Abrocitinib (Monograph)

Brand name: Cibinqo
Drug class: Skin and Mucous Membrane Agents, Miscellaneous
Chemical name: N-[3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl]propane-1-sulfonamide
Molecular formula: C₁₄H₂₁N₅O₂S
CAS number: 1622902-68-4

Medically reviewed by Drugs.com on Dec 1, 2022. Written by ASHP.

Introduction

Janus kinase (JAK) inhibitor.

Uses for Abrocitinib

Atopic Dermatitis

Treatment of adults with refractory, moderate to severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

Not recommended in combination with other Janus kinase (JAK) inhibitors, biologic immunomodulators, or with other immunosuppressants.

Abrocitinib Dosage and Administration

General

Pretreatment Screening

• Consider the risks and benefits of treatment prior to initiating abrocitinib in patients with chronic or recurrent infection, patients who have been exposed to tuberculosis, patients with a history of a serious or an opportunistic infection, patients who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, and patients with underlying conditions that may predispose them to infection.

• Evaluate for active and latent tuberculosis infection prior to initiating therapy. Abrocitinib is not recommended in patients with active tuberculosis. For patients with latent tuberculosis or those with a negative latent tuberculosis test who are at high risk for tuberculosis, start preventive therapy for latent tuberculosis prior to initiation of abrocitinib.

• Screen for viral hepatitis; abrocitinib is not recommended for patients with active hepatitis B (HBV) or hepatitis C (HBC).

• Perform complete blood count (CBC). Abrocitinib is not recommended in patients with platelet count <150,000/mm³, absolute lymphocyte count <500/mm³, absolute neutrophil count <1000/mm³, or hemoglobin <8 g/dL.

• Complete any necessary immunizations, including herpes zoster vaccinations, in accordance with current immunization guidelines prior to initiation of therapy.

Patient Monitoring

• Perform CBC 4 weeks after start of treatment and 4 weeks after dosage increase. May extend laboratory evaluations for patients on chronic therapy who develop hematologic abnormalities.

• Monitor for signs and symptoms of infection during and after treatment. Discontinue abrocitinib for serious or opportunistic infections and initiate appropriate diagnostic tests and antimicrobial therapy.

• Monitor all patients for active tuberculosis during treatment even in patients with an initial negative latent tuberculosis test.

• Consider yearly screening for tuberculosis in patients living in highly endemic areas for tuberculosis.

• Perform viral hepatitis screening and monitoring for reactivation of hepatitis during therapy according to clinical guidelines.

• Monitor patients with inactive HBV for expression of HBV DNA. Consult a liver specialist if HBV DNA is detected during therapy.

• Perform periodic skin examinations in patients at increased risk for skin cancers.

• Assess lipid profile approximately 4 weeks after start of therapy; manage hyperlipidemia according to current guidelines.

Administration

Oral Administration

Administer orally once daily without regard to meals at approximately the same time each day.

Swallow tablets whole with water; do not crush, split, or chew.

If a dose is missed, administer the dose as soon as possible unless it is less than 12 hours before the next dose; if it is less than 12 hours until the next dose, skip the missed dose and resume abrocitinib at the regular scheduled time.

Dosage

Adults

Atopic Dermatitis

Oral

100 mg once daily. Dosage can be increased to 200 mg once daily if response is inadequate after 12 weeks. Discontinue therapy if inadequate response at the higher dosage.

May be used with or without topical corticosteroids.

Dosage Modification for Toxicity

Oral

Dosing interruption, dosage reduction, and/or discontinuance of therapy may be necessary for hematologic abnormalities as described in Table 1.

Concomitant Use of Drugs or Foods Affecting Hepatic Microsomal Enzymes

Reduce dosage to 50 mg once daily with concurrent strong CYP2C19 inhibitors. If no response is seen after 12 weeks, dosage of abrocitinib may be increased to 100 mg once daily. Discontinue treatment if an adequate response is not seen with the increased dosage.

Avoid concurrent use of drugs that are strong inhibitors of both CYP2C19 and CYP2C9.

Avoid concurrent use of drugs that are strong inducers of CYP2C19 or CYP2C9.

