Jump to content

Cilostazol: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous edit
Content deleted Content added
VisualWikitext
Citation bot (talk | contribs)
Bots
5,424,766 edits
Add: website. | Use this bot. Report bugs. | Suggested by Whywhenwhohow | #UCB_webform 262/1172
 
(37 intermediate revisions by 23 users not shown)
Line 1: Line 1:
{{Short description|Chemical compound}}
{{Drugbox
{{Drugbox
| Watchedfields = changed
| Watchedfields = changed
| verifiedrevid = 460037234
| verifiedrevid = 460037234
| IUPAC_name = 6-[4-(1-Cyclohexyl-1''H''-tetrazol-5-yl)butoxy]-<br>3,4-dihydro-2(1''H'')-quinolinone
| IUPAC_name = 6-[4-(1-Cyclohexyl-1''H''-tetrazol-5-yl)butoxy]-<br />3,4-dihydro-2(1''H'')-quinolinone
| image = Cilostazol.svg
| image = Cilostazol.svg
| width = 250
| width = 250
Line 8: Line 9:
<!--Clinical data-->
<!--Clinical data-->
| pronounce = {{IPAc-en|s|ᵻ|ˈ|l|ɒ|s|t|ə|z|ɒ|l}}<br />{{respell|sil|OS|tə-zol}}
| pronounce = {{IPAc-en|s|ᵻ|ˈ|l|ɒ|s|t|ə|z|ɒ|l}}<br />{{respell|sil|OS|tə-zol}}
| tradename = Pletaal
| tradename = Pletal
| Drugs.com = {{drugs.com|monograph|cilostazol}}
| Drugs.com = {{drugs.com|monograph|cilostazol}}
| MedlinePlus = a601038
| MedlinePlus = a601038
| DailyMedID = Cilostazol
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = C
| pregnancy_US = C
Line 23: Line 25:
| bioavailability =
| bioavailability =
| protein_bound = 95–98%
| protein_bound = 95–98%
| metabolism = [[Liver|Hepatic]] ([[CYP3A4]]- and [[CYP2C19]]-mediated)
| metabolism = [[Liver]] ([[CYP3A4]]- and [[CYP2C19]]-mediated)
| elimination_half-life = 11–13 hours
| elimination_half-life = 11–13 hours
| excretion = [[Kidney|Renal]]
| excretion = [[Kidney]]


<!--Identifiers-->
<!--Identifiers-->
Line 49: Line 51:
<!--Chemical data-->
<!--Chemical data-->
| C=20 | H=27 | N=5 | O=2
| C=20 | H=27 | N=5 | O=2
| molecular_weight = 369.46 g/mol
| smiles = O=C4Nc3c(cc(OCCCCc1nnnn1C2CCCCC2)cc3)CC4
| smiles = O=C4Nc3c(cc(OCCCCc1nnnn1C2CCCCC2)cc3)CC4
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
Line 56: Line 57:
| StdInChIKey = RRGUKTPIGVIEKM-UHFFFAOYSA-N
| StdInChIKey = RRGUKTPIGVIEKM-UHFFFAOYSA-N
}}
}}
<!-- Definition and medical uses -->
'''Cilostazol''', sold under the brand name '''Pletal''' among others, is a [[medication]] used to help the symptoms of [[intermittent claudication]] in [[peripheral vascular disease]].<ref name=AHFS2019>{{cite web |title=Cilostazol Monograph for Professionals |url=https://www.drugs.com/monograph/cilostazol.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=23 March 2019 |language=en}}</ref> If no improvement is seen after 3 months, stopping the medication is reasonable.<ref name=BNF76/> It may also be used to prevent [[stroke]].<ref name=AHFS2019/> It is taken by mouth.<ref name=AHFS2019/>


