Adult: For the reduction of elevated IOP: As ophthalmic solution: Initially, instil 1 drop of 0.25% w/v solution bid into the affected eye(s); may be increased to 1 drop of 0.5% w/v solution bid if needed. May reduce the dose to 1 drop once daily if the intraocular pressure is controlled. As 0.25% or 0.5% gel-forming ophthalmic solution: Instil 1 drop into the affected eye(s) once daily. As 0.1% ophthalmic gel: Instil 1 drop into the affected eye(s) once daily, in the morning.
Oral Angina pectoris
Adult: For cases due to ischaemic heart disease: Initially, 5 mg bid, increased in increments of 10 mg daily every 3-4 days. Usual dose range: 5-30 mg bid. Elderly: Initiate with the lowest possible dose, then adjust according to individual response.
Oral Secondary prophylaxis of myocardial infarction
Adult: For the reduction of CV mortality and risk of reinfarction in patients who survived an acute MI: Initially, 5 mg bid for 2 days, then increased to the target dose of 10 mg bid if no adverse effects are observed. Elderly: Initiate with the lowest possible dose, then adjust according to individual response.
Oral Prophylaxis of migraine
Adult: Initially, 10 mg once daily or bid, may be increased up to Max of 30 mg daily given in divided doses based on clinical response and tolerability. Elderly: Initiate with the lowest possible dose, then adjust according to individual response.
Oral Hypertension
Adult: Monotherapy or in combination with other antihypertensive agents (particularly thiazide-type diuretics): Initially, 10 mg daily or bid, then gradually increased at intervals of ≥7 days according to individual response. Usual maintenance dose: 10-40 mg daily. Max: 60 mg daily. Doses of >30 mg daily must be given in 2 equally divided doses. Elderly: Initiate with the lowest possible dose, then adjust according to individual response.
Renal Impairment
Oral:
Dose reduction may be needed.
Hepatic Impairment
Oral:
Dose reduction may be needed.
Administration
Should be taken with food.
Contraindications
Reactive airway diseases including current or history of bronchial asthma and severe COPD, sinus bradycardia, sick sinus syndrome, sino-atrial block, 2nd- or 3rd-degree atrioventricular (AV) block, overt heart failure, cardiogenic shock. Hypotension, uncontrolled heart failure, severe peripheral vascular disease (PVD) or Raynaud's disease, Prinzmetal's angina, metabolic acidosis (oral); untreated phaeochromocytoma (oral, 0.1% ophthalmic gel); corneal dystrophies (0.1% ophthalmic gel).
Special Precautions
Patient with CV disease (e.g. coronary heart disease, 1st-degree AV block, compensated heart failure), mild to moderate COPD, current or history of bronchospastic disease (other than current or history of bronchial asthma); corneal diseases, history of atopy or severe anaphylaxis to various allergens; cerebrovascular disease or insufficiency, myasthenia gravis, diabetes mellitus especially labile diabetes, thyroid disease, psoriasis. Patients subject to spontaneous hypoglycaemia and those undergoing major surgery. Timolol may mask signs of hyperthyroidism (e.g. tachycardia) and acute hypoglycaemia. Ophthalmic: Patient with Prinzmetal’s angina, hypotension, peripheral vascular disease, Raynaud’s disease. If used for angle-closure glaucoma, timolol must be used with a miotic agent and not alone as it has little or no effect on pupillary constriction. Treatment recommendations may vary among individual products or between countries (refer to detailed product guidelines). Avoid abrupt withdrawal (particularly in patients with ischaemic heart disease). Renal and hepatic impairment (oral). Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Exacerbation of angina and MI (following abrupt withdrawal), bradycardia, may precipitate or aggravate symptoms of arterial insufficiency (in patients with PVD and Raynaud's disease); induction or exacerbation of psoriasis, anaphylactic reactions; induction of dryness of eyes, choroidal detachment. Rarely, worsening of myasthenia gravis or myasthenic symptoms (e.g. diplopia, ptosis, generalised weakness). Cardiac disorders: Palpitation, chest pain. Ear and labyrinth disorders: Vertigo, tinnitus. Eye disorders: Ocular irritation (e.g. burning and stinging sensation, tearing, redness, itching), blurred vision, discharge, foreign body