Special Populations

Hepatic Impairment

Not recommended in patients with severe (Child-Pugh class C) hepatic impairment. Dosage adjustment not needed in mild (Child-Pugh class A) to moderate (Child-Pugh class B) hepatic impairment.

Renal Impairment

Dosage adjustment required in patients with renal impairment as described in Table 2. For patients with mild or moderate renal impairment, dosage may be doubled if an adequate response is not seen after 12 weeks.

Poor Metabolizers of CYP2C19

For patients known or suspected to be CYP2C19 poor metabolizers, the recommended dosage of abrocitinib is 50 mg once daily. If no response is seen after 12 weeks of treatment, dosage may be increased to 100 mg once daily.

Geriatric Patients

No specific dosage recommendations.

Cautions for Abrocitinib

Contraindications

• Antiplatelet therapies, except for low-dose aspirin (<81 mg daily), during the first 3 months of treatment.

Warnings/Precautions

Warnings

Boxed warnings about the risk of serious infections, a higher rate of all-cause mortality, malignancies, major adverse cardiovascular events (MACE), and thrombosis are included in the prescribing information for abrocitinib.

Serious Infections

Serious bacterial, fungal, viral, or opportunistic infections, which may lead to hospitalization or death, may occur. (See Boxed Warning.) Closely monitor patients for signs and symptoms of infection during and after treatment with abrocitinib; discontinue drug if serious or opportunistic infections occur. Initiate complete diagnostic testing and appropriate antimicrobial therapy. Consider risks and benefits prior to reinitiating therapy.

Avoid use in patients with active, serious infection, including localized infections.

Tuberculosis

Evaluate and test patients for latent tuberculosis before and during treatment and treat if necessary prior to using abrocitinib. Monitor for active tuberculosis during treatment with abrocitinib, even if initial testing was negative.

Viral Reactivation

Viral reactivation, including herpes virus reactivation, reported. Consider interrupting therapy for development of herpes zoster until the episode resolves.

HBV reactivation reported with JAK inhibitors. Screen for hepatitis and monitor for reactivation based on available guidelines before and during therapy.

Not recommended in patients with active HBV or HCV.

Monitor for expression of HBV DNA in patients with inactive HBV. Consult a liver specialist if HBV DNA is detected during therapy.

Mortality

Another JAK inhibitor used for rheumatoid arthritis associated with a higher risk of all-cause mortality. (See Boxed Warning.)

Abrocitinib is not approved for use in rheumatoid arthritis.

Consider the benefits and risks of abrocitinib for the individual patient prior to initiating or continuing therapy with the drug.

Malignancies

Malignancies, including non-melanoma skin cancer, reported with abrocitinib. (See Boxed Warning.) Other JAK inhibitors used to treat inflammatory conditions associated with a higher rate of malignancies, including lymphoma, compared with TNF blockers. Current or former smokers may be at higher risk.

Perform skin examination in patients at increased risk for skin cancers periodically. Limit exposure to sunlight and UV light by wearing protective clothing and using broad-spectrum sunscreen.

Consider benefits and risks of abrocitinib prior to initiating or continuing therapy, particularly in patients with a known malignancy, patients who develop a malignancy while on treatment, and patients who are current or past smokers.

Major Adverse Cardiovascular Events

Risk of major adverse cardiovascular events (MACE), defined as cardiovascular death, non-fatal MI, and non-fatal stroke. (See Boxed Warning.)

Consider benefits and risks of abrocitinib prior to initiating or continuing therapy, especially in current or past smokers and patients with other cardiovascular risk factors.

Discontinue abrocitinib in patients who have experienced MI or stroke.

Thrombosis

DVT and PE reported. (See Boxed Warning.) Avoid use in patients who may be at increased risk of thrombosis.

If symptoms of thrombosis occur, discontinue abrocitinib and evaluate and treat patients appropriately.

Other Warnings/Precautions

Hematologic Abnormalities

Thrombocytopenia and lymphopenia reported. CBC evaluations are recommended prior to initiation of abrocitinib therapy, at 4 weeks after initiation, and at 4 weeks after a dosage increase. Discontinue drug if reductions in platelets (below 50,000/mm³), lymphocytes (below 500/mm³), neutrophils (below 1000/mm³), and hemoglobin (below 8 g/dL) occur.