<!-- Side effects and mechanisms -->
'''Cilostazol''' is a quinolinone-derivative [[medication]] used in the alleviation of the [[symptom]]s of [[intermittent claudication]] in individuals with [[peripheral vascular disease]]. It is manufactured by [[Otsuka Pharmaceutical|Otsuka Pharmaceutical Co.]] under the [[trade name]] '''Pletaal'''.
Common side effects include headache, diarrhea, dizziness, and cough.<ref name=AHFS2019/> Serious side effects may include decreased survival in those with [[heart failure]], [[low platelets]], and [[low white blood cells]].<ref name=AHFS2019/> Cilostazol is a [[phosphodiesterase 3 inhibitor]] which works by [[Platelet aggregation inhibitor|inhibiting platelet aggregation]] and dilating arteries.<ref name=AHFS2019/>


<!-- History and culture -->
Although drugs similar to cilostazol have increased the risk of death in patients with [[Heart failure|congestive heart failure]], studies of significant size have not addressed people without the disease.
Cilostazol was approved for medical use in the United States in 1999.<ref name=AHFS2019/> It is available as a [[generic medication]].<ref name=BNF76>{{cite book|title=British national formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=231–232|edition=76}}</ref> In 2019, it was the 347th most commonly prescribed medication in the United States, with more than 800{{nbsp}}thousand prescriptions.<ref>{{cite web | title = Cilostazol - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Cilostazol | access-date = 7 October 2022}}</ref>


==Medical uses==
Cilostazol is a [[phosphodiesterase 3 inhibitor]] with therapeutic focus on [[cyclic adenosine monophosphate]] (cAMP). It [[Platelet aggregation inhibitor|inhibits platelet aggregation]] and widens arteries (direct arterial vasodilator). Its main effects are dilation of the [[artery|arteries]] supplying blood to the legs and decreasing [[platelet]] [[coagulation]].
Cilostazol is approved for the treatment of intermittent claudication in the United States and United Kingdom.<ref name=AHFS2019/><ref>{{cite web |title=CILOSTAZOL |url=https://bnf.nice.org.uk/drug/cilostazol.html |website=BNF |publisher=NICE |access-date=20 February 2021}}</ref>


Cilostazol is also used for secondary stroke prevention,<ref name=AHFS2019/> though to date no regulatory body has approved it specifically for that indication.
==Mechanism==
⚫
Cilostazol is a selective inhibitor of phosphodiesterase type 3 ([[Phosphodiesterase 3|PDE<sub>3</sub>]]) with therapeutic focus on increasing cAMP. An increase in cAMP results in an increase in the active form of [[protein kinase A]] (PKA), which is directly related with an inhibition in platelet aggregation. PKA also prevents the activation of an enzyme (myosin light-chain kinase) that is important in the contraction of smooth muscle cells, thereby exerting its vasodilatory effect.


==Clinical use==
===Heart failure===
⚫
Cilostazol is dangerous for people with severe heart failure. Cilostazol has been studied in people without heart failure, without evidence of harm, but much more data would be needed to determine no risk exists. Although cilostazol would not be approvable for a trivial condition the Cardio-Renal Advisory Committee and FDA concluded that fully informed patients and physicians should be able to choose to use it to treat intermittent claudication. Patient and physician labeling will describe the basis for concern and the incomplete information available.<ref>{{cite web |url=https://www.fda.gov/cder/news/cilostazol/approval.htm |date=August 11, 1999 |access-date=2007-04-30 |author=Center for Drug Evaluation and Research |author-link=Center for Drug Evaluation and Research |title=Approval of Cilostazol |publisher=U.S. [[Food and Drug Administration]] |url-status=dead |archive-url=https://web.archive.org/web/20070427021345/https://www.fda.gov/cder/news/cilostazol/approval.htm |archive-date=2007-04-27 }}</ref>
Cilostazol is approved for the treatment of intermittent claudication. The typical dose is 100&nbsp;[[Kilogram#SI_multiples|mg]] twice a day. The effects may take as long as 3 months to be evident and has been shown to improve pain-free walking distance by 50%.

