Timolol Maleate Ophthalmic Gel Forming Solution

Description

DESCRIPTION Timolol maleate ophthalmic gel forming 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: 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

What Is Timolol Maleate Ophthalmic Gel Forming Solution Used For?

INDICATIONS AND USAGE Timolol maleate sterile ophthalmic gel forming solution is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.

Dosage and Administration

DOSAGE AND ADMINISTRATION Patients should be instructed to invert the closed container and shake once before each use. It is not necessary to shake the container more than once. Other topically applied ophthalmic medications should be administered at least 10 minutes before timolol maleate ophthalmic gel forming solution [see PRECAUTIONS, Information for Patients and accompanying INSTRUCTIONS FOR USE ]. Timolol Maleate Sterile Ophthalmic Gel Forming Solution is available in concentrations of 0.25% and 0.5%. The dose is one drop of Timolol Maleate Ophthalmic Gel Forming Solution (either 0.25% or 0.5%) in the affected eye(s) once a day. Because in some patients the pressure-lowering response to timolol maleate ophthalmic gel forming 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 gel forming solution. Dosages higher than one drop of 0.5% timolol maleate ophthalmic gel forming solution once a day have not been studied. If the patient's intraocular pressure is still not at a satisfactory level on this regimen, concomitant therapy can be considered. The concomitant use of two topical beta-adrenergic blocking agents is not recommended [see PRECAUTIONS, Drug Interactions, Beta-adrenergic blocking agents ]. When patients have been switched from therapy with TIMOPTIC administered twice daily to timolol maleate ophthalmic gel forming solution administered once daily, the ocular hypotensive effect has remained consistent.

Side Effects (Adverse Reactions)

ADVERSE REACTIONS In clinical trials, transient blurred vision upon instillation of the drop was reported in approximately one in three patients (lasting from 30 seconds to 5 minutes). Less than 1% of patients discontinued from the studies due to blurred vision. The frequency of patients reporting burning and stinging upon instillation was comparable between timolol maleate ophthalmic gel forming solution and TIMOPTIC (approximately one in eight patients). Adverse experiences reported in 1-5% of patients were: Ocular: Pain, conjunctivitis, discharge (e.g., crusting), foreign body sensation, itching and tearing; Systemic: Headache, dizziness, and upper respiratory infections. The following additional adverse experiences have been reported with the ocular administration of this or other timolol maleate formulations: BODY AS A WHOLE Asthenia/fatigue, and chest pain. CARDIOVASCULAR Bradycardia, arrhythmia, hypotension, hypertension, syncope, heart block, cerebrovascular 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 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, 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, Diabetes Mellitus ]. SPECIAL SENSES Signs and symptoms of ocular irritation including blepharitis, keratitis, 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 Fosun Pharma USA Inc. at 1-866-611-3762 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions

Drug Interactions Beta-Adrenergic Blocking Agents Patients who are receiving a beta-adrenergic blocking agent orally and timolol maleate ophthalmic gel forming 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 gel forming solution, and oral or intravenous calcium antagonists because of possible atrioventricular conduction disturbances, left ventricular failure, or 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 ]

Contraindications

CONTRAINDICATIONS Timolol maleate ophthalmic gel forming solution is contraindicated in patients with (1) bronchial asthma; (2) a history of bronchial asthma; (3) severe chronic obstructive pulmonary disease [see WARNINGS, Obstructive Pulmonary Disease ]; (4) sinus bradycardia; (5) second or third degree atrioventricular block; (6) overt cardiac failure [see WARNINGS, Cardiac Failure ]; (7) cardiogenic shock; or (8) hypersensitivity to any component of this product.

Pregnancy and Breastfeeding

Pregnancy Teratogenic Effects 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 recommended human 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 gel forming solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers Timolol maleate has been detected in human milk following oral and ophthalmic drug administration. Because of the potential for serious adverse reactions from timolol maleate ophthalmic gel forming solution in nursing 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.

Overdosage

OVERDOSAGE No data are available in regard to human overdosage with or accidental oral ingestion of timolol maleate ophthalmic gel forming solution. There have been reports of inadvertent overdosage with TIMOPTIC 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 ADVERSE REACTIONS ]. Overdosage has been reported with timolol maleate tablets. A 30-year-old female ingested 650 mg of 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.

How Supplied

HOW SUPPLIED Timolol maleate ophthalmic gel forming solution is a colorless to nearly colorless, slightly opalescent, and slightly viscous solution. Timolol maleate ophthalmic gel forming solution, 0.25% timolol equivalent, is supplied in a white low density polyethylene (LDPE) dispenser with a controlled drop tip and a yellow polypropylene cap as follows: NDC 72266-199-01 , 5 mL in a 5 mL capacity bottle. Timolol maleate ophthalmic gel forming solution, 0.5% timolol equivalent, is supplied in a white low density polyethylene (LDPE) dispenser with a controlled drop tip and a yellow polypropylene cap as follows: NDC 72266-200-01 , 5 mL in a 5 mL capacity bottle. Storage Store at 15° to 25°C (59° to 77°F). Avoid Freezing. Protect from light. Distributed by: Fosun Pharma USA Inc. Princeton, NJ 08540 Made in India Issued: 02/2023 1313000729-01