Lipid Elevations

Dose-dependent increase in blood lipid parameters have been reported, starting at week 4 and continuing over 16 weeks of treatment.

Assess lipid parameters approximately 4 weeks following initiation of abrocitinib therapy. Manage hyperlipidemia based on current clinical guidelines.

Immunizations

Complete all age-appropriate vaccinations, including herpes zoster vaccinations, prior to initiating abrocitinib treatment. Avoid vaccination with live vaccines immediately prior to, during, and immediately after abrocitinib therapy.

Retinal Detachment

During clinical trials, 3 cases of retinal detachment reported.

Creatine Phosphokinase (CPK) Elevations

Dose-related elevations in CPK, mostly transient, reported; no cases of rhabdomyolysis reported.

Fetal/Neonatal Morbidity and Mortality

In animal reproduction studies, skeletal variations, reduced offspring body weight, and decreased postnatal survival observed.

Specific Populations

Pregnancy

Data on use in pregnancy limited. A pregnancy exposure registry has been established. Pregnant females exposed to abrocitinib and health care providers are encouraged to call the pregnancy exposure registry at 877-311-3770.

Lactation

Data on distribution of abrocitinib into human milk, effects of abrocitinib on the breast-fed infant, or effects on milk production are lacking. Distributed into milk of lactating rats; therefore, likely present in human milk. Avoid breast-feed during therapy and for one day after drug discontinuance.

Females and Males of Reproductive Potential

May impair female fertility based on findings in rats. This effect was reversible in animal studies after 1 month after discontinuing therapy.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

In clinical trials, 4.6% of patients were ≥65 years of age, while 0.8% were ≥75 years of age. Clinical trials did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger adult patients.

Hepatic Impairment

Avoid use in patients with severe (Child-Pugh class C) hepatic impairment.

Dosage adjustment not required in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.

Renal Impairment

Not recommended in patients with severe renal impairment and end-stage renal disease, including those on renal replacement.

Dosage reduction recommended in moderate renal impairment. No dosage adjustment required in mild renal impairment (eGFR 60–89 mL/minute).

Common Adverse Effects

The most common adverse reactions (≥1%) in patients receiving abrocitinib 100 mg and 200 mg were nasopharyngitis, nausea, headache, herpes simplex, increased blood creatinine phosphokinase, dizziness, urinary tract infection, fatigue, acne, vomiting, oropharyngeal pain, influenza, and gastroenteritis.

The most common adverse reactions (≥1%) in patients receiving either 100 mg or 200 mg of abrocitinib were impetigo, hypertension, contact dermatitis, upper abdominal pain, abdominal discomfort, herpes zoster, and thrombocytopenia.

Drug Interactions

Metabolism mediated by multiple CYP enzymes, principally by CYP2C19 and CYP2C9.

Drugs Affecting Hepatic Microsomal Enzymes

Strong CYP2C19 inhibitors: Possible increased systemic exposure to abrocitinib and its active metabolites, M1 and M2, and increased toxicity. Dosage reduction recommended with concomitant use of strong CYP2C19 inhibitors.

Moderate to strong inhibitors of both CYP2C19 and CYP2C9: Possible increased systemic exposure to abrocitinib and its active metabolites, M1 and M2, and increased toxicity. Avoid concurrent use.

Strong inducers of CYP2C19 or CYP2C9: Possible decreased systemic exposure to abrocitinib and its active metabolites, M1 and M2, and reduced clinical response. Avoid concurrent use.

Substrates of P-glycoprotein (P-gp)

Possible increased systemic exposure to P-gp substrate, and increased adverse reactions, especially where small changes in concentrations (e.g., digoxin) may lead to serious toxicities. Monitor or titrate dosage of P-gp substrate.

Specific Drugs

Abrocitinib Pharmacokinetics

Absorption

Bioavailability

Following oral administration, peak plasma concentrations are attained within 1 hour.

Steady-state concentrations are achieved within 48 hours with once-daily administration.

Absolute bioavailability is approximately 60%.

