LATANOPROST / TIMOLOL

Posology 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. 5% w/v eye drops, solution in children and adolescents has not been established.

Method of administration Ocular use. 4). If more than one topical ophthalmic drug is being used, the medicinal products should be administered at least five minutes apart. When using nasolacrimal occlusion or closing the eyelids for 2 minutes, the systemic absorption is reduced.

This may result in a decrease in systemic side effects and an increase in local activity.

For latanoprost, the majority of adverse events relate to the ocular system. In data from the extension phase of the latanoprost/timolol eye drops pivotal trials, 16 - 20% of patients developed increased iris pigmentation, which may be permanent.

4). 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.

Like other topically applied ophthalmic drugs, timolol is absorbed into the systemic circulation. This may cause similar undesirable effects as seen with systemic beta- blocking agents. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration.

Listed adverse reactions include reactions seen within the class of ophthalmic beta-blockers. 5% w/v eye drops, solution: 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) and very rare (<1/10,000).

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, blurred vision, 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 latanoprost/timolol eye drops either in clinical studies, spontaneous reports or in the available literature.

For latanoprost, these are:

Infections and Infestations: Herpetic keratitis.

Nervous System Disorders:

Dizziness.

Eye Disorders:

Eyelash and vellus hair changes (increased length, thickness, pigmentation, and number), punctate 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, iris cyst, photophobia, periorbital and lid changes resulting in deepening of the eyelid sulcus.

Cardiac Disorders:

Aggravation of angina in patients with pre-existing disease, palpitations.

Gastrointestinal disorders:

Nausea; vomiting (frequency: uncommon) Respiratory, Thoracic and Mediastinal Disorders: Asthma, asthma aggravation, dyspnoea, Skin and Subcutaneous Tissue Disorders: Darkening of palpebral skin.

Musculoskeletal and Connective Tissue Disorders:

Joint pain, muscle pain.

General disorders and Administration Site Conditions:

Chest pain.

For timolol, these are:

Immune System Disorders: Systemic allergic reactions including angioedema, urticaria, localized and generalized rash, pruritus, anaphylactic reaction.

Metabolism and nutrition disorders:

Hypoglycaemia Psychiatric Disorders: Depression, memory loss, insomnia, nightmares.

Nervous System Disorders:

Dizziness, paraesthesia, cerebral ischaemia, cerebrovascular accident, increase in signs and symptoms of myasthenia gravis, syncope and headache. g. 4), decreased corneal sensitivity, dry eyes, corneal erosion, diplopia, ptosis.

Ear and Labyrinth Disorders:

Tinnitus.

Cardiac Disorders:

Palpitation, arrhythmia, bradycardia, chest pain, cardiac arrest, oedema, congestive heart failure, atrioventricular block, cardiac failure.

Vascular Disorders:

Hypotension, Raynaud’s phenomenon, cold hands and feet.

Respiratory, Thoracic and Mediastinal Disorders:

Bronchospasm (predominately in patients with pre-existing bronchospastic disease), dyspnoea, cough.

Gastrointestinal Disorders:

Dysgeusia, nausea, diarrhoea, dyspepsia, dry mouth, abdominal pain, vomiting.

Skin and Subcutaneous Tissue Disorders:

Alopecia, psoriasiform rash or exacerbation of psoriasis, skin rash.

Musculoskeletal and connective tissue disorders:

Myalgia Reproductive system and breast disorders: Sexual dysfunction, decreased libido General disorders and administration site conditions: Asthenia/fatigue. Cases of corneal calcification have been reported very rarely in association with the use of phosphate containing eye drops in some patients with significantly damaged corneas.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

5% w/v eye drops, solution is absorbed systemically. Due to the beta-adrenergic component timolol, the same types of cardiovascular pulmonary and other adverse reactions seen with systemic beta-adrenergic blocking agents may occur. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration.

2. g. coronary heart disease, Prinzmetal’s angina, cardiac failure) and hypotension the therapy with beta-blockers should be critically assessed and the therapy with other active substances should be considered. Patients with cardiovascular diseases should be watched for signs of deterioration of these diseases and of adverse reactions.

Due to its negative effect on conduction time, beta-blockers should only be given with caution to patients with first degree heart block. Cardiac reactions, and rarely, death in association with cardiac failures have been reported following administration of timolol.

e. severe forms of Raynaud’s disease or Raynaud’s syndrome) should be treated with caution. Respiratory disorders Respiratory reactions including death due to bronchospasm in patients with asthma have been reported following administration of some ophthalmic beta-blockers.

5% w/v eye drops, solution should be used with caution, in patients with mild/moderate chronic obstructive pulmonary disease (COPD) and only if the potential benefit outweighs the potential risk. Hypoglycaemia/diabetes Beta-blockers should be administered with caution in patients subject to spontaneous hypoglycaemia or to patients with labile insulin-dependent diabetes, as beta-blockers may mask the signs and symptoms of acute hypoglycaemia.

Beta-blockers may also mask the signs of hyperthyroidism. Corneal diseases Ophthalmic beta-blockers may induce dryness of eyes. 5). The use of two local beta-blockers or two local prostaglandins is not recommended. Other beta-blocking agents The effect on intraocular pressure or the known effects of systemic beta-blockade may be potentiated when timolol is given to patients already receiving a systemic beta-blocking agent.

The response of these patients should be closely observed. 5). 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 more reactive to repeated challenge with such allergens and unresponsive to the usual doses of adrenaline used to treat anaphylactic reactions.

Ocular effects Latanoprost may gradually change 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 eye drops for up to one year (based on photographs).

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 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 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 the 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. There is no documented experience with latanoprost in inflammatory, neovascular, chronic angle closure or congenital glaucoma, in open angle glaucoma of pseudophakic patients and in pigmentary glaucoma.

Latanoprost has no or little effect on the pupil but there is no documented experience in acute attacks of closed angle glaucoma. 5% w/v eye drops, solution } should be used with caution in these conditions until more experience is obtained.

Latanoprost should be used with caution in patients with a history of herpetic keratitis, and should be avoided in cases of active herpes simplex keratitis and in patients with a history of recurrent herpetic keratitis specifically associated with prostaglandin analogues.

Macular oedema, including cystoid macular oedema, 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 oedema.

5% w/v eye drops, solution should be used with caution in these patients. g. timolol, […]

5% w/v eye drops, solution is contraindicated in patients with: - Reactive airway disease including bronchial asthma or a history of bronchial asthma, severe chronic obstructive pulmonary disease. - Sinus bradycardia, sick sinus syndrome sino-atrial block, second or third degree atrioventricular block not controlled with pace-maker.

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