Drug Facts
Composition & Profile
Identifiers & Packaging
HOW SUPPLIED Timolol maleate ophthalmic solution, USP is a clear, colorless to light yellow solution. Timolol maleate ophthalmic solution, USP 0.5% timolol equivalent, is supplied in a white opaque low density polyethylene (LDPE) bottle with a natural LDPE nozzle and yellow HDPE cap in the following sizes: 5 mL in a 10 mL bottle NDC 65145-152-01 10 mL in a 10 mL bottle NDC 65145-153-01 15 mL in a 15 mL bottle NDC 65145-154-01 Storage Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from freezing. Protect from light. After opening timolol maleate ophthalmic solution can be used until the expiration date on the bottle.; PACKAGE LABEL.PRINCIPAL DISPLAY PANEL Container Label - 5 mL NDC 65145- 152 -01 Rx only Timolol Maleate Ophthalmic Solution, USP 0.5% Timolol Equivalent (timolol maleate 6.8 mg/mL equivalent to 5 mg/mL timolol) For eye use only Sterile 5 mL Carton Label - 5 mL NDC 65145- 152 -01 Rx only Timolol Maleate Ophthalmic Solution, USP 0.5% Timolol Equivalent (timolol maleate 6.8 mg/mL equivalent to 5 mg/mL timolol) For eye use only Sterile 5 mL Container Label - 10 mL NDC 65145- 153 -01 Rx only Timolol Maleate Ophthalmic Solution, USP 0.5% Timolol Equivalent (timolol maleate 6.8 mg/mL equivalent to 5 mg/mL timolol) For eye use only Sterile 10 mL Carton Label - 10 mL NDC 65145- 153 -01 Rx only Timolol Maleate Ophthalmic Solution, USP 0.5% Timolol Equivalent (timolol maleate 6.8 mg/mL equivalent to 5 mg/mL timolol) For eye use only Sterile 10 mL Container Label - 15 mL NDC 65145- 154 -01 Rx only Timolol Maleate Ophthalmic Solution, USP 0.5% Timolol Equivalent (timolol maleate 6.8 mg/mL equivalent to 5 mg/mL timolol) For eye use only Sterile 15 mL Carton Label - 15 mL NDC 65145- 154 -01 Rx only Timolol Maleate Ophthalmic Solution, USP 0.5% Timolol Equivalent (timolol maleate 6.8 mg/mL equivalent to 5 mg/mL timolol) For eye use only Sterile 15 mL timolol-5ml-bottle timolol-5ml-carton timolol-10ml-bottle timolol-10ml-carton timolol-15ml-bottle timolol-15ml-carton
- HOW SUPPLIED Timolol maleate ophthalmic solution, USP is a clear, colorless to light yellow solution. Timolol maleate ophthalmic solution, USP 0.5% timolol equivalent, is supplied in a white opaque low density polyethylene (LDPE) bottle with a natural LDPE nozzle and yellow HDPE cap in the following sizes: 5 mL in a 10 mL bottle NDC 65145-152-01 10 mL in a 10 mL bottle NDC 65145-153-01 15 mL in a 15 mL bottle NDC 65145-154-01 Storage Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from freezing. Protect from light. After opening timolol maleate ophthalmic solution can be used until the expiration date on the bottle.
