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{{Short description|Combination medication}}
{{Drugbox
{{Use dmy dates|date=May 2022}}
| Watchedfields = changed
{{Infobox drug
| verifiedrevid = 447540425
| type = combo
| image =
| alt =


<!--Combo data-->
<!-- Combo data -->
| type = Combination eye drops
| component1 = Dorzolamide hydrochloride
| component1 = Dorzolamide hydrochloride
| class1 = [[Carboanhydrase]] inhibitor
| class1 = [[Carbonic anhydrase inhibitor]]
| component2 = Timolol maleate
| component2 = Timolol maleate
| class2 = [[Beta blocker]]
| class2 = [[Beta blocker]]


<!--Clinical data-->
<!-- Clinical data -->
| tradename = Cosopt
| tradename = Cosopt, others
| Drugs.com = {{drugs.com|pro|cosopt}}
| MedlinePlus =
| DailyMedID = Dorzolamide and timolol
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = C
| pregnancy_category =
| pregnancy_category =
⚫
| routes_of_administration = [[Ophthalmic drug administration|Eye drop]]
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
⚫
| ATC_prefix = S01
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
⚫
| ATC_suffix = ED51

| legal_AU = S4
| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024}}</ref>
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Product monograph brand safety updates | website=Health Canada | date=February 2024 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html | access-date=24 March 2024}}</ref>
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_US = Rx-only
| legal_US = Rx-only
| legal_US_comment = <ref name="Cosopt FDA label">{{cite web | title=Cosopt- dorzolamide hydrochloride and timolol maleate solution/ drops | website=DailyMed | date=2 December 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b7aa1986-1c24-4733-96b3-e6d8e1d44558 | access-date=7 June 2023 | archive-date=24 January 2022 | archive-url=https://web.archive.org/web/20220124005940/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b7aa1986-1c24-4733-96b3-e6d8e1d44558 | url-status=live }}</ref><ref>{{cite web | title=Cosopt PF- dorzolamide hydrochloride and timolol maleate solution/ drops | website=DailyMed | date=8 November 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=535fc801-8c3f-4974-a120-3eff1d5a5062 | access-date=7 June 2023}}</ref>
| legal_status =
| legal_status =
⚫
| routes_of_administration = Ophthalmic


<!--Identifiers-->
<!-- Identifiers -->
⚫
| CAS_number = 146235-46-3
| CAS_number_Ref = {{cascite|correct|??}}
⚫
| CAS_number =
⚫
| ATC_prefix = S01
⚫
| ATC_suffix = ED51
| PubChem = 56841571
| PubChem = 56841571
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =
| DrugBank =
}}


<!-- Definition and medical uses -->
<!--Chemical data-->
'''Dorzolamide/timolol''', sold under the brand name '''Cosopt''' among others, is a medication used to treat [[high pressure inside the eye]] including [[glaucoma]].<ref name="Cosopt FDA label" /><ref name="He_2013">{{cite journal | vauthors = He M, Wang W, Huang W | title = Efficacy and tolerability of the fixed combinations latanoprost/timolol versus dorzolamide/timolol in patients with elevated intraocular pressure: a meta-analysis of randomized controlled trials | journal = PLOS ONE | volume = 8 | issue = 12 | pages = e83606 | date = 2013 | pmid = 24349536 | pmc = 3859645 | doi = 10.1371/journal.pone.0083606 | bibcode = 2013PLoSO...883606H | doi-access = free }}</ref><ref name="Konstas_2021">{{cite journal | vauthors = Konstas AG, Schmetterer L, Katsanos A, Hutnik CM, Holló G, Quaranta L, Teus MA, Uusitalo H, Pfeiffer N, Katz LJ | display-authors = 6 | title = Dorzolamide/Timolol Fixed Combination: Learning from the Past and Looking Toward the Future | journal = Advances in Therapy | volume = 38 | issue = 1 | pages = 24–51 | date = January 2021 | pmid = 33108623 | pmc = 7854404 | doi = 10.1007/s12325-020-01525-5 }}</ref> It is a combination of [[dorzolamide]] hydrochloride and [[timolol]] maleate.<ref name="Cosopt FDA label" /> It may be used when a [[beta blocker]], like timolol, is not sufficient alone.<ref name=BNF76>{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=1149|edition=76}}</ref> It is used as an eye drop.<ref name="Cosopt FDA label" />
|drug_name=Dorzolamide hydrochloride/Timolol maleate eye drops|image=https://img.medscapestatic.com/pi/features/drugdirectory/octupdate/A3628360.jpg|alt=|caption=|MedlinePlus=|licence_EU=|licence_US=}}


