Cibinqo

— THERAPEUTIC CATEGORIES —
  • Atopic dermatitis
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Cibinqo Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Abrocitinib 50mg, 100mg, 200mg; tabs.

    Pharmacological Class

    Janus kinase (JAK) inhibitor.

    How Supplied

    Tabs—30

    How Supplied

    Tablets

    • 50mg: pink, oval, debossed with "PFE" on one side and "ABR 50" on the other.
    • 100mg: pink, round, debossed with "PFE" on one side and "ABR 100: on the other.
    • 200mg: pink, oval, debossed with "PFE" on one side and "ABR 200" on the other.

    Storage

    Store Cibinqo at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F).

    Keep in original package. 

    Manufacturer

    Pfizer Inc.

    Generic Availability

    NO

    Mechanism of Action

    Abrocitinib reversibly inhibits JAK1 by blocking the adenosine triphosphate (ATP) binding site. The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.

    Cibinqo Indications

    Indications

    For patients 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.

    Limitations of Use

    Not recommended in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants.

    Cibinqo Dosage and Administration

    Prior to Treatment Evaluations

    Before initiating Cibinqo, perform the following tests and evaluations:

    • Tuberculosis (TB) infection evaluation.
      • Initiation is not recommended in patients with active TB or those with a negative latent TB test who are at high risk for TB; start preventive therapy for latent TB prior to initiating.
    • Viral hepatitis screening in accordance with clinical guidelines.
      • Not recommended in patients with active hepatitis B or hepatitis C.
    • Complete blood count.
      • Not recommended in patients with a platelet count
        <150,000/mm3, an absolute lymphocyte count <500/mm3, an absolute neutrophil count <1,000/mm3, or a hemoglobin value <8g/dL.
    • Complete any necessary immunizations, including herpes zoster vaccinations, in agreement with current immunization guidelines.

    Adult

    Swallow whole. Use lowest effective dose to maintain response. 100mg once daily; if inadequate response, consider increasing to 200mg once daily; discontinue if adequate response not achieved with 200mg once daily. May be used with or without topical corticosteroids. Moderate renal impairment (eGFR 30–59mL/min): 50mg once daily; if inadequate response, consider increasing to 100mg once daily. Poor CYP2C19 metabolizers or concomitant strong CYP2C19 inhibitors: 50mg once daily; if inadequate response, consider increasing to 100mg once daily; discontinue therapy if inadequate response after dosage increase to 100mg once daily.

    Children

    <12yrs: not established.

    Renal impairment

    Mild renal impairment (eGFR 60-89mL/min): 100mg once daily.

    Moderate renal impairment (eGFR 30-59mL/min): 50mg once daily.

    Severe renal impairment or end-stage renal disease (eGFR <15mL/min): Not recommended.

    In patients with mild and moderate renal impairment, if an adequate response is not achieved with initial dose, the dose of Cibinqo can be doubled.

    Hepatic Impairment

    Not recommended for use in patients with severe hepatic impairment.

    Other Modifications

    CYP2C19 poor metabolizers: 50mg once daily; if inadequate response, increase to 100mg once daily; discontinue if inadequate response after dosage increase to 100mg once daily.

    Concomitant strong CYP2C19 inhibitors: 50mg once daily; if inadequate response, increase to 100mg once daily; discontinue if inadequate response after dosage increase to 100mg once daily.

    Serious or opportunistic infections: If patient develops, risks and benefits of Cibinqo treatment should be carefully considered prior to reinitating therapy.

    Hematologic abnormalities: 

    • Platelet count <50,000/mm3: Discontinue and follow up with CBC until >100,000/mm3.
    • Absolute lymphocyte count (ALC) <500/mm3: Temporarily discontinue and restart once ALC returns above this value.
    • Absolute neutrophil count (ANC) <1000/mm3: Temporarily discontinue and restart once ANC above this value.
    • Hemoglobin (Hb) value <8g/dL: Temporarily discontinue and restart once Hb above this value.
       

    Administration

    Administer with or without food at approximately the same time each day.

    Swallow tablet whole; do not crush, split, or chew.

    Cibinqo Contraindications

    Contraindications

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

    Cibinqo Boxed Warnings

    Boxed Warning

    Serious infections. Mortality. Malignancy. Major adverse cardiovascular events (MACE). Thrombosis.

