Timolol

Timolol
Names
Trade namesBetimol, Istalol, others[1]
IUPAC name
  • (S)-1-(tert-Butylamino)-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol
Clinical data
Drug classBeta blocker
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
    Routes of
    use    		By mouth, topical (eye drop)
    Defined daily dose0.2 ml (Timolol maleate) via ophthalmic drops[2]
    20 mg (by mouth)
    or 20 mg (parenteral) [3]
    External links
    AHFS/Drugs.comEyes: Monograph
    Systemic: Monograph
    MedlinePlusa684029
    Legal
    License data
    Legal status
    Pharmacokinetics
    Bioavailability60%
    MetabolismLiver (80%)
    Elimination half-life2.5–5 hours
    ExcretionKidney
    Chemical and physical data
    FormulaC13H24N4O3S
    Molar mass316.42 g·mol−1
    3D model (JSmol)
    SMILES
    • CC(C)(C)NCC(COC1=NSN=C1N2CCOCC2)O
    InChI
    • InChI=1S/C13H24N4O3S/c1-13(2,3)14-8-10(18)9-20-12-11(15-21-16-12)17-4-6-19-7-5-17/h10,14,18H,4-9H2,1-3H3/t10-/m0/s1 checkY
    • Key:BLJRIMJGRPQVNF-JTQLQIEISA-N checkY

    Timolol is a medication used either by mouth or as eye drops.[4][5] As eye drops it is used to treat increased pressure inside the eye such as in ocular hypertension and glaucoma.[4] By mouth it is used for high blood pressure, chest pain due to insufficient blood flow to the heart, to prevent further complications after a heart attack, and to prevent migraines.[5]

    Common side effects with the drops is irritation of the eye.[4] Common side effects by mouth include tiredness, slow heart beat, itchiness, and shortness of breath.[5] Other side effects include masking the symptoms of low blood sugar in those with diabetes.[4] Use is not recommended in those with asthma, uncompensated heart failure, or COPD.[4] It is unclear if use during pregnancy is safe for the baby.[6] Timolol is a non-selective beta blocker.[4]

    Timolol was patented in 1968, and came into medical use in 1978.[7] It is on the World Health Organization's List of Essential Medicines.[8] Timolol is available as a generic medication.[4] The wholesale cost in the developing world is about US$0.86–2.29 per 5 ml bottle.[9] In the United States it costs US$25–50 per month.[10] In 2017, it was the 146th most commonly prescribed medication in the United States, with more than four million prescriptions.[11][12]

    Medical uses

    By mouth

    In its by mouth form, it is used:

    Eye drops

    In its eye drop form it is used to treat open-angle and, occasionally, secondary glaucoma.[4][14] The mechanism of action of timolol is probably the reduction of the formation of aqueous humor[4] in the ciliary body in the eye. It was the first beta blocker approved for topical use in treatment of glaucoma in the United States (1978).[15] When used by itself, it depresses intraocular pressure (IOP) 18–34% below baseline within first few treatments. However, there are short-term escape and long-term drift effects in some people. That is, tolerance develops. It may reduce the extent of diurnal IOP curve up to 50%. IOP higher during sleep. Efficacy of timolol in lowering IOP during the sleep period may be limited.[16][17][18] It is 5–10× more potent β blocker than propranolol. Timolol is light-sensitive; it is usually preserved with 0.01% benzalkonium chloride (BAC), but also comes BAC-free. Can also be used in adjunctive therapy with pilocarpine or carbonic anhydrase inhibitors.[19]

    A Cochrane review compared the effect of timolol versus brimonidine in slowing the progression of open angle glaucoma in adults but found insufficient evidence to come to conclusions.[20]

    On the skin

    In its gel form it is used on the skin to treat infantile hemangiomas.[21]

    Dosage

    The defined daily dose is 0.2 ml (Timolol maleate) via ophthalmic drops for glaucoma[2] and 20 mg (by mouth) or 20 mg (parenteral) arrhythmia treatment[3]

    Contraindications

    The medication should not be taken by individuals with:[22]

    Side effects

    See also: Beta blocker toxicity

    The most serious possible side effects include cardiac arrhythmias and severe bronchospasms.[22] Timolol can also lead to fainting, congestive heart failure, depression, confusion, worsening of Raynaud's syndrome and impotence.[22]

    Side effects when given in the eye include: burning sensation, eye redness, superficial punctate keratopathy, corneal numbness.[24][14]

    Formulations

    It is available in tablet and liquid formulations.[22][24]

    For ophthalmic use, timolol is also available combined:

    Brand names

    Timolol is marketed under many trade names worldwide.[1] Timolol eye drops are marketed under the brand name Istalol among others.[25][26]

    Society and culture

    Cost

    The wholesale cost in the developing world is about US$0.86–2.29 per 5 ml bottle.[9] In the United States it costs US$25–50 per month.[10] In 2017, it was the 146th most commonly prescribed medication in the United States, with more than four million prescriptions.[11][12]

    • Timolol costs (US)
      Timolol costs (US)
    • Timolol prescriptions (US)
      Timolol prescriptions (US)

