Timoptol-XE

Timoptol-XE

timolol

Manufacturer:

Santen Pharma

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Timolol maleate.
Description
TIMOPTOL XE 0.5% contains 2.5ml solution.
Action
TIMOPTOL-XE (Timolol maleate) is a formulation of TIMOPTOL (Timolol maleate) containing a novel delivery vehicle. It is available with preservative, benzododecinium bromide. TIMOPTOL-XE 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.
Clinical studies have shown that the intraocular pressure lowering effect of TIMOPTOL-XE administered once a day is equivalent to TIMOPTOL administered twice a day. The vehicle of TIMOPTOL-XE increases the contact time of the drug with the eye.
Gellan solution contains a highly purified anionic heteropolysaccharide derived from gellan gum. Aqueous solutions of gellan gum form a clear transparent gel at low polymer concentrations in the presence of cations. When TIMOPTOL-XE contacts the precorneal tear film, it becomes a gel.
Maximum reduction of intraocular pressure occurs in two to four hours with TIMOPTOL-XE. Significant lowering of intraocular pressure has been maintained for 24 hours with both 0.25% and 0.5% TIMOPTOL-XE.
TIMOPTOL-XE has a safety profile similar to that of TIMOPTOL, and both are generally well tolerated. Bradycardia was reported less frequently with TIMOPTOL-XE than with TIMOPTOL. In the three studies comparing TIMOPTOL-XE 0.5% once a day to TIMOPTOL 0.5% twice a day, TIMOPTOL-XE did not reduce mean heart rate as much as TIMOPTOL (see PRECAUTIONS). At trough (24 hours post-dose TIMOPTOL-XE, 12 hours post-dose TIMOPTOL), the mean reduction was 0.8 beats/minute for TIMOPTOL-XE and 3.6 beats/minute for TIMOPTOL; whereas at two hours post-dose, the mean reduction in heart rate was comparable (3.8 beats/minute for TIMOPTOL-XE and 5 beats/minute for TIMOPTOL). There was a higher incidence of transient blurred vision following instillation in patients administered TIMOPTOL-XE.
Timolol maleate is a nonselective beta-adrenergic receptor blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity.
Onset of action of timolol maleate is usually rapid, occurring approximately 20 minutes after topical application to the eye. The precise mechanism of action of timolol maleate in lowering intraocular pressure is not clearly established. 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.
In clinical studies timolol maleate was generally effective in more patients and produced fewer and less severe side effects than either pilocarpine or epinephrine.
Unlike miotics, timolol maleate 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 the 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 TIMOPTOL-XE, refraction may be necessary after the effects of the miotic have passed.
As with other antiglaucoma drugs, diminished responsiveness to timolol maleate after prolonged therapy has been reported in some patients. However, in clinical studies of TIMOPTOL in which 164 patients were followed for at least 3 years, no significant difference in mean intraocular pressure was observed after initial stabilization. This indicates that the intraocular pressure-lowering effect of timolol maleate is well maintained.
Indications/Uses
Timoptol-XE is indicated for the reduction of elevated intraocular pressure in patients with: ocular hypertension; chronic open-angle glaucoma; aphakia and glaucoma; secondary glaucoma (some cases); 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).
Dosage/Direction for Use
The usual starting dose is one drop of TIMOPTOL-XE in the affected eye(s) once a day. Invert the closed container and shake once before each use. It is not necessary to shake the container more than once. If needed, concomitant therapy with other agent(s) for lowering intraocular pressure may be given with TIMOPTOL-XE. The use of two topical beta-adrenergic blocking agents is not recommended (see PRECAUTIONS). Other topically applied medications should be administered no less than 10 minutes before TIMOPTOL-XE.
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 TIMOPTOL to TIMOPTOL-XE, TIMOPTOL should be discontinued after proper dosing on one day, and treatment with the same concentration of TIMOPTOL-XE started on the following day.
When a patient is transferred from another topical ophthalmic beta-adrenergic blocking agent, that agent should be discontinued after proper dosing on one day and treatment with TIMOPTOL-XE started on the following day with one drop of 0.5% TIMOPTOL-XE once a day.
