What is the appropriate treatment for Timosan?

Timolol Treatment Overview

Timolol is a non-selective beta-adrenergic receptor antagonist used topically for treating thin and/or superficial infantile hemangiomas (IHs) and as an ophthalmic solution for glaucoma and ocular hypertension. 1

Primary Indication: Infantile Hemangiomas

When to Use Topical Timolol Maleate

Topical timolol maleate is recommended specifically for thin and/or superficial infantile hemangiomas, with best responses observed in lesions less than 1 mm thick. 1

• The American Academy of Pediatrics recommends topical timolol as a therapy option for thin and superficial IHs (Grade B, moderate recommendation) 1
• Early treatment (infants ≤6 months of age, with 41% being ≤3 months) may inhibit IH growth 1
• Only 7% of infants treated with topical timolol required subsequent systemic β-blocker therapy 1

Dosing and Administration

• Use ophthalmic timolol maleate 0.5% gel-forming solution applied topically to the lesion 1
• Treatment duration typically ranges from 1 to 3 months, with improvement noted in nearly 70% of patients at this timeframe and 92.3% with continued treatment 1

Safety Profile and Monitoring

Adverse events occur in approximately 3.4% of patients, with local irritation being the most common (nearly half of all adverse events). 1

• Reported adverse effects include: 1
  • Local irritation (most common)
  • Bronchospasm (rare, 3 cases in 731 patients)
  • Sleep disturbance
  • Cold extremities
  • Bradycardia (rare)
• No cardiovascular events were reported in the large cohort of 731 patients 1
• No adverse events were significant enough to require drug discontinuation 1

Critical Precautions

Exercise greater caution in preterm infants and those with ulcerated skin (non-intact skin barrier), as systemic absorption may be increased. 1

• Timolol is significantly more potent than propranolol 1
• Topical application bypasses first-pass liver metabolism, potentially increasing systemic exposure 1
• Timolol maleate can be detected in blood or urine of some treated infants despite topical administration 1

Exclusions

Do not use topical timolol for: 1

• Large-sized hemangiomas
• Significantly elevated/thick lesions (>1 mm)
• Deep or mixed IHs
• Life-threatening hemangiomas (these require systemic therapy)

Secondary Indication: Glaucoma and Ocular Hypertension

Ophthalmic Use

For glaucoma treatment, timolol maleate 0.5% solution reduces intraocular pressure (IOP) by 6-7 mm Hg at peak and 5-6 mm Hg at trough (approximately 25-28% reduction from baseline). 2

• Once-daily formulations (timolol-LA) are equivalent in efficacy to twice-daily standard timolol maleate solution 2
• Sustained IOP reductions occur with continuous administration from 1 to 18 months 3
• Effects are additive to miotics and carbonic anhydrase inhibitors in some patients 3

Systemic Effects from Ophthalmic Use

Ophthalmic timolol causes systemic beta-blockade due to absorption into systemic circulation, with heart rate changes being the most striking effect. 4

• 0.5% aqueous formulations produce larger systemic effects than 0.1% hydrogel formulations, especially during exercise 4
• Plasma levels correlate with heart rate changes 4
• Mild slowing of resting pulse rate occurs with systemic absorption 3
• No noteworthy effects on blood pressure (compensatory increase in systemic vascular resistance offsets HR reduction) 4
• No remarkable effects on pulmonary parameters (PEF, FEV1) in non-asthmatic patients 4

Pharmacogenetic Considerations

CYP2D6 poor metabolizers have higher peak plasma concentrations, longer elimination half-lives, and greater area-under-the-curve, making them more prone to bradycardia during ophthalmic timolol treatment. 4

Common Pitfalls to Avoid

• Do not use topical timolol for thick or deep hemangiomas – efficacy is limited to superficial lesions <1 mm thick 1
• Do not dismiss the risk of systemic absorption – timolol can be detected systemically and is more potent than propranolol 1
• Do not use in patients with compromised skin integrity without increased monitoring – ulcerated skin increases systemic absorption risk 1
• Do not confuse timosaponin A-III with timolol – these are completely different compounds (timosaponin A-III is an herbal extract with anti-wrinkle properties, not a beta-blocker) 5, 6