Drug Monograph
Cibinqo (Abrocitinib)
abrocitinib
Pharmacokinetic Profile
Half-Life
3–5 h (parent & active metabolites)
Metabolism
CYP2C19 (53%), CYP2C9 (30%), CYP3A4 (11%)
Protein Binding
~64% (parent)
Bioavailability
~60%
Volume of Distribution
~100 L
Clinical Information
Drug Class
Selective JAK1 Inhibitor
Available Doses
50 mg, 100 mg, 200 mg tablets
Route
Oral (once daily)
Renal Adjustment
Yes — reduce in moderate impairment; avoid in severe
Hepatic Adjustment
None for mild/moderate; avoid in severe (Child-Pugh C)
Pregnancy
Insufficient data; animal studies show skeletal variations
Lactation
Not recommended
Schedule / Legal Status
Prescription only (not a controlled substance)
Generic Available
No
Black Box Warning
Yes — infections, mortality, malignancy, MACE, thrombosis
Abrocitinib Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Refractory moderate-to-severe atopic dermatitis | Adults and adolescents ≥12 years (≥25 kg) | Monotherapy or combination with topical corticosteroids | FDA Approved |
Abrocitinib is positioned as a treatment option for patients whose atopic dermatitis has not responded adequately to other systemic therapies, including biologics, or for whom those treatments are not advisable. The FDA approved the drug for adults in January 2022 and expanded the indication to include adolescents aged 12 to less than 18 years in February 2023, based on the JADE clinical trial programme. It is not intended for first-line systemic therapy and should not be combined with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.
Off-Label Uses Under Investigation
Chronic hand eczema: Early case series suggest benefit in refractory hand dermatitis. Evidence quality: very low.
Other inflammatory dermatoses (vitiligo, alopecia areata): Preliminary reports exist but no controlled trial data are available for abrocitinib specifically. Evidence quality: very low.
Abrocitinib Dosing
Adult and Adolescent Dosing (≥12 years, ≥25 kg)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Moderate-to-severe AD — standard initiation | 100 mg QD | 100 mg QD | 200 mg/day | Increase to 200 mg QD if inadequate response at 100 mg Use lowest effective dose to maintain response |
| AD refractory to 100 mg — dose escalation | 200 mg QD | 200 mg QD | 200 mg/day | Discontinue if inadequate response persists at 200 mg Consider stepping down to 100 mg once response is achieved |
| Moderate renal impairment (eGFR 30–59 mL/min) | 50 mg QD | 50 mg QD | 100 mg/day | If inadequate response at 50 mg, may increase to 100 mg QD Avoid in severe renal impairment (eGFR <30) or ESRD |
| Mild renal impairment (eGFR 60–89 mL/min) | 100 mg QD | 100 mg QD | 200 mg/day | Standard dosing applies; may escalate if needed |
| CYP2C19 poor metabolizer (known or suspected) | 50 mg QD | 50 mg QD | 100 mg/day | 2.3-fold higher AUC in poor metabolizers Discontinue if inadequate response at 100 mg |
| Co-administration with strong CYP2C19 inhibitor (e.g., fluvoxamine) | 50 mg QD | 50 mg QD | 100 mg/day | Applies to strong CYP2C19-only inhibitors; may increase to 100 mg if inadequate response Avoid moderate/strong dual CYP2C19 + CYP2C9 inhibitors (e.g., fluconazole) — exposure increases ~4.8-fold |
Clinical Pearl: Administration
Abrocitinib may be taken with or without food. However, phase I data suggest that gastrointestinal symptoms—particularly nausea—occur more frequently in the fasted state and may be mitigated by administering with food. Tablets must be swallowed whole and not crushed, split, or chewed.