Cilostazol is also frequently used off-label, at the same dose, for treatment of intracranial atherosclerosis and secondary stroke prevention.<ref>{{cite journal | last1 = Kwon | first1 = SU | last2 = Cho | first2 = YJ | last3 = Koo | first3 = JS | last4 = Bae | first4 = HJ | last5 = Lee | first5 = YS | last6 = Hong | first6 = KS | last7 = Lee | first7 = JH | last8 = Kim | first8 = JS | title = Cilostazol Prevents the Progression of the Symptomatic Intracranial Arterial Stenosis: The Multicenter Double-Blind Placebo-Controlled Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis | journal = Stroke | date = 3 March 2005 | volume = 36 | issue = 4 | pages = 782–6 | doi = 10.1161/01.STR.0000157667.06542.b7 | pmid = 15746463 | url = http://stroke.ahajournals.org/content/strokeaha/36/4/782.full.pdf | accessdate = 27 December 2016}}</ref>

===In people with heart failure===
⚫
Cilostazol is dangerous for people with severe heart failure. Cilostazol has been studied in people without heart failure, without evidence of harm, but much more data would be needed to determine no risk exists. Although cilostazol would not be approvable for a trivial condition the Cardio-Renal Advisory Committee and FDA concluded that fully informed patients and physicians should be able to choose to use it to treat intermittent claudication. Patient and physician labeling will describe the basis for concern and the incomplete information available.<ref>{{cite web |url=http://www.fda.gov/cder/news/cilostazol/approval.htm |date=August 11, 1999 |accessdate=2007-04-30 |author=[[Center for Drug Evaluation and Research]] |title=Approval of Cilostazol |publisher=U.S. [[Food and Drug Administration]] |deadurl=yes |archiveurl=https://web.archive.org/web/20070427021345/http://www.fda.gov/cder/news/cilostazol/approval.htm |archivedate=2007-04-27 |df= }}</ref>


==Adverse effects==
==Adverse effects==
Possible side effects of cilostazol use include [[headache]] (the most common), [[diarrhea]], severe [[heat intolerance]], abnormal [[human feces|stool]]s, [[tachycardia|increased heart rate]], and [[palpitations]].<ref name=FDA_PI/>
Possible side effects of cilostazol use include [[headache]] (the most common), [[diarrhea]], severe [[heat intolerance]], abnormal [[human feces|stool]]s, [[tachycardia|increased heart rate]], and [[palpitations]].<ref name=FDA_PI/>


==Interactions==
== Interactions ==
⚫
Cilostazol is metabolized by [[CYP3A4]] and [[CYP2C19]], two [[isoenzyme]]s of the [[cytochrome P450]] system. Drugs that [[enzyme induction and inhibition|inhibit]] CYP3A4, such as [[itraconazole]], [[erythromycin]], [[ketoconazole]], and [[diltiazem]], are known to [[drug interaction|interact]] with cilostazol. The [[proton pump inhibitor]] [[omeprazole]], a potent inhibitor of CYP2C19, increases exposure to the active [[metabolite]] of cilostazol.<ref name=FDA_PI/>