- PACKAGE LABEL.PRINCIPAL DISPLAY PANEL Container Label - 5 mL NDC 65145- 152 -01 Rx only Timolol Maleate Ophthalmic Solution, USP 0.5% Timolol Equivalent (timolol maleate 6.8 mg/mL equivalent to 5 mg/mL timolol) For eye use only Sterile 5 mL Carton Label - 5 mL NDC 65145- 152 -01 Rx only Timolol Maleate Ophthalmic Solution, USP 0.5% Timolol Equivalent (timolol maleate 6.8 mg/mL equivalent to 5 mg/mL timolol) For eye use only Sterile 5 mL Container Label - 10 mL NDC 65145- 153 -01 Rx only Timolol Maleate Ophthalmic Solution, USP 0.5% Timolol Equivalent (timolol maleate 6.8 mg/mL equivalent to 5 mg/mL timolol) For eye use only Sterile 10 mL Carton Label - 10 mL NDC 65145- 153 -01 Rx only Timolol Maleate Ophthalmic Solution, USP 0.5% Timolol Equivalent (timolol maleate 6.8 mg/mL equivalent to 5 mg/mL timolol) For eye use only Sterile 10 mL Container Label - 15 mL NDC 65145- 154 -01 Rx only Timolol Maleate Ophthalmic Solution, USP 0.5% Timolol Equivalent (timolol maleate 6.8 mg/mL equivalent to 5 mg/mL timolol) For eye use only Sterile 15 mL Carton Label - 15 mL NDC 65145- 154 -01 Rx only Timolol Maleate Ophthalmic Solution, USP 0.5% Timolol Equivalent (timolol maleate 6.8 mg/mL equivalent to 5 mg/mL timolol) For eye use only Sterile 15 mL timolol-5ml-bottle timolol-5ml-carton timolol-10ml-bottle timolol-10ml-carton timolol-15ml-bottle timolol-15ml-carton
Overview
Timolol maleate, USP is a non-selective beta-adrenergic receptor blocking agent. Its chemical name is (-)-1-( tert -butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy]-2-propanol maleate (1:1) (salt). Timolol maleate possesses an asymmetric carbon atom in its structure and is provided as the levo-isomer. The optical rotation of timolol maleate is: 25° [α] in 1.0N HCl (C = 5%) = -12.2° (-11.7° to -12.5°) 405 nm Its molecular formula is C 13 H 24 N 4 O 3 S•C 4 H 4 O 4 and its structural formula is: Timolol maleate has a molecular weight of 432.50. It is a white or almost white, crystalline powder which is soluble in water; sparingly soluble in ethanol; slightly soluble in chloroform; practically insoluble in ether. Timolol maleate ophthalmic solution, USP is stable at room temperature. Timolol maleate ophthalmic solution, USP is supplied as a sterile, isotonic, buffered, aqueous solution of timolol maleate in one dosage strength. Each mL of timolol maleate ophthalmic solution 0.5% contains 5 mg of timolol (6.8 mg of timolol maleate). Inactive ingredients: monobasic and dibasic sodium phosphate, sodium hydroxide to adjust pH (6.5 to 7.5), and water for injection. Benzalkonium chloride 0.01% is added as preservative. str
Indications & Usage
Timolol maleate ophthalmic solution is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.
Dosage & Administration
Timolol maleate ophthalmic solution is available in concentrations of 0.25% and 0.5%. The usual starting dose is one drop of timolol maleate ophthalmic solution 0.25% 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% solution in the affected eye(s) twice a day. Since in some patients the pressure-lowering response to timolol maleate may require a few weeks to stabilize, evaluation should include a determination of intraocular pressure after approximately 4 weeks of treatment with timolol maleate. 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. Dosages above one drop of timolol maleate ophthalmic solution 0.5% 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 other agent(s) for lowering intraocular pressure can be instituted. The concomitant use of two topical beta-adrenergic blocking agents is not recommended [see Precautions, Drug Interactions, Beta-adrenergic blocking agents].
Warnings & Precautions
WARNINGS As with many topically applied ophthalmic drugs, this drug 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 reactions 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 ophthalmic administration of timolol maleate [see Contraindications]. Cardiac Failure Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition of beta-adrenergic receptor blockade may precipitate more severe 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. At the first sign or symptom of cardiac failure, timolol maleate should be discontinued. 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, in which timolol maleate is contraindicated [see Contraindications] should, in general, not receive beta-blockers, including timolol maleate. Major Surgery The necessity or desirability of withdrawal of beta-adrenergic blocking agents prior to 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 experienced protracted severe hypotension during anesthesia. Difficulty in restarting and maintaining the heartbeat has also been reported. For these reasons, in patients undergoing elective surgery, some authorities recommend gradual withdrawal of beta-adrenergic receptor blocking agents. If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of 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 that might precipitate a thyroid storm.
Contraindications
Timolol maleate is contraindicated in patients with (1) bronchial asthma; (2) a history of bronchial asthma; (3) severe chronic obstructive pulmonary disease [see Warnings] ; (4) sinus bradycardia; (5) second or third degree atrioventricular block; (6) overt cardiac failure [see Warnings] ; (7) cardiogenic shock; or (8) hypersensitivity to any component of this product.