Pharmacology
Mechanism of Action
Abrocitinib is a small-molecule inhibitor that reversibly and selectively blocks Janus kinase 1 (JAK1) by occupying the adenosine triphosphate (ATP) binding site. In cell-free enzyme assays, it demonstrates selectivity for JAK1 over JAK2 (28-fold), JAK3 (greater than 340-fold), and TYK2 (43-fold). By inhibiting JAK1, abrocitinib disrupts the JAK-STAT signalling cascade for multiple cytokines implicated in atopic dermatitis pathophysiology, including interleukin-4, interleukin-13, interleukin-31, interleukin-22, and thymic stromal lymphopoietin (TSLP). This dampens Th2-driven inflammation, reduces pruritus signalling through neuronal JAK1 pathways, and improves skin barrier integrity. Both the parent compound and its two active metabolites (M1 and M2) contribute to pharmacological activity with comparable JAK1 selectivity.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Oral absorption >90%; F ~60%; Tmax ~1 h | Rapid onset of action; high absorption but significant first-pass metabolism; food does not meaningfully affect exposure |
| Distribution | Vd ~100 L; protein binding ~64% (parent), 37% (M1), 29% (M2); bound predominantly to albumin | Distributes equally between red blood cells and plasma; large Vd suggests extensive tissue distribution |
| Metabolism | CYP2C19 (53%), CYP2C9 (30%), CYP3A4 (11%), CYP2B6 (~6%); active metabolites M1 and M2 | CYP2C19 poor metabolizers require dose reduction; M2 has potency comparable to parent; M1 is less active |
| Elimination | t½ 3–5 h; ~85% renal (metabolites); systemic clearance 64.2 L/h | Short half-life requires once-daily dosing; steady state by day 4; no metabolite accumulation with once-daily dosing |
Side Effects
Side effect data are derived from the integrated placebo-controlled clinical trial programme (n = 1,540 in the placebo-controlled cohort; up to 16 weeks). Incidence rates reported below are for the 200 mg dose unless otherwise stated, as this captures the maximum observed frequency. The safety profile was similar in adults and adolescents aged 12 to 17.
≥10%
Very Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Nausea | 14.6% (200 mg); 6.1% (100 mg) | Most common cause of early discontinuation; typically self-limiting within 1–2 weeks; may be reduced by taking with food |
1–10%
Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Headache | 7.8% (200 mg); 5.9% (100 mg) | Usually mild and transient; onset typically within first 2 weeks |
| Acne | 4.7% (200 mg); 1.6% (100 mg) | Class effect seen across JAK inhibitors; dose-dependent; treatable with standard acne therapies |
| Herpes simplex | 4.2% (200 mg); 2.8% (100 mg) | More frequent with prior HSV or eczema herpeticum history; mostly non-serious oral or cutaneous reactivation |
| Blood CPK increase | 3.8% (200 mg) | Transient; no cases of rhabdomyolysis reported; generally does not require discontinuation |
| Vomiting | 3.5% (200 mg) | Often accompanies nausea; self-limiting; food intake may mitigate |
| Dizziness | 3.4% (200 mg) | Dose-dependent; advise caution with driving until effect known |
| Upper abdominal pain | 2.2% (200 mg) | Usually mild; consider administration with food |
| Nasopharyngitis | 8.7% (200 mg); 12.4% (100 mg) | Not dose-dependent (higher at lower dose); placebo rate 7.9%; likely not causally related to abrocitinib |
| Urinary tract infection | 2.2% (200 mg) | Standard antibiotic management; monitor for recurrence |
| Herpes zoster | 1.2% (200 mg); 0.6% (100 mg) | Mostly single-dermatome; consider vaccination before starting treatment |
Serious
Serious Adverse Effects (Regardless of Frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Serious infections (herpes simplex, herpes zoster, pneumonia) | 2.3–2.7 per 100 PY | Any time during treatment | Discontinue abrocitinib; initiate appropriate antimicrobial therapy; reassess risk-benefit before re-initiation |
| Venous thromboembolism (DVT/PE) | 0.30 per 100 PY | Variable | Discontinue immediately; initiate anticoagulation; avoid re-challenge in patients with thrombotic risk factors |
| Major adverse cardiovascular events (MACE) | <0.5 per 100 PY | Variable | Discontinue after MI or stroke; assess cardiovascular risk factors before initiating |
| Malignancy (including NMSC, lymphoma) | <0.5 per 100 PY | Variable; increased risk with longer exposure | Periodic skin examinations; discuss risk with current/former smokers; weigh risk-benefit in each patient |
