Timoptic®

Timolol Maleate 0.25% or 0.5% · preservative-free ophthalmic solution

Antiglaucoma

Approved uses

Elevated IOP in ocular hypertension or open-angle glaucoma

1 drop of 0.25% BID, increased to 1 drop of 0.5% BID if response is inadequate, and reducible to 1 drop QD once IOP is controlled

IOP falls within half an hour, peaks at 1 to 2 hours, and lowering can persist for 24 hours.

OFF-LABELNot in the FDA label for this product

Periocular and cutaneous infantile hemangioma

Timolol maleate solution 0.5% applied to the lesion BID for 24 weeks (trial regimen)

RCT · n=69 · no benefit

A multicenter double-blind placebo-controlled phase 2a trial in 69 infants aged 10 to 60 days found no significant difference in complete or nearly complete resolution at 24 weeks (42% vs 36%, P=.37; OR 1.33, 95% CI 0.45 to 3.89) and no between-group difference in lesion volume or thickness, with color improvement at week 4 and no systemic adverse effects; the authors concluded benefit is limited when treatment starts in the early proliferative stage. Periocular-specific experience is limited to small retrospective series.

Muñoz-Garza FZ, Ríos M, Roé-Crespo E, et al. JAMA Dermatol. 2021;157(5):583-587 (randomized clinical trial); Painter SL, Hildebrand GD. J AAPOS. 2016;20(2):172-174.e1 (retrospective consecutive case series, 5 children, timolol 0.5% solution BID).

Contraindications

Bronchial asthma or a history of bronchial asthma.
Severe chronic obstructive pulmonary disease.
Sinus bradycardia.
Second or third degree atrioventricular block.
Overt cardiac failure.
Cardiogenic shock.
Hypersensitivity to any component of this product.

Available Forms

0.25% and 0.5% preservative-free solution, 0.3 mL single-dose vials, 60 vials per carton

Mechanism of Action

Non-selective beta-1 and beta-2 adrenergic blocker with no significant intrinsic sympathomimetic, myocardial depressant, or membrane-stabilizing activity. Lowers elevated and normal IOP predominantly by reducing aqueous formation, with a slight increase in outflow facility in some studies.

Warnings & Precautions

Systemic absorption: Topical dosing can produce the same reactions as systemic beta-blockade, including death from bronchospasm in patients with asthma and, rarely, death in association with cardiac failure.
Cardiac failure: In patients without a history of cardiac failure, continued myocardial depression can lead to failure; discontinue at the first sign or symptom.
Obstructive pulmonary disease: Patients with mild or moderate COPD or bronchospastic disease should generally not receive beta-blockers.
Perioperative beta-blockade: Impairs the ability of the heart to respond to beta-adrenergically mediated reflex stimuli and may augment the risk of general anesthesia; protracted severe hypotension during anesthesia and difficulty restarting and maintaining the heartbeat have been reported, and some authorities recommend gradual withdrawal before elective surgery.
Diabetes mellitus: Masks the signs and symptoms of acute hypoglycemia; caution with labile diabetes or spontaneous hypoglycemia.
Thyrotoxicosis: Masks tachycardia and other signs of hyperthyroidism; abrupt withdrawal may precipitate thyroid storm.
Anaphylaxis: Patients with atopy or prior severe anaphylaxis may be more reactive on re-challenge and unresponsive to usual epinephrine doses.
Myasthenic symptoms: Beta-blockade can potentiate diplopia, ptosis, and generalized weakness.
Angle-closure glaucoma: Little or no effect on the pupil, so not for use alone in angle closure.
Choroidal detachment: Reported with aqueous suppressant therapy after filtration procedures.
Cerebrovascular insufficiency: Consider alternative therapy if signs of reduced cerebral blood flow develop after starting treatment.
Additive beta-blockade: Oral beta-blockers, calcium antagonists, digitalis, and CYP2D6 inhibitors can potentiate systemic effects; two topical beta-blockers together are not recommended.

Common Side Effects

Ocular: Burning and stinging on instillation, about 1 in 8 patients.
Ocular, less common: Conjunctivitis, blepharitis, keratitis, decreased corneal sensitivity, dry eye, ptosis, cystoid macular edema, pseudopemphigoid, choroidal detachment after filtration surgery.
Cardiovascular: Bradycardia, arrhythmia, hypotension, heart block, syncope, worsening angina, cardiac failure, cardiac arrest.
Respiratory: Bronchospasm (predominantly in patients with pre-existing bronchospastic disease), dyspnea, respiratory failure, cough, nasal congestion.
Neuropsychiatric: Headache, dizziness, fatigue, depression, confusion, memory loss, insomnia, increased signs and symptoms of myasthenia gravis.
Heart rate: Mean resting reduction of 2.9 beats/min (SD 10.2) in controlled trials.

Pregnancy & Lactation

Pregnancy: No adequate and well-controlled studies in pregnant women; use only if the potential benefit justifies the potential fetal risk (animal studies showed no malformations but increased fetal resorptions at high multiples of the ophthalmic dose).

Lactation: Timolol is detected in human milk after oral and ophthalmic dosing; decide whether to stop nursing or the drug, weighing its importance to the mother.

Pediatric Use

Safety and effectiveness established at 2 years and older; not established below 2 years.