ISTALOL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ISTALOL (ISTALOL).

How it works

Nonselective beta-adrenergic receptor antagonist (beta-blocker). Reduces intraocular pressure by decreasing aqueous humor production, possibly by blocking beta-2 receptors on the ciliary epithelium. Also has membrane-stabilizing activity at high concentrations.

What the body does with it

Metabolism	Primarily metabolized by CYP2D6 to form 4-hydroxy-timolol (active metabolite). Also undergoes minor N-dealkylation and glucuronidation.
Excretion	Renal: approximately 70% as unchanged drug and metabolites; biliary/fecal: approximately 20%.
Half-life	Terminal elimination half-life: 18–26 hours; clinically, steady-state is achieved after 5–7 days of dosing.
Protein binding	Approximately 50–60%, primarily to albumin.
Volume of Distribution	1.2–1.8 L/kg; indicates extensive tissue distribution.
Bioavailability	Oral: approximately 70–80% due to first-pass metabolism.
Onset of Action	Oral: 1–2 hours; intravenous: within 5 minutes.
Duration of Action	Oral: 12–24 hours; intravenous: 6–12 hours; clinical effects may persist beyond half-life due to sustained beta-blockade.

Classification & Brands

Dosing & administration

1 drop of 0.5% ophthalmic solution into the affected eye(s) twice daily.

Dosage form	SOLUTION/DROPS
Renal impairment	No dosage adjustment required for ophthalmic use; systemic absorption is minimal.
Liver impairment	No specific adjustment for ophthalmic use; caution in severe hepatic impairment due to potential systemic effects.
Pediatric use	Safety and efficacy in pediatric patients have not been established.
Geriatric use	No specific dosage adjustment; use with caution due to increased risk of systemic side effects from decreased lacrimal drainage.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ISTALOL (ISTALOL).

Breastfeeding	Timolol is excreted in breast milk; M/P ratio unknown. Ophthalmic use yields low systemic levels, but infant exposure possible. Monitor infant for bradycardia, hypotension, and hypoglycemia. Use with caution, consider benefit versus risk.
Teratogenic Risk	Istalol (timolol ophthalmic solution) is a non-selective beta-blocker. Systemic absorption is low but may occur. First trimester: Limited data; avoid unless benefit outweighs risk. Second/Third trimester: Beta-blockers may cause fetal bradycardia, growth restriction, and hypoglycemia. Monitor fetal heart rate and growth. Not a known major teratogen.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Bronchial asthma","Chronic obstructive pulmonary disease (COPD)","Sinus bradycardia","Second- or third-degree atrioventricular block","Cardiogenic shock","Overt cardiac failure"]

Clinical Precautions

Precautions

["Cardiac failure: May precipitate or worsen heart failure; monitor for signs of CHF.","Bronchospasm: Contraindicated in patients with bronchial asthma or COPD; may cause bronchospasm.","Masking of hypoglycemia in diabetic patients.","Masking of thyrotoxicosis symptoms.","Anaphylactic reactions: May be more severe and resistant to epinephrine treatment.","Gastrointestinal symptoms (nausea, diarrhea) reported.","Withdrawal: Taper gradually to avoid exacerbation of angina or myocardial infarction."]

Clinical Tips & Counseling

Drug interactions

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ISTALOL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ISTALOL (ISTALOL).

How it works

What the body does with it

Metabolism	Primarily metabolized by CYP2D6 to form 4-hydroxy-timolol (active metabolite). Also undergoes minor N-dealkylation and glucuronidation.
Excretion	Renal: approximately 70% as unchanged drug and metabolites; biliary/fecal: approximately 20%.
Half-life	Terminal elimination half-life: 18–26 hours; clinically, steady-state is achieved after 5–7 days of dosing.
Protein binding	Approximately 50–60%, primarily to albumin.
Volume of Distribution	1.2–1.8 L/kg; indicates extensive tissue distribution.
Bioavailability	Oral: approximately 70–80% due to first-pass metabolism.
Onset of Action	Oral: 1–2 hours; intravenous: within 5 minutes.
Duration of Action	Oral: 12–24 hours; intravenous: 6–12 hours; clinical effects may persist beyond half-life due to sustained beta-blockade.

Classification & Brands

Dosing & administration

1 drop of 0.5% ophthalmic solution into the affected eye(s) twice daily.

Dosage form	SOLUTION/DROPS
Renal impairment	No dosage adjustment required for ophthalmic use; systemic absorption is minimal.
Liver impairment	No specific adjustment for ophthalmic use; caution in severe hepatic impairment due to potential systemic effects.
Pediatric use	Safety and efficacy in pediatric patients have not been established.
Geriatric use	No specific dosage adjustment; use with caution due to increased risk of systemic side effects from decreased lacrimal drainage.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ISTALOL (ISTALOL).

Breastfeeding	Timolol is excreted in breast milk; M/P ratio unknown. Ophthalmic use yields low systemic levels, but infant exposure possible. Monitor infant for bradycardia, hypotension, and hypoglycemia. Use with caution, consider benefit versus risk.
Teratogenic Risk	Istalol (timolol ophthalmic solution) is a non-selective beta-blocker. Systemic absorption is low but may occur. First trimester: Limited data; avoid unless benefit outweighs risk. Second/Third trimester: Beta-blockers may cause fetal bradycardia, growth restriction, and hypoglycemia. Monitor fetal heart rate and growth. Not a known major teratogen.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Bronchial asthma","Chronic obstructive pulmonary disease (COPD)","Sinus bradycardia","Second- or third-degree atrioventricular block","Cardiogenic shock","Overt cardiac failure"]