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'''Oclacitinib''' (brand name '''Apoquel''') is a veterinary medication used in the control of [[pruritus]] associated with allergic [[dermatitis]] and the control of [[atopic dermatitis]] in dogs at least 12 months of age.<ref name="Apoquel PI" /><ref>{{cite web|title=FDA Approves Apoquel (oclacitinib tablet) to Control Itch and Inflammation in Allergic Dogs|url=http://news.zoetis.com/press-release/companion-animals/fda-approves-apoquel-oclacitinib-tablet-control-itch-and-inflammatio|publisher=Zoetis|accessdate=23 February 2017|date=16 May 2013}}</ref> Chemically, it is a cyclohexylamino pyrrolopyrimidine [[janus kinase inhibitor]] that is relatively selective for [[Janus kinase 1|JAK1]] ([[IC50|IC<sub>50</sub>]] = 10 nM).<ref name="Gonzales">{{cite journal|last1=Gonzales|first1=AJ|last2=Bowman|first2=JW|last3=Fici|first3=GJ|last4=Zhang|first4=M|last5=Mann|first5=DW|last6=Mitton-Fry|first6=M|title=Oclacitinib (Apoquel<sup>®</sup>) Is a Novel Janus Kinase Inhibitor with Activity Against Cytokines Involved in Allergy|journal=Journal of Veterinary Pharmacology and Therapeutics|date=August 2014|volume=37|issue=4|pages=317–24|doi=10.1111/jvp.12101|pmid=24495176|pmc=4265276}}</ref>
'''Oclacitinib''' (brand name '''Apoquel''') is a veterinary medication used in the control of [[pruritus]] associated with allergic [[dermatitis]] and the control of [[atopic dermatitis]] in dogs at least 12 months of age.<ref name="Apoquel PI" /><ref>{{cite web|title=FDA Approves Apoquel (oclacitinib tablet) to Control Itch and Inflammation in Allergic Dogs|url=http://news.zoetis.com/press-release/companion-animals/fda-approves-apoquel-oclacitinib-tablet-control-itch-and-inflammatio|publisher=Zoetis|accessdate=23 February 2017|date=16 May 2013}}</ref> Chemically, it is a cyclohexylamino pyrrolopyrimidine [[janus kinase inhibitor]] that is relatively selective for [[Janus kinase 1|JAK1]] ([[IC50|IC<sub>50</sub>]] = 10 nM).<ref name="Gonzales">{{cite journal|last1=Gonzales|first1=AJ|last2=Bowman|first2=JW|last3=Fici|first3=GJ|last4=Zhang|first4=M|last5=Mann|first5=DW|last6=Mitton-Fry|first6=M|title=Oclacitinib (Apoquel<sup>®</sup>) Is a Novel Janus Kinase Inhibitor with Activity Against Cytokines Involved in Allergy|journal=Journal of Veterinary Pharmacology and Therapeutics|date=August 2014|volume=37|issue=4|pages=317–24|doi=10.1111/jvp.12101|pmid=24495176|pmc=4265276}}</ref>