| Severe thrombocytopenia (platelets <50,000/mm³) | Rare (<0.5%) | Nadir ~week 4 | Discontinue abrocitinib; monitor CBC until platelets >100,000/mm³ |
| Opportunistic infections (multi-dermatomal zoster, disseminated herpes) | Rare | Any time during treatment | Interrupt or discontinue treatment; treat infection; consider antiviral prophylaxis for high-risk patients |
Discontinuation
Discontinuation Rates
Overall (Adults + Adolescents)
5.1%
Top reasons: Nausea, worsening of atopic dermatitis, thrombocytopenia
Placebo-Controlled Trials Context
68.3% any AE (200 mg) vs 55.0% placebo
94.2% of events were mild or moderate; SAE rates were similar across groups
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| Nausea | ~0.3% | Most nausea resolved without dose change; only 4 patients across both dose groups discontinued |
| Worsening atopic dermatitis | ~1% | More common in early weeks before full therapeutic effect |
| Thrombocytopenia | <0.5% | Dose-dependent; most resolved after dose interruption or discontinuation |
| Herpes-related events | <0.5% | Primarily herpes simplex or zoster reactivation in predisposed patients |
Managing Nausea
Nausea is the most frequent adverse reaction leading to early concern, particularly at the 200 mg dose. It generally resolves within the first two weeks. Administration with food appears to reduce gastric symptoms based on phase I data showing nausea occurred primarily in the fasted state. Consider starting patients at 100 mg with a subsequent increase to 200 mg if clinically needed, which reduces early gastrointestinal intolerance.
Drug Interactions
Abrocitinib is metabolised primarily through CYP2C19 (53%) and CYP2C9 (30%), making it susceptible to inhibitors and inducers of these enzymes. Abrocitinib itself does not significantly inhibit or induce major CYP or UGT enzymes. It does inhibit organic cation transporter 1 (OCT1) and P-glycoprotein (P-gp), which has clinical relevance for certain co-administered substrates.
Major
Antiplatelet Agents (clopidogrel, prasugrel, ticagrelor)
MechanismAbrocitinib transiently reduces platelet count; additive antiplatelet effect
EffectIncreased bleeding risk, particularly in the first 3 months when platelet nadir occurs
ManagementContraindicated during the first 3 months of abrocitinib therapy; low-dose aspirin (≤81 mg/day) is permitted
FDA PI
Major
Fluconazole (strong CYP2C19 + moderate CYP2C9 inhibitor)
MechanismDual inhibition of CYP2C19 and CYP2C9, the two primary metabolic pathways
EffectApproximately 4.8-fold increase in abrocitinib systemic exposure
ManagementAvoid concomitant use of moderate-to-strong dual inhibitors of both CYP2C19 and CYP2C9
FDA PI
Major
Fluvoxamine (strong CYP2C19 inhibitor)
MechanismStrong inhibition of CYP2C19, the dominant metabolic pathway
EffectSignificant increase in abrocitinib plasma concentration
ManagementReduce abrocitinib to 50 mg QD; may increase to 100 mg QD if response is inadequate
FDA PI
Major
Other JAK Inhibitors / Biologic Immunomodulators
MechanismAdditive immunosuppressive effects
EffectHeightened risk of serious infection and immune-related adverse events
ManagementDo not combine with other JAK inhibitors, biologic immunomodulators, or immunosuppressants
FDA PI
Moderate
Digoxin (P-gp substrate with narrow therapeutic index)
MechanismAbrocitinib inhibits P-glycoprotein, reducing efflux of P-gp substrates
EffectPotential increase in digoxin exposure (dabigatran AUC increased ~53% in PK studies)
ManagementMonitor digoxin levels; titrate dose as clinically indicated for narrow-TI P-gp substrates
FDA PI
Moderate
Strong CYP2C19 or CYP2C9 Inducers (e.g., rifampicin)
MechanismEnhanced metabolic clearance of abrocitinib through CYP induction
EffectReduced abrocitinib efficacy due to lower systemic exposure
ManagementAvoid concomitant use with strong inducers of CYP2C19 or CYP2C9
FDA PI
Minor
Oral Contraceptives (ethinyl estradiol/levonorgestrel)
MechanismNo clinically significant pharmacokinetic interaction demonstrated
EffectHormonal contraceptive efficacy is maintained
ManagementNo dose adjustment needed for either drug
FDA PI
Minor
Midazolam (CYP3A4 substrate)
MechanismAbrocitinib does not inhibit or induce CYP3A4
EffectNo clinically meaningful change in midazolam exposure
ManagementNo dose adjustment required
Clinical PK StudyMonitoring
-
Complete Blood Count
Baseline, 4 weeks after start, 4 weeks after dose increase