    Cibinqo Warnings/Precautions

    Warnings/Precautions

    Increased risk of serious infections (eg, TB, bacterial, viral, invasive fungal, or other opportunistic pathogens). Avoid in active, serious, or localized infections. Consider the risks/benefits in chronic, recurrent, or history of serious or opportunistic infections. Travel to, or residence in, areas with endemic TB or mycoses. Conditions that predispose to infection. Test/treat latent TB infection prior to and per applicable guidelines during therapy. Monitor closely if new infection, active TB (even if initial latent test is negative), reactivation of herpes virus or hepatitis occurs; interrupt treatment if serious or opportunistic infection. Screen for viral hepatitis before starting therapy. RA patients age ≥50yrs with ≥1 CV risk factor treated with another JAK inhibitor: increased rate of all-cause mortality (including sudden CV death), MACE (CV death, MI, stroke), or thrombosis. Discontinue in those with previous MI or stroke, or with symptoms of thrombosis. Avoid in those with increased risk for thrombosis. Increased rate of malignancies (esp. lymphomas, lung cancers). Consider benefits/risks prior to or continuing therapy (esp. smokers, with other CV risk factors, or with a known malignancy). Perform periodic skin exam in those with skin cancer risk. Update immunizations based on current guidelines prior to initiation. Do not initiate therapy if platelets <150,000/mm3, lymphocytes <500/mm3, ANC <1000/mm3, or hemoglobin <8g/dL. Monitor CBCs at baseline, 4 weeks after initiation, and 4 weeks after dose increase. Monitor lipids 4 weeks following initiation and manage hyperlipidemia. Severe hepatic or renal impairment (eGFR 15–29mL/min), ESRD (eGFR <15mL/min): not recommended. CYP2C19 poor metabolizers. Elderly. Pregnancy. Nursing mothers: not recommended (during and for 1 day after the last dose).

    Pregnancy Considerations

    Data not available to establish drug-associated risk. Pregnancy registry: 877-311-3770.

    Nursing Mother Considerations

    Do not breastfeed during treatment with Cibinqo and for 1 day after the last dose (approximately 5-6 elimination half-lives).

    Pediatric Considerations

    Safety and effectiveness not established in pediatric patients under 12 years of age.

    Geriatric Considerations

    Clinical trials did not include sufficient number of patients aged 65 years and older to determine difference in response. 

    Renal Impairment Considerations

    Severe (eGFR <30 mL/min) and moderate (eGFR 30-59 mL/min) renal impairment: Combined exposure of abrocitinib and its 2 active metabolites, M1 and M2, is increased compared with normal renal function. 

    Not recommended for patients with severe renal impairment and ESRD including those on renal replacement therapy.

    Dosage reduction required in patients with moderate renal impairment.

    Dosage adjustment required in patients with mild renal impairment.

    Hepatic Impairment Considerations

    Severe hepatic impairment (Child-Pugh C): Avoid use.

    No dosage adjustment needed in mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.

    Other Considerations for Specific Populations

    In patients who are CYP2C19 poor metabolizers, the AUC of abrocitinib is increased compared with CYP2C19 normal metabolizers due to reduced metabolic clearance.

    Reduce dose in CYP2C19 poor metabolizers. 

    Cibinqo Pharmacokinetics

    Absorption

    Abrocitinib is absorbed with over 91% extent of oral absorption and absolute oral bioavailability of ~60%. The peak plasma concentrations of abrocitinib are reached within 1 hour.

    Distribution

    After intravenous administration, the volume of distribution of abrocitinib is ~100 L. Approximately 64%, 37% and 29% of circulating abrocitinib and its active metabolites M1 and M2, respectively, are bound to plasma proteins. Abrocitinib and its active metabolites M1 and M2 bind predominantly to albumin and distribute equally between red blood cells and plasma.

    Metabolism

    The metabolism of abrocitinib is mediated by multiple CYP enzymes, CYP2C19 (~53%), CYP2C9 (~30%), CYP3A4 (~11%) and CYP2B6 (~6%).

    Elimination

    Primarily eliminated by metabolic clearance mechanisms. The mean elimination half-lives of abrocitinib and its two active metabolites, M1 and M2, range 3–5 hours. The metabolites of abrocitinib, M1 and M2 are excreted predominantly in urine, and are substrates of OAT3 transporter.

     

    Cibinqo Interactions

    Interactions

    See Contraindications. Increased risk of bleeding with antiplatelet drugs. Avoid concomitant live vaccines. Potentiated by strong CYP2C19 inhibitors: reduce dose (see Adult). Potentiated by moderate to strong inhibitors of both CYP2C19 and CYP3A4 inhibitors: avoid. Antagonized by strong CYP2C19 or CYP2C9 inducers: avoid. Potentiates P-gp substrates (eg, digoxin); monitor or titrate substrate dose appropriately.

