Product Elements:
Timolol maleate timolol maleate sodium phosphate, dibasic, dodecahydrate sodium phosphate, monobasic, dihydrate sodium chloride benzalkonium chloride sodium hydroxide water timolol maleate timolol anhydrous
Drug Interactions:
Drug interactions although timolol maleate ophthalmic solution used alone has little or no effect on pupil size, mydriasis resulting from concomitant therapy with timolol maleate ophthalmic solution and epinephrine has been reported occasionally. beta-adrenergic blocking agents: patients who are receiving a beta-adrenergic blocking agent orally and timolol maleate ophthalmic solution 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 ophthalmic solution, 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
Read more...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 )
Indications and Usage:
Indications and usage timolol maleate ophthalmic solution is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.
Warnings:
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. 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 asthm
Read more...a or a history of bronchial asthma, in which timolol maleate ophthalmic solution is contraindicated [see contraindications ]) should, in general, not receive beta-blockers, including timolol maleate ophthalmic solution. 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.
Dosage and Administration:
Dosage and administration timolol maleate ophthalmic solution is available in concentrations of 0.25 and 0.5 percent. the usual starting dose is one drop of 0.25 percent timolol maleate ophthalmic solution 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. since in some patients the pressure-lowering response to timolol maleate ophthalmic solution may require a few weeks to stabilize, evaluation should include a determination of intraocular pressure after approximately 4 weeks of treatment with timolol maleate ophthalmic solution. 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
Read more.... dosages above one drop of 0.5 percent timolol maleate ophthalmic solution 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 . )
Contraindications:
Contraindications timolol maleate ophthalmic solution 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:
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, hallucination
Read more...s, 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 pre-existing 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 rising pharmaceuticals, inc. at 866-562-4597 or fda at 1-800-fda-1088 or www.fda.gov/medwatch.
Drug Interactions:
Drug interactions although timolol maleate ophthalmic solution used alone has little or no effect on pupil size, mydriasis resulting from concomitant therapy with timolol maleate ophthalmic solution and epinephrine has been reported occasionally. beta-adrenergic blocking agents: patients who are receiving a beta-adrenergic blocking agent orally and timolol maleate ophthalmic solution 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 ophthalmic solution, 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
Read more...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 )
Use in Pregnancy:
Pregnancy: teratogenic effects â pregnancy category c. teratogenicity studies with timolol in mice, rats, and rabbits at oral doses up to 50 mg/kg/day (7,000 times the systemic exposure following the maximum recommendedhuman ophthalmic dose) demonstrated no evidence of fetal malformations. 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. timolol maleate ophthalmic solution should be used during pregnancy only if the potentia
Read more...l benefit justifies the potential risk to the fetus.
Pediatric Use:
Pediatric use safety and effectiveness in pediatric patients have not been established.
Geriatric Use:
Geriatric use no overall differences in safety or effectiveness have been observed between elderly and younger patients.
Overdosage:
Overdosage there have been reports of inadvertent overdosage with timolol maleate ophthalmic solution 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 adverse reactions ). overdosage has been reported with timolol maleate tablets. a 30-year-old female ingested 650 mg timolol maleate tablets (maximum recommended oral daily dose is 60 mg) and experienced second and third degree heart block. she recovered without treatment but approximately two months later developed irregular heartbeat, hypertension, dizziness, tinnitus, faintness, increased pulse rate, and borderline first degree heart block. an in vitro hemodialysis study, using 14 c timolol added to human plasma or whole blood, showed that timolol was readily dialyzed from these fluids; however, a study of patients with renal failure showed that timolol did not dialyze readily.