<!-- Side effects and mechanism -->
'''Dorzolamide/timolol''' eye drops (trade name '''Cosopt''') are used to lower intraocular pressure in the eye to normal and as a treatment for [[glaucoma]]. This medication is a combination of two compounds: [[dorzolamide]] hydrochloride and [[timolol]] maleate. Both compounds work by decreasing the production of [[aqueous humor]], which works to lower intraocular pressure. It gained [[Food and Drug Administration]] (FDA) approval in April 1998, and is supplied by [[Merck & Co.|Merck]].<ref name=":2">{{Cite web|url=https://www.newswise.com/articles/merck-receives-fda-approval-to-market-cosopt|title=Merck Receives FDA Approval to Market 'Cosopt'|website=www.newswise.com|access-date=2017-10-20}}</ref>
Common side effects include eye discomfort, eye redness, taste changes, and blurry vision.<ref name="Cosopt FDA label" /> Serious side effects may include [[allergic reactions]] and [[heart failure]].<ref name="Cosopt FDA label" /> Use is not recommended in those with [[asthma]], a [[sulfonamide allergy]], or a [[bradycardia|slow heart rate]].<ref name="Cosopt FDA label" /><ref name=BNF76/> Dorzolamide is a [[carbonic anhydrase inhibitor]] and timolol is a beta blocker.<ref name="Cosopt FDA label" /> Both work by decreasing the amount of [[aqueous humor]] made by the [[eye]].<ref name="Cosopt FDA label" />

<!-- Society and culture -->
The combination was approved for medical use in the United States in 1998.<ref name="Cosopt FDA label" /> It is available as a [[generic medication]].<ref name=BNF76/> In 2022, it was the 225th most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Dorzolamide; Timolol Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/DorzolamideTimolol | access-date = 30 August 2024 }}</ref>

⚫
== Adverse effects ==
⚫
Common adverse effects include temporarily blurred vision, cloudy vision, double vision, temporary burning/stinging/itching of the eye, watery eyes, feeling as if something is in the eye, drooping eyelid, sensitivity to light, cough, flu symptoms, nausea, and stomach pain.<ref name=":5">{{Cite news|url=https://www.rxlist.com/cosopt-side-effects-drug-center.htm|title=Common Side Effects of Cosopt (Dorzolamide Hydrochloride-Timolol Maleate Ophthalmic Solution) Drug Center - RxList|work=RxList|access-date=30 October 2017|archive-date=7 November 2017|archive-url=https://web.archive.org/web/20171107014829/https://www.rxlist.com/cosopt-side-effects-drug-center.htm|url-status=live}}</ref>

⚫
More serious adverse effects include dizziness, slow or irregular heartbeat, muscle weakness, mental/mood changes, and coldness/numbness/pain in the hands or feet.<ref name=":5" />