Routine Platelet count is critical: do not initiate if <150,000/mm³. Discontinue if confirmed <50,000/mm³. Also monitor ALC (<500 requires hold), ANC (<1,000 requires hold), and haemoglobin (<8 g/dL requires hold). Platelet nadir typically occurs around week 4. -
Lipid Panel
~4 weeks after initiation, then per CV risk
Routine Dose-dependent increases in total cholesterol, LDL, and HDL observed. Manage lipid elevations according to standard cardiovascular risk guidelines. -
TB Screening
Baseline; consider annually in endemic areas
Routine Do not initiate in active TB. Treat latent TB before starting abrocitinib. Monitor for TB signs even with a negative baseline test. -
Viral Hepatitis
Baseline screening
Routine Screen for hepatitis B and C per clinical guidelines before starting. Not recommended in patients with active HBV or HCV. Monitor inactive HBV carriers for DNA reactivation during treatment. -
Infection Signs
Every visit
Routine Watch for symptoms of serious bacterial, viral, or fungal infection. Pay particular attention to herpes zoster and herpes simplex reactivation. Consider interruption for herpes zoster episodes. -
Skin Examination
Periodic
Routine Screen for non-melanoma skin cancer, particularly in patients at increased risk (fair skin, prior skin cancer, prolonged UV exposure). Counsel on sun protection. -
Cardiovascular Risk
Baseline assessment
Trigger-based Assess MACE risk before initiation, especially in current/former smokers and patients with cardiovascular risk factors. Discontinue if MI or stroke occurs. -
VTE Risk
Baseline and ongoing
Trigger-based Evaluate thrombotic risk before starting. Educate patients on DVT/PE symptoms. Discontinue immediately if thrombosis occurs.
Contraindications & Cautions
Absolute Contraindications
- Antiplatelet therapy (except low-dose aspirin ≤81 mg/day) during the first 3 months of treatment—risk of bleeding due to transient platelet reduction
Relative Contraindications (Specialist Input Recommended)
- Active serious infection (including localised infections)—do not initiate until infection is controlled
- Active or latent tuberculosis—treat latent TB prior to initiating; contraindicated in active TB
- Active hepatitis B or C—risk of viral reactivation under immunosuppression
- Severe renal impairment (eGFR <30 mL/min) or ESRD—not recommended due to insufficient data and altered drug exposure
- Severe hepatic impairment (Child-Pugh C)—not studied in this population; avoid use
- Baseline platelet count <150,000/mm³, ALC <500/mm³, ANC <1,000/mm³, or Hb <8 g/dL—do not initiate
- Pregnancy—insufficient human data; animal studies demonstrated skeletal variations at high exposure multiples
Use with Caution
- History of herpes zoster or herpes simplex—higher reactivation risk; consider vaccination prior to initiation
- Current or former smokers—additional increased risk of malignancies and MACE based on JAK inhibitor class data
- Patients with cardiovascular risk factors—weigh individual MACE and thrombotic risk
- History of VTE or thrombotic risk factors—DVT and PE have been observed in clinical trials
- Elderly (≥65 years)—limited data; clinical trials included only 4.6% of patients in this age group
- CYP2C19 poor metabolizers—require dose reduction due to 2.3-fold higher exposure; 3–5% of White/Black populations, 15–20% of Asian populations
- Immunisation status—complete all age-appropriate vaccines, including herpes zoster vaccination, before starting; avoid live vaccines during treatment
FDA Boxed Warning
Serious Infections, Mortality, Malignancy, MACE, and Thrombosis
Abrocitinib carries an FDA boxed warning consistent with all JAK inhibitors used for inflammatory conditions. The warning covers increased risk of serious bacterial, fungal, viral, and opportunistic infections leading to hospitalisation or death; higher rate of all-cause mortality (including sudden cardiovascular death) observed with another JAK inhibitor vs. TNF blockers in RA; malignancies including lymphoma and lung cancer; MACE (cardiovascular death, MI, stroke); and thrombosis (DVT, PE, arterial thrombosis). While these events were observed at low rates in the abrocitinib atopic dermatitis trial programme, the boxed warning applies to the entire JAK inhibitor class based on postmarketing safety data from another JAK inhibitor studied in RA patients aged 50+ with cardiovascular risk factors.
