Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Allergan Limited, Marlow International, The Parkway, Marlow, Buckinghamshire, SL7 1YL, United Kingdom
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Reactive airway disease including bronchial asthma or a history of bronchial asthma or severe chronic obstructive pulmonary disease.
Sinus bradycardia, sick sinus syndrome, sino-atrial block, second and third degree atrioventricular block not controlled with a pace maker, overt cardiac failure or cardiogenic shock.
Like other topically applied ophthalmic agents, levobunolol is absorbed systemically. Due to the beta-adrenergic component of Betagan (levobunolol), the same types of cardiovascular, pulmonary and adverse reactions as seen with systemic beta-blockers may occur. Incidence of systemic ADRs after topical ophthalmic administration are lower than for systemic administration. To reduce the systemic absorption, see 4.2.
Cardiac disorders: In patients with cardiovascular diseases (e.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 their negative effect on conduction time, beta-blockers should only be given with caution to patients with first degree atrioventricular block.
Vascular disorders: Patients with severe peripheral circulatory disturbance disorders (i.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 levobunolol.
Betagan 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 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 β-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 exaggerated when levobunolol is given to patients already receiving a systemic beta blocking agent. The response of these patients should be closely observed. The use of two topical beta-adrenergic blocking agents is not recommended (see section 4.5).
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.
Choroidal detachment: Choroidal detachment has been reported with administration of aqueous suppressant therapy (e.g. timolol, acetazolamide) after filtration procedures.
Surgical anaesthesia: β-blocking ophthalmological preparations may block systemic β-agonist effects e.g. of adrenaline. The anaesthetist must be informed when the patient is receiving levobunolol.
No specific drug interaction studies have been performed with levobunolol.
There is a potential for additive effects resulting in hypotension, and/or marked bradycardia when ophthalmic beta-blocker solutions are administered concomitantly with oral calcium channel blockers, beta-adrenergic blocking agents, anti-arrhythmics (including amiodarone), digitalis glycosides or parasympathomimetics or guanethidine.
Mydriasis resulting from concomitant use of ophthalmic beta-blockers and adrenaline (epinephrine) has been reported occasionally.
There are no adequate data for the use of levobunolol in pregnant women. levobunolol should not be used during pregnancy unless clearly necessary. To reduce the systemic absorption, see 4.2.
Epidemiological studies have not revealed malformative effects but show a risk for intra uterine growth retardation when beta-blockers are administered by the oral route. In addition, signs and symptoms of beta-blockade (e.g. bradycardia, hypotension, respiratory distress and hypoglycaemia) have been observed in the neonate when beta-blockers have been administered until delivery. If Betagan is administered until delivery, the neonate should be carefully monitored during the first days of life. Animal studies with levobunolol have shown reproductive toxicity at doses significantly higher than would be used in clinical practice.
Beta-blockers are excreted in breast milk. However, at therapeutic doses of levobunolol in eye drops, it is not likely that sufficient amounts would be present in breast milk to produce clinical symptoms of beta-blockade in the infant. To reduce the systemic absorption, see 4.2.
If treatment with levobunolol during lactation is considered necessary for the benefit of the mother, consideration should be given to the cessation of breast feeding.
Betagan has minor influence on the ability to drive and use machines. Betagan may cause transient blurring of vision, fatigue and/or drowsiness which may impair the ability to drive or operate machines. The patient should wait until these symptoms have cleared before driving or using machinery.
Like other topically applied ophthalmic drugs, levobunolol 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 of beta-blocking agents is lower than for systemic administration
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. The following terminologies have been used in order to classify the occurrence of undesirable effects: 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 (cannot be estimated from the available data).
Not known: Depression
Not known: Confusion, Dizziness, Somnolence, Lethargy, Headache, Insomnia
Very Common: Eye irritation, Eye pain
Common: Blepharitis, Conjunctivitis
Not known: Conjunctival/Ocular hyperemia, Conjuctivitis allergic, Corneal reflex decreased, Iridocyclitis, Keratitis, Vision blurred, Punctate keratitis, Eye/Eyelids pruritus, Eye/Eyelid oedema, Eye discharge, Lacrimation increased, Dry eye, Foreign body sensation in eyes
Not known: Syncope, Bradycardia, Atrioventricular block, Palpitations
Not known: Hypotension, Raynaud’s phenomenon
Not known: Asthma, Dyspnoea, Throat irritation, Nasal discomfort
Not known: Nausea
Not known: Urticaria, Dermatitis contact (including allergic contact dermatitis), Rash, Erythema of eyelid, Eyelid eczema, Skin exfoliation, Lichenoid keratosis, Pruritus, Alopecia
Not known: Face oedema, Fatigue/asthenia
Not known: Hypersensitivity reaction including symptoms or signs of eye allergy and skin allergy
Additional adverse reactions have been seen with other ophthalmic beta-blockers and may potentially occur with Betagan:
Eye Disorders: Choroidal detachment following filtration surgery, Corneal erosion, Diplopia, Ptosis
Immune System Disorders: Anaphylactic reaction, Systemic allergic reactions including angioedema
Metabolism and Nutrition Disorders: Hypoglycaemia
Psychiatric disorders: Memory loss, Nightmares
Nervous System Disorders: Cerebral ischemia, Cerebrovascular accident, Increases in signs and symptoms of myasthenia gravis, Paraesthesia
Cardiac Disorders: Arrhythmia, Cardiac arrest, Cardiac failure, Chest pain, Congestive heart failure, Oedema
Vascular disorders: Cold hands and feet
Respiratory, Thoracic, and Mediastinal Disorders: Bronchospasm (predominantly in patients with pre-existing bronchospastic disease), Cough
Gastrointestinal Disorders: Abdominal pain, Diarrhoea, Dysgeusia, Dry mouth, Dyspepsia, vomiting
Skin and Subcutaneous Tissue Disorders: Psoriasiform rash or exacerbation of psoriasis
Musculoskeletal and Connective Tissue Disorders: Myalgia
Reproductive System and Breast Disorders: Decreased libido, Sexual dysfunction
Adverse reactions reported in eye drops containing phosphates:
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 suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard.
No major incompatibilities have been reported from topical use of levobunolol.
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