== Pharmacology ==
== Pharmacology ==
Dorzolamide is a carboanydrase inhibitor<ref>{{Cite web|url=https://www.drugbank.ca/drugs/DB00869|title=Dorzolamide|website=www.drugbank.ca|access-date=2017-10-27}}</ref>. Timolol is a non-selective beta-adrenergic antagonist.<ref>{{Cite web|url=https://www.drugbank.ca/drugs/DB00373|title=Timolol|website=www.drugbank.ca|access-date=2017-10-27}}</ref>
Dorzolamide is a human [[Carboanhydrase|carboanydrase]] II inhibitor.<ref>{{Cite web|url=https://www.drugbank.ca/drugs/DB00869|title=Dorzolamide|website=www.drugbank.ca|access-date=27 October 2017|archive-date=2 July 2017|archive-url=https://web.archive.org/web/20170702161412/https://www.drugbank.ca/drugs/DB00869|url-status=live}}</ref> Inhibition of carboanhydrase in the [[ciliary processes]] of the eye decreases aqueous humor secretion supposedly by decreasing the formation rate of [[bicarbonate]] ions.<ref name=":6">{{Cite news|url=https://www.drugs.com/pro/cosopt.html|title=Cosopt - FDA prescribing information, side effects and uses|work=Drugs.com|access-date=30 October 2017|archive-date=7 November 2017|archive-url=https://web.archive.org/web/20171107031601/https://www.drugs.com/pro/cosopt.html|url-status=live}}</ref> This results in reduction in both sodium and fluid transport.


Timolol is a non-selective beta-adrenergic antagonist.<ref>{{Cite web|url=https://www.drugbank.ca/drugs/DB00373|title=Timolol|website=www.drugbank.ca|access-date=27 October 2017|archive-date=28 October 2017|archive-url=https://web.archive.org/web/20171028093158/https://www.drugbank.ca/drugs/DB00373|url-status=live}}</ref>
⚫
== Adverse Effects ==
⚫
Common adverse effects of Dorzolamide hydrochloride/timolol maleate eye drops include temporarily blurred vision, cloudy vision, double vision, temporary burning/stinging/itching of the eye, watery eyes, feeling as if something is in the eye, drooping eyelid, sensitivity to light, cough, flu symptoms, nausea, and stomach pain<ref name=":5">{{Cite news|url=https://www.rxlist.com/cosopt-side-effects-drug-center.htm|title=Common Side Effects of Cosopt (Dorzolamide Hydrochloride-Timolol Maleate Ophthalmic Solution) Drug Center - RxList|work=RxList|access-date=2017-10-30|language=en}}</ref>.

⚫
More serious adverse effects include dizziness, slow or irregular heartbeat, muscle weakness, mental/mood changes, and coldness/numbness/pain in the hands or feet<ref name=":5" />.


== Comparison to other products ==
== Comparison to other products ==
Despite each of the active ingredients being availed in their own respective formulations, combination formulations are typically more convenient for the patient without sacrificing any quality in therapy. In the case of Cosopt, the combination formulation dosed twice daily provides equivalent treatment to both dorzolamide 2% dosed two times daily and timolol 0.5% dosed three times daily<ref name=":3">{{Cite book|title=Clinical Ocular Pharmacology|last=Bartlett|first=Jimmy|publisher=|year=2008|isbn=|location=https://books.google.com/books?id=Eybg7fbs65MC&pg=PA166&lpg=PA166&dq=cosopt+pharmacology&source=bl&ots=gFP7IEk7yz&sig=QznLSog1YWagh_FKcB3D5TkcWnA&hl=en&sa=X&ved=0ahUKEwjM2qPr3ZbXAhVCLyYKHa0UBrEQ6AEIVzAJ#v=onepage&q=cosopt%20pharmacology&f=false|pages=166}}</ref>. Specifically, the mean reduction in intraocular pressure was 27.4% for the combination product, 15.5% for dorzolamide 2%, and 22.2% for timolol 0.5%.
Despite each of the active ingredients being availed in their own respective formulations, combination formulations are typically more convenient for the patient without sacrificing any quality in therapy. In the case of Cosopt, the combination formulation dosed twice daily provides equivalent treatment to both dorzolamide 2% dosed two times daily and [[timolol]] 0.5% dosed three times daily.<ref name=":3">{{Cite book|title=Clinical Ocular Pharmacology| vauthors = Bartlett J |year=2008|url=https://books.google.com/books?id=Eybg7fbs65MC&dq=cosopt+pharmacology&pg=PA166|pages=166| publisher = Elsevier Health Sciences |isbn=978-0750675765}}</ref> Specifically, the mean reduction in intraocular pressure was 27.4% for the combination product, 15.5% for dorzolamide 2%, and 22.2% for timolol 0.5%.