Patient Counselling
Purpose of Therapy
Abrocitinib is prescribed to control moderate-to-severe atopic dermatitis (eczema) when other systemic treatments have not been effective or are not suitable. It works by blocking a specific enzyme in the body called JAK1, which helps reduce the inflammation and itching associated with eczema. It is taken as a tablet once daily and can be used alongside topical moisturisers and corticosteroids.
How to Take
Take one tablet at the same time each day, swallowed whole with water. The tablet should not be crushed, split, or chewed. It may be taken with or without food, although taking it with a meal may help reduce any nausea. If a dose is missed, take it as soon as remembered unless it is less than 12 hours before the next dose; in that case, skip the missed dose and resume the regular schedule.
Nausea & Stomach Upset
Tell patient
Nausea is the most common early side effect and usually improves within 1–2 weeks. Taking the tablet with food can help reduce this. Vomiting and abdominal discomfort may also occur but are typically mild and short-lived.
Call prescriber
If nausea or vomiting is persistent, prevents eating or drinking, or worsens after the first two weeks.
Infection Risk
Tell patient
This medication may lower your ability to fight infections. Avoid close contact with people who have active infections when possible. Cold sores (herpes simplex) and shingles (herpes zoster) are the most common infections seen during treatment. Ensure all recommended vaccines are up to date before starting.
Call prescriber
If you develop fever, chills, persistent cough, unusual fatigue, painful skin blisters, or any signs of infection that do not resolve within a few days.
Blood Clots
Tell patient
Although uncommon, blood clots in the legs (DVT) or lungs (PE) have been reported with this class of medication. Risk factors include immobility, recent surgery, smoking, and personal or family history of clots.
Call prescriber
Seek immediate medical attention if you experience sudden leg swelling, leg pain or tenderness, unexplained shortness of breath, or chest pain.
Bleeding Precaution
Tell patient
During the first three months, this medication temporarily lowers platelet count. You must not take blood-thinning medications (such as clopidogrel) during this period except for low-dose aspirin. Inform your dentist and any other healthcare providers that you are on this medication.
Call prescriber
If you notice unusual bruising, prolonged bleeding from cuts, blood in urine or stools, or nosebleeds that do not stop.
Acne
Tell patient
New-onset acne is a recognised side effect of this medication class. It is dose-dependent and can usually be managed with standard acne treatments such as topical retinoids or benzoyl peroxide.
Call prescriber
If acne becomes severe, widespread, or does not respond to standard treatments.
Pregnancy & Contraception
Tell patient
There is insufficient human data on the safety of abrocitinib during pregnancy. Animal studies have shown developmental effects at high doses. Effective contraception should be used during treatment. Breastfeeding is not recommended during treatment and for one day after the last dose.
Call prescriber
Immediately if you become pregnant or plan to become pregnant while on treatment.
Sources
Regulatory (PI / SmPC)
- Pfizer Inc. CIBINQO (abrocitinib) tablets, for oral use. Full prescribing information. Revised 12/2023. labeling.pfizer.com Primary source for dosing, indications, contraindications, boxed warning, and pharmacokinetic data in this monograph.
