Timolol + Dorzolamide

Ophthalmic
Ocular hypertension, Open-angle glaucoma

CrCl	Dosage
<30	Not recommended.

Hypersensitivity to any of the components or sulphonamide. History or current bronchial asthma, severe COPD, sinus bradycardia, 2nd or 3rd degree AV block, overt cardiac failure, cardiogenic shock, CrClr <30 ml/min and hyperchloraemic acidosis.

Hepatic impairment, mild to moderate renal impairment, children <2 yr. Avoid use in pregnancy and lactation. Prinzmetal's angina, cardiac disease, hypotension, myasthenia gravis, history of renal calculi, history of intra-ocular surgery, pre-existing chronic corneal defects. May worsen severe peripheral and central circulatory disorders. May mask symptoms of hypoglycaemia and hyperthyroidism. Withdraw gradually, especially in patients with coronary heart disease. Discontinue treatment at the first signs or symptoms of cardiac failure. Contact lenses to be removed before eyedrop application and wait at least 15 minutes before reinsertion. Apply other eyedrops 10 minutes apart. May affect ability to drive or operate machinery as it may cause blurred vision.

Ocular irritation, burning, stinging, itching and tearing; conjunctival inj, eyelid inflammation or irritation, corneal erosion, blurred vision, headache, sinusitis, taste perversion, nausea, fatigue.
Potentially Fatal: Cardiac failure, bronchospasm.

Ophth: C

Symptoms: Timolol: Dizziness, headache, dyspnoea, bradycardia, bronchospasm and cardiac arrest. Dorzolamide: Nausea, dizziness, headache, electrolyte imbalance, acidosis. Management: Treatment is symptomatic and supportive with monitoring of serum electrolyte levels (especially potassium) and blood pH levels.

Additive hypotension and bradycardia with oral calcium channel blockers, catecholamine-depleting drugs or β-blockers, antiarrhythmics (e.g. amiodarone), digitalis glycosides, parasympathomimetics, narcotics and MAOIs. Additive systemic side effects with oral carbonic anhydrase or β-blockers; avoid concurrent use. Additive systemic β-blockade with CYP2D6 inhibitors (e.g. quinidine, SSRIs) and timolol.

Description: Timolol maleate, a nonselective β-adrenergic blocker, reduces aqueous humor formation. Dorzolamide, a carbonic anhydrase inhibitor, has actions similar to acetazolamide. By inhibiting carbonic anhydrase in the ciliary processes of the eye, dorzolamide decreases aqueous humor secretion. Used together, there is additional intraocular pressure reduction compared to using either component alone, but the reduction is not as much as concomitant admin of dorzolamide tid and timolol bid.
Onset: Intraocular pressure reduction: Timolol 15-30 minutes; dorzolamide: Peaks within 2-3 hr.
Duration: Intraocular pressure reduction: Timolol 24 hr; dorzolamide ≥8 hr.
Pharmacokinetics:
Absorption: Timolol: Low plasma concentrations found after ophthalmic admin. Dorzolamide: Peak concentrations in cornea, iris/ciliary body, and aqueous humor reached within 1-2 hr; amount of drug delivered by oral dose of 2 mg bid is similar to that of ophthalmic admin of dorzolamide 2% tid.
Distribution: Timolol: Low protein binding, crosses placenta and distributed into breast milk. Dorzolamide: Protein binding: 33%; unknown if it crosses placenta or distributed into breastmilk; preferentially distributed into erythrocytes.
Metabolism: Timolol: Undergoes extensive hepatic metabolism. Dorzolamide: Metabolised in liver by cytochrome P-450 isoenzymes to N-desethyldorzolamide.
Excretion: Timolol: Excreted in urine as metabolites and unchanged drug. Dorzolamide: Excreted mainly as unchanged drug (80%) and N-desethyldorzolamide; terminal elimination half-life in erythrocytes: 120 days.

Store between 15-30°C (59-86°F). Protect from light.

Antiglaucoma Preparations