⚫
Cilostazol is metabolized by [[CYP3A4]] and [[CYP2C19]], two [[isoenzyme]]s of the [[cytochrome P450]] system. Drugs that [[enzyme induction and inhibition|inhibit]] CYP3A4, such as [[itraconazole]], [[erythromycin]], [[ketoconazole]], and [[diltiazem]], are known to [[drug interaction|interact]] with cilostazol. The [[proton pump inhibitor]] [[omeprazole]], an inhibitor of CYP2C19, increases exposure to the active [[metabolite]] of cilostazol.<ref name=FDA_PI/><ref>{{cite web |url=https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers |access-date=2020-03-25 |author=FDA |author-link=FDA |title=Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers|website=[[Food and Drug Administration]] }}</ref>
⚫
A single report has been made of [[grapefruit juice]] possibly increasing the effects of cilostazol;<ref>{{cite journal | last1 = Taniguchi | first1 = K | last2 = Ohtani | first2 = H | last3 = Ikemoto | first3 = T | last4 = Miki | first4 = A | last5 = Hori | first5 = S | last6 = Sawada | first6 = Y | title = Possible Case of Potentiation of the Antiplatelet Effect of Cilostazol by Grapefruit Juice | journal = Journal of Clinical Pharmacy and Therapeutics | date = October 2007 | volume = 32 | issue = 5 | pages = 457–9 | doi = 10.1111/j.1365-2710.2007.00844.x | pmid = 17875111}}</ref> some drug information sources list this as a possible interaction.<ref>{{cite web |url=http://health.yahoo.com/other-other/cilostazol-for-peripheral-arterial-disease/healthwise--aa127481.html |title=Cilostazol for peripheral arterial disease |publisher=Yahoo! Health |accessdate=2008-09-21}}</ref><ref>{{cite web |url=http://www.medicinenet.com/cilostazol/article.htm |title=Cilostazol |publisher=MedicineNet.com |date=May 25, 1999 |accessdate=2008-09-22}}</ref><ref>{{cite web |url=https://www.drugs.com/mtm/cilostazol.html |date=November 29, 2007 |author=Cerner-Multum, Inc. |title=Consumer Drug Information: Cilostazol |publisher=Drugs.com |accessdate=2008-09-22}}</ref> The FDA-approved labeling of cilostazol notes that grapefruit juice (which is a CYP3A4 inhibitor) increases the drug's [[CMax|maximum concentration]] by around 50%.<ref name=FDA_PI>{{cite web |url=https://www.drugs.com/pro/cilostazol.html |title=Cilostazol: Official FDA information, side effects and uses. |date=February 2008 |publisher=Drugs.com |accessdate=2008-09-22}}</ref>


⚫
A single report has been made of [[grapefruit juice]] possibly increasing the effects of cilostazol;<ref>{{cite journal | vauthors = Taniguchi K, Ohtani H, Ikemoto T, Miki A, Hori S, Sawada Y | title = Possible case of potentiation of the antiplatelet effect of cilostazol by grapefruit juice | journal = Journal of Clinical Pharmacy and Therapeutics | volume = 32 | issue = 5 | pages = 457–9 | date = October 2007 | pmid = 17875111 | doi = 10.1111/j.1365-2710.2007.00844.x | s2cid = 42556945 }}</ref> some drug information sources list this as a possible interaction.<ref>{{cite web |url=http://health.yahoo.com/other-other/cilostazol-for-peripheral-arterial-disease/healthwise--aa127481.html |archive-url=https://archive.today/20091001071106/http://health.yahoo.com/other-other/cilostazol-for-peripheral-arterial-disease/healthwise--aa127481.html |url-status=dead |archive-date=2009-10-01 |title=Cilostazol for peripheral arterial disease |publisher=Yahoo! Health |access-date=2008-09-21 }}</ref><ref>{{cite web |url=http://www.medicinenet.com/cilostazol/article.htm |title=Cilostazol |publisher=MedicineNet.com |date=May 25, 1999 |access-date=2008-09-22}}</ref><ref>{{cite web |url=https://www.drugs.com/mtm/cilostazol.html |date=November 29, 2007 |author=Cerner-Multum, Inc. |title=Consumer Drug Information: Cilostazol |publisher=Drugs.com |access-date=2008-09-22}}</ref> The FDA-approved labeling of cilostazol notes that grapefruit juice (which is a CYP3A4 inhibitor) increases the drug's [[CMax|maximum concentration]] by around 50%.<ref name=FDA_PI>{{cite web |url=https://www.drugs.com/pro/cilostazol.html |title=Cilostazol: Official FDA information, side effects and uses. |date=February 2008 |publisher=Drugs.com |access-date=2008-09-22}}</ref>
==See also==
* [[Aripiprazole]] — an [[atypical antipsychotic]] with similar dihydroquinolinone core structure.


