Dorzolamide + Timolol


Generic Medicine Info
Indications and Dosage
Ophthalmic
Ocular hypertension, Open-angle glaucoma, 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
<30 Not recommended.
Contraindications
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.
Special Precautions
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.
Adverse Reactions
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.
Patient Counseling Information
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.
Overdosage
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.
Drug Interactions
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.
Action
Description: 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.
Pharmacokinetics:
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.
Chemical Structure

Chemical Structure Image

Source: National Center for Biotechnology Information. PubChem Database. Dorzolamide, CID=5284549, https://pubchem.ncbi.nlm.nih.gov/compound/Dorzolamide (accessed on Jan. 21, 2020)


Chemical Structure Image
Timolol

Source: National Center for Biotechnology Information. PubChem Database. Timolol, CID=33624, https://pubchem.ncbi.nlm.nih.gov/compound/Timolol (accessed on Jan. 21, 2020)

Storage
Store below 30°C. Protect from light. Storage recommendation may vary among countries or individual products. Refer to specific product guideline.
ATC Classification
S01ED51 - timolol, combinations ; Belongs to the class of beta blocking agents. Used in the treatment of glaucoma.
References
Anon. Dorzolamide and Timolol. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/01/2021.

Anon. Dorzolamide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/01/2021.

Anon. Timolol (Ophthalmic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 07/01/2021.

Buckingham R (ed). Dorzolamide Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/01/2021.

Buckingham R (ed). Timolol Maleate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 07/01/2021.

Cosopt (Santen Pharma Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 13/01/2021.

Cosopt PF (Akorn, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 13/01/2021.

Dorzolamide 20 mg/mL and Timolol 5 mg/mL Eye Drops Solution (FDC Pharma). MHRA. https://products.mhra.gov.uk. Accessed 07/01/2021.

Dorzolamide/Timolol 20 mg/mL + 5 mg/mL Eye Drops, Solution (Accord-UK Ltd). MHRA. https://products.mhra.gov.uk. Accessed 10/03/2021.

Dorzolamide; Timolol. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 12/01/2021.

Joint Formulary Committee. Dorzolamide with Timolol. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/03/2021.

Mylan New Zealand Ltd. Dortimopt 20 mg/mL + 5 mg/mL Ophthalmic Solution data sheet 12 November 2019. Medsafe. http://www.medsafe.govt.nz. Accessed 07/01/2021.

Disclaimer: This information is independently developed by MIMS based on Dorzolamide + Timolol from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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