Adverse Reactions
The most frequently reported adverse experiences have been burning and stinging upon instillation (approximately one in eight patients). The following additional adverse experiences have been reported less frequently with ocular administration of this or other timolol maleate formulations: Body as a Whole Headache, asthenia/fatigue, and chest pain. Cardiovascular Bradycardia, arrhythmia, hypotension, hypertension, syncope, heart block, cerebral vascular accident, cerebral ischemia, cardiac failure, worsening of angina pectoris, palpitation, cardiac arrest, pulmonary edema, edema, claudication, Raynaud's phenomenon, and cold hands and feet. Digestive Nausea, diarrhea, dyspepsia, anorexia, and dry mouth. Immunologic Systemic lupus erythematosus. Nervous System/Psychiatric Dizziness, increase in signs and symptoms of myasthenia gravis, paresthesia, somnolence, insomnia, nightmares, behavioral changes and psychic disturbances including depression, confusion, hallucinations, anxiety, disorientation, nervousness, and memory loss. Skin Alopecia and psoriasiform rash or exacerbation of psoriasis. Hypersensitivity Signs and symptoms of systemic allergic reactions, including anaphylaxis, angioedema, urticaria, and localized and generalized rash. Respiratory Bronchospasm (predominantly in patients with preexisting bronchospastic disease), respiratory failure, dyspnea, nasal congestion, cough and upper respiratory infections. Endocrine Masked symptoms of hypoglycemia in diabetic patients [see Warnings]. Special Senses Signs and symptoms of ocular irritation including conjunctivitis, blepharitis, keratitis, ocular pain, discharge (e.g., crusting), foreign body sensation, itching and tearing, and dry eyes; ptosis; decreased corneal sensitivity; cystoid macular edema; visual disturbances including refractive changes and diplopia; pseudopemphigoid; choroidal detachment following filtration surgery [see Precautions, General]; and tinnitus. Urogenital Retroperitoneal fibrosis, decreased libido, impotence, and Peyronie's disease. The following additional adverse effects have been reported in clinical experience with ORAL timolol maleate or other ORAL beta-blocking agents and may be considered potential effects of ophthalmic timolol maleate: Allergic : Erythematous rash, fever combined with aching and sore throat, laryngospasm with respiratory distress; Body as a Whole : Extremity pain, decreased exercise tolerance, weight loss; Cardiovascular : Worsening of arterial insufficiency, vasodilatation; Digestive : Gastrointestinal pain, hepatomegaly, vomiting, mesenteric arterial thrombosis, ischemic colitis; Hematologic : Nonthrombocytopenic purpura; thrombocytopenic purpura, agranulocytosis; Endocrine : Hyperglycemia, hypoglycemia; Skin : Pruritus, skin irritation, increased pigmentation, sweating; Musculoskeletal : Arthralgia; Nervous System/Psychiatric : Vertigo, local weakness, diminished concentration, reversible mental depression progressing to catatonia, an acute reversible syndrome characterized by disorientation for time and place, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics; Respiratory: Rales, bronchial obstruction; Urogenital: Urination difficulties. To report SUSPECTED ADVERSE REACTIONS, contact Caplin Steriles Limited at 1-866-978-6111 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug Interactions
Although timolol maleate used alone has little or no effect on pupil size, mydriasis resulting from concomitant therapy with timolol maleate and epinephrine has been reported occasionally. Beta-adrenergic blocking agents Patients who are receiving a beta-adrenergic blocking agent orally and timolol maleate should be observed for potential additive effects of beta-blockade, both systemic and on intraocular pressure. The concomitant use of two topical beta-adrenergic blocking agents is not recommended. Calcium antagonists Caution should be used in the coadministration of beta-adrenergic blocking agents, such as timolol maleate, and oral or intravenous calcium antagonists because of possible atrioventricular conduction disturbances, left ventricular failure, and hypotension. In patients with impaired cardiac function, coadministration should be avoided. 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 result in vertigo, syncope, or postural hypotension. 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. CYP2D6 inhibitors 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. Clonidine Oral beta-adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. There have been no reports of exacerbation of rebound hypertension with ophthalmic timolol maleate. Injectable epinephrine [See Precautions, General, Anaphylaxis].
Similar Drugs
Related medications based on brand, generic name, substance, active ingredients.