Compared to other products such as Latanoprost, both are equally efficacious with regard to lowering intraocular pressure and getting patients to reach their target intraocular pressure<ref name=":3" />. Cosopt, though, is typically less well tolerated than other treatments due to a well documented feeling of ocular burning upon administration.
Compared to other products such as latanoprost, both are equally efficacious with regard to lowering intraocular pressure and getting patients to reach their target intraocular pressure.<ref name=":3" /> Cosopt, though, is typically less well tolerated than other treatments due to a well documented feeling of ocular burning upon administration.


== History ==
== History ==
Cosopt gained [[Food and Drug Administration]] (FDA) approval in April 1998, and is supplied by [[Merck & Co.|Merck]]<ref name=":2" />. In 2016, Merck & Co. had $95.3 billion in total assets, $40.3 billion in total equity, $24.3 billion in long term debt, and $13.4 billion in working capital.<ref>{{Cite web|url=http://s21.q4cdn.com/488056881/files/doc_financials/2017/Q4/merck-q4-10k.pdf|title=Merck Form 10-K|last=|first=|date=|website=Merck|archive-url=|archive-date=|dead-url=|access-date=2017-10-27}}</ref> This same year Merck & Co spent $20 billion total split virtually evenly between research and development (R&D) and marketing efforts.  Cosopt had annual sales of $342 million during the 12 months before June 2008.<ref name=":0">{{Cite web|url=http://www.leydig.com/publications/articles_publications-61|title=FDA Says Hi-Tech Forfeited Exclusivity; Way Paved for Approval of All Cosopt ANDAs|last=|first=|date=2008-11-07|website=Leydig|archive-url=|archive-date=|dead-url=|access-date=2017-10-27}}</ref> In September 2013,  Merck & Co. sold the U.S. rights to their ophthalmic product line (including Cosopt) to Akorn Inc. for $52.8 million cash.<ref>{{Cite news|url=http://www.businesswire.com/news/home/20131115005439/en/Akorn-Acquires-Branded-Ophthalmic-Products-Merck|title=Akorn Acquires Three Branded Ophthalmic Products from Merck|last=|first=|date=2013-11-15|work=Business Wire|access-date=2017-10-27|archive-url=|archive-date=|dead-url=}}</ref>
Cosopt gained [[Food and Drug Administration]] (FDA) approval in April 1998 and was supplied initially by [[Merck & Co.|Merck]].<ref name=":2">{{Cite web|url=https://www.newswise.com/articles/merck-receives-fda-approval-to-market-cosopt|title=Merck Receives FDA Approval to Market 'Cosopt'|website=www.newswise.com|access-date=20 October 2017|archive-date=21 October 2017|archive-url=https://web.archive.org/web/20171021004458/https://www.newswise.com/articles/merck-receives-fda-approval-to-market-cosopt|url-status=live}}</ref> In 2016, Merck & Co. had $95.3 billion in total assets, $40.3 billion in total equity, $24.3 billion in long term debt, and $13.4 billion in working capital.<ref>{{Cite web|url=http://s21.q4cdn.com/488056881/files/doc_financials/2017/Q4/merck-q4-10k.pdf|title=Merck Form 10-K|website=Merck|access-date=27 October 2017|archive-date=28 October 2017|archive-url=https://web.archive.org/web/20171028043123/http://s21.q4cdn.com/488056881/files/doc_financials/2017/Q4/merck-q4-10k.pdf|url-status=live}}</ref> This same year Merck & Co spent $20 billion total split virtually evenly between research and development (R&D) and marketing efforts. &nbsp;Cosopt had annual sales of $342 million during the 12 months before June 2008.<ref name=":0">{{Cite web|url=http://www.leydig.com/publications/articles_publications-61|title=FDA Says Hi-Tech Forfeited Exclusivity; Way Paved for Approval of All Cosopt ANDAs|date=7 November 2008|website=Leydig|access-date=27 October 2017|archive-date=28 October 2017|archive-url=https://web.archive.org/web/20171028093033/http://www.leydig.com/publications/articles_publications-61|url-status=dead}}</ref> In September 2013, &nbsp;Merck & Co. sold the U.S. rights to their ophthalmic product line (including Cosopt) to Akorn Inc. for $52.8 million cash.<ref>{{Cite news|url=http://www.businesswire.com/news/home/20131115005439/en/Akorn-Acquires-Branded-Ophthalmic-Products-Merck|title=Akorn Acquires Three Branded Ophthalmic Products from Merck|date=15 November 2013|work=Business Wire|access-date=27 October 2017|archive-date=28 October 2017|archive-url=https://web.archive.org/web/20171028042858/http://www.businesswire.com/news/home/20131115005439/en/Akorn-Acquires-Branded-Ophthalmic-Products-Merck|url-status=live}}</ref>