Description:
Description timolol maleate ophthalmic solution 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: its molecular formula is c 13 h 24 n 4 o 3 sâ¢c 4 h 4 o 4 and its structural formula is: timolol maleate has a molecular weight of 432.50. it is a white, odorless, crystalline powder which is soluble in water, methanol, and alcohol. timolol maleate is stable at room temperature. timolol maleate ophthalmic solution is supplied as a sterile, isotonic, buffered, aqueous solution of timolol maleate in two dosage strengths: each ml of timolol maleate ophthalmic solution 0.25% contains 2.5 mg of timolol (3.4 mg of timolol maleate). the ph of the solution is approximately 7.0, and the osmolarity is 274-328 mosm. 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 chloride, sodium hydroxide to adjust ph, and water for injection. benzalkonium chloride 0.01% is added as preservative. timolol optical rotation timolol structure
Clinical Pharmacology:
Clinical pharmacology mechanism of action timolol maleate is a beta 1 and beta 2 (non-selective) adrenergic receptor blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity. beta-adrenergic receptor blockade reduces cardiac output in both healthy subjects and patients with heart disease. in patients with severe impairment of myocardial function, beta-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. timolol maleate ophthalmic solution, when applied topically on the eye, has the action of reducing elevated as well as normal intraocular pressure, whether
Read more...or not accompanied by 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. the onset of reduction in intraocular pressure following administration of timolol maleate ophthalmic solution can usually be detected within one-half hour after a single dose. the maximum effect usually occurs in one to two hours and significant lowering of intraocular pressure can be maintained for periods as long as 24 hours with a single dose. repeated observations over a period of one year indicate that the intraocular pressure-lowering effect of timolol maleate ophthalmic solution is well maintained. the precise mechanism of the ocular hypotensive action of timolol maleate ophthalmic solution is not clearly established at this time. tonography and fluorophotometry studies in man suggest that its predominant action may be related to reduced aqueous formation. however, in some studies a slight increase in outflow facility was also observed. 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 ophthalmic solution 0.5%. the mean peak plasma concentration following morning dosing was 0.46 ng/ml and following afternoon dosing was 0.35 ng/ml. clinical studies in controlled multiclinic studies in patients with untreated intraocular pressures of 22 mmhg or greater, timolol maleate ophthalmic solution 0.25 percent or 0.5 percent administered twice a day produced a greater reduction in intraocular pressure than 1, 2, 3, or 4 percent pilocarpine solution administered four times a day or 0.5, 1, or 2 percent epinephrine hydrochloride solution administered twice a day. in these studies, timolol maleate ophthalmic solution was generally well tolerated and produced fewer and less severe side effects than either pilocarpine or epinephrine. a slight reduction of resting heart rate in some patients receiving timolol maleate ophthalmic solution (mean reduction 2.9 beats/minute standard deviation 10.2) was observed.
Mechanism of Action:
Mechanism of action timolol maleate is a beta 1 and beta 2 (non-selective) adrenergic receptor blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity. beta-adrenergic receptor blockade reduces cardiac output in both healthy subjects and patients with heart disease. in patients with severe impairment of myocardial function, beta-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. timolol maleate ophthalmic solution, when applied topically on the eye, has the action of reducing elevated as well as normal intraocular pressure, whether or not accompanied by 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. the onset of reduction in intraocular pressure following administration of timolol maleate ophthalmic solution can usually be detected within one-half hour after a single dose. the maximum effect usually occurs in one to two hours and significant lowering of intraocular pressure can be maintained for periods as long as 24 hours with a single dose. repeated observations over a period of one year indicate that the intraocular pressure-lowering effect of timolol maleate ophthalmic solution is well maintained. the precise mechanism of the ocular hypotensive action of timolol maleate ophthalmic solution is not clearly established at this time. tonography and fluorophotometry studies in man suggest that its predominant action may be related to reduced aqueous formation. however, in some studies a slight increase in outflow facility was also observed.
Pharmacokinetics:
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 ophthalmic solution 0.5%. the mean peak plasma concentration following morning dosing was 0.46 ng/ml and following afternoon dosing was 0.35 ng/ml.
