Timolol GFS (Timolol Maleate Ophthalmic) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Oral Beta-Adrenergic Receptor Inhibitors

Patients who are receiving a beta-adrenergic receptor inhibiting agents orally and Timolol GFS should be observed for potential additive effects of beta-blockade, both systemic and on intraocular pressure. Patients should not usually receive two topical ophthalmic beta-adrenergic receptor inhibiting agents concurrently.

Digitalis and Calcium Antagonists

The concomitant use of beta-adrenergic receptor inhibiting agents with digitalis and calcium antagonists may have additive effects in prolonging atrioventricular conduction time.

Caution should be used in the coadministration of beta-adrenergic receptor inhibitors, such as Timolol GFS, and oral or intravenous calcium antagonists because of possible atrioventricular conduction disturbances, left ventricular failure, or hypotension. In patients with impaired cardiac function, co-administration should be avoided.

Catecholamine-Depleting Drugs

Close observation of the patient is recommended when a beta receptor inhibitor 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.

Quinidine

Potentiated systemic beta-blockade (e.g., decreased heart rate) has been reported during combined treatment with quinidine and timolol, possibly because quinidine inhibits the metabolism of timolol via the P-450 enzyme, CYP2D6.

Clonidine

Oral beta-adrenergic receptor inhibitor 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 Warnings and Precautions (5.11) ]

OVERDOSAGE

No data are available with regard to human overdose with, or accidental oral ingestion of Timolol GFS. There have been reports of inadvertent overdose with Timolol maleate ophthalmic solution resulting in systemic effects similar to those seen with systemic beta-adrenergic receptor inhibitors such as dizziness, headache, shortness of breath, bradycardia, bronchospasm, and cardiac arrest [see also Adverse Reactions (6) ].

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 ¹⁴C 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.

CONTRAINDICATIONS

Timolol GFS is contraindicated in patients with:

• bronchial asthma
• history of bronchial asthma
• severe chronic obstructive pulmonary disease
• sinus bradycardia
• second or third degree atrioventricular block
• overt cardiac failure
• cardiogenic shock
• hypersensitivity to any component of this product.