Oclacitinib

Overview

Oclacitinib, sold under the brand name Apoquel among others, is a veterinary medication used in the control of atopic dermatitis and pruritus from allergic dermatitis in dogs at least 12 months of age. Chemically, it is a synthetic cyclohexylamino-pyrrolopyrimidine Janus kinase inhibitor (JAK inhibitor) that is relatively selective for JAK1. It inhibits signal transduction when the JAK is activated and thereby helps downregulate expression of inflammatory cytokine.[1][2][3] WP⚠ Part of this sentence could not be copied from the source. Open the source to read it in full.

Oclacitinib was approved for use in the United States in 2013 and in the European Union in 2023. A flavored chewable form was approved for use in the United States in 2023.[2][4][5][6] WP

Drug class

JAK inhibitor WP

From the Wikipedia article's infobox.

Uses, dosage and effects

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. While some say it is best only for acute flares of itchiness, others claim that it is also useful in chronic atopic dermatitis. It is considered to be highly effective in dogs and has been established as safe for at least short-term use. Its efficacy is comparable to prednisolone early in treatment, and although oclacitinib has been shown to be more effective in the short term for itchiness and dermatitis, its long-term safety is incompletely established. It has been found to have a faster onset and cause less gastrointestinal issues than cyclosporine. There is some off-label use of oclacitinib to treat asthma and allergic dermatitis in cats, but its efficacy has not been established.[7–14] WP⚠ Wikipedia itself has flagged this text: weasel inline.

Risks and side effects

Contraindications

Oclacitinib is not labeled for use in dogs younger than one year due to reports of it causing demodicosis. It should also be avoided in dogs less than 3 kg. Most of the other contraindications are avoiding cases where a potential side effect exacerbates a pre-existing condition: for example, because oclacitinib can cause lumps or tumors, it should not be used in dogs with cancer or a history of it; because it is an immune system suppressant, it should not be used in dogs with serious infections.[11][14][15] WP⚠ The source also gives this in other units.

Oclacitinib, by virtue of its low plasma protein binding, has little chance of reacting with other drugs. Nonetheless, concurrent use of steroids and oclacitinib has not been tested and is thus not recommended.[11] WP

Side effects

Oclacitinib lacks the side effects that most JAK inhibitors have in humans; instead, side effects are infrequent, mild, and mostly self-limiting. The most common side effects are gastrointestinal problems (vomiting, diarrhea, and appetite loss) and lethargy. The GI problems can sometimes be alleviated by giving oclacitinib with food. New cutaneous or subcutaneous lumps, such as papillomas, can appear, and dogs face an increased susceptibility to infections such as demodicosis. There is a transient decrease in neutrophils, eosinophils, and monocytes, as well as in serum globulin, while cholesterol and lipase levels increase. The decrease in white blood cells lasts only around 14 days. None of the increases or decreases are clinically significant (i.e. none push their corresponding values out of normal ranges).[1][9][11][14–18] WP

Less common side effects of oclacitinib include bloody diarrhea; pneumonia; infections of the skin, ear, and/or urinary tract; and histiocytomas (benign tumors). Increases in appetite, aggression, and thirst have also been reported.[11][15] WP

Pharmacology

Mechanism of action

Oclacitinib is not a corticosteroid or antihistamine, but rather modulates the production of signal molecules called cytokines in some cells. Normally, a cytokine binds to a JAK (Janus kinase) receptor, driving the two individual chains to come together and self-phosphorylate. This brings in STAT proteins, which are activated and then go to the nucleus to increase transcription of genes coding for cytokines, thus increasing cytokine production.[14][19] WP

Oclacitinib inhibits signal JAK family members (JAK1, JAK2, JAK3, and tyrosine kinase 2), most effectively JAK1, while not significantly inhibiting non-JAK kinases.[3][19] WP⚠ A table follows this text in the source and is not copied here. Open the source to see it.

This causes the inhibition of pro-inflammatory and pruritogenic (itch-causing) cytokines that depend on JAK1 and JAK3, which include IL-2, IL-4, IL-6, IL-13, and IL-31 (TSLP, another pruritogenic cytokine that uses JAKs, has also been found to be inhibited). IL-31 is a key cytokine at the pruritogenic receptors at neurons near the skin, and also induces peripheral blood mononuclear cells and keratinocytes to release pro-inflammatory cytokines. Suppression of IL-4 and IL-13 causes a decrease of Tₕ2-cell differentiation, which plays a role in atopic dermatitis. Oclacitinib's relatively little effect on JAK2 prevent it from suppressing hematopoiesis or the innate immune response.[1][7][13][14][16][19][20][21] WP