sensation, conjunctivitis, keratitis, diplopia, refractive changes, corneal erosion. Gastrointestinal disorders: Dyspepsia, nausea, vomiting, dry mouth, diarrhoea, abdominal pain. General disorders and administration site conditions: Fatigue, asthenia. Immune system disorders: SLE. Metabolism and nutrition disorders: Hypoglycaemia, anorexia. Musculoskeletal and connective tissue disorders: Myalgia, arthralgia. Nervous system disorders: Headache, dizziness, somnolence, paraesthesia. Psychiatric disorders: Insomnia, depression, confusion, hallucination, memory loss, nightmare. Reproductive system and breast disorders: Decreased libido, impotence. Respiratory, thoracic and mediastinal disorders: Dyspnoea, cough. Skin and subcutaneous tissue disorders: Alopecia, rash, pruritus. Vascular disorders: Hypotension, syncope, peripheral coldness. Potentially Fatal: Severe respiratory reactions, including those due to bronchospasm (particularly in asthma patients); severe cardiac reactions, including cardiac failure.
This drug may cause dizziness, fatigue, and visual disturbances (e.g. mild and transient blurred vision, ptosis, refractive changes); if affected do not drive or operate machinery. Ophthalmic: If another topical ophthalmic agent is to be used, separate the administration of the other product by at least 5-10 minutes. For 0.25% or 0.5% ophthalmic solution: Remove soft contact lenses prior to instillation of eye drops and wait at least 15 minutes before reinsertion.
Monitoring Parameters
Monitor blood pressure, heart rate, and apical and radial pulses periodically; intraocular pressure after approx 4 weeks of treatment (ophthalmic).
Overdosage
Symptoms: Dizziness, headache, shortness of breath, symptomatic bradycardia, hypotension, impaired consciousness, bronchospasm, AV block, acute heart failure, cardiogenic shock, and cardiac arrest. Management: Symptomatic treatment. Closely monitor the patient's CV, respiratory, and renal function including blood glucose and electrolyte levels. If ingestion is recent, administer activated charcoal, induce vomiting, or perform gastric lavage to prevent further absorption. For symptomatic bradycardia, administer 0.25-2 mg IV atropine sulfate to induce vagal blockade. If bradycardia persists, give IV isoprenaline hydrochloride cautiously. May consider cardiac pacemaker in refractory cases. For hypotension, administer sympathomimetic agents (e.g. norepinephrine, metaraminol), inotropic agents (e.g. dopamine, dobutamine) or atropine. To relieve bronchospasm, may consider giving isoprenaline hydrochloride, aminophylline, or IV β2-stimulants (e.g. terbutaline). For AV block, temporary pacing and use of isoprenaline hydrochloride or transverse cardiac pacemaker may be required. IV glucagon may also be given to reverse the effects of excessive β blockade. Immediately treat acute heart failure with the conventional therapy of using digitalis, diuretics, and oxygen. In refractory cases, administer IV aminophylline and then followed by glucagon if necessary. Based on studies, timolol may not be removed by haemodialysis.
Drug Interactions
Additive blood pressure-lowering effect with other antihypertensive agents, TCAs, phenothiazines, and barbiturates. May increase the blood sugar-lowering effects of insulin and oral antidiabetic agents. May cause attenuated reflex tachycardia and increased risk of hypotension with anaesthetics. May cause additive effects and produce hypotension or marked bradycardia (resulting in vertigo, syncope, postural hypotension) with catecholamine-depleting drugs (e.g. reserpine, guanethidine). Hypotension may occur when given with dihydropyridine Ca channel blockers (e.g. nifedipine); AV conduction disturbances or left ventricular failure may occur with verapamil and diltiazem. May increase the AV conduction time with digitalis glycosides. NSAIDs may diminish the therapeutic effects of timolol. May increase the risk of bradycardia with antiarrhythmics including amiodarone. May result in potentiated systemic β-blockade (e.g. depression, decreased heart rate) with CYP2D6 inhibitors (e.g. quinidine, paroxetine, fluoxetine). Timolol may exacerbate the rebound hypertensive effect of clonidine when it is abruptly withdrawn. May increase the vasoconstricting effects of ergot preparations. Mydriasis may occur when ophthalmic timolol is given with epinephrine.
