Timolol 5 MG/ML Ophthalmic Solution


As with other topically applied ophthalmic drugs, Betimol ® is absorbed systemically.

The same adverse reactions found with systemic administration of beta-adrenergic blocking agents may occur with topical administration.

For example, severe respiratory and cardiac reactions, including death due to bronchospasm in patients with asthma, and rarely, death in association with cardiac failure have been reported following systemic or topical administration of beta-adrenergic blocking agents.

Cardiac Failure Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe cardiac failure.

In patients without a history of cardiac failure, continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure.

Betimol ® should be discontinued at the first sign or symptom of cardiac failure.

Obstructive Pulmonary Disease Patients with chronic obstructive pulmonary disease (e.g.

chronic bronchitis, emphysema) of mild or moderate severity, bronchospastic disease, or a history of bronchospastic disease (other than bronchial asthma or a history of bronchial asthma which are contraindications) should in general not receive beta-blocking agents.

Major Surgery The necessity or desirability of withdrawal of beta-adrenergic blocking agents prior to a major surgery is controversial.

Beta-adrenergic receptor blockade impairs the ability of the heart to respond to beta-adrenergically mediated reflex stimuli.

This may augment the risk of general anesthesia in surgical procedures.

Some patients receiving beta-adrenergic receptor blocking agents have been subject to protracted severe hypotension during anesthesia.

Difficulty in restarting and maintaining the heartbeat has also been reported.

For these reasons, in patients undergoing elective surgery, gradual withdrawal of beta-adrenergic receptor blocking agents is recommended.

If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of beta-adrenergic agonists.

Diabetes Mellitus Beta-adrenergic blocking agents should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents.

Beta-adrenergic receptor blocking agents may mask the signs and symptoms of acute hypoglycemia.

Thyrotoxicosis Beta-adrenergic blocking agents may mask certain clinical signs (e.g.

tachycardia) of hyperthyroidism.

Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blocking agents which might precipitate a thyroid storm.


Drug Interactions Beta-adrenergic blocking agents Patients who are receiving a beta-adrenergic blocking agent orally and Betimol ® should be observed for a potential additive effect either on the intraocular pressure or on the known systemic effects of beta-blockade.

Patients should not usually receive two topical ophthalmic beta-adrenergic blocking agents concurrently.

Catecholamine-depleting drugs Close observation of the patient is recommended when a beta-blocker is administered to patients receiving catecholamine-depleting drugs such as reserpine, because of possible additive effects and the production of hypotension and/or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.

Calcium antagonists Caution should be used in the co-administration of beta-adrenergic blocking agents and oral or intravenous calcium antagonists, because of possible atrioventricular conduction disturbances, left ventricular failure, and hypotension.

In patients with impaired cardiac function, co-administration should be avoided.

Digitalis and calcium antagonists The concomitant use of beta-adrenergic blocking agents with digitalis and calcium antagonists may have additive effects in prolonging atrioventricular conduction time.

Injectable Epinephrine (See PRECAUTIONS, General, Anaphylaxis .)


No information is available on overdosage with Betimol ® .

Symptoms that might be expected with an overdose of a beta-adrenergic receptor blocking agent are bronchospasm, hypotension, bradycardia, and acute cardiac failure.


Betimol ® (timolol ophthalmic solution), 0.25% and 0.5%, is a non-selective beta-adrenergic antagonist for ophthalmic use.

The chemical name of the active ingredient is (S)-1-[(1,1-dimethylethyl)amino]-3-[(4-(4-morpholinyl)-1,2,5-thiadiazol-3-yl]oxy]-2-propanol.

Timolol hemihydrate is the levo isomer.

Specific rotation is [α] 25 405nm =-16° (C=10% as the hemihydrate form in 1N HCl).

The molecular formula of timolol is Formula C 13 H 24 N 4 O 3 S and its structural formula is: Timolol (as the hemihydrate) is a white, odorless, crystalline powder which is slightly soluble in water and freely soluble in ethanol.

Timolol hemihydrate is stable at room temperature.

