Glauspec 20 mg, 5 mg Ophthalmic Solution

GLAUSPEC is indicated for the treatment of elevated intra-ocular pressure (IOP) in patients with ocular hypertension, open-angle glaucoma, pseudoexfoliative glaucoma or other secondary open-angle glaucomas when concomitant therapy is appropriate.

Posology

Adults

The dose is one drop of GLAUSPEC in the affected eye(s) two times daily. When substituting GLAUSPEC for another ophthalmic antiglaucoma agent(s), discontinue the other agent(s) after proper dosing on one day, and start GLAUSPEC on the next day. If another topical ophthalmic agent is being used, GLAUSPEC and the other agent should be administered at least ten minutes apart.

Paediatrics

Safety and efficacy in paediatric patients below the age of 2 years have not been established. Although GLAUSPEC has been used in children 2 to 6 years of age, however data on safety and efficacy are insufficient to recommend a safe and effective dose.

Method of administration

For ophthalmic use only. Step 1: The tamper-proof seal on the bottle neck must be unbroken before the product is being used for the first time. A gap between the bottle and the cap is normal for an unopened bottle. Step 2: The cap of the bottle should be taken off. Step 3: The patientu2019s head must be tilted back and the lower eyelid must be pulled gently down to form a small pocket between the eyelid and the eye. Step 4: The bottle should be inverted and squeezed until a single drop is dispensed into the eye. The eye or eyelid must not be touched with the dropper tip. Step 5: Steps 3 & 4 should be repeated with the other eye if it is necessary. Step 6: The cap must be put back on and the bottle must be closed straight after it has been used. When using nasolacrimal occlusion or closing the eyelids for 2 minutes, the systemic absorption is reduced. This may result in a decrease in systemic adverse reactions and an increase in local activity.

GLAUSPEC is contraindicated in:

• Hypersensitivity to dorzolamide, timolol 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-artrial block, second- or third-degree atrioventricular block not controlled with pacemaker, overt cardiac failure and cardiogenic shock;
• Severe renal impairment (CrCl < 30 ml/min) or hyperchloraemic acidosis;
• GLAUSPEC contains the preservative benzalkonium chloride, which may be deposited in soft contact lenses. Therefore, GLAUSPEC should not be administered while wearing these lenses. The lenses should be removed before application of the drops and not be reinserted earlier than 15 minutes after use (see section 4.4);
• The safety of GLAUSPEC in pregnant and lactating woman has not been established (see section 4.6).

Benzalkonium chloride

As the possibility of adverse effects on the corneal permeability, and the danger of disruption of the corneal epithelium with prolonged or repeated usage of benzalkonium chloride preserved ophthalmological preparations cannot be excluded. Regular ophthalmological examination is required. Caution should be exercised in the use of benzalkonium chloride preserved topical medication over an extended period in patients with extensive ocular surface disease.

Cardio-respiratory reactions

GLAUSPEC is absorbed systemically. Due to 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 adverse drug reactions (ADRs) after topical ophthalmic administration is lower than for systemic administration. Because of the timolol maleate component, cardiac failure should be adequately controlled before beginning therapy with GLAUSPEC.

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 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.

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 some ophthalmic beta-blockers. GLAUSPEC should be used with caution, in patients with mild/moderate chronic obstructive pulmonary disease (COPD).

Immunology and hypersensitivity

GLAUSPEC is absorbed systemically. The dorzolamide component is a sulfonamide. Therefore, the same types of adverse reactions found with systemic administration of sulphonamides may occur with GLAUSPEC. If signs of serious reactions or hypersensitivity occur, discontinue use of this preparation. In clinical studies, local ocular adverse effects, primarily conjunctivitis and lid reactions, were reported with chronic administration of dorzolamide hydrochloride ophthalmic solution. Some of these reactions had the clinical appearance and course of an allergic-type reaction that resolved upon discontinuation of therapy. Similar reactions have been reported with GLAUSPEC. If such reactions are observed, discontinuation of treatment with GLAUSPEC should be considered. While taking beta-blockers, including timolol, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to accidental, diagnostic, or therapeutic repeated challenge with such allergens. Such patients may be unresponsive to the usual doses of epinephrine (adrenaline) used to treat anaphylactic reactions.

Renal and hepatic impairment

GLAUSPEC is contraindicated in patients with severe renal impairment (CrCl less than 30 ml/min) (see section 4.3). Because dorzolamide hydrochloride and its metabolite are excreted predominantly by the kidney, GLAUSPEC is not recommended in such patients. GLAUSPEC has not been studied in patients with hepatic impairment.

Concomitant therapy

There is a potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving oral and topical carbonic anhydrase inhibitors concomitantly. The concomitant administration of GLAUSPEC and oral carbonic anhydrase inhibitors has not been studied and is not recommended. Patients who are already receiving a beta-adrenergic blocking agent systemically and who are given GLAUSPEC should be observed for a potential additive effect either on the intra-ocular pressure or on the known systemic effects of beta-blockade. The use of two topical beta-adrenergic blocking agents is not recommended.