==Inhibitory activity==
== Uses ==
Oclacitinib is labeled to treat [[atopic dermatitis]] and [[itchiness]] (pruritus) caused by [[allergies in dogs]], though it has also been used to reduce the itchiness and [[dermatitis]] caused by [[flea]] infestations.<ref>{{cite book|url=https://books.google.com/books?id=Jl0SCAAAQBAJ&pg=PA363|title=Pharmacology of Itch|last1=Cowan|first1=Alan|last2=Yosipovitch|first2=Gil|publisher=Springer|year=2015|isbn=978-3-662-44605-8|pages=363–364|ref=harv}}</ref><ref name=hnilica>{{cite book|url=https://books.google.com/books?id=xT_UDAAAQBAJ&pg=PA190|title=Small Animal Dermatology - E-Book: A Color Atlas and Therapeutic Guide|last1=Hnilica|first1=Keith A.|last2=Patterson|first2=Adam P.|publisher=Elsevier Health Sciences|year=2016|isbn=978-0-323-39067-5|page=190|ref=harv}}</ref> It is considered to be highly effective in dogs, and has been established as safe for at least short-term use.<ref>{{cite book|url=https://books.google.com/books?id=NmziBQAAQBAJ&pg=PA1765|title=Clinical Veterinary Advisor - E-Book: Dogs and Cats|last=Cote|first=Etienne|publisher=Elsevier Health Sciences|year=2014|isbn=978-0-323-24074-1|page=1765|ref=harv}}</ref><ref name=falk>{{cite journal|last1=Falk|first1=Elisabeth|last2=Ferrer|first2=Lluís|date=December 2015|title=Oclacitinib|url=https://www.cliniciansbrief.com/sites/default/files/attachments/MEDS_Oclacitinib.pdf|journal=Clinician's Brief|ref=harv}}</ref><ref>{{cite web|url=https://www.merckvetmanual.com/integumentary-system/atopic-dermatitis/canine-atopic-dermatitis|title=Canine Atopic Dermatitis|last=Moriello|first=Karen|work=Merck Veterinary Manual|accessdate=27 February 2018}}</ref> Its efficacy equals that of prednisolone at first, though oclacitinib has been found to be more effective in the long term in terms of itchiness and dermatitis.<ref name=papich>{{cite book|url=https://books.google.com/books?id=ip8_CwAAQBAJ&pg=PA574|title=Saunders Handbook of Veterinary Drugs: Small and Large Animal|last=Papich|first=Mark G.|publisher=Elsevier Health Sciences|year=2015|isbn=978-0-323-24485-5|page=574|ref=harv}}</ref> It has been found to have a faster onset and cause less gastrointestinal issues than cyclosporine.<ref name=falk /><ref>{{cite book|url=https://books.google.com/books?id=YdREDwAAQBAJ&pg=PT2955|title=Veterinary Pharmacology and Therapeutics|last1=Riviere|first1=Jim E.|last2=Papich|first2=Mark G.|publisher=John Wiley & Sons|year=2017|isbn=978-1-118-85588-1|pages=2955-2966|ref=harv}}</ref>

While safe in the short term, oclacitinib's long-term safety is unknown.<ref name=falk /><ref name=sarid>{{cite journal|last1=Saridomichelakis|first1=Manolis N.|last2=Olivry|first2=Thierry|date=1 January 2016|title=An update on the treatment of canine atopic dermatitis|journal=The Veterinary Journal|volume=207|pages=29-37|doi=10.1016/j.tvjl.2015.09.016|issn=1090-0233|ref=harv}}</ref> While some say it is best only for acute flares of itchiness, others claim that it is also useful in chronic atopic dermatitis.<ref name=hnilica /><ref name=sarid />

There is some off-label use of oclacitinib in treating asthma and allergic dermatitis in cats, but the exact efficacy has not been established.<ref name=papich /><ref name=hnilica />

==Mechanism of action==
In isolated enzyme systems, oclacitinib was shown to inhibit JAK family members, most effectively JAK1, while not significantly inhibiting a variety of other non-JAK kinases, suggesting oclacitinib is a selective JAK inhibitor.<ref name="Gonzales" />
In isolated enzyme systems, oclacitinib was shown to inhibit JAK family members, most effectively JAK1, while not significantly inhibiting a variety of other non-JAK kinases, suggesting oclacitinib is a selective JAK inhibitor.<ref name="Gonzales" />
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Revision as of 00:58, 28 February 2018

Oclacitinib
Clinical data
Trade namesApoquel
Other namesPF-03394197
Routes of
administration		By mouth (tablets)
ATCvet code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability89%
Protein binding66.3–69.7%
Elimination half-life3.1–5.2 hours[1]
Identifiers
  • N-Methyl{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin- 4-yl)amino]cyclohexyl}methanesulfonamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC15H23N5O2S
Molar mass337.44 g·mol−1
3D model (JSmol)
  • CNS(=O)(=O)C[C@@H]1CC[C@H](CC1)N(C)c2[nH]cnc3nccc23
  • InChI=1S/C15H23N5O2S/c1-16-23(21,22)9-11-3-5-12(6-4-11)20(2)15-13-7-8-17-14(13)18-10-19-15/h7-8,10-12,16H,3-6,9H2,1-2H3,(H,17,18,19)/t11-,12-
  • Key:HJWLJNBZVZDLAQ-HAQNSBGRSA-N

Oclacitinib (brand name Apoquel) is a veterinary medication used in the control of pruritus associated with allergic dermatitis and the control of atopic dermatitis in dogs at least 12 months of age.[1][2] Chemically, it is a cyclohexylamino pyrrolopyrimidine janus kinase inhibitor that is relatively selective for JAK1 (IC50 = 10 nM).[3]

