Timoptol

Timolol maleate.

TIMOLOL MALEATE (TIMOPTOL) contains 5.0 mg of timolol (6.8 mg of timolol maleate).
TIMOLOL MALEATE (TIMOPTOL) reduces elevated and normal intraocular pressure whether or not associated with glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss. The higher the level of intraocular pressure, the greater the likelihood of glaucomatous visual field loss and optic nerve damage. TIMOLOL MALEATE (TIMOPTOL) is available with or without preservative, benzalkonium chloride.
Onset of action of TIMOLOL MALEATE (TIMOPTOL) is usually rapid, occurring approximately 20 minutes after topical application to the eye. Maximum reduction of intraocular pressure occurs in one to two hours. Significant lowering of intraocular pressure has been maintained for as long as 24 hours with 0.25 percent or 0.5 percent Ophthalmic Solution TIMOLOL MALEATE (TIMOPTOL). This extended duration of action permits control of intraocular pressure over the usual sleeping hours. Repeated observations over a period of three years indicate that the intraocular pressure-lowering effect of TIMOLOL MALEATE (TIMOPTOL) is well maintained.
Timolol maleate is a nonselective β-adrenergic receptor blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity.
The precise mechanism of action of TIMOLOL MALEATE (TIMOPTOL) in lowering intraocular pressure is not clearly established at this time, although a fluorescein study and tonography studies indicate that the predominant action may be related to reduced aqueous formation. However, in some studies a slight increase in outflow facility was also observed.
Unlike miotics, TIMOLOL MALEATE (TIMOPTOL) reduces intraocular pressure with little or no effect on accommodation or pupil size. Thus, changes in visual acuity due to increased accommodation are uncommon, and dim or blurred vision and night blindness produced by miotics are not evident. In addition, in patients with cataracts the inability to see around lenticular opacities when the pupil is constricted by miotics is avoided. When changing patients from miotics to TIMOLOL MALEATE (TIMOPTOL) a refraction might be necessary when these effects of the miotic have passed.
In clinical studies TIMOLOL MALEATE (TIMOPTOL) was generally effective in more patients and produced fewer and less severe side effects than either pilocarpine or epinephrine.
As with the use of other antiglaucoma drugs, diminished responsiveness to TIMOLOL MALEATE (TIMOPTOL) after prolonged therapy has been reported in some patients. However, in clinical studies in which 164 patients have been followed for at least three years, no significant difference in mean intraocular pressure has been observed after initial stabilization.
TIMOLOL MALEATE (TIMOPTOL) has also been used in patients with glaucoma wearing conventional hard contact lenses, and has generally been well tolerated. TIMOLOL MALEATE (TIMOPTOL) has not been studied in patients wearing lenses made with materials other than polymethylmethacrylate.
TIMOLOL MALEATE (TIMOPTOL) is a β-adrenergic receptor blocking agent. The chemical name is (S)-1-[(1,1-dimethylethyl)amino]-3-[[4-(4-morpholinyl) -1,2,5- thiadiazol-3-yl] oxy]-2-propanol (Z)-2-butenedioate(1:1) (salt). Timolol maleate possesses an asymmetric carbon atom in the structure and is provided as the levo isomer. The empirical formula is C₁₃H₂₄N₄0₃S•C₄H₄0₄. TIMOLOL MALEATE (TIMOPTOL) is a β-adrenergic receptor blocking agent. The chemical name is (S)-1-[(1,1-dimethylethyl)amino]-3-[[4-(4-morpholinyl) -1,2,5- thiadiazol-3-yl] oxy]-2-propanol (Z)-2-butenedioate(1:1) (salt). Timolol maleate possesses an asymmetric carbon atom in the structure and is provided as the levo isomer. The empirical formula is C₁₃H₂₄N₄0₃SC₄H₄0₄.
TIMOLOL MALEATE (TIMOPTOL) has a molecular weight of 432.50. It is a white, odorless, crystalline powder which is soluble in water, methanol, and alcohol. TIMOLOL MALEATE (TIMOPTOL) is stable at room temperature.

Pharmacology: Mechanism of Action: Timolol maleate is a nonselective ß-adrenergic receptor blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity. Timolol maleate combines reversibly with a part of the cell membrane, the β-adrenergic receptor, and thus inhibits the usual biologic response that would occur with stimulation of that receptor. This specific competitive antagonism blocks stimulation of the β-adrenergic receptors by catecholamines having β-adrenergic stimulating (agonist) activity, whether these originate from an endogenous or exogenous source. Reversal of this blockade can be accomplished by increasing the concentration of the agonist, which will restore the usual biologic response.
Pharmacodynamics: Beta-adrenergic receptor blockade reduces cardiac output in both healthy subjects and patients with heart disease. In patients with severe impairment of myocardial function β-adrenergic receptor blockade may inhibit the stimulatory effect of the sympathetic nervous system necessary to maintain adequate cardiac function. Beta-adrenergic receptor blockade in the bronchi and bronchioles results in increased airway resistance from unopposed parasympathetic activity. Such an effect in patients with asthma or other bronchospastic conditions is potentially dangerous.
Pharmacokinetics: In a study of plasma drug concentration in six subjects, the systemic exposure to timolol was determined following twice-daily administration of TIMOLOL MALEATE (TIMOPTOL) 0.5%. The mean peak plasma concentration following morning dosing was 0.46 ng/mL and following afternoon dosing was 0.35 ng/mL.

