- dorzolamide hydrochloride
- timolol maleate
POM: Prescription only medicine
This information is intended for use by health professionals
Paediatric population:Efficacy in paediatric patients has not been established. Safety in paediatric patients below the age of two years has not been established. (For information regarding safety in paediatric patients 2 and < 6 years of age, see section 5.1).Patients should be instructed to wash their hands before use and avoid allowing the tip of the dispensing container to contact the eye or surrounding structures. In order to secure correct dosage - the dropper tip should not be enlarged.Patients should also be instructed that ocular solutions, if handled improperly, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions. Patients should be informed of the correct handling of the ophthalmic Tidomat.
Usage instructions: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. 2. The cap of the bottle should be taken off.3. The patient's 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. 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. 5. Steps 3 & 4 should be repeated with the other eye if it is necessary. 6. The cap must be put back on and the bottle must be closed straight after it has been used.
Hepatic impairmentDorzolamide/Timolol eye drops solution has not been studied in patients with hepatic impairment and therefore should be used with caution in such patients.
Immunology and hypersensitivityAs with other topically-applied ophthalmic agents, this drug may be absorbed systemically. The dorzolamide component is a sulphonamide. Therefore the same types of adverse reactions found with systemic administration of sulphonamides may occur with topical administration. If signs of serious reactions or hypersensitivity occur, discontinue use of this preparation. Local ocular adverse effects, similar to those observed with dorzolamide hydrochloride eye drops, have been seen with Dorzolamide/Timolol eye drops solution. If such reactions occur, discontinuation of Tidomat should be considered. While taking β-blockers, 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 used to treat anaphylactic reactions.
Concomitant therapyThe following concomitant medication is not recommended: − dorzolamide and oral carbonic anhydrase inhibitors − topical betaadrenergic blocking agents.
Withdrawal of therapyAs 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-blockadeTherapy with beta-blockers may mask certain symptoms of hypoglycaemia in patients with diabetes mellitus or hypoglycaemia. Therapy with beta-blockers may mask certain symptoms of hyperthyroidism. Abrupt withdrawal of beta-blocker therapy may precipitate a worsening of symptoms. Therapy with beta-blockers may aggravate symptoms of myasthenia gravis.
Additional effects of carbonic anhydrase inhibitionTherapy 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 Dorzolamide/Timolol eye drops solution, urolithiasis has been reported infrequently. Because Tidomat 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 Tidomat.
OtherThe management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. Dorzolamide/Timolol eye drops solution has not been studied in patients with acute angle-closure glaucoma. Corneal oedema and irreversible corneal decompensation have been reported in patients with pre-existing chronic corneal defects and/or a history of intra-ocular surgery while using dorzolamide. Topical dorzolamide should be used with caution in such patients. Choroidal detachment concomitant with ocular hypotony have been reported after filtration procedures with administration of aqueous suppressant therapies. As with the use of other antiglaucoma drugs, diminished responsiveness to ophthalmic timolol maleate after prolonged therapy has been reported in some patients. However, in clinical studies in which 164 patients have been followed for at least three years, no significant difference in mean intra-ocular pressure has been observed after initial stabilisation.
Contact lens useTidomat contains the preservative benzalkonium chloride, which may cause eye irritation. Benzalkonium chloride is known to discolour soft contact lenses. Remove contact lenses prior to application and wait at least 15 minutes before reinsertion.
Paediatric useSee section 5.1.
PregnancyTidomat should not be used during pregnancy.DorzolamideNo adequate clinical data in exposed pregnancies are available. In rabbits, dorzolamide produced teratogenic effects at maternotoxic doses (see Section 5.3).TimololWell controlled epidemiological studies with systemic beta blockers showed no evidence of teratogenic effects, but some pharmacological effects such as bradycardia were observed in fetuses or neonates. If Tidomat is administered until delivery, the neonate should be carefully monitored during the first days of life.
LactationIt is not known whether dorzolamide is excreted in human milk. In lactating rats receiving dorzolamide, decreases in the body weight gain of offspring were observed. Timolol does appear in human milk. Tidomat should not be used during lactation.