Withdrawal therapy

As with systemic beta-blockers, if discontinuation of ophthalmic timolol is needed in patients with coronary heart disease, therapy should be withdrawn gradually.

Additional effects of Beta-Blockade

Hypoglycaemia and 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. Abrupt withdrawal of beta-blocker therapy may precipitate a worsening of symptoms.

Corneal diseases

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

Surgical anaesthesia

Beta-blocking ophthalmological preparations may block systemic beta-agonist effects e.g., of adrenaline. The anaesthesiologist should be informed when the patient is receiving timolol. Therapy with beta-blockers may aggravate symptoms of myasthenia gravis.

Additional effects of carbonic anhydrase inhibition

Therapy with oral carbonic anhydrase inhibitors has been associated with urolithiasis as a result of acid-base disturbances, especially in patients with a prior history of renal calculi. Although no acid-base disturbances have been observed with this medicine, urolithiasis has been reported infrequently. Because GLAUSPEC contains a topical carbonic anhydrase inhibitor that is absorbed systemically, patients with a prior history of renal calculi may be at increased risk of urolithiasis while using GLAUSPEC.

Use in the Elderly

Of the total number of patients in clinical studies of GLAUSPEC, 49 % were 65 years of age and over, while 13 % were 75 years of age and over. No overall differences in effectiveness or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Other

The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive medicines. GLAUSPEC has not been studied in patients with acute angle-closure glaucoma. Choroidal detachment has been reported with administration of aqueous suppressant therapy (e.g., timolol, acetazolamide, dorzolamide) after filtration procedures. There is an increased potential for developing corneal oedema in patients with low endothelial cell counts. Precautions should be used when prescribing GLAUSPEC to this group of patients.

Contact lens use

GLAUSPEC contains the preservative, benzalkonium chloride, which may be deposited in soft contact lenses. Therefore, GLAUSPEC should not be administered while wearing these lenses. The lenses should be removed before application of the drops and not be reinserted earlier than 15 minutes after use (see section 4.3).

Specific interaction studies have not been performed with GLAUSPEC. In clinical studies, GLAUSPEC was used concomitantly with the following systemic medications without evidence of adverse interactions: ACE- inhibitors, calcium channel blockers, diuretics, non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, and hormones (e.g., oestrogen, insulin, thyroxine). The potential exists for additive effects and production of hypotension and/or marked bradycardia when timolol maleate ophthalmic solution is administered together with oral calcium channel blockers, catecholamine-depleting medicines or beta-adrenergic blocking agents. Potentiated systemic beta-blockade (e.g., decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g., quinidine, selective serotonin uptake inhibitors) and timolol. The dorzolamide component of GLAUSPEC is a carbonic anhydrase inhibitor and although administered topically, is absorbed systemically. In clinical studies, dorzolamide hydrochloride ophthalmic solution was not associated with acid-base disturbances. However, these disturbances have been reported with oral carbonic anhydrase inhibitors and have in some instances, resulted in interactions (e.g., toxicity associated with high-dose salicylate therapy). Therefore, the potential for such interactions should be considered in patients receiving GLAUSPEC. Although GLAUSPEC alone has little or no effect on pupil size, mydriasis resulting from concomitant use of ophthalmic beta-blockers and adrenaline (epinephrine) has been reported occasionally. Beta-blockers may increase the hypoglycaemic effect of antidiabetic medicines. Oral beta-adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine.

Pregnancy

The safety of GLAUSPEC in pregnant and lactating woman has not been established (see section 4.3). GLAUSPEC should not be used during pregnancy.

Breastfeeding

Lactation is not recommended if treatment with [PROUCT NAME] is required.

Fertility

There is no data available on fertility with GLAUSPEC.

Possible side effects such as blurred vision may affect some patients' ability to drive and/or operate machinery. Caution is advised until the effects of GLAUSPEC in patients on treatment are known (see section 4.8).

a. Tabulated summary of adverse reactions

GLAUSPEC

Dorzolamide Hydrochloride

Timolol Maleate

No data is available with regard to human overdosage by accidental or deliberate ingestion of [PROUCT NAME]. There have been reports of inadvertent overdosage with timolol maleate ophthalmic solution resulting in systemic effects similar to those seen with systemic beta-adrenergic blocking agents such as dizziness, headache, shortness of breath, bradycardia, bronchospasm, and cardiac arrest. The most common signs and symptoms to be expected with overdosage of dorzolamide are electrolyte imbalance, development of an acidotic state, and possibly central nervous system effects (see section 4.8). Treatment should be symptomatic and supportive. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored. Studies have shown that timolol does not dialyse readily.