TIMOLOL MALEATE (TIMOPTOL) is indicated for the reduction of elevated intraocular pressure.
In clinical trials it has been shown to reduce intraocular pressure in: Patients with ocular hypertension, patients with chronic open-angle glaucomaphakic patients with glaucoma, some patients with secondary glaucoma, patients with narrow angles and a history of spontaneous or iatrogenically induced narrow-angle closure in the opposite eye in whom reduction of intraocular pressure is necessary (see PRECAUTIONS).
TIMOLOL MALEATE (TIMOPTOL) is also indicated as concomitant therapy in patients with pediatric glaucoma, who are inadequately controlled with other antiglaucoma therapy.

The usual starting dose is one drop of 0.25 percent timolol maleate ophthalmic solution in the affected eye(s) as directed. 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 needed, concomitant therapy with other agent(s) for lowering intraocular pressure may be given with TIMOLOL MALEATE (TIMOPTOL). The use of two topical beta-adrenergic blocking agents is not recommended (see WARNINGS AND PRECAUTIONS).
Since in some patients the pressure-lowering response to TIMOLOL MALEATE (TIMOPTOL) may require a few weeks to stabilize, evaluation should include a determination of intraocular pressure after approximately 4 weeks of treatment with TIMOLOL MALEATE (TIMOPTOL).
If the intraocular pressure is maintained at satisfactory levels, many patients can be placed on once-a-day therapy.
When using nasolacrimal occlusion or closing the eyelids for 2 minutes, the systemic absorption is reduced. This may result in an increase in local activity.
HOW TO TRANSFER PATIENTS FROM OTHER THERAPY: When a patient is transferred from another topical ophthalmic β-adrenergic blocking agent, that agent should be discontinued after proper dosing on one day and treatment with TIMOLOL MALEATE (TIMOPTOL) started on the following day with one drop of 0.25 percent timolol maleate ophthalmic solution in the affected eye(s) as directed. The dose may be increased to one drop of 0.5 percent TIMOLOL MALEATE (TIMOPTOL) in the affected eye twice a day if the clinical response is not adequate.
When a patient is transferred from a single antiglaucoma agent, other than a topical ophthalmic beta‑adrenergic blocking agent, continue the agent already being used and add one drop of 0.25 percent timolol maleate ophthalmic solution in the affected eye(s) as directed. On the following day, discontinue the previously used antiglaucoma agent completely and continue with the TIMOLOL MALEATE (TIMOPTOL) ophthalmic solution. If a higher dosage is required substitute one drop of 0.5 percent TIMOLOL MALEATE (TIMOPTOL) in each affected eye twice a day.
Use in children: The usual starting dosage is one drop 0.25 percent TIMOLOL MALEATE (TIMOPTOL) in the affected eye(s) every 12 hours, in addition to other antiglaucoma medication. The dosage may be increased to one drop of 0.5 percent solution in the affected eye(s) every 12 hours, if necessary. The use of TIMOLOL MALEATE (TIMOPTOL) is not recommended in premature infants or neonates.

There have been reports of inadvertent overdosage with TIMOLOL MALEATE (TIMOPTOL) resulting in systemic effects similar to those seen with systemic β-adrenergic blocking agents eg, dizziness, headache, shortness of breath, bradycardia, bronchospasm and cardiac arrest (see Adverse Reactions).

TIMOLOL MALEATE (TIMOPTOL) is contraindicated in patients with: Reactive airway disease, bronchial asthma or with a history of bronchial asthma, or severe chronic obstructive pulmonary disease, sinus bradycardia; sino-atrial block; second and third degree atrioventricular block; overt cardiac failure; cardiogenic shock, hypersensitivity to any component of this product