Oclacitinib inhibits JAK, not the pruritogenic cytokines themselves; studies in mice showed that suddenly stopping the medication caused an increase in itchiness caused by a rebound effect, where more cytokines were produced to overcome lack of response by JAK.[21] WP

Pharmacokinetics

Oclacitinib is absorbed well when taken orally; it takes less than an hour to reach peak plasma concentration and has a bioavailability of 89%. In most dogs, pruritus begins to subside within four hours and is completely gone within 24. Oclacitinib is cleared mostly by being metabolized in the liver, though there is some kidney and bile duct clearance as well.[1] WP

Chemistry

Formula

C15H23N5O2S PC

CAS number

1208319-26-9 PC

Molar mass (g/mol)

337.4 PC

IUPAC name (computed by PubChem)

N-methyl-1-[4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl]methanesulfonamide PC

SMILES

CNS(=O)(=O)CC1CCC(CC1)N(C)C2=NC=NC3=C2C=CN3 PC

InChIKey

HJWLJNBZVZDLAQ-UHFFFAOYSA-N PC

PubChem CID

44631938

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Apoquel- oclacitinib maleate tablet, coated. 28 July 2021
2. Other FDA Approves Apoquel (oclacitinib tablet) to Control Itch and Inflammation in Allergic Dogs. 16 May 2013
3. Journal / agency Gonzales AJ, Bowman JW, Fici GJ, Zhang M, Mann DW, Mitton-Fry M. Oclacitinib (Apoquel) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy. Journal of Veterinary Pharmacology and Therapeutics. August 2014. doi:10.1111/jvp.12101 · PMID 24495176 · PMC4265276
4. Journal / agency Prolevare EPAR. 17 February 2023
5. Other Prolevare Film-coated tablet. 23 April 2023
6. Journal / agency Preventing Accidental Apoquel Chewable Overdoses. 2026-07-02
7. Other Cowan A, Yosipovitch G. Pharmacology of Itch. 2015
8. Other Hnilica KA, Patterson AP. Small Animal Dermatology - E-Book: A Color Atlas and Therapeutic Guide. 2016
9. Journal / agency Saridomichelakis MN, Olivry T. An update on the treatment of canine atopic dermatitis. Veterinary Journal. January 2016. doi:10.1016/j.tvjl.2015.09.016 · PMID 26586215
10. Other Cote E. Clinical Veterinary Advisor - E-Book: Dogs and Cats. 2014
11. Journal / agency Falk E, Ferrer L. Oclacitinib. Clinician's Brief. December 2015
12. Other Moriello K. Canine Atopic Dermatitis
13. Other Papich MG. Saunders Handbook of Veterinary Drugs: Small and Large Animal. 2015
14. Other Riviere JE, Papich MG. Veterinary Pharmacology and Therapeutics. 2017
15. Other Barnette C. Oclacitinib. 2017
16. Other Layne EA, Moriello KA. What's new with an old problem: Drug options for treating the itch of canine allergy. 1 April 2015
17. Journal / agency Apoquel, INN-oclacitinib maleate
18. Journal / agency Cosgrove SB, Wren JA, Cleaver DM, Walsh KF, Follis SI, King VI, Tena JK, Stegemann MR. A blinded, randomized, placebo-controlled trial of the efficacy and safety of the Janus kinase inhibitor oclacitinib (Apoquel) in client-owned dogs with atopic dermatitis. Veterinary Dermatology. December 2013. doi:10.1111/vde.12088 · PMID 24581322 · PMC4286885
19. Journal / agency Damsky W, King BA. JAK inhibitors in dermatology: The promise of a new drug class. Journal of the American Academy of Dermatology. April 2017. doi:10.1016/j.jaad.2016.12.005 · PMID 28139263 · PMC6035868
20. Journal / agency Olivry T, Mayhew D, Paps JS, Linder KE, Peredo C, Rajpal D, Hofland H, Cote-Sierra J. Early Activation of Th2/Th22 Inflammatory and Pruritogenic Pathways in Acute Canine Atopic Dermatitis Skin Lesions. The Journal of Investigative Dermatology. October 2016. doi:10.1016/j.jid.2016.05.117 · PMID 27342734
21. Journal / agency Fukuyama T, Ganchingco JR, Bäumer W. Demonstration of rebound phenomenon following abrupt withdrawal of the JAK1 inhibitor oclacitinib. European Journal of Pharmacology. January 2017. doi:10.1016/j.ejphar.2016.11.020 · PMID 27847179

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