Upon the original patent expiration, Hi-Tech Pharma was the first of many generic competitors to submit an abbreviated new drug application (ANDA) for Dorzolamide hydrochloride/Timolol maleate eye drops.<ref name=":1">{{Cite news|url=https://www.law360.com/articles/68255/hi-tech-sues-fda-to-get-generic-cosopt-exclusivity|title=Hi-Tech Sues FDA To Get Generic Cosopt Exclusivity|last=|first=|date=2008-08-04|work=Law360|access-date=2017-10-27|archive-url=|archive-date=|dead-url=}}</ref> Hi-Tech Pharma’s ANDA was approved on October 28, 2008.  At the time, controversy surrounded the approval of this first ANDA.  Hi-Tech sued the FDA for their right to 180 market exclusivity as laid out in the Hatch-Waxman Act. Apotex argued that Hi-Tech “forfeited its rights to market exclusivity because it has failed to market the drug within 30 months of its ANDA submission or within 75 days after Merck withdrew its patent information.”<ref name=":1" /> The FDA upheld their previous exclusivity decisions on acarbose and granisetron, allowing both Hi-Tech and Apotex to make a generic version of Cosopt.<ref name=":0" /> Soon after, ANDAs from Sandoz, Bausch & Laumb, TEVA and others were also approved.<ref name=":4">{{Cite web|url=https://www.drugs.com/availability/generic-cosopt.html|title=Generic Cosopt Availability|last=|first=|date=|website=Drugs.com|archive-url=|archive-date=|dead-url=|access-date=2017-10-27}}</ref>
Upon the original patent expiration, Hi-Tech Pharma was the first of many generic competitors to submit an abbreviated new drug application (ANDA) for dorzolamide hydrochloride/timolol maleate eye drops.<ref name=":1">{{Cite news|url=https://www.law360.com/articles/68255/hi-tech-sues-fda-to-get-generic-cosopt-exclusivity|title=Hi-Tech Sues FDA To Get Generic Cosopt Exclusivity|date=4 August 2008|work=Law360|access-date=27 October 2017|archive-date=28 October 2017|archive-url=https://web.archive.org/web/20171028093106/https://www.law360.com/articles/68255/hi-tech-sues-fda-to-get-generic-cosopt-exclusivity|url-status=live}}</ref> Hi-Tech Pharma's ANDA was approved on 28 October 2008. &nbsp;At the time, controversy surrounded the approval of this first ANDA. &nbsp;Hi-Tech sued the FDA for their right to 180 market exclusivity as laid out in the Hatch-Waxman Act. Apotex, another firm seeking an ANDA approval for generic Cosopt, argued that Hi-Tech "forfeited its rights to market exclusivity because it has failed to market the drug within 30 months of its ANDA submission or within 75 days after Merck withdrew its patent information."<ref name=":1" /> The FDA upheld their previous exclusivity decisions on acarbose and granisetron, allowing both Hi-Tech and Apotex to make a generic version of Cosopt.<ref name=":0" /> Soon after, ANDAs from Sandoz, Bausch & Laumb, Teva and others were also approved.<ref name=":4">{{Cite web|url=https://www.drugs.com/availability/generic-cosopt.html|title=Generic Cosopt Availability|website=Drugs.com|access-date=27 October 2017|archive-date=28 October 2017|archive-url=https://web.archive.org/web/20171028043435/https://www.drugs.com/availability/generic-cosopt.html|url-status=live}}</ref>


