BIMATOPROST/TIMOLOL

Posology Recommended dosage in adults (including older people) The recommended dose is one drop of Abimet Duo in the affected eye(s) once daily, administered either in the morning or in the evening. It should be administered at the same time each day.

Existing literature data for bimatoprost/timolol suggest that evening dosing may be more effective in IOP lowering than morning dosing. 1). 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.

Renal and hepatic impairment Abimet Duo has not been studied in patients with hepatic or renal impairment. Therefore caution should be used in treating such patients. Paediatric population The safety and efficacy of Abimet Duo in children aged 0 to 18 years has not been established.

No data are available. Method of administration If more than one topical ophthalmic medicinal product is to be used, each one should be instilled at least 5 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.

Bimatoprost/Timolol medicinal product Summary of the safety profile The adverse reactions reported in clinical studies using bimatoprost/timolol were limited to those earlier reported for either of the single active substances bimatoprost and timolol.

No new adverse reactions specific for bimatoprost/timolol have been observed in clinical studies. The majority of adverse reactions reported in clinical studies using bimatoprost/timolol were ocular, mild in severity and none were serious.

5 % of patients. Tabulated list of adverse reactions Table 1 presents the adverse reactions that have been reported during clinical trials with bimatoprost/timolol formulations (multi-dose and single-dose) (within each frequency grouping, adverse reactions are presented in order of decreasing seriousness) or in the post- marketing period.

The frequency of possible adverse reactions listed below is defined using the following convention: Very common ≥1/10 Common ≥1/100 to <1/10 Uncommon ≥1/1,000 to <1/100 Rare ≥1/10,000 to <1/1,000 Very rare <1/10,000 Not known Frequency cannot be estimated from available data Table 1 System Organ Class Frequency Adverse reaction Immune system disorders Not known Hypersensitivity reactions including signs or symptoms of allergic dermatitis, angioedema, eye allergy Psychiatric disorders Not known Insomnia2, nightmare2 Common HeadacheNervous system disorders Not known Dysgeusia2, dizziness Very common Prostaglandin analogue periorbitopathy, conjunctival hyperaemia Eye disorders Common Punctuate keratitis, corneal erosion2, burning System Organ Class Frequency Adverse reaction sensation2, conjunctival irritation1, eye pruritus, stinging sensation in the eye2, foreign body sensation, dry eye, erythema of eyelid, eye pain, photophobia, eye discharge, visual disturbance2, eyelid pruritus, visual acuity worsened2, blepharitis2, eyelid oedema, eye irritation, lacrimation increased, growth of eyelashes Uncommon Iritis2, conjunctival oedema2, eyelid pain2, abnormal sensation in the eye1, asthenopia, trichiasis2, iris hyperpigmentation2, eyelid retraction2, eyelash discolouration (darkening)1 Not known Cystoid macular oedema2, eye swelling, vision blurred2, ocular discomfort Cardiac disorders Not known Bradycardia Vascular disorders Not known Hypertension Common Rhinitis2 Uncommon Dyspnoea Respiratory, thoracic and mediastinal disorders Not known Bronchospasm (predominantly in patients with pre- existing bronchospastic disease)2, asthma Common Blepharal pigmentation2, hirsutism2, skin hyperpigmentation (periocular) Skin and subcutaneous tissue disorders Not known Alopecia, skin discoloration (periocular) General disorders and administration site conditions Not known Fatigue 1 adverse reactions only observed with bimatoprost/timolol single-dose formulation 2 adverse reactions only observed with bimatoprost/timolol multi-dose formulation Like other topically applied ophthalmic drugs, Abimet Duo (bimatoprost/timolol) is absorbed into the systemic circulation.

