Latanoprost & Timolol Stada

Latanoprost & Timolol Stada

latanoprost + timolol

Manufacturer:

Stada

Distributor:

HK Medical Supplies
/
Health Express
Full Prescribing Info
Contents
Latanoprost, timolol.
Description
1 ml solution contains 50 micrograms Latanoprost and 6.8 mg Timolol maleate corresponding to 5 mg Timolol.
Excipients/Inactive Ingredients: Benzalkonium chloride 0.2 mg; Sodium chloride, Sodium dihydrogen phosphate dihydrate; Disodium hydrogen phosphate dodecahydrate; Purified water; Sodium hydroxide for pH adjustment; Hydrochlo­ric acid for pH adjustment.
Action
Pharmacotherapeutic group: Antiglaucoma preparations and miotics; beta-blocking agents; timolol combinations. ATC Code: S01ED51.
Pharmacology: Pharmacodynamics: Mechanism of action: Latanoprost and Timolol 50 micrograms/5mg eye drops, solution consists of two components: Latanoprost and Timolol maleate. These two components decrease elevated intraocular pressure (IOP) by different mechanisms of action and the combined effect results in additional IOP reduction compared to either compound administered alone.
Latanoprost, a prostaglandin F2alpha analogue, is a selective prostanoid FP receptor agonist that reduces the IOP by increasing the outflow of aqueous humour. The main mechanism of action is increased uveoscleral outflow. Additionally, some increase in outflow facility (decrease in trabecular outflow resistance) has been reported in man. Latanoprost has no significant effect on the production of aqueous humour, the blood-aqueous barrier or the intraocular blood circulation. Latanoprost has not induced fluorescein leakage in the posterior segment of pseudo­phakic human eyes during short-treatment.
Timolol is a beta-1 and beta-2 (non-selective) adrenergic receptor blocking agent that has no significant intrinsic sympathomimetic, direct myocardial depressant or membrane-stabilising activity. Timolol lowers IOP by decreasing the formation of aqueous in the ciliary epithelium. Timolol has not been found to significantly affect the permeability of the blood-aqueous barrier to plasma proteins.
Pharmacokinetics: Latanoprost: Latanoprost is an isopropyl ester prodrug, which per se is inactive, but after hydrolysis by esterases in the cornea to the acid of Latanoprost, becomes biologically active. The prodrug is well absorbed through the cornea and all drug that enters the aqueous humor is hydrolyzed during the passage through the cornea.
The acid of Latanoprost has a plasma clearance of 0.40 l/h/kg and a small volume of distribution, 0.16 l/kg, resulting in a rapid half-life in plasma, 17 minutes. After topical ocular administration the systemic bioavailability of the acid of Latanoprost is 45%. The acid of Latanoprost has a plasma protein binding of 87%.
There is practically no metabolism of the acid of Latanoprost in the eye. The main metabolism occurs in the liver. The main metabolites, the 1,2-dinor and 1,2,3,4-tetranor metabolites, exert no or only weak biological activity and are excreted primarily in the urine.
Timolol: The maximum concentration of Timolol in the aqueous humor is reached about 1 hour after topical administration of eye drops. Part of the dose is absorbed systemically and a maximum plasma concentration of 1 ng/ml is reached 10-20 minutes after topical administration of one eye drop to each eye once daily (300 micrograms/day). The half-life of Timolol in plasma is about 6 hours. Timolol is extensively metabolised in the liver. The metabolites are excreted in the urine together with some unchanged Timolol.
Latanoprost and Timolol: No pharmacokinetic interactions between Latanoprost and timolol were observed although there was an approximately 2-fold increased concentration of the acid of Latanoprost in aqueous humour 1-4 hours after administration of Latanoprost/timolol compared to monotherapy.
Indications/Uses
Reduction of intraocular pressure (IOP) in patients with open angle glaucoma and ocular hypertension who are insufficiently responsive to topical beta-blockers or prostaglandin analogues.
Dosage/Direction for Use
Adults (including the elderly): Recommended therapy is one eye drop in the affected eye(s) once daily. If one dose is missed, treatment should continue with the next dose as planned. The dose should not exceed one drop in the affected eye(s) daily.
Method of administration: Contact lenses should be removed before instillation of the eye drops and may be reinserted after 15 minutes.
If one more topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes apart.
Paediatric population: Safety and effectiveness in children and adolescents has not been established.
Overdosage
No data available in humans with regards to overdose with Latanoprost and Timolol.
Symptoms of systemic Timolol overdose are: bradycardia, hypotension, bronchospasm and cardiac arrest. If such symptoms occur the treatment should be symptomatic and supportive.
Apart from ocular irritation and conjunctival hyperaemia no other ocular or systemic side effects are known if Latanoprost is overdosed.
If Latanoprost is accidentally ingested orally the following information may be useful: Treatment: Gastric lavage if needed. Symptomatic treatment.