    References

    1. 1 2 "Timolol". Drugs.com. Archived from the original on 7 March 2016. Retrieved 28 December 2016.
    2. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 1 July 2021. Retrieved 16 September 2020.
    3. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 19 December 2020. Retrieved 16 September 2020.
    4. 1 2 3 4 5 6 7 8 9 "Timolol eent". The American Society of Health-System Pharmacists. Archived from the original on 28 December 2016. Retrieved 8 December 2016.
    5. 1 2 3 "Timolol Maleate". The American Society of Health-System Pharmacists. Archived from the original on 28 December 2016. Retrieved 8 December 2016.
    6. ↑ "Timolol ophthalmic Use During Pregnancy". The American Society of Health-System Pharmacists. Archived from the original on 28 December 2016. Retrieved 28 December 2016.
    7. ↑ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 460. ISBN 9783527607495. Archived from the original on 28 December 2016.
    8. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
    9. 1 2 "Timolol Maleate". International Drug Price Indicator Guide. Archived from the original on 22 January 2018. Retrieved 8 December 2016.
    10. 1 2 Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 411. ISBN 9781284057560.
    11. 1 2 "The Top 300 of 2020". ClinCalc. Archived from the original on 18 March 2020. Retrieved 11 April 2020.
    12. 1 2 "Timolol - Drug Usage Statistics". ClinCalc. Archived from the original on 8 July 2020. Retrieved 11 April 2020.
    13. ↑ Marcus, Dawn A.; Bain, Philip A. (27 February 2009). Effective Migraine Treatment in Pregnant and Lactating Women: A Practical Guide. シュプリンガー・ジャパン株式会社. pp. 141–. ISBN 978-1-60327-438-8. Archived from the original on 5 November 2017. Retrieved 14 November 2010.
    14. 1 2 "Timolol Ophthalmic". MedlinePlus. 15 April 2017. Archived from the original on 7 October 2019. Retrieved 31 December 2019.
    15. ↑ Sambhara D, Aref AA (January 2014). "Glaucoma management: relative value and place in therapy of available drug treatments". Therapeutic Advances in Chronic Disease. 5 (1): 30–43. doi:10.1177/2040622313511286. PMC 3871276. PMID 24381726.
    16. ↑ Liu JH, Kripke DF, Weinreb RN (September 2004). "Comparison of the nocturnal effects of once-daily timolol and latanoprost on intraocular pressure". American Journal of Ophthalmology. 138 (3): 389–95. doi:10.1016/j.ajo.2004.04.022. PMID 15364220.
    17. ↑ Liu JH, Medeiros FA, Slight JR, Weinreb RN (March 2009). "Comparing diurnal and nocturnal effects of brinzolamide and timolol on intraocular pressure in patients receiving latanoprost monotherapy". Ophthalmology. 116 (3): 449–54. doi:10.1016/j.ophtha.2008.09.054. PMID 19157559.
    18. ↑ Liu JH, Slight JR, Vittitow JL, Scassellati Sforzolini B, Weinreb RN (September 2016). "Efficacy of Latanoprostene Bunod 0.024% Compared With Timolol 0.5% in Lowering Intraocular Pressure Over 24 Hours". American Journal of Ophthalmology. 169: 249–257. doi:10.1016/j.ajo.2016.04.019. PMID 27457257.
    19. ↑ Strohmaier K, Snyder E, Adamsons I (July 1998). "A multicenter study comparing dorzolamide and pilocarpine as adjunctive therapy to timolol: patient preference and impact on daily life". Journal of the American Optometric Association. 69 (7): 441–51. PMID 9697378.
    20. ↑ Sena DF, Lindsley K (January 2017). "Neuroprotection for treatment of glaucoma in adults". The Cochrane Database of Systematic Reviews. 1 (1): CD006539. doi:10.1002/14651858.CD006539.pub4. PMC 5370094. PMID 28122126.
    21. ↑ Novoa M, Baselga E, Beltran S, Giraldo L, Shahbaz A, Pardo-Hernandez H, Arevalo-Rodriguez I (April 2018). "Interventions for infantile haemangiomas of the skin". The Cochrane Database of Systematic Reviews. 4: CD006545. doi:10.1002/14651858.CD006545.pub3. PMC 6513200. PMID 29667726.
    22. 1 2 3 4 "Timolol Maleate tablet". DailyMed. 17 August 2006. Archived from the original on 23 January 2021. Retrieved 1 December 2019.
    23. ↑ "Package leaflet: Information for the user Timolol" (PDF). hpra.ie. Archived (PDF) from the original on 16 August 2018. Retrieved 15 August 2018.
    24. 1 2 "Betimol- timolol solution". DailyMed. 18 March 2010. Archived from the original on 4 August 2020. Retrieved 1 December 2019.
    25. ↑ "Generic Istalol Availability". Drugs.com. Archived from the original on 21 June 2019. Retrieved 20 June 2019.
    26. ↑ "Istalol". Drugs.com. 1 August 2018. Archived from the original on 21 June 2019. Retrieved 19 July 2019.
    Identifiers:
    • "Timolol". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 1 January 2020. Retrieved 1 January 2020.
    • "Timolol Ophthalmic". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 6 August 2019. Retrieved 1 January 2020.
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