Uses

Oclacitinib is labeled to treat atopic dermatitis and itchiness (pruritus) caused by allergies in dogs, though it has also been used to reduce the itchiness and dermatitis caused by flea infestations.[4][5] It is considered to be highly effective in dogs, and has been established as safe for at least short-term use.[6][7][8] Its efficacy equals that of prednisolone at first, though oclacitinib has been found to be more effective in the long term in terms of itchiness and dermatitis.[9] It has been found to have a faster onset and cause less gastrointestinal issues than cyclosporine.[7][10]

While safe in the short term, oclacitinib's long-term safety is unknown.[7][11] While some say it is best only for acute flares of itchiness, others claim that it is also useful in chronic atopic dermatitis.[5][11]

There is some off-label use of oclacitinib in treating asthma and allergic dermatitis in cats, but the exact efficacy has not been established.[9][5]

Mechanism of action

In isolated enzyme systems, oclacitinib was shown to inhibit JAK family members, most effectively JAK1, while not significantly inhibiting a variety of other non-JAK kinases, suggesting oclacitinib is a selective JAK inhibitor.[3]

Assay Mean IC50 ± SE (nM)
JAK1 10 ± 1
JAK2 18 ± 2
JAK3 99 ± 20
TYK2 84 ± 12

References

  1. ^ a b "Apoquel (oclacitinib maleate tablet) Full Prescribing Information" (PDF). Zoetis Inc. Kalamazoo, MI 49007. Retrieved 23 February 2017.
  2. ^ "FDA Approves Apoquel (oclacitinib tablet) to Control Itch and Inflammation in Allergic Dogs". Zoetis. 16 May 2013. Retrieved 23 February 2017.
  3. ^ a b Gonzales, AJ; Bowman, JW; Fici, GJ; Zhang, M; Mann, DW; Mitton-Fry, M (August 2014). "Oclacitinib (Apoquel®) Is a Novel Janus Kinase Inhibitor with Activity Against Cytokines Involved in Allergy". Journal of Veterinary Pharmacology and Therapeutics. 37 (4): 317–24. doi:10.1111/jvp.12101. PMC 4265276. PMID 24495176.
  4. ^ Cowan, Alan; Yosipovitch, Gil (2015). Pharmacology of Itch. Springer. pp. 363–364. ISBN 978-3-662-44605-8. {{cite book}}: Invalid |ref=harv (help)
  5. ^ a b c Hnilica, Keith A.; Patterson, Adam P. (2016). Small Animal Dermatology - E-Book: A Color Atlas and Therapeutic Guide. Elsevier Health Sciences. p. 190. ISBN 978-0-323-39067-5. {{cite book}}: Invalid |ref=harv (help)
  6. ^ Cote, Etienne (2014). Clinical Veterinary Advisor - E-Book: Dogs and Cats. Elsevier Health Sciences. p. 1765. ISBN 978-0-323-24074-1. {{cite book}}: Invalid |ref=harv (help)
  7. ^ a b c Falk, Elisabeth; Ferrer, Lluís (December 2015). "Oclacitinib" (PDF). Clinician's Brief. {{cite journal}}: Invalid |ref=harv (help)
  8. ^ Moriello, Karen. "Canine Atopic Dermatitis". Merck Veterinary Manual. Retrieved 27 February 2018.
  9. ^ a b Papich, Mark G. (2015). Saunders Handbook of Veterinary Drugs: Small and Large Animal. Elsevier Health Sciences. p. 574. ISBN 978-0-323-24485-5. {{cite book}}: Invalid |ref=harv (help)
  10. ^ Riviere, Jim E.; Papich, Mark G. (2017). Veterinary Pharmacology and Therapeutics. John Wiley & Sons. pp. 2955–2966. ISBN 978-1-118-85588-1. {{cite book}}: Invalid |ref=harv (help)
  11. ^ a b Saridomichelakis, Manolis N.; Olivry, Thierry (1 January 2016). "An update on the treatment of canine atopic dermatitis". The Veterinary Journal. 207: 29–37. doi:10.1016/j.tvjl.2015.09.016. ISSN 1090-0233. {{cite journal}}: Invalid |ref=harv (help)

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