==References==
==Mechanism==
⚫
Cilostazol is a selective inhibitor of phosphodiesterase type 3 ([[Phosphodiesterase 3|PDE<sub>3</sub>]]) with therapeutic focus on increasing cAMP. An increase in cAMP results in an increase in the active form of [[protein kinase A]] (PKA), which is directly related with an inhibition in platelet aggregation. PKA also prevents the activation of an enzyme (myosin light-chain kinase) that is important in the contraction of smooth muscle cells, thereby exerting its vasodilatory effect.

== References ==
{{Reflist}}
{{Reflist}}


==External links==
== External links ==
⚫
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/cilostazol | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Cilostazol }}
* [http://www.drugdigest.org/DD/DVH/Uses/0,3915,733|Pletal,00.html Supplementary information provided by Drug Digest] (Link not working 2/8/12)

⚫
* [http://druginfo.nlm.nih.gov/drugportal/dpdirect.jsp?name=Cilostazol U.S. National Library of Medicine: Drug Information Portal - Cilostazol]
{{Clear}}
{{Clear}}
{{Antithrombotics}}
{{Antithrombotics}}
{{Purinergics}}
{{Purinergics}}
{{Portal bar | Medicine}}


⚫
[[Category:CYP3A4 inhibitors]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Antiplatelet drugs]]
[[Category:Antiplatelet drugs]]
[[Category:Vasodilators]]
[[Category:Vasodilators]]
[[Category:Tetrazoles]]
[[Category:Tetrazoles]]
[[Category:2-Quinolones]]
[[Category:2-Quinolone ethers at the benzene ring]]
⚫
[[Category:Phenol ethers]]
[[Category:PDE3 inhibitors]]
[[Category:PDE3 inhibitors]]
[[Category:Otsuka Pharmaceutical]]
[[Category:Otsuka Pharmaceutical]]
[[Category:Cyclohexyl compounds]]
[[Category:Delta-lactams]]

Latest revision as of 06:23, 24 January 2023

Cilostazol
Clinical data
Pronunciation/sɪˈlɒstəzɒl/
sil-OS-tə-zol
Trade namesPletal
AHFS/Drugs.comMonograph
MedlinePlusa601038
License data
Routes of
administration		By mouth (tablets)
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: WARNING[1]Rx-only
Pharmacokinetic data
Protein binding95–98%
MetabolismLiver (CYP3A4- and CYP2C19-mediated)
Elimination half-life11–13 hours
ExcretionKidney
Identifiers
  • 6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)butoxy]-
    3,4-dihydro-2(1H)-quinolinone
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.215.897 Edit this at Wikidata
Chemical and physical data
FormulaC20H27N5O2
Molar mass369.469 g·mol−1
3D model (JSmol)
  • O=C4Nc3c(cc(OCCCCc1nnnn1C2CCCCC2)cc3)CC4
  • InChI=1S/C20H27N5O2/c26-20-12-9-15-14-17(10-11-18(15)21-20)27-13-5-4-8-19-22-23-24-25(19)16-6-2-1-3-7-16/h10-11,14,16H,1-9,12-13H2,(H,21,26) checkY
  • Key:RRGUKTPIGVIEKM-UHFFFAOYSA-N checkY
  (verify)

Cilostazol, sold under the brand name Pletal among others, is a medication used to help the symptoms of intermittent claudication in peripheral vascular disease.[2] If no improvement is seen after 3 months, stopping the medication is reasonable.[3] It may also be used to prevent stroke.[2] It is taken by mouth.[2]

Common side effects include headache, diarrhea, dizziness, and cough.[2] Serious side effects may include decreased survival in those with heart failure, low platelets, and low white blood cells.[2] Cilostazol is a phosphodiesterase 3 inhibitor which works by inhibiting platelet aggregation and dilating arteries.[2]

Cilostazol was approved for medical use in the United States in 1999.[2] It is available as a generic medication.[3] In 2019, it was the 347th most commonly prescribed medication in the United States, with more than 800 thousand prescriptions.[4]

Medical uses

[edit]

Cilostazol is approved for the treatment of intermittent claudication in the United States and United Kingdom.[2][5]

Cilostazol is also used for secondary stroke prevention,[2] though to date no regulatory body has approved it specifically for that indication.