Lab Interference
Oral: May result in false-positive aldosterone/renin ratio.
Action
Description: Timolol, a non-selective β1- and β2-adrenergic receptor blocker, has no significant intrinsic sympathomimetic, direct myocardial depressant or membrane-stabilising (local anaesthetic) activity. It decreases blood pressure by inhibiting the adrenergic receptors and reducing sympathetic outflow. It may also produce negative chronotropic and inotropic activity by an unknown mechanism. The precise mechanism of action to reduce intraocular pressure (IOP) is not clearly established; however, it may be by inhibiting aqueous humour production in the ciliary epithelium or by increasing the outflow of aqueous humour. Onset: Hypotensive effect: 15-45 minutes (oral). Reduction of IOP: Approx 20-30 minutes (ophthalmic). Duration: 24 hours. Pharmacokinetics: Absorption: Rapidly and almost completely absorbed from the gastrointestinal tract (oral); absorbed systemically (ophthalmic). Bioavailability: 50% (oral). Time to peak plasma concentration: Approx 1-2 hours (oral). Distribution: Crosses the placenta and enters breast milk. Ophthalmic: Detectable in plasma at low concentrations. Volume of distribution: 1.7 L/kg (oral). Metabolism: Extensively metabolised in the liver via CYP2D6 isoenzyme. Excretion: Via urine (15-20% as unchanged drug). Elimination half-life: Approx 4 hours.
Chemical Structure
Timolol Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 33624, Timolol. https://pubchem.ncbi.nlm.nih.gov/compound/Timolol. Accessed Nov. 28, 2022.
Storage
Tab: Store between 20-25°C. Protect from light. Ophthalmic solution, gel-forming solution, 0.1% gel: Store between 15-25°C. Do not freeze. Protect from light.
C07AA06 - timolol ; Belongs to the class of non-selective beta-blocking agents. Used in the treatment of cardiovascular diseases. S01ED01 - timolol ; Belongs to the class of beta blocking agents. Used in the treatment of glaucoma.
References
Anon. Timolol (Ophthalmic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 10/06/2022.Anon. Timolol (Systemic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 10/06/2022.Buckingham R (ed). Timolol Maleate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/06/2022.Joint Formulary Committee. Timolol Maleate. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 10/06/2022.Teva Pharma (New Zealand) Limited. Arrow Timolol, 0.25% w/v and 0.5% w/v, Eye Drops, Solution data sheet 1 November 2018. Medsafe. http://www.medsafe.govt.nz. Accessed 10/06/2022.Timolol 0.5% w/v Eye Drops Solution (Blumont Pharma Ltd). MHRA. https://products.mhra.gov.uk. Accessed 10/06/2022.Timolol Maleate 10 mg Tablets (Strandhaven Limited t/a Somex Pharma). MHRA. https://products.mhra.gov.uk. Accessed 10/06/2022.Timolol Maleate Ophthalmic Gel Forming Solution, 0.25% and 0.5% (Alembic Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 10/06/2022.Timolol Maleate Tablet (Mylan Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 10/06/2022.Timoptic Solution (Bausch & Lomb Incorporated). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 10/06/2022.Timoptol-LA 0.25% w/v Gel-forming Eye Drops, Solution (Santen Oy). MHRA. https://products.mhra.gov.uk. Accessed 10/06/2022.Timoptol-XE Ophthalmic Gellan Solution (Santen Pharma Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 10/06/2022.Tiopex 1 mg/g, Eye Gel in Single-dose Container (Laboratoires THEA). MHRA. https://products.mhra.gov.uk. Accessed 10/06/2022.
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