    Cibinqo Adverse Reactions

    Adverse Reactions

    Nasopharyngitis, nausea, headache, herpes simplex, increased blood creatinine phosphokinase, dizziness, UTI, fatigue, acne, vomiting, oropharyngeal pain, influenza, gastroenteritis, impetigo, hypertension, contact dermatitis, upper abdominal pain, abdominal discomfort, herpes zoster, thrombocytopenia; other serious or opportunistic infections, TB, malignancies, thrombosis, cytopenias, lipid elevations, non-melanoma skin cancer, retinal detachment.

    Cibinqo Clinical Trials

    Clinical Trials

    The approval was based on data from the phase 3 JADE clinical trial program consisting of JADE MONO-1 (ClinicalTrials.gov Identifier: NCT03349060) and JADE MONO-2 (ClinicalTrials.gov Identifier: NCT03575871), which compared abrocitinib 100mg and 200mg once daily to placebo in patients aged 12 years and older with moderate to severe atopic dermatitis. The program also included the JADE COMPARE (ClinicalTrials.gov Identifier: NCT03720470) trial, which compared abrocitinib 100mg and 200mg once daily to subcutaneous dupilumab 300mg every 2 weeks or placebo in combination with background topical corticosteroids in patients aged 18 years and older.

    The coprimary endpoints across all 3 trials included the Investigator’s Global Assessment (IGA) score of clear (0) or almost clear (1) and a reduction from baseline of at least 2 points; and 75% improvement from baseline on the Eczema Area and Severity Index (EASI) at week 12.

    Results showed a significantly greater proportion of patients treated with abrocitinib met the coprimary endpoints at week 12 compared with placebo.

    IGA response rate in the abrocitinib 100mg, 200mg and placebo arms, respectively:

    • JADE MONO-1: 24%, 44%, 8%;
    • JADE MONO-2: 28%, 38%, 9%;
    • JADE COMPARE: 36%, 47%, 14%.

    EASI-75 response rate in the abrocitinib 100mg, 200mg, and placebo arms, respectively:

    • JADE MONO-1: 40%, 62%,12%;
    • JADE MONO-2: 44%, 61%, 10%;
    • JADE COMPARE: 58%, 68%, 27%.

    Additionally, abrocitinib was associated with a statistically significant reduction in pruritus as early as week 2 with at least a 4-point improvement as measured by the pruritus numerical rating scale (secondary endpoint).

    Examination of age, gender, race, weight, and previous systemic atopic dermatitis therapy did not identify differences in response to Cibinqo.

    Adolescent Trial

    The approval in adolescent patients was based on data from previous studies that included 124 adolescent patients, as well as the phase 3 JADE TEEN study (ClinicalTrials.gov Identifier: NCT03796676), which compared the efficacy and safety of abrocitinib to placebo in 285 patients 12 to less than 18 years of age with moderate to severe atopic dermatitis. Patients were randomly assigned to receive abrocitinib 100mg, 200mg or placebo orally once daily for 12 weeks while on background topical therapy. 

    The coprimary end points were the proportion of patients who achieved an IGA of clear (0) or almost clear (1) and a ≥2 point reduction from baseline at week 12; and the proportion of patients who achieved EASI-75 response at week 12. 

    Results from JADE TEEN showed that 39% and 46% of patients treated with abrocitinib 100mg and 200mg, respectively, achieved an IGA 0 or 1 response compared with 24% of patients treated with placebo. At week 12, 71% and 64% of patients treated with abrocitinib 100mg and 200mg, respectively, achieved an EASI-75 response compared with 41% of patients who received placebo.

    Additionally, a greater proportion of patients treated with abrocitinib 100mg and 200mg achieved at least a 4-point decrease from baseline in Peak Pruritus Numerical Rating Scale score at week 2 compared with placebo (13% and 25% vs 8%, respectively).

    Cibinqo Note

    Not Applicable

    Cibinqo Patient Counseling

    Patient Counseling

    Report serious infections while taking Cibinqo.

    Risk of herpes zoster increased while on treatment.

    May increase the risk of certain cancers; periodic skin examinations are recommended. 

    Limit exposure to sunlight and UV light; wear protective clothing and use broad spectrum sunscreen.

    May increase the risk of major adverse cardiovascular events, especially in current or past smokers or those with CV risk factors.

    DVT and PE have been reported; report immediately if signs/symptoms develop.

    May affect certain blood tests.

    Avoid live vaccines right before, during, and right after Cibinqo treatment.

    Retinal detachment has been reported; report immediately if sudden vision changes occur.

    Cibinqo may impair fertility.

    Avoid breastfeeding during treatment.

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