Timolol Maleate

What is Timolol Maleate?

DESCRIPTION Timolol maleate 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 S•C 4 H 4 O 4 , and its structural formula is: Timolol maleate has a molecular weight of 432.49. It is a white, odorless, crystalline powder which is soluble in water; sparingly soluble in ethanol; slightly soluble in chloroform; practically insoluble in ether. Timolol maleate is stable at room temperature. Timolol maleate ophthalmic solution is supplied in two formulations: Timolol Maleate Ophthalmic Solution, which contains the preservative benzalkonium chloride; and Timolol Maleate Ophthalmic Solution, the preservative-free formulation. Preservative-free Timolol Maleate Ophthalmic Solution is supplied in OCUDOSE ® , a unit dose container, as a sterile, isotonic, buffered, aqueous solution of timolol maleate. Each mL of Preservative-free Timolol Maleate Ophthalmic Solution in OCUDOSE

Uses of Timolol Maleate

Established uses

• INDICATIONS AND USAGE Preservative-free Timolol Maleate Ophthalmic Solution in OCUDOSE is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.
• Preservative-free Timolol Maleate Ophthalmic Solution in OCUDOSE may be used when a patient is sensitive to the preservative in Timolol Maleate Ophthalmic Solution, benzalkonium chloride, or when use of a preservative-free topical medication is advisable.

How to take Timolol Maleate

DOSAGE AND ADMINISTRATION Preservative-free Timolol Maleate Ophthalmic Solution in OCUDOSE is a sterile solution that does not contain a preservative. The solution from one individual unit is to be used immediately after opening for administration to one or both eyes. Since sterility cannot be guaranteed after the individual unit is opened, the remaining contents should be discarded immediately after administration. Preservative-free Timolol Maleate Ophthalmic Solution in OCUDOSE is available in concentrations of 0.25 and 0.5%. The usual starting dose is one drop of 0.25% Preservative-free Timolol Maleate Ophthalmic Solution in OCUDOSE in the affected eye(s) administered twice a day. Apply enough gentle pressure on the individual container to obtain a single drop of solution. If the clinical response is not adequate, the dosage may be changed to one drop of 0.5% solution in the affected eye(s) administered twice a day. Since in some patients the pressure-lowering response to Preservative-free Timolol Maleate Ophthalmic Solution in OCUDOSE may require a few weeks to stabilize, evaluation should include a determination of intraocular pressure after approximately 4 weeks of treatment

Dosage

Follow the dose prescribed by your doctor or pharmacist. The ranges below are general information, not a personal prescription.

Adults

DOSAGE AND ADMINISTRATION Preservative-free Timolol Maleate Ophthalmic Solution in OCUDOSE is a sterile solution that does not contain a preservative. The solution from one individual unit is to be used immediately after opening for administration to one or both eyes. Since sterility cannot be guaranteed after the individual unit is opened, the remaining contents should be discarded immediately after administration. Preservative-free Timolol Maleate Ophthalmic Solution in OCUDOSE is available in concentrations of 0.25 and 0.5%. The usual starting dose is one drop of 0.25% Preservative-free Timolol Maleate Ophthalmic Solution in OCUDOSE in the affected eye(s) administered twice a day. Apply enough gentle pressure on the individual container to obtain a single drop of solution. If the clinical response is not adequate, the dosage may be changed to one drop of 0.5% solution in the affected eye(s) administered twice a day. Since in some patients the pressure-lowering response to Preservative-free Timolol Maleate Ophthalmic Solution in OCUDOSE may require a few weeks to stabilize, evaluation should include a determination of intraocular pressure after approximately 4 weeks of treatment

Side effects of Timolol Maleate

Common

• 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.

Warnings and who should not take it

Who should NOT take Timolol Maleate?

• CONTRAINDICATIONS Preservative-free Timolol Maleate Ophthalmic Solution in OCUDOSE 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 );

Warnings and 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 by 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, Preservative-free Timolol Maleate Ophthalmic Solution in OCUDOSE should be discontinued.

Overdose

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 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.

Frequently asked questions