When a patient is transferred from a single antiglaucoma agent, other than a topical ophthalmic beta-adrenergic blocking agent, continue the agent and add one drop of TIMOPTOL-XE to each affected eye once a day. On the following day, discontinue the previously used antiglaucoma agent completely and continue with TIMOPTOL-XE.
Overdosage
There have been reports of inadvertent overdosage with TIMOPTOL-XE resulting in systemic effects similar to those seen with systemic beta-adrenergic blocking agents such as dizziness, headache, shortness of breath, bradycardia, bronchospasm, and cardiac arrest (see also SIDE EFFECTS).
Contraindications
TIMOPTOL-XE is contraindicated in patients with: Reactive airway disease, bronchial asthma or anamnestic bronchial asthma, or severe chronic obstructive pulmonary disease,
Sinus bradycardia; sick sinus syndrome, sino-atrial block; second or third degree atrioventricular block not controlled with a pacemaker; overt cardiac failure; cardiogenic shock,
Hypersensitivity to any component of this product.
Special Precautions
As with other topically applied ophthalmic drugs, this drug may be absorbed systemically.
The same adverse reactions found with systemic administration of beta-adrenergic blocking agents may occur with topical administration.
Cardio-respiratory reactions: Cardiac failure should be adequately controlled before beginning therapy with TIMOPTOL-XE. 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 monitored.
Due to its negative effect on conduction time, beta-blockers should be given with caution to patients with first degree heart block.
Respiratory complications, including death due to bronchospasm in patients with asthma, and cardiac complications, including rarely death in association with cardiac failure, have been reported following administration of beta-adrenergic blocking agents. These are potential complications of therapy with TIMOPTOL-XE.
In patients with mild/moderate chronic obstructive pulmonary disease (COPD), TIMOPTOL-XE should be used with caution, and only if the potential benefit outweighs the potential risk.
Vascular Disorders: Patients with severe peripheral circulatory disturbance/ disorders (e.g. severe forms 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 (e.g., tachycardia). Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blocking agents which might precipitate a thyroid storm.
Surgical Anesthesia: The necessity or desirability of withdrawal of beta- adrenergic blocking agents prior to major surgery is controversial. If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of adrenergic agonists. The anaesthesiologist should be informed if the patient has received timolol.
Other: Patients who are already receiving a beta-adrenergic blocking agent systemically and who are given TIMOPTOL-XE should be observed for a potential additive effect either on the intraocular pressure or on the known systemic effects of beta-blockade. The use of two topical beta-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 has little or no effect on the pupil. Should TIMOPTOL-XE be 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 (e.g. timolol, acetazolamide) after filtration procedures.
TIMOPTOL-XE has not been studied in patients wearing contact lenses. In a clinical study, the time required to eliminate 50% of the gellan solution from the eye was up to 30 minutes.
Ophthalmic beta-blockers may induce dryness of eyes. Patients with corneal diseases should be treated with caution.
Risk from Anaphylactic Reaction: While taking beta-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.
Drug Interactions: Although timolol maleate used alone has little or no effect on pupil size, mydriasis resulting from concomitant therapy with epinephrine has been reported occasionally. The potential for mydriasis exists from concomitant therapy with TIMOPTOL-XE and epinephrine.
The potential exists for additive effects and production of hypotension and/or marked bradycardia when TIMOPTOL-XE is administered together with a calcium-channel blocker, a catecholamine-depleting drug, antiarrhythmics (including amiodarone), digitalis glycosides, parasympathomimetics, guanethidine or another beta-adrenergic blocking agent (see INTERACTIONS).
Oral β-adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine.
Use in Pregnancy: TIMOPTOL-XE has not been studied in human pregnancy. The use of TIMOPTOL-XE requires that the anticipated benefit be weighed against possible hazards.