Nervous system and Psychiatric disorders:
Dorzolamide hydrochloride ophthalmic solution:Common: headache* Rare: dizziness*, paresthesia*
Timolol maleate ophthalmic solution:Common: headache* Uncommon: dizziness*, depression* Rare: insomnia*, nightmares*, memory loss, paraesthesia*, increase in signs and symptoms of myasthenia gravis, decreased libido*, cerebrovascular accident*
Eye disorders:Dorzolamide/Timolol ophthalmic solution:Very Common: burning and stinging Common: conjunctival injection, blurred vision, corneal erosion, ocular itching, tearing Dorzolamide hydrochloride ophthalmic solution:Common: eyelid inflammation*, eyelid irritation* Uncommon: iridocyclitis* Rare: irritation including redness*, pain*, eyelid crusting*, transient myopia (which resolved upon discontinuation of therapy), corneal oedema*, ocular hypotony*, choroidal detachment (following filtration surgery)* Timolol maleate ophthalmic solution:Common: signs and symptoms of ocular irritation including blepharitis*, keratitis*, decreased corneal sensitivity, and dry eyes* Uncommon: visual disturbances including refractive changes (due to withdrawal of miotic therapy in some cases)* Rare: ptosis, diplopia, choroidal detachment (following filtration surgery)*
Ear and labyrinth disorders:Timolol maleate ophthalmic solution:Rare: tinnitus*
Cardiac and Vascular disorders:Timolol maleate ophthalmic solution:Uncommon: bradycardia*, syncope* Rare: hypotension*, chest pain*, palpitation*, oedema*, arrhythmia*, congestive heart failure*, heart block*, cardiac arrest*, cerebral ischaemia, claudication, Raynaud's phenomenon*, cold hands and feet* Respiratory, thoracic, and mediastinal disorders:Dorzolamide/Timolol ophthalmic solution: Common: sinusitis Rare: shortness of breath, respiratory failure, rhinitis Dorzolamide hydrochloride ophthalmic solution:Rare: epistaxis* Timolol maleate ophthalmic solution:Uncommon: dyspnoea* Rare: bronchospasm (predominantly in patients with pre-existing bronchospastic disease)*, cough*
Gastro-intestinal disorders:Dorzolamide/Timolol ophthalmic solution: Very Common: taste perversion Dorzolamide hydrochloride ophthalmic solution:Common: nausea* Rare: throat irritation, dry mouth* Timolol maleate ophthalmic solution:Uncommon: nausea*, dyspepsia* Rare: diarrhoea, dry mouth*
Skin and subcutaneous tissue disorders:Dorzolamide/Timolol ophthalmic solution: Rare: contact dermatitis Dorzolamide hydrochloride ophthalmic solution:Rare: rash* Timolol maleate ophthalmic solution:Rare: alopecia*, psoriasiform rash or exacerbation of psoriasis*
Musculoskeletal and connective tissue disorders:Timolol maleate ophthalmic solution:Rare: systemic lupus erythematosus
Renal and Urinary disorders:Dorzolamide/Timolol ophthalmic solution: Uncommon: urolithiasis
Reproductive system and breast disorders:Timolol maleate ophthalmic solution:Rare: Peyronie's disease*
General disorders and administration site disorders:Dorzolamide/Timolol ophthalmic solution:Rare: signs and symptoms of systemic allergic reactions, including angioedema, urticaria, pruritus, rash, anaphylaxis, rarely bronchospasm Dorzolamide hydrochloride ophthalmic solution:Common: asthenia/fatigue* Timolol maleate ophthalmic solution:Uncommon: asthenia/fatigue* *These adverse reactions were also observed with Dorzolamide/Timolol ophthalmic solution during post-marketing experience.
Laboratory findingsDorzolamide/Timolol eye drops solution was not associated with clinically meaningful electrolyte disturbances in clinical studies.
ATC code: S01E D51
Mechanism of actionDorzolamide/Timolol eye drops solution is comprised of two components: dorzolamide hydrochloride and timolol maleate. Each of these two components decreases elevated intra-ocular pressure by reducing aqueous humor secretion, but does so by a different mechanism of action. Dorzolamide hydrochloride is a potent inhibitor of human carbonic anhydrase II. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. Timolol maleate is a non-selective beta-adrenergic receptor blocking agent. The precise mechanism of action of timolol maleate in lowering intra-ocular pressure is not clearly established at this time, although a fluorescein study and tonography studies indicate that the predominant action may be related to reduced aqueous formation. However, in some studies a slight increase in outflow facility was also observed. The combined effect of these two agents results in additional intra-ocular pressure reduction compared to either component administered alone. Following topical administration, Dorzolamide/Timolol eye drops solution reduces elevated intra-ocular pressure, whether or not associated with glaucoma. Elevated intra-ocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. Dorzolamide/Timolol eye drops solution reduces intra-ocular pressure without the common side effects of miotics such as night blindness, accommodative spasm and pupillary constriction.
Adult PatientsClinical studies of up to 15 months duration were conducted to compare the IOP-lowering effect of Dorzolamide/Timolol eye drops solution b.i.d. (dosed morning and bedtime) to individually- and concomitantly-administered 0.5% timolol and 2.0% dorzolamide in patients with glaucoma or ocular hypertension for whom concomitant therapy was considered appropriate in the trials. This included both untreated patients and patients inadequately controlled with timolol monotherapy. The majority of patients were treated with topical beta-blocker monotherapy prior to study enrollment. In an analysis of the combined studies, the IOP-lowering effect of Dorzolamide/Timolol eye drops solution b.i.d. was greater than that of monotherapy with either 2% dorzolamide t.i.d. or 0.5% timolol b.i.d. The IOP-lowering effect of Dorzolamide/Timolol eye drops solution b.i.d. was equivalent to that of concomitant therapy with dorzolamide b.i.d. and timolol b.i.d. The IOP-lowering effect of Dorzolamide/Timolol eye drops solution b.i.d. was demonstrated when measured at various time points throughout the day and this effect was maintained during long-term administration.Paediatric PopulationA three month controlled study, with the primary objective of documenting the safety of 2% dorzolamide hydrochloride ophthalmic solution in children under the age of 6 years has been conducted. In this study, 30 patients under six and greater than or equal to two years of age whose IOP was not adequately controlled with monotherapy by dorzolamide or timolol received Dorzolamide/Timolol eye drops solution in an open label phase. Efficacy in those patients has not been established. In this small group of patients, twice daily administration of Dorzolamide/Timolol eye drops solution was generally well tolerated with 19 patients completing the treatment period and 11 patients discontinuing for surgery, a change in medication, or other reasons.
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