Just over a year before Merck sold their ophthalmic line to Akorn, Akorn developed a new formulation of Dorzolamide hydrochloride/timolol maleate called Cosopt PF, which is simply a preservative free formulation of Cosopt<ref>{{Cite web|url=https://www.drugpatentwatch.com/p/tradename/COSOPT+PF|title=October 2017 - When do the COSOPT PF patents expire, and when will generic COSOPT PF be available?|website=Deep knowledge on small-molecule drugs and the 120,000 global patents covering them|language=en|access-date=2017-10-29}}</ref>. It gained FDA approval in July 2012 and is currently protected by market exclusivity.
Just over a year before Merck sold their ophthalmic line to Akorn, Akorn developed a new formulation of dorzolamide hydrochloride/timolol maleate called Cosopt PF, which is simply a preservative free formulation of Cosopt.<ref>{{Cite web|url=https://www.drugpatentwatch.com/p/tradename/COSOPT+PF|title=October 2017 - When do the Cosopt PF patents expire, and when will generic Cosopt PF be available?|website=Deep knowledge on small-molecule drugs and the 120,000 global patents covering them|access-date=29 October 2017|archive-date=7 November 2017|archive-url=https://web.archive.org/web/20171107015636/https://www.drugpatentwatch.com/p/tradename/COSOPT+PF|url-status=live}}</ref>


== Legality ==
==References==
{{Reflist}}
In the United States, Cosopt, as well as its generics, is only available to patients with a valid prescription<ref name=":4" />.

== Cost ==
The brand name Cosopt currently costs upwards of $200 after discounts<ref>{{Cite web|url=https://www.goodrx.com/cosopt|title=Prices and Coupons for Cosopt|access-date=2017-10-29}}</ref> while the generic formulation costs around $70 cash<ref>{{Cite web|url=https://www.goodrx.com/cosopt|title=Prices and Coupons for Cosopt|website=www.goodrx.com|access-date=2017-10-29}}</ref>. Interestingly, the more recent preservative free formulation can be purchased fore less than the original brand name formulation at around $160<ref>{{Cite web|url=https://www.goodrx.com/cosopt-pf|title=Prices and Coupons for Cosopt PF|website=www.goodrx.com|access-date=2017-10-29}}</ref>

==External links==
*[http://www.cosopt.com The drug's web site]
*[http://www.cosopt.com/cosopt/shared/documents/english/cosopt_pi.pdf The drug's label]


{{Antiglaucoma preparations and miotics}}
{{Antiglaucoma preparations and miotics}}


{{DEFAULTSORT:Dorzolamide timolol}}
{{DEFAULTSORT:Dorzolamide Timolol}}
[[Category:Combination drugs]]
[[Category:Drugs developed by Merck & Co.]]
[[Category:Ophthalmology drugs]]
[[Category:Ophthalmology drugs]]
[[Category:Combination drugs]]
[[Category:Wikipedia medicine articles ready to translate]]


{{Pharma-stub}}
{{Eye-stub}}

Latest revision as of 07:00, 30 November 2024

Dorzolamide/timolol
Combination of
Dorzolamide hydrochlorideCarbonic anhydrase inhibitor
Timolol maleateBeta blocker
Clinical data
Trade namesCosopt, others
AHFS/Drugs.comFDA Professional Drug Information
License data
Routes of
administration		Eye drop
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
CompTox Dashboard (EPA)

