abrocitinib

Contraindicated in:

Concurrent use of antiplatelet therapies (excluding low-dose aspirin [≤81 mg/day]) for the first 3 mo of treatment;
Active infection;
Platelet count <150,000/mm³, lymphocyte count <500 cells/mm³, absolute neutrophil count <1000 cells/mm³, or hemoglobin level <8 g/dL;
Increased risk for thrombosis;
Severe renal impairment or end-stage renal disease;
Severe hepatic impairment;
Lactation: Lactation.

Use Cautiously in:

Patients who are >50 yr old and have ≥1 cardiovascular risk factor (↑ risk of all-cause mortality, cardiovascular death, MI, stroke, and thrombosis);
Chronic or recurrent infection;
Previously exposed to tuberculosis;
History of serious or opportunistic infection;
Resided or traveled in areas of endemic tuberculosis or endemic mycoses;
Underlying conditions that predispose to infection;
Malignancy (other than successfully treated non-melanoma skin cancer);
Known or suspected CYP2C19 poor metabolizers (↓ dose);
Moderate renal impairment (↓ dose);
OB: Other agents for atopic dermatitis preferred in pregnancy;
Pedi: Children <12 yr (safety and effectiveness not established);
Geri: Older adults may have ↑ risk of lymphopenia, thrombocytopenia, and herpes infection.

Adv. Reactions/Side Effects ⬆ ⬇

CV: CARDIOVASCULAR DEATH, DEEP VEIN THROMBOSIS (DVT), hypertension, MI

Derm: acne, contact dermatitis, impetigo

EENT: nasopharyngitis, retinal detachment

GI: nausea, abdominal pain, oropharyngeal pain, vomiting

Hemat: lymphopenia, thrombocytopenia

Metab: hyperlipidemia

MS: ↑creatine kinase

Neuro: dizziness, fatigue, headache

Resp: PULMONARY EMBOLISM (PE)

Misc: INFECTION (INCLUDING TUBERCULOSIS, BACTERIAL, INVASIVE FUNGAL, VIRAL, OR OPPORTUNISTIC INFECTIONS), MALIGNANCY (INCLUDING NON-MELANOMA SKIN CANCER)

Interactions ⬆ ⬇

Drug-drug:

May ↑ risk of bleeding and thrombocytopenia when used with antiplatelet drugs, excluding low-dose aspirin (≤81 mg/day); concurrent use during first 3 mo of abrocitinib contraindicated
Moderate-to-strong inhibitors of both CYP2C9 and CYP2C19, including fluconazole, significantly ↑ levels and risk of toxicity; avoid concurrent use.
Strong CYP2C9 inducers and strong CYP2C19 inducers, including rifampin, ↓ levels and effectiveness; avoid concurrent use.
Strong CYP2C19 inhibitors, including fluvoxamine, may ↑ levels and risk of toxicity; ↓ abrocitinib dose
May ↑ levels and risk of toxicity of P-glycoprotein substrates, including dabigatran; closely monitor.
May ↑ risk of adverse reactions and ↓ antibody response to live vaccines; avoid concurrent use.

Availability ⬆ ⬇

Tablets: 50 mg; 100 mg; 200 mg

Route/Dosage ⬆ ⬇

PO (Adults and Children ≥12 yr): 100 mg once daily initially; if adequate response not achieved after 12 wk, may ↑ to 200 mg once daily. Discontinue therapy if inadequate response after dose ↑ to 200 mg once daily. CYP2C19 poor metabolizers or concurrent use of strong CYP2C19 inhibitors: 50 mg once daily initially; if adequate response not achieved after 12 wk, may ↑ to 100 mg once daily. Discontinue therapy if inadequate response after dose ↑ to 100 mg once daily.

Renal Impairment

PO (Adults and Children ≥12 yr): Moderate renal impairment (CCr 30–59 mL/min): 50 mg once daily initially; if adequate response not achieved after 12 wk, may ↑ to 100 mg once daily. Discontinue therapy if inadequate response after dose ↑ to 100 mg once daily.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits JAK enzymes which prevents the signaling of interleukin-4, interleukin-13, and other cytokines involved in the pathogenesis of atopic dermatitis.

Therapeutic effects:

Improvement in clinical and symptomatic parameters of atopic dermatitis.

Classifications ⬆ ⬇

Therapeutic Classification: anti-inflammatories

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP2C19, CYP2C9, CYP3A4, and CYP2B6 isoenzymes into two active metabolites (M1 and M2). 2% of Whites, 4% of Blacks, and 14% of Asians have CYP2C19 genotype that results in reduced metabolism of abrocitinib. Primarily excreted in urine (<1% as unchanged drug).

Half-Life: 3–5 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	rapid	<1 hr	unknown

Patient/Family Teaching ⬆ ⬇

Instruct patient to take abrocitinib as directed. Take missed dose as soon as possible unless <12 hrs before next dose. If <12 hrs before next dose, omit dose and resume dosing at the regular scheduled time.
Advise patient to notify health care professional if signs and symptoms of infection (fever, sweating, or chills, blood in phlegm, diarrhea or stomach pain, muscle aches, weight loss, burning during urination or urinating more often than usual, cough or shortness of breath, warm, red, or painful skin or sores on body, feeling very tired).
Caution patients with signs and symptoms of a heart attack or stroke (discomfort in the center of chest that lasts for more than a few minutes, or that goes away and comes back; severe tightness, pain, pressure, or heaviness in chest, throat, neck, or jaw; pain or discomfort in arms, back, neck, jaw, or stomach; weakness in one part or on one side of your body; slurred speech; shortness of breath with or without chest discomfort; breaking out in a cold sweat; nausea or vomiting; feeling lightheaded) to notify health care professional immediately.
Inform patient of increased risk of DVT and pulmonary embolism. If signs and symptoms (swelling, pain or tenderness in one or both legs; sudden, unexplained chest or upper back pain; shortness of breath or difficulty breathing) occur, stop therapy and get immediate medical care. Notify health care professional if you have had blood clots in the veins of your legs or lungs in the past.
May increase risk of cancer. Advise patient to have skin checked for skin cancer during therapy. Limit amount of time spent in sunlight. Avoid using tanning beds or sunlamps. Wear protective clothing and use sunscreen with a high protection factor (SPF 30 and above). Especially important for patients with very fair skin or with a family history of skin cancer. Instruct patient to notify health care professional if you have ever had any type of cancer.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected. Advise to avoid breastfeeding during and for 1 day after last dose. May impair female fertility; may be reversible. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to abrocitinib during pregnancy. Pregnant women exposed to abrocitinib and health care providers are encouraged to call 1- 877-311-3770 or www.cibinqopregnancyregistry.com.

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Indications ⬇

Contraind./Precautions ⬆ ⬇