Bimat Ls Tm

Uses

Bimatoprost is used for Ocular hypertension, Open-angle glaucoma

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

Bimat Ls Tm 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 Bimat Ls Tm 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

Bimat Ls Tm dosage

Adult: Instill 1 drop into affected eye(s) once every night.

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 side effects are: Burning/stinging/irritation/ redness/discomfort of the eye, Feeling as if something is in your eye, Dry eyes, Watering eyes, Temporary unstable vision, Increased sensitivity to light, Dizziness.

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

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

May increase pigmentation of the iris, periorbital tissue and eyelashes. Active intraocular inflammation. Safety and efficacy have not been evaluated in the treatment of inflammatory, neovascular or angle closure glaucoma. Ensure at least an interval of 5 minutes between admin of ophthalmic preparations. Contact lenses should be removed prior to admin. Pregnancy, lactation.

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

There is not known drug interactions and none well documented.

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

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

Pregnancy Category C. Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

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

Known hypersensitivity.

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

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 at 2-25° C.

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

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