Peak plasma concentrations and systemic exposure increase in a dose-proportional manner up to 200 mg.

Food

High-fat, high-caloric meal had no clinically relevant effect on abrocitinib exposure.

Special Populations

Mild hepatic impairment (Child-Pugh class A) decreased systemic exposure to abrocitinib and its metabolites (M1 and M2) by 4% and moderate impairment (Child-Pugh class B) had a 15% increase; both considered clinically insignificant.

Not studied in patients with severe hepatic impairment (Child-Pugh class C) or with active HBV or HCV.

Severe (eGFR <30 mL/minute) and moderate (eGFR 30–59 mL/minute) renal impairment increased AUC of abrocitinib and its active metabolites by 191 and 110%, respectively. No clinically significant increase in exposure expected with mild renal impairment (eGFR 60–89 mL/minute).

Not studied in patients on renal replacement therapy.

In CYP2C19 poor metabolizers, dose-normalized AUC is 2.3-fold higher compared with normal metabolizers.

Body weight, sex, race, and age do not have a clinically meaningful effect on abrocitinib exposure.

Distribution

Extent

Likely distributed into human milk.

Protein Binding

Approximately 64, 37, and 29% protein bound for abrocitinib, M1, and M2, respectively.

Elimination

Metabolism

Metabolized by multiple CYP enzymes: CYP2C19 (53%), CYP2C9 (30%), CYP3A4 (11%), and CYP2B6 (6%).

Elimination Route

Eliminated by metabolic clearance mechanisms. Abrocitinib and its metabolites are predominantly excreted in urine.

Half-life

Mean terminal half-lives of abrocitinib, M1, and M2: 3–5 hours.

Stability

Storage

Oral

Tablets

20–25°C (excursions permitted between 15 to 30°C).

Store in original container.

Actions

• Abrocitinib reversibly inhibits JAK1 by blocking the adenosine triphosphate (ATP) binding site.

• In a cell-free isolated enzyme assay, abrocitinib was selective for JAK1 over JAK2 (28-fold), JAK3 (>340-fold), and tyrosine kinase (TYK) 2 (43-fold), as well as the broader kinome. The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.

• Both the parent compound and the active metabolites (M1 and M2) inhibit JAK1 activity in vitro with similar levels of selectivity.

• Metabolite M1 is less active than abrocitinib; M2 is as active as abrocitinib.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (medication guide).

• Pregnancy registry: Advise patients to report pregnancy to 877-311-3770.

• Inform patients that they may develop infections when taking abrocitinib. Instruct patients to tell their healthcare provider if they develop any signs or symptoms of an infection.

• Advise patients that the risk of herpes zoster is increased in patients treated with abrocitinib and some cases can be serious.

• Inform patients that abrocitinib may increase their risk of certain cancers, including skin cancers. Periodic skin examinations are recommended while taking abrocitinib. Advise patients that exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum sunscreen.

• Inform patients that abrocitinib may increase their risk of major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular death. Instruct all patients, especially current or past smokers or patients with other cardiovascular risk factors, to be alert for the development of signs and symptoms of cardiovascular events.

• Advise patients that events of DVT and PE have been reported in clinical trials with abrocitinib. Instruct patients to seek immediate medical attention if they develop any signs or symptoms of a DVT or PE.

• Inform patients that abrocitinib may affect certain laboratory tests, and that blood tests are required before and during abrocitinib treatment.

• Advise patients that vaccination with live vaccines is not recommended during abrocitinib treatment and immediately prior to or after abrocitinib treatment. Instruct patients to inform their healthcare provider that they are taking abrocitinib prior to a potential vaccination.

• Inform patients that retinal detachment has been reported in clinical trials for atopic dermatitis in patients who received abrocitinib. Advise patients to immediately inform their healthcare provider if they develop any sudden changes in vision while receiving abrocitinib.

• Advise females of reproductive potential that abrocitinib may impair fertility.

• Advise females not to breastfeed during treatment with abrocitinib.

• Advise patients not to chew, crush, or split abrocitinib tablets.

• Advise patients of the importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, vitamins, and herbal supplements, as well as any concomitant illnesses.

• Advise patients of the importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

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