Heart failure

[edit]

Cilostazol is dangerous for people with severe heart failure. Cilostazol has been studied in people without heart failure, without evidence of harm, but much more data would be needed to determine no risk exists. Although cilostazol would not be approvable for a trivial condition the Cardio-Renal Advisory Committee and FDA concluded that fully informed patients and physicians should be able to choose to use it to treat intermittent claudication. Patient and physician labeling will describe the basis for concern and the incomplete information available.[6]

Adverse effects

[edit]

Possible side effects of cilostazol use include headache (the most common), diarrhea, severe heat intolerance, abnormal stools, increased heart rate, and palpitations.[7]

Interactions

[edit]

Cilostazol is metabolized by CYP3A4 and CYP2C19, two isoenzymes of the cytochrome P450 system. Drugs that inhibit CYP3A4, such as itraconazole, erythromycin, ketoconazole, and diltiazem, are known to interact with cilostazol. The proton pump inhibitor omeprazole, an inhibitor of CYP2C19, increases exposure to the active metabolite of cilostazol.[7][8]

A single report has been made of grapefruit juice possibly increasing the effects of cilostazol;[9] some drug information sources list this as a possible interaction.[10][11][12] The FDA-approved labeling of cilostazol notes that grapefruit juice (which is a CYP3A4 inhibitor) increases the drug's maximum concentration by around 50%.[7]

Mechanism

[edit]

Cilostazol is a selective inhibitor of phosphodiesterase type 3 (PDE3) with therapeutic focus on increasing cAMP. An increase in cAMP results in an increase in the active form of protein kinase A (PKA), which is directly related with an inhibition in platelet aggregation. PKA also prevents the activation of an enzyme (myosin light-chain kinase) that is important in the contraction of smooth muscle cells, thereby exerting its vasodilatory effect.

References

[edit]
  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ a b c d e f g h i "Cilostazol Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 23 March 2019.
  3. ^ a b British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 231–232. ISBN 9780857113382.
  4. ^ "Cilostazol - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  5. ^ "CILOSTAZOL". BNF. NICE. Retrieved 20 February 2021.
  6. ^ Center for Drug Evaluation and Research (August 11, 1999). "Approval of Cilostazol". U.S. Food and Drug Administration. Archived from the original on 2007-04-27. Retrieved 2007-04-30.
  7. ^ a b c "Cilostazol: Official FDA information, side effects and uses". Drugs.com. February 2008. Retrieved 2008-09-22.
  8. ^ FDA. "Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers". Food and Drug Administration. Retrieved 2020-03-25.
  9. ^ Taniguchi K, Ohtani H, Ikemoto T, Miki A, Hori S, Sawada Y (October 2007). "Possible case of potentiation of the antiplatelet effect of cilostazol by grapefruit juice". Journal of Clinical Pharmacy and Therapeutics. 32 (5): 457–9. doi:10.1111/j.1365-2710.2007.00844.x. PMID 17875111. S2CID 42556945.
  10. ^ "Cilostazol for peripheral arterial disease". Yahoo! Health. Archived from the original on 2009-10-01. Retrieved 2008-09-21.
  11. ^ "Cilostazol". MedicineNet.com. May 25, 1999. Retrieved 2008-09-22.
  12. ^ Cerner-Multum, Inc. (November 29, 2007). "Consumer Drug Information: Cilostazol". Drugs.com. Retrieved 2008-09-22.
[edit]
  • "Cilostazol". Drug Information Portal. U.S. National Library of Medicine.
Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Cilostazol&oldid=1135366408"