increased to a maximum of 20 mg once daily. For glaucoma, the dose is one drop of 0.25% or 0.5% solution twice daily. Elderly patients should start with a lower dose of 5 mg daily. Pediatric use is not recommended for oral use.

Q2: How does Betaxolol differ from other beta-blockers?

A: Betaxolol is cardioselective, meaning it preferentially blocks beta-1 receptors. This selectivity reduces the likelihood of bronchospasm compared to non-selective beta-blockers, but caution is still advised in patients with respiratory conditions.

Q3: Can Betaxolol be used in patients with asthma?

A: Use with extreme caution and at the lowest effective dose in patients with mild asthma or COPD. Closely monitor for respiratory adverse effects. Avoid using in patients with severe reactive airway disease. Have a bronchodilator readily available.

Q4: What are the most serious side effects of Betaxolol?

A: Bradycardia, heart block, hypotension, and bronchospasm are potentially serious side effects that require immediate attention. Worsening of heart failure can also occur.

Q5: Are there any drug interactions I should be aware of?

A: Calcium channel blockers can exacerbate bradycardia and hypotension. Clonidine can lead to rebound hypertension if withdrawn while on betaxolol. Digoxin can increase the risk of bradycardia.

Q6: Can Betaxolol be used during pregnancy or breastfeeding?

A: Betaxolol is Pregnancy Category C. Use only if benefits outweigh risks. It is excreted in breast milk and may cause adverse effects in infants. Use with caution during breastfeeding.

Q7: How should Betaxolol be discontinued?

A: Taper the dose gradually over 1-2 weeks to avoid rebound hypertension or angina exacerbation. Closely monitor patients during withdrawal.

Q8: What should I monitor in patients taking Betaxolol?

A: Monitor heart rate, blood pressure, renal function, intraocular pressure (in glaucoma patients), and blood glucose (in diabetics).

Q9: Can Betaxolol be used in patients with renal impairment?

A: Yes, but with dosage adjustments. For severe renal impairment, the initial dose is 5 mg once daily, with increases every 2 weeks as needed, up to a maximum of 20 mg daily. Similar dosing is recommended for patients on dialysis.

Q10: Is Betaxolol effective for acute management of cardiac conditions?

A: No. Betaxolol is generally not used for acute management of conditions like cardiac arrest or status epilepticus. Other medications are preferred in such emergent settings. Betaxolol is typically used for chronic conditions like hypertension and glaucoma.