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.

Patients with severe peripheral circulatory disturbance disorders (i.e. severe forms of Raynaud’s disease or Raynaud’s syndrome) should be treated with caution.

Ophthalmic β-blockers may induce dryness of eyes. Patients with corneal diseases should be treated with caution.

Due to their negative effect on conduction time, beta-blockers should only be given with caution to patients with first degree atrioventricular block.

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.

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.

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.

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 levobunolol 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.

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.

Levobunolol has minor influence on the ability to drive and use machines. Levobunolol 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).

Psychiatric Disorders

Not known: Depression

Nervous System Disorders

Not known: Confusion, Dizziness, Somnolence, Lethargy, Headache, Insomnia

Eye Disorders

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

Cardiac Disorders

Not known: Syncope, Bradycardia, Atrioventricular block, Palpitations

Vascular Disorders

Not known: Hypotension, Raynaud’s phenomenon

Respiratory, Thoracic, and Mediastinal Disorders

Not known: Asthma, Dyspnoea, Throat irritation, Nasal discomfort

Gastrointestinal Disorders

Not known: Nausea

Skin and Subcutaneous Tissue Disorders

Not known: Urticaria, Dermatitis contact (including allergic contact dermatitis), Rash, Erythema of eyelid, Eyelid eczema, Skin exfoliation, Lichenoid keratosis, Pruritus, Alopecia

General Disorders and Administration Site Conditions

Not known: Face oedema, Fatigue/asthenia

Immune System Disorders

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 levobunolol:

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.