- Cibinqo 100 mg film-coated tablets. Summary of Product Characteristics (SmPC). Electronic Medicines Compendium (EMC). medicines.org.uk European regulatory label providing additional adverse reaction frequency data for the integrated safety analysis.
- FDA Drug Trials Snapshot: CIBINQO. U.S. Food and Drug Administration. fda.gov Provides demographic breakdown and key efficacy endpoints from the original approval trials.
Key Clinical Trials
- Simpson EL, Sinclair R, Forman S, et al. Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet. 2020;396(10246):255–266. doi:10.1016/S0140-6736(20)30732-7 Pivotal phase 3 monotherapy trial establishing efficacy of abrocitinib 100 mg and 200 mg vs placebo over 12 weeks.
- Bieber T, Simpson EL, Silverberg JI, et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis (JADE COMPARE). N Engl J Med. 2021;384(12):1101–1112. doi:10.1056/NEJMoa2019380 Head-to-head comparison with dupilumab showing superior itch response at week 2 for abrocitinib 200 mg; key safety comparison data.
- Blauvelt A, Silverberg JI, Lynde CW, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: results from the JADE REGIMEN phase 3 trial. J Am Acad Dermatol. 2022;86(1):104–112. doi:10.1016/j.jaad.2021.05.075 Demonstrates relapse rates upon withdrawal (81% placebo vs 19% with 200 mg maintenance) and supports long-term maintenance dosing.
- Eichenfield LF, Flohr C, Engelman D, et al. Efficacy and safety of abrocitinib in adolescents with moderate-to-severe atopic dermatitis: results from the JADE TEEN phase 3 trial. Presented at AAD 2022; data supporting sNDA for adolescent indication. JADE TEEN data formed the basis for the February 2023 adolescent indication expansion (IGA 0/1: 46% at 200 mg vs 24% placebo at week 12).
Guidelines
- Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis: Section 1 & 2. J Am Acad Dermatol. 2014;70(2):338–351. doi:10.1016/j.jaad.2013.10.010 AAD guidelines establishing the framework for stepwise AD management and criteria for systemic therapy initiation.
Mechanistic / Basic Science
- Vazquez ML, Kaila N, Bhatt V, et al. Identification of N-{cis-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide (PF-04965842): a selective JAK1 clinical candidate for the treatment of autoimmune diseases. J Med Chem. 2018;61(3):1130–1152. doi:10.1021/acs.jmedchem.7b01598 Discovery chemistry paper detailing the JAK1 selectivity rationale and structure-activity relationships for abrocitinib.
Pharmacokinetics / Special Populations
- Dowty ME, Lin TH, Jesson MI, et al. The pharmacokinetics, metabolism, and clearance mechanisms of abrocitinib, a selective Janus kinase inhibitor, in humans. Drug Metab Dispos. 2022;50(8):1106–1118. doi:10.1124/dmd.122.000829 Definitive human ADME study establishing bioavailability (60%), Vd (100 L), clearance (64.2 L/h), and metabolite profile.
- Simpson EL, Silverberg JI, Nosbaum A, et al. Integrated safety analysis of abrocitinib for the treatment of moderate-to-severe atopic dermatitis from the Phase II and Phase III clinical trial program. Am J Clin Dermatol. 2021;22(5):693–707. doi:10.1007/s40257-021-00618-3 Integrated safety analysis (n = 2,856; 1,614 PY) providing incidence rates for all adverse events, infections, and thrombotic events cited in this monograph.
- Wang X, Zhang A, Bello A, et al. Assessment of the effects of abrocitinib on the pharmacokinetics of probe substrates of CYP1A2, CYP2B6 and CYP2C19 enzymes and hormonal oral contraceptives. Clin Pharmacokinet. 2024;63(5):697–709. doi:10.1007/s40262-024-01359-0 Drug-drug interaction study confirming abrocitinib does not affect CYP3A4 (midazolam), CYP1A2 (caffeine), or oral contraceptive pharmacokinetics.