Intaprost T

Uses

This Eye Drops is used for the reduction of intraocular pressure in adult patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to mono-therapy.

Intaprost T is also used to associated treatment for these conditions: Hypotrichosis of the eyelashes, Increased Intra Ocular Pressure (IOP), Ocular HypertensionIncreased Intra Ocular Pressure (IOP), Migraine, Ocular Hypertension, Open Angle Glaucoma (OAG)

How Intaprost T works

Bimatoprost imitates the effects of prostamides, specifically prostaglandin F2α. Bimatoprost mildly stimulates aqueous humor outflow, relieving elevated intraocular pressure and decreasing the risk of optic nerve damage. It is thought that bimatoprost reduces intraocular pressure (IOP) in humans by causing an increase in outflow of the aqueous humor via the trabecular meshwork and uveoscleral pathways. It achieves the above effects by decreasing tonographic resistance to aqueous humor outflow. Bimatoprost does not affect aqueous humor production.

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

Intaprost T dosage

The recommended dose is one drop in the affected eye(s) once-daily.

Side Effects

In clinical trials, Ocular hyperemia was reported in approximately 26% of patients. 5 to 10 % in these clinical studies included decreased visual acuity, eye discomfort, foreign body sensation, pain and pruritis.

Toxicity

No information is available at this time regarding bimatoprost overdose in humans. Provide supportive symptomatic treatment if an overdose occurs.

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

Like other topically applied ophthalmic medicinal products, the active substances Timolol/ Bimatoprost may be absorbed systemically. Due to the beta-adrenergic component, Timolol, the same types of cardiovascular, pulmonary and other adverse reactions as seen with systemic beta-blockers may occur. Caution should be exercised in treating patients with severe or unstable and uncontrolled cardiovascular Disease.

Interaction

There is a potential for bradycardia when ophthalmic beta blockers solution is administered concomitantly with oral calcium channel blockers, guanethidine, beta-adrenergic blocking agents, parasympathomimetics, anti-arrhythmics and digitalis glycosides. Concomitant ocular medications should be administered at least 5 min apart from the instillations of this Eye Drops

Volume of Distribution

The volume of distribution at steady state is 0.67 L/kg.. It penetrates the human cornea and sclera.

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

This drug is absorbed systemically when administered to the eye. A study was performed on 15 healthy volunteers and bimatoprost ophthalmic solution 0.03% was administered once daily for 14 days. The mean Cmax was approximately 0.08 ng/mL and AUC0-24hr was approximately 0.09 on days 7 and 14 of the study. By 10 minutes, peak blood concentration was achieved. Bimatoprost was not detectable at 1.5 hours after administration in most subjects. The maximum blood concentration in a study of 6 healthy volunteers was determined to be 12.2 ng/mL. Steady state was reached in the first week of dosing.

One drug label mentions that onset of decreased intraocular pressure occurs approximately 4 hours after the first administration and the peak effect occurs in the range of 8-12 hours. Bimatoprost effects may last up to 24 hours.

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

The elimination half-life of bimatoprost is approximately 45 minutes.

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

Clearance

The clearance was measured to be 1.5 L/hr/kg in healthy subjects receiving IV administration of bimatoprost dosed at 3.12 ug/kg.

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

One pharmacokinetic study of bimatoprost in 6 healthy volunteers determined that 67% of the administered dose was found to be excreted in the urine while 25% of the dose was recovered in the feces.

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

Pregnancy & Breastfeeding use

Use in Pregnancy: There are no adequate data from the use of the Bimatoprost / Timolol fixed combination in pregnant women. It should not be used during pregnancy unless clearly necessary.

Use in Lactation: Animal studies showed Bimatoprost is excreted in rat’s milk. & Timolol is excreted in human milk. Therefore, Bimatoprost / Timolol should not be used during breastfeeding.

Contraindication

It is contraindicated in patients with known hypersensitivity to any ingredient of this formulation.

Special Warning

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

Acute Overdose

Treatment is symptomatic.

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 below 25° C in a dry place protected from light. Keep out of reach of children. Solution can be used up to 28 days after first opening.

Innovators Monograph

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