Clinical Studies:
Clinical studies in controlled multiclinic studies in patients with untreated intraocular pressures of 22 mmhg or greater, timolol maleate ophthalmic solution 0.25 percent or 0.5 percent administered twice a day produced a greater reduction in intraocular pressure than 1, 2, 3, or 4 percent pilocarpine solution administered four times a day or 0.5, 1, or 2 percent epinephrine hydrochloride solution administered twice a day. in these studies, timolol maleate ophthalmic solution was generally well tolerated and produced fewer and less severe side effects than either pilocarpine or epinephrine. a slight reduction of resting heart rate in some patients receiving timolol maleate ophthalmic solution (mean reduction 2.9 beats/minute standard deviation 10.2) was observed.
How Supplied:
How supplied sterile ophthalmic solution of timolol maleate is a clear, colorless solution. timolol maleate ophthalmic solution usp, 0.25% timolol equivalent, is supplied in a labeled translucent ldpe bottle with insert cap assembly comprising of a yellow colored hdpe screw cap over a ldpe nozzle with tamper-evident ldpe dust- cover sealing the bottle cap. ndc 64980-513-05, 5 ml in a 5 ml bottle ndc 64980-513-01, 10 ml in a 10 ml bottle ndc 64980-513-15, 15 ml in a 15 ml bottle timolol maleate ophthalmic solution usp, 0.5% timolol equivalent, is supplied in a labeled translucent ldpe bottle with insert cap assembly comprising of a yellow colored hdpe screw cap over a ldpe nozzle with tamper-evident ldpe dust- cover sealing the bottle cap. ndc 64980-514-05, 5 ml in a 5 ml bottle ndc 64980-514-01, 10 ml in a 10 ml bottle ndc 64980-514-15, 15 ml in a 15 ml bottle storage store at 25°c (77°f); excursions permitted 15°c to 30°c (59°f to 86°f)[see usp controlled room temper
Read more...ature] protect from freezing. protect from light. manufactured by: fdc limited, b-8, midc industrial area, waluj, aurangabad - 431 136, maharashtra, india distributed by: rising pharmaceuticals, inc. saddle brook, nj 07663 toll free number: 1-800-521-5340 revised : 02/2018 rx only sterile ophthalmic solution timolol maleate ophthalmic solution usp 0.25% and 0.5% instructions for use please follow these instructions carefully when using timolol maleate ophthalmic solution. use timolol maleate ophthalmic solution as prescribed by your doctor. 1. if you use other topically applied ophthalmic medications, they should be administered at least 10 minutes before or after the use of timolol maleate ophthalmic solution. 2. wash hands before each use. 3. before using the medication for the first time, be sure the dust cover seal is unbroken. 4. refer (i-vi) 5. 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 you think your medication may be contaminated, or if you develop an eye infection, contact your doctor immediately concerning continued use of this bottle. 6. repeat (v) and (vi) with the other eye if instructed to do so by your doctor. 7. the insert tip is designed to provide a premeasured drop; therefore, do not enlarge the hole of the insert tip. 8. after you have used all doses, there will be some timolol maleate ophthalmic solution left in the bottle. you should not be concerned since an extra amount of timolol maleate ophthalmic solution has been added and you will get the full amount of timolol maleate ophthalmic solution that your doctor prescribed. do not attempt to remove excess medicine from the bottle. warning: keep out of reach of children. if you have any questions about the use of timolol maleate ophthalmic solution, please consult your doctor. figure 1 figure 2 figure 3 figure 4 figure 5 figure 6
Information for Patients:
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, if handled improperly or if the tip of the dispensing container contacts the eye or surrounding structures, 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 should also be advised that if they have ocular surgery or develop an intercurrent ocular condition (e.g., trauma or infection), they should immediately seek their physician's advice concerning the continued use of the present multidose container. 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 n
Read more...ot to take this product. (see contraindications .) patients should be advised that timolol maleate ophthalmic solution contains benzalkonium chloride which may be absorbed by soft contact lenses. contact lenses should be removed prior to administration of the solution. lenses may be reinserted 15 minutes following timolol maleate ophthalmic solution administration.
Package Label Principal Display Panel:
Timolol maleate ophthalmic solution 0.5% 5 ml carton 5 ml