Timolet P

Uses

Pilocarpine is used for chronic open angle glaucoma, acute or chronic narrow angle glaucoma, suspected glaucoma and ocular hypertension.

Timolol Maleate Ophthalmic Solution is used for the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.

Timolet P is also used to associated treatment for these conditions: Dry Mouth, Glaucoma, Closed-Angle, Glaucoma, Narrow Angle, Increased Intra Ocular Pressure (IOP), Ocular Hypertension, Open Angle Glaucoma (OAG), Open-angle Glaucoma (OAG), Acute Angle closure glaucoma, Chronic open-angle glaucomaIncreased Intra Ocular Pressure (IOP), Migraine, Ocular Hypertension, Open Angle Glaucoma (OAG)

How Timolet P works

Pilocarpine is a cholinergic parasympathomimetic agent. It increase secretion by the exocrine glands, and produces contraction of the iris sphincter muscle and ciliary muscle (when given topically to the eyes) by mainly stimulating muscarinic receptors.

Timolol competes with adrenergic neurotransmitters for binding to beta(1)-adrenergic receptors in the heart and the beta(2)-receptors in the vascular and bronchial smooth muscle. This leads to diminished actions of catecholamines, which normally bind to adrenergic receptors and exert sympathetic effects leading to an increase in blood pressure and heart rate. Beta(1)-receptor blockade by timolol leads to a decrease in both heart rate and cardiac output during rest and exercise, and a decrease in both systolic and diastolic blood pressure. In addition to this, a reduction in reflex orthostatic hypotension may also occur. The blockade of beta(2) receptors by timolol in the blood vessels leads to a decrease in peripheral vascular resistance, reducing blood pressure.

The exact mechanism by which timolol reduces ocular pressure is unknown at this time, however, it likely decreases the secretion of aqueous humor in the eye. According to one study, the reduction of aqueous humor secretion may occur through the decreased blood supply to the ciliary body resulting from interference with the active transport system or interference with prostaglandin biosynthesis.

Dosage

Timolet P dosage

Instill 1 drop 2-4 times daily. To minimize systemic absorption of the active ingredient of the eye drops, pressure should be applied for one minute on the tear duct after application.

Eye drops Solution: Initially, instill 1 drop of 0.25% solution bid into the affected eye(s), may increase to 1 drop of 0.5% solution bid if there is inadequate response; decrease to 1 drop once daily if controlled. Do not exceed 1 drop bid of 0.5% solution.

Gel-forming eye drops:0.25% or 0.5% Gel-forming eye drops: Instill 1 drop into the affected eye(s) once daily.

Side Effects

Common: Temporary blurred vision, burning, stinging, redness, watering of the eyes, decrease in night vision, eye irritation, headache.

Rare: Eye pain, increased sweating, muscle tremors, nausea, vomiting, diarrhea, watering of the mouth, troubled breathing or wheezing.

Burning and stinging sensation of the eyes, bradycardia, hypotension, arrhythmia and AV or SA nodal block, CHF, pulmonary oedema, Raynaud's phenomenon, headache, dizziness, fatigue, asthenia, abdominal discomfort, nausea, constipation, hypoglycaemia.

Toxicity

The oral LD50 for timolol maleate is 1028 mg/kg in the rat and 1137 mg/kg in the mouse.

Symptoms of timolol overdose may include dizziness, headache, shortness of breath, bradycardia, in addition to bronchospasm. Sometimes, an overdose may lead to cardiac arrest. An overdose of timolol can be reversed with dialysis, however, patients with renal failure may not respond as well to dialysis treatment.

Precaution

If blurred vision or changes in near or far sight occur, especially at night, patients should exercise caution when involved in night driving or hazardous work in poor light. It is recommended that intraocular pressure measurements be performed regularly during therapy.

Patients with inadequate cardiac function, DM, myasthenia gravis, cerebrovascular insufficiency, history of atopy. Avoid abrupt withdrawal as it may exacerbate angina symptoms or precipitate MI in patients with coronary artery disease, or precipitate thyroid crisis in patients with thyrotoxicosis. Patients undergoing major surgery. May mask signs of hyperthyroidism and hypoglycaemia. Ophth soln should not be used as monotherapy for angle-closure glaucoma. Renal and hepatic impairment. Pregnancy and lactation.

Interaction

Belladonna alkaloids or cyclopentolate used ophthalmically may interfere with the miotic effects of pilocarpine and may have their own mydriatic effects dampened. This latter may be used to therapeutic advantage.

Although Timolol used alone has little or no effect on pupil size, mydriasis resulting from concomitant therapy with Timolol Maleate and epinephrine has been reported occasionally. Drug interactions of Timolol Maleate have been noticed with concomitant administration of beta-adrenergic blocking agents (both oral and topical), calcium antagonists, catecholamine-depleting drugs, digitalis, quinidin, clonidine, injectable epinephrine.

Volume of Distribution

1.3 - 1.7 L/kg

Timolol is distributed to the following tissues: the conjunctiva, cornea, iris, sclera, aqueous humor, kidney, liver, and lung.

Elimination Route

There was a decrease in the rate of absorption of pilocarpine from SALAGEN Tablets when taken with a high fat meal by 12 healthy male volunteers

The systemic bioavailability of the ophthalmic eyedrop in one study of healthy volunteers was 78.0 ± 24.5% , indicating that caution must be observed when this drug is administered, as it may be significantly absorbed and have various systemic effects. Another study measured the bioavailability of timolol eyedrops to be 60% in healthy volunteers.

The peak concentration of ophthalmic timolol in plasma, Cmax was about 1.14 ng/ml in most subjects within 15 minutes following the administration of timolol by the ophthalmic route. The mean area under the curve (AUC) was about 6.46 ng/ml per hour after intravenous injection and about 4.78 ng/ml per hour following eyedrop administration.

Half Life

0.76 hours

Timolol half-life was measured at 2.9 ± 0.3 h hours in a clinical study of healthy volunteers.

Clearance

One pharmacokinetic study in healthy volunteers measured the total plasma clearance of timolol to be 557 ± 61 ml/min. Another study determined the total clearance 751.5 ± 90.6 ml/min and renal clearance to be 97.2 ± 10.1 ml/min in healthy volunteers.

Elimination Route

Timolol and its metabolites are mainly found excreted in the urine.

Pregnancy & Breastfeeding use

Safe use during pregnancy has not been established. Problems in human pregnancy have not been documented. However, ophthalmic Pilocarpine is systemically absorbed.

Pregnancy: There are no adequate and well-controlled studies in pregnant women. Timolol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Timolol has been detected in breast milk following oral and ophthalmic drug administration. Because of the potential for serious adverse reactions from Timolol 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.

Contraindication

Hypersensitivity to any ingredient including excipients. Conditions where pupillary constriction is undesirable (e.g. acute iritis). Retinal detachment; past history of retinal detachment or conditions that predispose to retinal detachment.

Timolol is contraindicated in patients with bronchial asthma, a 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.

Acute Overdose

Dilution with water and other fluids is the usual response to accidental or deliberate overdose.

There have been reports of inadvertent overdosage with Timolol 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.

Storage Condition

Store at room temperature and protect from light. It is desirable that the contents should not be used more than 4 weeks after first opening of the bottle.

Store between 15-30° C. Avoid freezing and protect from light.

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