As with other topically applied ophthalmic drugs, Timoptol may be absorbed systemically.
The same adverse reactions found with systemic administration of β-adrenergic blocking agents may occur with topical administration.
Cardio-respiratory reactions: Cardiac failure should be adequately controlled before beginning therapy with Timoptol. Patients with a history of cardiovascular disease including cardiac failure, should be watched for signs of deterioration of these diseases, and pulse rates should be checked.
Due to its negative effect on conduction time, β-blockers should be given with caution to patients with first degree heart block.
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 administration of Timoptol.
In patients with mild/moderate chronic obstructive pulmonary disease (COPD), Timoptol should be used with caution, and only if the potential benefit outweighs the potential risk.
Vascular Disorders: Patients with severe peripheral circulatory disturbance/disorders (eg, severe form of Raynaud's disease or Raynaud's syndrome) should be treated with caution.
Masking of Hypoglycemic Symptoms in Patients with 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 blocking agents may mask the signs and symptoms of acute hypoglycemia.
Masking of Thyrotoxicosis: Beta-adrenergic blocking agents may mask certain clinical signs of hyperthyroidism (eg, tachycardia). Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of β-adrenergic blocking agents which might precipitate a thyroid storm.
Surgical Anesthesia: The necessity or desirability of withdrawal of β-adrenergic blocking agents prior to major surgery is controversial. If necessary during surgery, the effects of β-adrenergic blocking agents may be reversed by sufficient doses of adrenergic agonists.
Others: Patients who are already receiving a β-adrenergic blocking agent systemically and who are given TIMOLOL MALEATE (TIMOPTOL) should be observed for a potential additive effect either on the intraocular pressure or on the known systemic effects of β-blockade. The use of 2 topical β-adrenergic blocking agents is not recommended.
In patients with angle-closure glaucoma, the immediate objective of treatment is to reopen the angle. This requires constricting the pupil with a miotic. TIMOLOL MALEATE (TIMOPTOL) has little or no effect on the pupil. When TIMOLOL MALEATE (TIMOPTOL) is used to reduce elevated intraocular pressure in angle-closure glaucoma, it should be used with a miotic and not alone.
Choroidal detachment has been reported with administration of aqueous suppressant therapy (eg, timolol, acetazolamide) after filtration procedures.
TIMOLOL MALEATE (TIMOLOL) contains the preservative benzalkonium chloride, which may be absorbed in soft contact lenses; therefore, TIMOLOL MALEATE (TIMOPTOL) should not be used while wearing these lenses. The lenses should be removed before application of the drops and not be reinserted earlier than 15 minutes after use.
Risk from Anaphylactic Reaction: While taking β-blockers, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge with such allergens, either accidental, diagnostic or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat anaphylactic reactions.

TIMOLOL MALEATE (TIMOPTOL) has not been studied in human pregnancy. The use of TIMOLOL MALEATE (TIMPOTOL) requires that the anticipated benefit be weighed against possible hazards.
Timolol is detectable in human milk. Because of the potential for serious adverse reactions from TIMOLOL MALEATE (TIMOPTOL) in 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.

TIMOLOL MALEATE (TIMOPTOL) is usually well tolerated. The following adverse reactions have been reported with ocular administration of this or other timolol maleate formulations, either in clinical trials or since the drug has been marketed.
Special Senses: Signs and symptoms of ocular irritation, including burning and stinging, conjunctivitis, blepharitis, keratitis, decreased corneal sensitivity and dry eyes. Visual disturbances, including refractive changes (due to withdrawal of miotic therapy in some cases), diplopia, ptosis, choroidal detachment following filtration surgery (see Precautions), tinnitus.
Cardiovascular: Bradycardia, arrhythmia, hypotension, syncope, heart block, cerebrovascular accident, cerebral ischemia, congestive heart failure, palpitation, cardiac arrest, edema, claudication, Raynaud's phenomenon, cold hands and feet.
Respiratory: Bronchospasm (predominantly in patients with preexisting bronchospastic disease), respiratory failure, dyspnea, cough.
Body As a Whole: Headache, asthenia, fatigue, chest pain.
Integumentary: Alopecia, psoriasiform rash or exacerbation of psoriasis.
Hypersensitivity: Signs and symptoms of allergic reactions including anaphylaxis, angioedema, urticaria, localized and generalized rash.
Nervous System/Psychiatric: Dizziness, depression, insomnia, nightmares, memory loss, increase in signs and symptoms of myasthenia gravis, paresthesia.
Digestive: Nausea, diarrhea, dyspepsia, dry mouth.
Urogenital: Decreased libido, Peyronie's disease, sexual dysfunction.
Immunologic: Systemic lupus erythematosus.
Musculoskeletal: Myalgia.
Potential Side Effects: Side effects reported in clinical experience with systemic timolol maleate may be considered potential side effects of ophthalmic timolol maleate.

Although TIMOLOL MALEATE (TIMOPTOL) used alone has little or no effect on pupil size, mydriasis resulting from concomitant therapy with TIMOLOL MALEATE TIMOPTOL) and therapy has been reported occasionally.
Potentiated systemic beta-blockers (eg, decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (eg, quinidine, SSRIs) and timolol.
The potential exists for additive effects and production of hypotension and/or marked bradycardia when TIMOLOL MALEATE (TIMOPTOL) is administered together with an oral calcium-entry blocker, catecholamine-depleting drugs, antiarrhythmics, parasympathomimetics or β-adrenergic blocking agents.
Oral β-adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine.

TIMOLOL MALEATE (TIMOPTOL) is stable at temperatures not exceeding 30°C. Protect from light.

Antiglaucoma Preparations

S01ED01 - timolol ; Belongs to the class of beta blocking agents. Used in the treatment of glaucoma.

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