Dorzolamide/timolol, sold under the brand name Cosopt among others, is a medication used to treat high pressure inside the eye including glaucoma.[3][5][6] It is a combination of dorzolamide hydrochloride and timolol maleate.[3] It may be used when a beta blocker, like timolol, is not sufficient alone.[7] It is used as an eye drop.[3]

Common side effects include eye discomfort, eye redness, taste changes, and blurry vision.[3] Serious side effects may include allergic reactions and heart failure.[3] Use is not recommended in those with asthma, a sulfonamide allergy, or a slow heart rate.[3][7] Dorzolamide is a carbonic anhydrase inhibitor and timolol is a beta blocker.[3] Both work by decreasing the amount of aqueous humor made by the eye.[3]

The combination was approved for medical use in the United States in 1998.[3] It is available as a generic medication.[7] In 2022, it was the 225th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[8][9]

Adverse effects

[edit]

Common adverse effects include temporarily blurred vision, cloudy vision, double vision, temporary burning/stinging/itching of the eye, watery eyes, feeling as if something is in the eye, drooping eyelid, sensitivity to light, cough, flu symptoms, nausea, and stomach pain.[10]

More serious adverse effects include dizziness, slow or irregular heartbeat, muscle weakness, mental/mood changes, and coldness/numbness/pain in the hands or feet.[10]

Pharmacology

[edit]

Dorzolamide is a human carboanydrase II inhibitor.[11] Inhibition of carboanhydrase in the ciliary processes of the eye decreases aqueous humor secretion supposedly by decreasing the formation rate of bicarbonate ions.[12] This results in reduction in both sodium and fluid transport.

Timolol is a non-selective beta-adrenergic antagonist.[13]

Comparison to other products

[edit]

Despite each of the active ingredients being availed in their own respective formulations, combination formulations are typically more convenient for the patient without sacrificing any quality in therapy. In the case of Cosopt, the combination formulation dosed twice daily provides equivalent treatment to both dorzolamide 2% dosed two times daily and timolol 0.5% dosed three times daily.[14] Specifically, the mean reduction in intraocular pressure was 27.4% for the combination product, 15.5% for dorzolamide 2%, and 22.2% for timolol 0.5%.

Compared to other products such as latanoprost, both are equally efficacious with regard to lowering intraocular pressure and getting patients to reach their target intraocular pressure.[14] Cosopt, though, is typically less well tolerated than other treatments due to a well documented feeling of ocular burning upon administration.

History

[edit]

Cosopt gained Food and Drug Administration (FDA) approval in April 1998 and was supplied initially by Merck.[15] In 2016, Merck & Co. had $95.3 billion in total assets, $40.3 billion in total equity, $24.3 billion in long term debt, and $13.4 billion in working capital.[16] This same year Merck & Co spent $20 billion total split virtually evenly between research and development (R&D) and marketing efforts.  Cosopt had annual sales of $342 million during the 12 months before June 2008.[17] In September 2013,  Merck & Co. sold the U.S. rights to their ophthalmic product line (including Cosopt) to Akorn Inc. for $52.8 million cash.[18]

Upon the original patent expiration, Hi-Tech Pharma was the first of many generic competitors to submit an abbreviated new drug application (ANDA) for dorzolamide hydrochloride/timolol maleate eye drops.[19] Hi-Tech Pharma's ANDA was approved on 28 October 2008.  At the time, controversy surrounded the approval of this first ANDA.  Hi-Tech sued the FDA for their right to 180 market exclusivity as laid out in the Hatch-Waxman Act. Apotex, another firm seeking an ANDA approval for generic Cosopt, argued that Hi-Tech "forfeited its rights to market exclusivity because it has failed to market the drug within 30 months of its ANDA submission or within 75 days after Merck withdrew its patent information."[19] The FDA upheld their previous exclusivity decisions on acarbose and granisetron, allowing both Hi-Tech and Apotex to make a generic version of Cosopt.[17] Soon after, ANDAs from Sandoz, Bausch & Laumb, Teva and others were also approved.[20]

