Glumol

Approved Indications:

• Ocular Hypertension: To reduce elevated intraocular pressure (IOP) in patients with ocular hypertension.
• Open-Angle Glaucoma (Chronic Simple Glaucoma): As monotherapy or adjunctive therapy to lower IOP.
• Secondary Glaucomas: Including aphakic glaucoma and some forms of angle-closure glaucoma with laser/surgical treatment.
• Postoperative IOP Elevation: Following anterior segment surgery (e.g., cataract extraction).
• Migraine Prophylaxis (Oral use): For the prevention of migraine headaches (off-label but clinically accepted).
• Essential Hypertension (Oral use): As an antihypertensive agent, although rarely used today due to availability of better alternatives.
• Angina Pectoris (Oral use): For chronic stable angina.
• Myocardial Infarction (Post-MI): Secondary prevention of reinfarction and mortality reduction.

Ophthalmic (Adults):

• Initial dose: 1 drop of 0.25% or 0.5% solution in the affected eye(s) twice daily.
• Maintenance: May reduce to once daily if IOP is controlled.
• Combination therapy: May be used with other IOP-lowering agents (e.g., prostaglandin analogs, carbonic anhydrase inhibitors).

Oral (Adults – less commonly used):

• Hypertension: 10–30 mg twice daily.
• Migraine prophylaxis: 10–20 mg twice daily.
• Post-MI and angina: 10 mg twice daily.

Pediatrics (Ophthalmic use):

• Use with caution. Often starts with 0.25% solution once or twice daily under strict medical supervision.

Renal/Hepatic Impairment:

• Use with caution; no specific dose adjustment, but monitor closely due to potential systemic accumulation.

Administration Notes:

• Ophthalmic: Apply gentle nasolacrimal occlusion for 1–2 minutes to minimize systemic absorption.
• Oral: Administer with or without food, at the same times each day.

Timolol Maleate is a non-selective beta-adrenergic receptor blocker (beta-1 and beta-2). In the eye, it reduces aqueous humor production by the ciliary body, leading to decreased intraocular pressure. It does not significantly affect aqueous outflow. Systemically, oral timolol reduces heart rate, myocardial contractility, and sympathetic outflow, resulting in reduced blood pressure and cardiac workload. These effects contribute to its efficacy in cardiovascular and neurological conditions such as hypertension, angina, and migraine prevention.

• Absorption: Well absorbed systemically even after ophthalmic administration; oral bioavailability ~60%.
• Distribution: Widely distributed; crosses the blood-brain barrier and placenta.
• Protein Binding: ~60%.
• Metabolism: Extensively hepatic via CYP2D6.
• Active Metabolites: None significantly.
• Elimination Half-Life: Approximately 4–5 hours (longer in poor CYP2D6 metabolizers).
• Excretion: Primarily via kidneys (urine), both unchanged and as metabolites.

• Pregnancy: Not assigned by FDA (previously Category C). Use only if clearly needed. Animal studies show adverse effects; human data are limited.
• Lactation: Timolol is excreted in breast milk after both oral and ophthalmic use. May cause beta-blockade in the infant (e.g., bradycardia, apnea). Use with caution and monitor the infant.

• Primary Class: Non-selective Beta-Adrenergic Blocker
• Subclass: Beta-Blocker (Non-Cardioselective), Ophthalmic and Systemic

• Hypersensitivity to Timolol or any component of the formulation
• Bronchial asthma or history of bronchospasm
• Severe chronic obstructive pulmonary disease (COPD)
• Sinus bradycardia
• Second or third-degree atrioventricular (AV) block
• Overt cardiac failure
• Cardiogenic shock

• Respiratory risk: May cause bronchospasm and respiratory failure in asthmatic or COPD patients.
• Cardiac risk: Risk of bradycardia, hypotension, and heart block; monitor ECG in at-risk patients.
• Masking of hypoglycemia: Can mask signs of hypoglycemia in diabetic patients.
• Myasthenia gravis: May worsen symptoms.
• Withdrawal: Abrupt discontinuation can exacerbate angina or precipitate MI.
• Systemic absorption (Ophthalmic use): May cause systemic beta-blockade; especially dangerous in neonates or patients with comorbidities.

Ophthalmic Use:

• Common:
• Burning or stinging in eyes
• Blurred vision
• Dry eyes
• Eye discomfort
• Systemic (due to absorption):
• Bradycardia
• Hypotension
• Fatigue
• Dizziness
• Headache
• Rare/Serious:
• Bronchospasm
• Depression
• Arrhythmias
• Heart failure
• Anaphylaxis

Oral Use:

• Common:
• Cold extremities
• Fatigue
• Dizziness
• Bradycardia
• Serious:
• Heart block
• Hypotension
• Depression
• Sexual dysfunction

• Other Beta-Blockers: Additive effect increases risk of bradycardia or hypotension.
• Calcium Channel Blockers (e.g., verapamil, diltiazem): Increased risk of AV block or cardiac failure.
• CYP2D6 inhibitors (e.g., quinidine, fluoxetine): May increase plasma levels of timolol.
• Insulin and oral hypoglycemics: May enhance hypoglycemic effect and mask symptoms.
• Clonidine: Abrupt withdrawal may lead to rebound hypertension when combined with beta-blockers.

• Ophthalmic beta-blockers are no longer first-line in glaucoma per newer AAO and NICE guidelines, which favor prostaglandin analogs. Timolol is now used more often as adjunct therapy.
• FDA has reinforced the need for nasolacrimal occlusion after ophthalmic administration to minimize systemic absorption.
• Enhanced warnings added for pediatric use, especially in neonates, due to risk of systemic side effects.

• Ophthalmic solution:
• Store at 15°C to 30°C.
• Protect from light and moisture.
• Keep container tightly closed.
• Do not freeze.
• Discard 4 weeks after opening.
• Oral tablets:
• Store at 20°C to 25°C (controlled room temperature).
• Protect from excessive heat and moisture.