Dorzolamide + timolol

Ophthalmic
Open-angle glaucoma, Ocular hypertension, Pseudoexfoliation glaucoma
Adult: Available preparation: Dorzolamide 20 mg and timolol 5 mg per mL of eye drops solution In patients with inadequate response to topical β-blocker monotherapy: Instil 1 drop into the conjunctival sac of the affected eye(s) bid.
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
<30	Not recommended.

Reactive airway disease (e.g. existing or history of bronchial asthma, severe COPD), sinus bradycardia, sick sinus syndrome, sino-atrial block, 2nd- or 3rd-degree atrioventricular block (not controlled with pacemaker), overt cardiac failure, cardiogenic shock.

Patients with history of atopy or severe anaphylaxis to allergens, history of CV disease (e.g. cardiac failure), 1st-degree heart block, cerebrovascular insufficiency, hyperchloraemic acidosis, severe peripheral circulatory disturbance or disorders (e.g. severe forms of Raynaud's disease), mild or moderate COPD, diabetes (particularly labile diabetes) or those who are subject to spontaneous hypoglycaemia; hyperthyroidism, corneal disease, myasthenia gravis, history of renal calculi, preexisting chronic corneal defects and/or history of intraocular surgery, low endothelial cell counts, history of psychiatric illness. Avoid abrupt withdrawal. Not recommended for use in narrow-angle glaucoma and severe renal impairment (CrCl <30 mL/min). Patients undergoing surgery. Hepatic and mild to moderate renal impairment. Pregnancy and lactation. Patient Counselling Remove contact lenses before administration and reinsert after 15 minutes. This drug may cause blurring of vision, if affected, do not drive or operate machinery. Monitoring Parameters Perform ophthalmic exams periodically. Monitor intraocular pressure (periodically) and systemic effects of β-blockade.

Significant: Local ocular reactions mainly lid reactions and conjunctivitis (chronic administration); dry eyes, choroidal detachment (post-filtration procedures), corneal oedema, irreversible corneal decompensation (in patients with preexisting chronic corneal defects and/or history of intraocular surgery), bacterial keratitis, hypersensitivity reaction (e.g. angioedema, urticaria, anaphylaxis, pruritus, rash). Rarely, exacerbation of myasthenia gravis, urolithiasis. Cardiac disorders: Bradycardia. Eye disorders: Ocular burning, stinging, itching; tearing, conjunctival hyperaemia, blurred vision, corneal erosion, iridocyclitis, blepharitis. Gastrointestinal disorders: Dysgeusia, nausea. General disorders and administration site conditions: Asthenia. Nervous system disorders: Headache, dizziness, paraesthesia. Psychiatric disorders: Depression. Respiratory, thoracic and mediastinal disorders: Sinusitis, dyspnoea. Skin and subcutaneous tissue disorders: Contact dermatitis. Vascular disorders: Syncope.
Potentially Fatal: Bronchospasm (in patients with asthma), Stevens-Johnson syndrome, toxic epidermal necrolysis. Rarely, cardiac failure.

Symptoms: Dizziness, headache, shortness of breath, bradycardia, bronchospasm, cardiac arrest, electrolyte imbalance, development of acidotic state, possible CNS effects. Management: Symptomatic and supportive treatment. Monitor serum electrolyte (especially K) and blood pH levels.

Dorzolamide: May result in additive effect with other oral and topical carbonic anhydrase inhibitors. Timolol: May have additive effects resulting in hypotension and/or marked bradycardia with Ca channel blockers, catecholamine-depleting drugs (e.g. reserpine), oral β-adrenergic blocking agents, parasympathomimetics, antiarrhythmics (e.g. amiodarone), digitalis glycosides, guanethidine, narcotics and MAOIs. Potentiated systemic β-blockade (e.g. decreased heart rate, depression) with CYP2D6 inhibitors (e.g. quinidine, paroxetine, fluoxetine). Concomitant use with epinephrine resulted in mydriasis. May increase the hypoglycaemic effect of antidiabetic agents.

Dorzolamide reversibly inhibits the carbonic anhydrase in the ciliary processes of the eye resulting in the reduced formation of the bicarbonate ions with subsequent reduction in Na and fluid transport, thus decreasing the production of aqueous humour and lowering intraocular pressure. Timolol is a non-selective β-adrenergic receptor antagonist. Although its exact mechanism in reducing intraocular pressure has not been clearly defined, it is suggested that its predominant action may be related to reducing aqueous humour production or probably by increasing the outflow of aqueous humour.
Onset: Timolol: Intraocular pressure reduction: 30 minutes.
Duration: Dorzolamide: 8-12 hours. Timolol: 24 hours.
Absorption: Dorzolamide: Absorbed systemically after topical administration to the eye. Timolol: Low concentrations are found in the plasma.
Distribution: Dorzolamide: Accumulates in the RBCs (during chronic dosing). Plasma protein binding: Approx 33%. Timolol: Crosses the placenta and enters the breast milk.
Metabolism: Dorzolamide: Metabolised into N-desethyl metabolite (less potent). Timolol: Extensively metabolised in the liver.
Excretion: Dorzolamide: Via urine (as unchanged drug and N-desethyl metabolite). Elimination half-life: Approx 4 months following rapid decline after nonlinear wash out from RBCs. Timolol: Via urine (as metabolites with some unchanged drug). Elimination half-life: 4 hours.

Ophthalmic: Store below 30°C. Protect from light. Storage recommendation may vary among countries or individual products. Refer to specific product guideline.

Antiglaucoma Preparations

S01ED01 - timolol ; Belongs to the class of beta blocking agents. Used in the treatment of glaucoma.
S01EC03 - dorzolamide ; Belongs to the class of carbonic anhydrase inhibitors. Used in the treatment of glaucoma.
C07AA06 - timolol ; Belongs to the class of non-selective beta-blocking agents. Used in the treatment of cardiovascular diseases.