TIIMODROP

Timolol is a nonselective beta-adrenergic antagonist given in an eye drop solution to reduce intraocular pressure, or pressure in the eyes.

It is also used in tablet form as a drug to treat hypertension.

Timolol was first approved by the

FDA in 1978.

This drug is marketed by several manufacturers and is an effective agent for the management of conditions such as open-angle glaucoma and hypertension.

Ophthalmic timolol is indicated for the treatment of increased intraocular pressure in patients with ocular hypertension or open-angle glaucoma.

The oral form of this drug is used to treat high blood pressure. 16, 17 In certain cases, timolol is used in the prevention of migraine headaches. 9,

Timolol, when administered by the ophthalmic route, rapidly reduces intraocular pressure.

When administered in the tablet form, it reduces blood pressure, heart rate, and cardiac output, and decreases sympathetic activity. 1, 2, 3, 17.

This drug has a fast onset of action, usually occurring within 20 minutes of the administration of an ophthalmic dose.

Timolol maleate can exert pharmacological actions for as long as 24 hours if given in the 0.5% or 0.25% doses.

The systemic bioavailability of the ophthalmic eyedrop in one study of healthy volunteers was 78.0 ± 24.5% 10, indicating that caution must be observed when this drug is administered, as it may be significantly absorbed and have various systemic effects.

Another study measured the bioavailability of timolol eyedrops to be 60% in healthy volunteers.

The peak concentration of ophthalmic timolol in plasma, Cmax was about 1.14 ng/ml in most subjects within 15 minutes following the administration of timolol by the ophthalmic route.

The mean area under the curve (AUC) was about 6.46 ng/ml per hour after intravenous injection and about 4.78 ng/ml per hour following eyedrop administration.

1.3-1.7 L/kg 22 Timolol is distributed to the following tissues: the conjunctiva, cornea, iris, sclera, aqueous humor, kidney, liver, and lung.

Timolol is metabolized in the liver by the cytochrome P450 2D6 enzyme, with minor contributions from CYP2C19. 12, 16 15-20% of a dose undergoes first-pass metabolism.

Despite its relatively low first pass metabolism, timolol is 90% metabolized.

Four metabolites of timolol have been identified, with a hydroxy metabolite being the most predominant.

Hover over products below to view reaction partners Timolol M1 metabolite, timolol.

Timolol and its metabolites are mainly found excreted in the urine.

Timolol half-life was measured at 2.9 ± 0.3 h hours in a clinical study of healthy volunteers.

One pharmacokinetic study in healthy volunteers measured the total plasma clearance of timolol to be 557 ± 61 ml/min.

Another study determined the total clearance 751.5 ± 90.6 ml/min and renal clearance to be 97.2 ± 10.1 ml/min in healthy volunteers.

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The oral

LD50 for timolol maleate is 1028 mg/kg in the rat and 1137 mg/kg in the mouse.

Symptoms of timolol overdose may include dizziness, headache, shortness of breath, bradycardia, in addition to bronchospasm.

Sometimes, an overdose may lead to cardiac arrest.

An overdose of timolol can be reversed with dialysis, however, patients with renal failure may not respond as well to dialysis treatment.

Dorzolamide hydrochloride and timolol maleate ophthalmic solution is contraindicated in patients with: 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. 4.1 Asthma, COPD Dorzolamide hydrochloride and timolol maleate ophthalmic solution is contraindicated in patients with bronchial asthma, a history of bronchial asthma, or severe chronic obstructive pulmonary disease. 4.2 Sinus Bradycardia, AV Block, Cardiac Failure, Cardiogenic Shock Dorzolamide hydrochloride and timolol maleate ophthalmic solution is contraindicated in patients with sinus bradycardia, second or third degree atrioventricular block, overt cardiac failure, and cardiogenic shock. 4.3 Hypersensitivity Dorzolamide hydrochloride and timolol maleate ophthalmic solution is contraindicated in patients who are hypersensitive to any component of this product.

& ADMINISTRATION The dose is one drop of dorzolamide hydrochloride and timolol maleate ophthalmic solution in the affected eye(s) two times daily.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart.

The dose is one drop of dorzolamide hydrochloride and timolol maleate ophthalmic solution in the affected eye(s) two times daily.

Dorzolamide hydrochloride and timolol maleate ophthalmic solution, USP 2%/0.5% is supplied in 10mL a natural, LDPE plastic ophthalmic dispenser with a natural nozzle and a dark blue, tamper-evident cap.

NDC 71921-226-10, 10 mL in a 10 mL capacity bottle.

Store dorzolamide hydrochloride and timolol maleate ophthalmic solution at 20° to 25°C (68° to 77°F) .

Protect from light.

After opening, dorzolamide hydrochloride and timolol maleate ophthalmic solution can be used until the expiration date on the bottle.

Developmental toxicity studies with dorzolamide hydrochloride in rabbits at oral doses of ≥ 2.5 mg/kg/day (37 times the recommended human ophthalmic dose) revealed malformations of the vertebral bodies.

These malformations occurred at doses that caused metabolic acidosis with decreased body weight gain in dams and decreased fetal weights.

No treatment-related malformations were seen at 1 mg/kg/day (15 times the recommended human ophthalmic dose).

Teratogenicity studies with timolol in mice, rats, and rabbits at oral doses up to 50 mg/kg/day (7,000 times the systemic exposure following the maximum recommended human ophthalmic dose) demonstrated no evidence of fetal malformations.

Although delayed fetal ossification was observed at this dose in rats, there were no adverse effects on postnatal development of offspring.

Doses of 1,000 mg/kg/day (142,000 times the systemic exposure following the maximum recommended human ophthalmic dose) were maternotoxic in mice and resulted in an increased number of fetal resorptions.

Increased fetal resorptions were also seen in rabbits at doses of 14,000 times the systemic exposure following the maximum recommended human ophthalmic dose, in this case without apparent maternotoxicity.

There are no adequate and well-controlled studies in pregnant women.

Dorzolamide hydrochloride and timolol maleate ophthalmic solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether dorzolamide is excreted in human milk.

Timolol maleate has been detected in human milk following oral and ophthalmic drug administration.

Because of the potential for serious adverse reactions from dorzolamide hydrochloride and timolol maleate ophthalmic solution in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

The safety and effectiveness of dorzolamide hydrochloride ophthalmic solution and timolol maleate ophthalmic solution have been established when administered individually in pediatric patients aged 2 years and older.

Use of these drug products in these children is supported by evidence from adequate and well-controlled studies in children and adults.

Safety and efficacy in pediatric patients below the age of 2 years have not been established.

No overall differences in safety or effectiveness have been observed between elderly and younger patients.