Zuellig Pharma
Full Prescribing Info
Timolol maleate.
Each vial of TIMOPTOL-XE 0.5% contains 5 mg timolol as the active ingredient.
TIMOPTOL-XE is an ophthalmic beta-blocking drug which lowers pressure in the eye.
TIMOPTOL-XE (timolol maleate) is a sterile eyedrop containing timolol as the active ingredient. This eyedrop also contains a new delivery vehicle which is obtained from a natural substance. This vehicle allows the eye drop to form a clear transparent gel when it contacts the eye. This gel increases the contact time of timolol with the eye.
Excipients/Inactive Ingredients: Gellan gum, mannitol, tromethamine, and water for injection. Benzododecinium bromide is added as preservative.
TIMOPTOL-XE (timolol maleate) is a formulation of TIMOPTOL (timolol maleate) containing a novel delivery vehicle. 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 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.
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 0.25% TIMOPTOL-XE in the affected eye(s) once a day. If the clinical response is not adequate, the dosage may be changed to one drop of 0.5% 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.
Transferring 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 0.25% TIMOPTOL-XE in the affected eye once a day. The dose may be increased to one drop of 0.5% TIMOPTOL-XE once 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 and add one drop of 0.25% TIMOPTOL-XE to each affected eye once a day. On the following day, discontinue the previously used antiglaucoma agent and continue TIMOPTOL-XE. If a greater response is required, substitute one drop of 0.5% TIMOPTOL-XE for the 0.25% dosage.
Missed Dose: Use TIMOPTOL-XE as prescribed by the physician. If the patient miss a dose, use it as soon as possible. However, if it is almost time for the next dose, skip the missed dose and go back to the regular dosing schedule.
There have been reports of inadvertent overdosage with TIMOPTOL 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 Side Effects).
Hypersensitivity to any component of Timoptol-XE.
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.
Special Precautions
As with other topically applied ophthalmic drugs, TIMOPTOL-XE 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 (eg, 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.
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 (see circular for systemic timolol maleate products). 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 (eg, 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.
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, parasympathomimetics or another β-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.
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.
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.
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% inactive treatment controlled clinical trials:
Ocular: Burning and stinging, conjunctival injection, 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.
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 (see circular for systemic timolol maleate products).
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) has been reported during combined treatment with CYP2D6 inhibitors (e.g. quinidine and SSRIs) and timolol.
Caution For Usage
Do not allow the tip of the container to touch the eye or areas around the eye. It may become contaminated with bacteria that can cause eye infections leading to serious damage of the eye, even loss of vision. To avoid possible contamination of the container, keep the tip of the container away from contact with any surface.
Instructions for Use: 1. Before using the medication for the first time, be sure the perforated seal on the front of the bottle is unbroken. A gap between the bottle and the cap is normal for an unopened bottle.
2. Invert the closed bottle and shake once before each use. (It is not necessary to shake the bottle more than once.)
3. To open the bottle, unscrew the cap by turning as indicated by the arrows on the top of the cap. When opening the bottle for the first time, do not pull the cap directly up and away from the bottle. Pulling the cap directly up will prevent the container from operating properly.
4. Tilt head back and pull lower eyelid down slightly to form a pocket between the eyelid and the eye.
5. Invert the bottle and press lightly with the thumb or index finger over the "Finger Push Area" until a single drop is dispensed into the eye as directed by the physician.
Do not touch the eye or eyelid with the dropper tip.
Ophthalmic medications, if handled improperly, can become contaminated by common bacteria known to cause eye infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated ophthalmic medications. If the medication may be contaminated, or if the patient develop an eye infection, contact a doctor immediately concerning continued use of the bottle.
6. After using TIMOPTOL-XE, press a finger into the corner of the eye by the nose for 2 minutes. This helps keep TIMOPTOL-XE in the eye.
7. If drop dispensing is difficult after opening for the first time, replace the cap on the bottle and tighten (do not overtighten) and then remove by turning the cap in the opposite direction as indicated by the arrows on top of the cap.
8. Repeat steps 4 & 5 with the other eye if instructed to do so by the physician.
9. Replace the cap by turning until it is firmly touching the bottle. The arrow on the left side of the cap must be aligned with the arrow on the left side of the bottle label for proper closure. Attempting to tighten the bottle beyond the resistance point (the point at which the arrows on the bottle label and cap are aligned) may damage the bottle and/or cap.
10. The dispenser tip is designed to provide a pre-measured drop; therefore, do not enlarge the hole of the dispenser tip.
11. After all doses have been used, there will be some TIMOPTOL-XE left in the bottle. The patient should not be concerned since an extra amount of TIMOPTOL-XE has been added and the patient will get the full amount of TIMOPTOL-XE that the physician prescribed. Do not attempt to remove excess medicine from the bottle.
Store at or below 25°C. Avoid freezing. Protect from light.
Shelf-Life: 4 weeks after the vial is first opened.
ATC Classification
S01ED01 - timolol ; Belongs to the class of beta blocking agents. Used in the treatment of glaucoma.
Ophth soln 0.5% (sterile, colorless to nearly colorless, slightly opalescent, slightly viscous, aqueous solution) x 2.5 mL x 1's.
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