While malformations have not been seen in epidemiological studies, they show a risk for foetal growth retardation when beta-blockers are administered by the oral route. In addition, symptoms of beta-blockade (e.g. bradycardia, hypotension, respiratory distress and hypoglycaemia) have been observed in the neonate when beta-blockers have been administered until delivery. If TIMOPTOL XE is administered until delivery, the neonate should be carefully monitored during the first days of life.
Use in Lactation: Timolol is detectable in human milk. Because of the potential for serious adverse reactions from TIMOPTOL-XE 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.
Use in Children: Timolol maleate ophthalmic solution has been shown to be efficacious and well-tolerated in children; however, the formulation of timolol maleate found in TIMOPTOL-XE has not been studied in the pediatric age group.
Use In Pregnancy & Lactation
Use in Pregnancy: TIMOPTOL-XE has not been studied in human pregnancy. The use of TIMOPTOL-XE requires that the anticipated benefit be weighed against possible hazards.
While malformations have not been seen in epidemiological studies, they show a risk for foetal growth retardation when beta-blockers are administered by the oral route. In addition, symptoms of beta-blockade (e.g. bradycardia, hypotension, respiratory distress and hypoglycaemia) have been observed in the neonate when beta-blockers have been administered until delivery. If TIMOPTOL XE is administered until delivery, the neonate should be carefully monitored during the first days of life.
Nursing Mothers: Timolol is detectable in human milk. Because of the potential for serious adverse reactions from TIMOPTOL-XE 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.
Side Effects
TIMOPTOL-XE is usually well tolerated. The most frequent drug-related complaint in the original clinical trials for TIMOPTOL-XE was transient blurred vision (6.0%), lasting from 30 seconds to 5 minutes, following instillation.
The following possibly, probably, or definitely drug-related adverse reactions occurred with a frequency of at least 1% in active treatment controlled clinical trials: Ocular: Burning and stinging, conjunctival redness, discharge, foreign body sensation, itching.
The following additional 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 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 pre-existing 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, paresthesia.
Neuromuscular: Increase in signs and symptoms of myasthenia gravis.
Digestive: Nausea, diarrhea, dyspepsia, dry mouth, abdominal pain.
Urogenital: Decreased libido, Peyronie's disease, sexual dysfunction.
Immunologic: Systemic lupus erythematosus.
Potential Side Effects: Side effects reported in clinical experience with systemic timolol maleate may be considered potential side effects of ophthalmic timolol maleate.
Musculoskeletal: Myalgia.
Drug Interactions
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.
The potential exists for hypotension, atrioventricular (AV) conduction disturbances and left ventricular failure to occur in patients receiving a beta-blocking agent when an oral calcium-channel blocker is added to the treatment regimen. The nature of any cardiovascular adverse effect tends to depend on the type of calcium-channel blocker used. Dihydropyridine derivatives, such as nifedipine, may lead to hypotension, whereas verapamil or diltiazem have a greater propensity to lead to AV conduction disturbances or left ventricular failure when used with a beta-blocker.
The concomitant use of beta-adrenergic blocking agents and digitalis with either diltiazem or verapamil may have additive effects in prolonging AV conduction time.
Oral calcium-channel antagonists may be used in combination with beta-adrenergic blocking agents when heart function is normal, but should be avoided in patients with impaired cardiac function.
Intravenous calcium-channel blockers should be used with caution in patients receiving beta-adrenergic blocking agents.
Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2d6 inhibitors (e.g. quinidine, SSRIs) and timolol.
Storage
Store at or below 30°C. Protect from light. Discard one month after opening.
ATC Classification
S01ED01 - timolol ; Belongs to the class of beta blocking agents. Used in the treatment of glaucoma.
Presentation/Packing
Ophth soln 0.5% (sterile, colorless to nearly colorless, slightly opalescent, slightly viscous, aqueous solution) x 2.5 mL.
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