LEVOBUNOLOL HYDROCHLORIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LEVOBUNOLOL HYDROCHLORIDE (LEVOBUNOLOL HYDROCHLORIDE).

How it works

Nonselective beta-adrenergic receptor antagonist; reduces intraocular pressure by decreasing aqueous humor production.

What the body does with it

Metabolism	Metabolized in the liver via glucuronidation and CYP2D6 to active metabolite dihydrolevobunolol.
Excretion	Renal: 15-20% unchanged; hepatic metabolism to dihydrolevobunolol (active, t1/2 7-8 hours) and other inactive metabolites; total renal excretion of drug and metabolites ~90%; fecal excretion minimal (<5%).
Half-life	Parent drug: 3-7 hours (mean 5 hours); active metabolite dihydrolevobunolol: 7-8 hours; prolonged in hepatic impairment, clinical context suggests b.i.d. dosing maintains therapeutic effect.
Protein binding	Parent drug: 25-30% (primarily to albumin); dihydrolevobunolol: 25-30%.
Volume of Distribution	Parent drug: 1-3 L/kg, indicating extensive tissue distribution; active metabolite volume not well defined.
Bioavailability	Ophthalmic: systemic absorption ~80% via nasolacrimal drainage, but therapeutic ocular effect from topical dose; oral: high bioavailability (~90%) but not used clinically due to systemic side effects.
Onset of Action	Ophthalmic: 30-60 minutes for intraocular pressure reduction; maximal effect at 2-6 hours.
Duration of Action	Ophthalmic: 24 hours (maintains IOP reduction for 24 hours with once or twice daily dosing); clinical note: continuous therapy required.

Classification & Brands

Dosing & administration

One drop of 0.25% or 0.5% solution in the affected eye(s) twice daily. May increase to 0.5% twice daily if response inadequate.

Dosage form	SOLUTION/DROPS
Renal impairment	No specific dose adjustments recommended for topical use; systemic absorption is minimal. Use caution in severe renal impairment (CrCl <30 mL/min) due to possible accumulation of active metabolite.
Liver impairment	No specific dose adjustments recommended for topical use. Use caution in severe hepatic impairment (Child-Pugh class C) due to reduced metabolism.
Pediatric use	Safety and efficacy in children have not been established. Limited data: 0.25% solution, one drop twice daily in affected eye(s) for children ≥6 years.
Geriatric use	No specific dose adjustment; initiate therapy at lowest concentration (0.25%) and monitor intraocular pressure and systemic effects closely due to increased sensitivity and higher prevalence of comorbidities.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LEVOBUNOLOL HYDROCHLORIDE (LEVOBUNOLOL HYDROCHLORIDE).

Breastfeeding	Levobunolol is excreted in human milk in small amounts. The milk-to-plasma ratio is unknown. Due to potential for serious adverse reactions in nursing infants, caution is advised. Consider discontinuing nursing or the drug, taking into account the importance of the drug to the mother.
Teratogenic Risk	Levobunolol hydrochloride is a beta-blocker. In animal studies, no teratogenic effects were observed at doses up to 24 mg/kg/day in rabbits and 32 mg/kg/day in rats. No adequate and well-controlled studies in pregnant women. Beta-blockers may cause fetal bradycardia, growth restriction, and hypoglycemia, especially in the second and third trimesters. Use only if potential benefit justifies risk.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Bronchial asthma","Severe COPD","Sinus bradycardia","Second- or third-degree AV block","Overt cardiac failure","Cardiogenic shock","Hypersensitivity to any component"]

Clinical Precautions

Precautions

["May exacerbate asthma and other respiratory conditions","May mask signs of hyperthyroidism","May potentiate muscle weakness in myasthenia gravis","Use with caution in patients with sinus bradycardia, heart block, or heart failure"]

Clinical Tips & Counseling

Drug interactions

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LEVOBUNOLOL HYDROCHLORIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LEVOBUNOLOL HYDROCHLORIDE (LEVOBUNOLOL HYDROCHLORIDE).

How it works

Nonselective beta-adrenergic receptor antagonist; reduces intraocular pressure by decreasing aqueous humor production.

What the body does with it

Metabolism	Metabolized in the liver via glucuronidation and CYP2D6 to active metabolite dihydrolevobunolol.
Excretion	Renal: 15-20% unchanged; hepatic metabolism to dihydrolevobunolol (active, t1/2 7-8 hours) and other inactive metabolites; total renal excretion of drug and metabolites ~90%; fecal excretion minimal (<5%).
Half-life	Parent drug: 3-7 hours (mean 5 hours); active metabolite dihydrolevobunolol: 7-8 hours; prolonged in hepatic impairment, clinical context suggests b.i.d. dosing maintains therapeutic effect.
Protein binding	Parent drug: 25-30% (primarily to albumin); dihydrolevobunolol: 25-30%.
Volume of Distribution	Parent drug: 1-3 L/kg, indicating extensive tissue distribution; active metabolite volume not well defined.
Bioavailability	Ophthalmic: systemic absorption ~80% via nasolacrimal drainage, but therapeutic ocular effect from topical dose; oral: high bioavailability (~90%) but not used clinically due to systemic side effects.
Onset of Action	Ophthalmic: 30-60 minutes for intraocular pressure reduction; maximal effect at 2-6 hours.
Duration of Action	Ophthalmic: 24 hours (maintains IOP reduction for 24 hours with once or twice daily dosing); clinical note: continuous therapy required.

Classification & Brands

Dosing & administration

One drop of 0.25% or 0.5% solution in the affected eye(s) twice daily. May increase to 0.5% twice daily if response inadequate.

Dosage form	SOLUTION/DROPS
Renal impairment	No specific dose adjustments recommended for topical use; systemic absorption is minimal. Use caution in severe renal impairment (CrCl <30 mL/min) due to possible accumulation of active metabolite.
Liver impairment	No specific dose adjustments recommended for topical use. Use caution in severe hepatic impairment (Child-Pugh class C) due to reduced metabolism.
Pediatric use	Safety and efficacy in children have not been established. Limited data: 0.25% solution, one drop twice daily in affected eye(s) for children ≥6 years.
Geriatric use	No specific dose adjustment; initiate therapy at lowest concentration (0.25%) and monitor intraocular pressure and systemic effects closely due to increased sensitivity and higher prevalence of comorbidities.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LEVOBUNOLOL HYDROCHLORIDE (LEVOBUNOLOL HYDROCHLORIDE).

Breastfeeding	Levobunolol is excreted in human milk in small amounts. The milk-to-plasma ratio is unknown. Due to potential for serious adverse reactions in nursing infants, caution is advised. Consider discontinuing nursing or the drug, taking into account the importance of the drug to the mother.
Teratogenic Risk	Levobunolol hydrochloride is a beta-blocker. In animal studies, no teratogenic effects were observed at doses up to 24 mg/kg/day in rabbits and 32 mg/kg/day in rats. No adequate and well-controlled studies in pregnant women. Beta-blockers may cause fetal bradycardia, growth restriction, and hypoglycemia, especially in the second and third trimesters. Use only if potential benefit justifies risk.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

["Bronchial asthma","Severe COPD","Sinus bradycardia","Second- or third-degree AV block","Overt cardiac failure","Cardiogenic shock","Hypersensitivity to any component"]