Just over a year before Merck sold their ophthalmic line to Akorn, Akorn developed a new formulation of dorzolamide hydrochloride/timolol maleate called Cosopt PF, which is simply a preservative free formulation of Cosopt.[21]

References

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  1. ^ "Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 30 March 2024.
  2. ^ "Product monograph brand safety updates". Health Canada. February 2024. Retrieved 24 March 2024.
  3. ^ a b c d e f g h i j "Cosopt- dorzolamide hydrochloride and timolol maleate solution/ drops". DailyMed. 2 December 2022. Archived from the original on 24 January 2022. Retrieved 7 June 2023.
  4. ^ "Cosopt PF- dorzolamide hydrochloride and timolol maleate solution/ drops". DailyMed. 8 November 2022. Retrieved 7 June 2023.
  5. ^ He M, Wang W, Huang W (2013). "Efficacy and tolerability of the fixed combinations latanoprost/timolol versus dorzolamide/timolol in patients with elevated intraocular pressure: a meta-analysis of randomized controlled trials". PLOS ONE. 8 (12): e83606. Bibcode:2013PLoSO...883606H. doi:10.1371/journal.pone.0083606. PMC 3859645. PMID 24349536.
  6. ^ Konstas AG, Schmetterer L, Katsanos A, Hutnik CM, Holló G, Quaranta L, et al. (January 2021). "Dorzolamide/Timolol Fixed Combination: Learning from the Past and Looking Toward the Future". Advances in Therapy. 38 (1): 24–51. doi:10.1007/s12325-020-01525-5. PMC 7854404. PMID 33108623.
  7. ^ a b c British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 1149. ISBN 9780857113382.
  8. ^ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  9. ^ "Dorzolamide; Timolol Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  10. ^ a b "Common Side Effects of Cosopt (Dorzolamide Hydrochloride-Timolol Maleate Ophthalmic Solution) Drug Center - RxList". RxList. Archived from the original on 7 November 2017. Retrieved 30 October 2017.
  11. ^ "Dorzolamide". www.drugbank.ca. Archived from the original on 2 July 2017. Retrieved 27 October 2017.
  12. ^ "Cosopt - FDA prescribing information, side effects and uses". Drugs.com. Archived from the original on 7 November 2017. Retrieved 30 October 2017.
  13. ^ "Timolol". www.drugbank.ca. Archived from the original on 28 October 2017. Retrieved 27 October 2017.
  14. ^ a b Bartlett J (2008). Clinical Ocular Pharmacology. Elsevier Health Sciences. p. 166. ISBN 978-0750675765.
  15. ^ "Merck Receives FDA Approval to Market 'Cosopt'". www.newswise.com. Archived from the original on 21 October 2017. Retrieved 20 October 2017.
  16. ^ "Merck Form 10-K" (PDF). Merck. Archived (PDF) from the original on 28 October 2017. Retrieved 27 October 2017.
  17. ^ a b "FDA Says Hi-Tech Forfeited Exclusivity; Way Paved for Approval of All Cosopt ANDAs". Leydig. 7 November 2008. Archived from the original on 28 October 2017. Retrieved 27 October 2017.
  18. ^ "Akorn Acquires Three Branded Ophthalmic Products from Merck". Business Wire. 15 November 2013. Archived from the original on 28 October 2017. Retrieved 27 October 2017.
  19. ^ a b "Hi-Tech Sues FDA To Get Generic Cosopt Exclusivity". Law360. 4 August 2008. Archived from the original on 28 October 2017. Retrieved 27 October 2017.
  20. ^ "Generic Cosopt Availability". Drugs.com. Archived from the original on 28 October 2017. Retrieved 27 October 2017.
  21. ^ "October 2017 - When do the Cosopt PF patents expire, and when will generic Cosopt PF be available?". Deep knowledge on small-molecule drugs and the 120,000 global patents covering them. Archived from the original on 7 November 2017. Retrieved 29 October 2017.
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