Betimol ® is a clear, colorless, isotonic, sterile, microbiologically preserved phosphate buffered aqueous solution.

It is supplied in two dosage strengths, 0.25% and 0.5%.

Each mL of Betimol ® 0.25% contains 2.56 mg of timolol hemihydrate equivalent to 2.5 mg Timolol.

Each mL of Betimol ® 0.5% contains 5.12 mg of timolol hemihydrate equivalent to 5.0 mg timolol.

Inactive ingredients: monosodium and disodium phosphate dihydrate to adjust pH (6.5 – 7.5) and water for injection, benzalkonium chloride 0.01% added as preservative.

The osmolality of Betimol ® is 260 to 320 mOsmol/kg.

Chemical Structure


Clinical Studies In two controlled multicenter studies in the U.S., Betimol ® 0.25% and 0.5% were compared with respective timolol maleate eyedrops.

In these studies, the efficacy and safety profile of Betimol ® was similar to that of timolol maleate.


Betimol ® (timolol ophthalmic solution) is a clear, colorless solution.

Betimol ® 0.25% is supplied in a white, opaque, plastic, ophthalmic dispenser bottle with a controlled drop tip as follows: NDC 68669-522-05 5.0mL fill in 5 cc container NDC 68669-522-10 10mL fill in 11 cc container NDC 68669-522-15 15mL fill in 15 cc container Betimol ® 0.5% is supplied in a white, opaque, plastic, ophthalmic dispenser bottle with a controlled drop tip as follows: NDC 68669-525-05 5.0mL fill in 5 cc container NDC 68669-525-10 10mL fill in 11 cc contalner NDC 68669-525-15 15mL fill in 15 cc container Rx Only STORAGE Store between 15-25°C (59-77°F).

Do not freeze.

Protect from light.


Betimol ® is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.


Pediatric use Safety and efficacy in pediatric patients have not been established.


Pregnancy Teratogenic effects Category C Teratogenicity of timolol (as the maleate) after oral administration was studied in mice and rabbits.

No fetal malformations were reported in mice or rabbits at a daily oral dose of 50 mg/kg (7,000 times the systemic exposure following the maximum recommended human ophthalmic dose).

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

Doses of 1000 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.

Betimol ® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.


Nursing mothers Because of the potential for serious adverse reactions in nursing infants from timolol, 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.


Information for Patients Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures.

Patients should also be instructed that ocular solutions can become contaminated by common bacteria known to cause ocular infections.

Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.

(See PRECAUTIONS, General .) Patients requiring concomitant topical ophthalmic medications should be instructed to administer these at least 5 minutes apart.

Patients with bronchial asthma, a history of bronchial asthma, severe chronic obstructive pulmonary disease, sinus bradycardia, second- or third-degree atrioventricular block, or cardiac failure should be advised not to take this product (See CONTRAINDICATIONS .)


Betimol ® Ophthalmic Solution is available in concentrations of 0.25 and 0.5 percent.

The usual starting dose is one drop of 0.25 percent Betimol ® in the affected eye(s) twice a day.

If the clinical response is not adequate, the dosage may be changed to one drop of 0.5 percent solution in the affected eye(s) twice a day.

If the intraocular pressure is maintained at satisfactory levels, the dosage schedule may be changed to one drop once a day in the affected eye(s).

Because of diurnal variations in intraocular pressure, satisfactory response to the once-a-day dose is best determined by measuring the intraocular pressure at different times during the day.

Since in some patients the pressure-lowering response to Betimol ® may require a few weeks to stabilize, evaluation should include a determination of intraocular pressure after approximately 4 weeks of treatment with Betimol ® .

Dosages above one drop of 0.5 percent Betimol ® twice a day generally have not been shown to produce further reduction in intraocular pressure.

If the patient’s intraocular pressure is still not at a satisfactory level on this regimen, concomitant therapy with pilocarpine and other miotics, and/or epinephrine, and/or systemically administered carbonic anhydrase inhibitors, such as acetazolamide, can be instituted.