Absorption of timolol may cause similar undesirable effects as seen with systemic beta-blocking agents. The incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. 2. 4)1, keratitis1, blepharospasm2, retinal haemorrhage2, uveitis2 Cardiac disorder Atrioventricular block1, cardiac arrest1, arrhythmia1, cardiac failure1, congestive heart failure1, chest pain1, palpitations1, oedema1 Vascular disorders Hypotension1, Raynaud’s phenomenon1, cold hands and feet1 Respiratory, thoracic and mediastinal disorders Asthma exacerbation2, COPD exacerbation2, cough1 Gastrointestinal disorders Nausea1,2, diarrhoea1, dyspepsia1, dry mouth1, abdominal pain1, vomiting1 Skin and subcutaneous tissue disorders Psoriasiform rash1 or exacerbation of psoriasis1, skin rash1 Musculoskeletal and connective tissue disorders Myalgia1 Reproductive system and breast disorders Sexual dysfunction1, decreased libido1 General disorders and administration site conditions Asthenia1,2 Investigations Liver function tests (LFT) abnormal2 1 adverse reactions observed with Timolol 2 adverse reactions observed with Bimatoprost monotherapy Description of selected adverse events Prostaglandin analogue periorbitopathy (PAP) Prostaglandin analogues including Abimet Duo can induce periorbital lipodystrophic changes which can lead to deepening of the eyelid sulcus, ptosis, enophthalmos, eyelid retraction, involution of dermatochalasis and inferior scleral show.

Changes are typically mild, can occur as early as one month after initiation of treatment with Abimet Duo, and may cause impaired field of vision even in the absence of patient recognition. PAP is also associated with periocular skin hyperpigmentation or discoloration and hypertrichosis.

All changes have been noted to be partially or fully reversible upon discontinuation or switch to alternative treatments. Iris hyperpigmentation Increased iris pigmentation is likely to be permanent. The […]

Like other topically applied ophthalmic medicinal products, the active substances (bimatoprost/timolol) in Abimet Duo may be absorbed systemically. No enhancement of the systemic absorption of the individual active substances has been observed.

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. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration.

2. g. coronary heart disease, Prinzmetal's angina and cardiac failure) and hypotension therapy with beta-blockers should be critically assessed and 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. 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.

Abimet Duo 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. Endocrine disorders Beta-adrenergic blocking medicinal products should be administered with caution in patients subject to spontaneous hypoglycemia or to patients with labile diabetes as beta-blockers may mask the signs and symptoms of acute hypoglycemia.

Beta-blockers may also mask the signs of hyperthyroidism. Corneal diseases Ophthalmic beta-blockers may induce dryness of eyes. Patients with corneal diseases should be treated with caution. Other beta-blocking agents The effect on intra-ocular pressure or the known effects of systemic beta-blockade may be potentiated when timolol is given to the 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 dose of adrenaline used to treat anaphylactic reactions.

g. timolol, acetazolamide) after filtration procedures. g. of adrenaline. The anaesthesiologist should be informed when the patient is receiving timolol. Hepatic In patients with a history of mild liver disease or abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin at baseline, bimatoprost had no adverse reactions on liver function over 24 months.

There are no known adverse reactions of ocular timolol on liver function. Ocular Before treatment is initiated, patients should be informed of the possibility of prostaglandin analogue periorbitopathy (PAP) and increased brown iris pigmentation since these have been observed during treatment with bimatoprost and bimatoprost/timolol.

8). Macular oedema, including cystoid macular oedema, has been reported with bimatoprost/timolol. g. intraocular surgery, retinal vein occlusions, ocular inflammatory disease and diabetic retinopathy). g. uveitis) because the inflammation may be exacerbated.

Skin There is a potential for hair growth to occur in areas where Abimet Duo solution comes repeatedly in contact with the skin surface. Thus, it is important to apply Abimet Duo as instructed and avoid it running onto the cheek or other skin areas.

Excipients The preservative in Abimet Duo, benzalkonium chloride, may cause eye irritation. Contact lenses must be removed prior to application, with at least a 15-minute wait before reinsertion. Benzalkonium chloride is known to discolour soft contact lenses.

Contact with soft contact lenses must be avoided. Benzalkonium chloride has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Therefore monitoring is required with frequent or prolonged use of Abimet Duo in dry eye patients or where the cornea is compromised.

Other conditions Bimatoprost/timolol has not been studied in patients with inflammatory ocular conditions, neovascular, inflammatory, angle-closure glaucoma, congenital glaucoma or narrow-angle glaucoma. 3 mg/ml in patients with glaucoma or ocular hypertension, it has been shown that more frequent exposure of the eye to more than 1 dose of bimatoprost daily may decrease the IOP-lowering effect.

Patients using Abimet Duo with other prostaglandin analogues should be monitored for changes to their intraocular pressure.

1. - 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.

Overt cardiac failure, cardiogenic shock.