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| Clinical data | |
|---|---|
| Trade names | Apoquel |
| Other names | PF-03394197 |
| AHFS/Drugs.com | Veterinary Use |
| Routes of administration | By mouth |
| Drug class | JAK inhibitor |
| ATCvet code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 89%[1] |
| Protein binding | 66.3–69.7%[1] |
| Metabolism | Liver[1] |
| Eliminationhalf-life | 3.1–5.2 hours[1] |
| Excretion | Mostly liver[1] |
| Identifiers | |
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| CAS Number | |
| PubChemCID | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| Chemical and physical data | |
| Formula | C15H23N5O2S |
| Molar mass | 337.44 g·mol−1 |
| 3D model (JSmol) | |
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Oclacitinib, sold under the brand nameApoquel among others, is aveterinary medication used in the control ofatopic dermatitis andpruritus from allergicdermatitis in dogs at least 12 months of age.[1][4] Chemically, it is a synthetic cyclohexylamino pyrrolopyrimidinejanus kinase inhibitor that is relatively selective forJAK1.[5] It inhibitssignal transduction when the JAK is activated and thus helpsdownregulate expression ofinflammatory cytokines.[medical citation needed]
Oclacitinib was approved for use in the United States in 2013,[4] and in the European Union in 2023.[2][6]
Oclacitinib is labeled to treatatopic dermatitis anditchiness (pruritus) caused byallergies in dogs, though it has also been used to reduce the itchiness anddermatitis caused byflea infestations.[7][8] It is considered to be highly effective in dogs, and has been established as safe for at least short-term use.[9][10][11] Its efficacy equals that ofprednisolone at first, though oclacitinib has been found to be more effective in the short term in terms of itchiness and dermatitis, long term safety is unknown.[12] It has been found to have a faster onset and cause less gastrointestinal issues thancyclosporine.[10][13]
While safe in the short term, oclacitinib's long-term safety is unknown.[10][14] While some say it is best only for acute flares of itchiness, others claim that it is also useful in chronic atopic dermatitis.[8][14]
There is some off-label use of oclacitinib in treatingasthma and allergic dermatitis in cats, but the exact efficacy has not been established.[12][8]
Oclacitinib is not labeled for use in dogs younger than one due to reports of it causingdemodicosis.[13] It should also be avoided in dogs less than 3 kg (6.6 lb). 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 ortumors, it should not be used in dogs withcancer or a history of it;[15] because it is animmune system suppressant, it should not be used in dogs with serious infections.[10]
Oclacitinib, by virtue of its lowplasma protein binding, has little chance of reacting with other drugs. Nonetheless, concurrent use ofsteroids and oclacitinib has not been tested and is thus not recommended.[10]
Oclacitinib lacks the side effects that most JAK inhibitors have in humans; instead, side effects are infrequent, mild, and mostly self-limiting.[13][14][16] The most common side effects aregastrointestinal problems (vomiting,diarrhea, andappetite loss) andlethargy. The GI problems can sometimes be alleviated by giving oclacitinib with food.[10][15] Newcutaneous orsubcutaneous lumps, such aspapillomas, can appear,[10][17] and dogs face an increased susceptibility to infections such as demodicosis.[1][15] There is a transient decrease inneutrophils,eosinophils, andmonocytes, as well as in serumglobulin, whilecholesterol andlipase levels increase. The decrease inwhite 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][17][18]
Less common side effects of oclacitinib include bloody diarrhea;pneumonia; infections of theskin,ear, and/orurinary tract; andhistiocytomas (benign tumors). Increases in appetite, aggression, andthirst have also been reported.[10][15]
Oclacitinib is not acorticosteroid orantihistamine, but rather modulates the production of signal molecules calledcytokines in some cells.[13] Normally, a cytokine binds to aJAK (Janus kinase) receptor, driving the two individual chains to come together and self-phosphorylate. This brings inSTAT proteins, which are activated and then go to the nucleus to increasetranscription of genes coding for cytokines, thus increasing cytokine production.[19]
Oclacitinib inhibits signal JAK family members (JAK1,JAK2,JAK3, andtyrosine kinase 2), most effectively JAK1, while not significantly inhibiting non-JAK kinases.[5][19]
| Receptor | MeanIC50 (nM) |
|---|---|
| JAK1 | 10 |
| JAK2 | 18 |
| JAK3 | 99 |
| TYK2 | 84 |
This causes the inhibition of pro-inflammatory and pruritogenic (itch-causing) cytokines that depend on JAK1 and JAK3, which includeIL-2,IL-4,IL-6,IL-13, andIL-31[1][12][13] (TSLP, another pruritogenic cytokine that uses JAKs, has also been found to be inhibited).[20][21] IL-31 is a key cytokine at the pruritogenic receptors at neurons near the skin, and also inducesperipheral blood mononuclear cells andkeratinocytes to release pro-inflammatory cytokines.[16] Suppression of IL-4 and IL-13 causes a decrease ofTh2-cell differentiation, which plays a role in atopic dermatitis.[19] Oclacitinib's relatively little effect on JAK2 prevent it from suppressinghematopoiesis or theinnate immune response.[7][13]
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]
Oclacitinib is absorbed well when taken orally; it takes less than an hour to reach peak plasma concentration and has abioavailability of 89%.[1] In most dogs, pruritus begins to subside within four hours and is completely gone within 24. Oclacitinib is cleared mostly by being metabolized in theliver, though there is somekidney andbile duct clearance as well.[1]
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