TIMOLOL

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Nonselective beta-adrenergic receptor antagonist (beta-blocker) that competively blocks beta-1 and beta-2 receptors, reducing heart rate, contractility, and cardiac output. In glaucoma, decreases intraocular pressure by reducing aqueous humor production.

What the body does with it

Metabolism	Primarily hepatic metabolism by CYP2D6; significant first-pass effect.
Excretion	Renal: ~20% unchanged; hepatic metabolism accounts for ~80%, with metabolites excreted renally; minor biliary/fecal elimination (<5%).
Half-life	Terminal half-life: 4-5 hours (healthy adults); prolonged to 7-10 hours in renal impairment, 11-16 hours in hepatic impairment; clinical context: once-daily dosing for hypertension/glaucoma.
Protein binding	~60% bound, primarily to albumin.
Volume of Distribution	Vd: 1.7-2.8 L/kg; indicates extensive tissue distribution (e.g., heart, lung, eye).
Bioavailability	Oral: ~75% (first-pass metabolism ~25%); ophthalmic: minimal systemic absorption (<10% due to nasolacrimal drainage).
Onset of Action	Oral: 1-2 hours; intravenous: within 1 minute; ophthalmic: 30-60 minutes (peak IOP reduction).
Duration of Action	Oral: 12-24 hours; intravenous: 6-12 hours; ophthalmic: 24 hours (reduces intraocular pressure for 24 hours with once-daily dosing).

Classification & Brands

Dosing & administration

0.25-0.5 mg ophthalmic solution instilled twice daily; for oral: 10-20 mg twice daily.

Dosage form	SOLUTION/DROPS
Renal impairment	GFR <30 mL/min: use with caution, reduce dose by 25-50%.
Liver impairment	Child-Pugh class C: avoid use; class A and B: use with caution, reduce dose by 50%.
Pediatric use	For hypertension: initial 0.1 mg/kg orally twice daily, titrate to 0.5-1 mg/kg/day; for glaucoma: 0.25% solution, one drop twice daily.
Geriatric use	Initiate at lowest dose (0.25% ophthalmic or 5 mg oral twice daily); monitor for bradycardia and bronchospasm.

Use during pregnancy

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

Clinical note

Other drugs that lower heart rate or blood pressure can have additive effects Can cause bronchospasm in patients with asthma.

Breastfeeding

Timolol is excreted into breast milk in low concentrations. The milk-to-plasma (M/P) ratio is approximately 0.8. At typical maternal doses, the estimated daily infant dose is less than 10% of the maternal weight-adjusted dose, generally considered compatible with breastfeeding. Monitor infant for signs of bradycardia or hypotension.

Teratogenic Risk

Timolol, a nonselective beta-blocker, is FDA Pregnancy Category C. In pregnancy, first trimester exposure may be associated with a slight increase in risk of congenital malformations, particularly cardiovascular defects, although data are limited. Second and third trimester exposure can cause fetal bradycardia, growth restriction, hypoglycemia, and respiratory depression due to beta-blockade. Use only if potential benefit justifies fetal risk.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning.

Side Effect Profile

Common Effects	hypertension
Serious Effects

Absolute Contraindications

["Bronchial asthma","Sinus bradycardia","Heart block (greater than first degree)","Cardiogenic shock","Overt cardiac failure","Hypersensitivity to timolol"]

Clinical Precautions

Precautions

["Cardiac failure: May precipitate or worsen heart failure.","Bronchospasm: Avoid in patients with asthma or COPD.","Abrupt withdrawal: May exacerbate angina or cause myocardial infarction.","Bradycardia: Can cause symptomatic bradycardia.","Peripheral vascular disease: May aggravate symptoms.","Diabetes: May mask hypoglycemia symptoms.","Thyrotoxicosis: May mask signs of hyperthyroidism.","Ophthalmic use: May cause systemic effects similar to oral form."]

Clinical Tips & Counseling

Drug interactions

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