Latanoprost is extensively metabolised during the first pass through liver. Intravenous infusion of 3 micrograms/kg in healthy volunteers induced no symptoms but a dose of 5.5-10 micrograms/kg caused nausea, abdominal pain, dizziness, fatigue, hot flushes and sweating. These events were mild to moderate in severity and resolved without treatment, within 4 hours after terminating the infusion.
Contraindications
Latanoprost and Timolol is contraindicated in patients with: Reactive airway disease including bronchial asthma or 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 the active substances or to any of the excipients.
Special Precautions
Systemic effects: Like other topically applied ophthalmic agents, Latanoprost and Timolol may be absorbed systemically. Due to the beta-adrenergic component Timolol, the same types of cardiovascular and pulmonary adverse reactions as seen with systemic beta-blockers may occur.
In patients with cardiovascular diseases (e.g. coronary heart disease, Prinzmetal's angina, cardiac failure) and hypotension therapy with beta-blockers should be critically assessed and treatment with other active substances should be considered. Patients with cardiovascular diseases should be watched for signs of deterioration of these diseases and adverse reactions.
Respiratory reactions, including death due to bronchospasm in patients with asthma have been reported following administration of some ophthalmic beta-blockers.
Beta-blockers should be administered with caution in patients subject to spontaneous hypoglycaemia or to patients with labile diabetes, as beta-blockers may mask the signs and symptoms of acute hypoglycaemia.
Beta-blockers may also mask the signs of hyperthyroidism.
Anaphylactic reactions: While taking beta-blockers, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be unresponsive to the usual doses of adrenaline used to treat anaphylactic reactions.
Concomitant therapy: Timolol may react with other drugs.
The effect on intraocular pressure or the known effects of systemic beta-blockade may be potentiated when Timolol is given to patients already receiving an oral beta-blocking agent. The use of two local beta-blockers is not recommended.
Ocular effects: Latanoprost may gradually change the eye colour by increasing the amount of brown pigment in the iris. Similar to experience with Latano­prost eye drops, increased iris pigmentation was seen in 16-20% of all patients treated with Latanoprost/Timolol for up to one year (based on photographs). This effect has predominantly been seen in patients with mixed coloured irides, i.e. green-brown, yellow-brown, or blue/grey-brown, and is due to increased melanin content in the stromal melanocytes of the iris. Typically the brown pigmentation around the pupil spreads concentrically towards the periphery in the affected eyes, but the entire iris or parts of it may become more brownish. In patients with homogeneously blue, grey, green or brown eyes, the change has only rarely been seen during two years of treatment in clinical trials with Latanoprost.
The change in iris colour occurs slowly and may not be noticeable for several months to years and it has not been associated with any symptom or pathological changes. No further increase in brown iris pigment has been observed after discontinuation of treatment, but the resultant colour change may be permanent.
Neither naevi nor freckles of the iris have been affected by treatment.
Accumulation of pigment in the trabecular meshwork or elsewhere in the anterior chamber has not been observed but patients should be examined regularly and, depending on the clinical situation, treatment may be stopped if increased iris pigmentation ensues. Before treatment is instituted patients should be informed of the possibility of a change in eye colour. Unilateral treatment can result in permanent heterochromia.
Latanoprost has no or little effect on the pupil but there is no documented experience in acute attacks of closed angle glaucoma. It is recommended, therefore, that Latanoprost/Timolol should be used with caution in these conditions until more experience is obtained.
Macular edema, including cystoids macular edema, has been reported during treatment with Latanoprost. These reports have mainly occurred in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema. Latanoprost/Timolol should be used with caution in these patients.
Choroidal detachment has been reported with administration of aqueous suppressant therapy (e.g. timolol, acetazolamide) after filtration procedures.
Use of contact lenses: Latanoprost and Timolol contains benzalkonium chloride, which is commonly used as a preservative in ophthalmic products. Benzalkonium chloride has been reported to cause punctuate keratopathy and/or toxic ulcerative keratopathy, may cause eye irritation and is known to discolour soft contact lenses. Close monitoring is required with frequent or prolonged use of Latanoprost and Timolol in dry eye patients, or in conditions where the cornea is compromised. Contact lenses may absorb benzalkonium chloride and these should be removed before instillation of the eye drops and may be reinserted after 15 minutes.
Effects on Ability to Drive and Use Machines: Instillation of eye drops may cause transient blurring of vision. Until this is resolved, patients should not drive or use machines.
Use In Pregnancy & Lactation
Pregnancy: Latanoprost: There are no adequate data from the use of Latanoprost in pregnant women.
Timolol: There are no adequate data for the use of Timolol in pregnant women.
Consequently Latanoprost and Timolol should not be used during pregnancy.
Lactation: Beta-blocker is excreted into breast milk. Latanoprost and its metabolites may pass into breast milk. Latanoprost and Timolol should therefore not be used in women who are breast-feeding.
Adverse Reactions
For Latanoprost, the majority of adverse events relate to the ocular system. Other ocular adverse events are generally transient and occur on dose administration. For Timolol, the most serious adverse events are systemic in nature, including bradycardia, arrhythmia, congestive heart failure, bronchospasm and allergic reactions.
Treatment related adverse events seen in clinical trials with Latanoprost and Timolol are listed as follows: Adverse events are categorized by frequency as follows: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1000 to <1/100), Rare (≥1/10,000 to <1/1000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).
Nervous System Disorders: Uncommon: Headache.
Eye Disorders: Very common: Increased iris pigmentation.
Common: Eye irritation (including stinging, burning and itching), eye pain.
Uncommon: Eye hyperaemia, conjunctivitis, vision blurred, Lacrimation increased, blepharitis, Corneal disorders.
Skin and Subcutaneous Tissue Disorders: Uncommon: Skin rash, pruritus.
Additional adverse events have been reported specific to the use of the individual components of the medicinal product either in clinical studies, spontaneous reports or in available literature.
For Latanoprost, these are: Nervous System Disorders: Dizziness.
Eye Disorders: Eyelash and vellus hair changes (increased length, thickness, pigmentation and number), punctuate epithelial erosions, periorbital oedema, iritis/uveitis, macular oedema (in aphakic, pseudophakic patients with torn posterior lens capsules or in patients with known risk factors for macular oedema), dry eye, keratitis, corneal oedema and erosions, misdirected eyelashes sometimes resulting in eye irritation and iris cyst.
Cardiac Disorders: Aggravation of angina in patients with pre-existing disease, palpitations.
Respiratory, Thoracic, and Mediastinal Disorders: Asthma, asthma aggravation, dyspnoea.
Skin and Subcutaneous Tissue Disorders: Darkening of palpebral skin.
Musculoskeletal, Connective Tissue and Bone Disorder: Joint pain, muscle pain.
General Disorders and Administration Site Conditions: Chest pain.
For Timolol, these are: Immune System Disorders: Signs and symptoms of systemic allergic reactions including angioedema, urticaria and localized and general rash.
Psychiatric Disorders: Depression, insomnia, nightmares, memory loss.
Nervous System Disorders: Dizziness, paraesthesia, cerebral ischemia, cerebrovascular accident, increase in signs and symptoms of myasthenia gravis, syncope.
Eye Disorders: Signs and symptoms of ocular irritation (e.g. burning, stinging, itching, tearing, redness), blepharitis, keratitis, blurred vision and choroidal detachment following filtration surgery, decreased corneal sensitivity, dry eyes, corneal erosion, ptosis and diplopia.
Ear and Labyrinth Disorders: Tinnitus.
Cardiac Disorders: Palpitation, arrhythmia, bradycardia, cardiac arrest, atrioventricular block, congestive heart failure.
Vascular Disorders: Hypotension, Raynaud's phenomenon, cold hands and feet.
Respiratory, Thoracic and Mediastinal Disorders: Bronchospasm (predominantly in patients with pre-existing bronchospastic disease), dyspnoea, cough.
Gastrointestinal Disorder: Nausea, diarrhea, dyspepsia, dry mouth.
Skin and Subcutaneous Tissue Disorders: Alopecia, psoriasiform rash or exacerbations of psoriasis.
General Disorder and Administration Site Conditions: Asthenia, fatigue.
Drug Interactions
Specific drug interaction studies have not been performed with Latanoprost/Timolol.
There have been reports of paradoxical elevations in intraocular pressure following the concomitant ophthalmic administration of two prostaglandin analogues. Therefore, the use of two or more prostaglandins, prostaglan­din analogues, or prostaglandin derivatives is not recommended.
The effect on intraocular pressure or the known effects of systemic beta-blockade may be potentiated when Latanoprost and Timolol is given to patients already receiving an oral beta-adrenergic agent, and the concomitant use of two or more topical beta-adrenergic blocking agents is not recommended.
Mydriasis resulting from concomitant use of ophthalmic beta-blockers and adrenaline (epinephrine) has been reported occasionally.
There is a potential for additive effects resulting in hypotension and/or marked bradycardia when eye drops with Timolol are administered concomitantly with oral calcium channel blockers, guanethidine or beta-blocking agents, anti-arrhythmics, digitalis glycosides or parasympa­thomimetics.
The hypertensive reaction to sudden withdrawal of clonidine can be potentiated when taking beta-blockers.
Beta-blockers may increase the hypoglycaemic effect of antidiabetic agents. Beta-blockers can mask signs and symptoms of hypoglycaemia.
Storage
Store in a refrigerator (2°C - 8°C).
Shelf life: After first opening: 28 days. Do not store above 25°C.
ATC Classification
S01ED51 - timolol, combinations ; Belongs to the class of beta blocking agents. Used in the treatment of glaucoma.
Presentation/Packing
Eye drops (clear colourless liquid) 2.5 mL x 1's.
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