CIBINQO is indicated for the treatment of adults and pediatric patients 12 years of age and older 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. CIBINQO is a Janus kinase (JAK) inhibitor indicated for the treatment of adults and pediatric patients 12 years of age and older 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.
( 1 ) Limitation of Use : CIBINQO is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or with other immunosuppressants. Limitations of Use CIBINQO is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.
Contraindications
CIBINQO is contraindicated in patients taking antiplatelet therapies, except for low-dose aspirin (≤81 mg daily), during the first 3 months of treatment [see Warnings and Precautions (5.6) , Drug Interactions (7.2) , and Clinical Pharmacology (12.2) ]. Antiplatelet therapies except for low-dose aspirin (≤81 mg daily), during the first 3 months of treatment. ( 4 )
Warnings and precautions
Laboratory Abnormalities : Laboratory monitoring is recommended due to potential changes in platelets, lymphocytes, and lipids. ( 5.6 )
Immunizations : Avoid use of live vaccines immediately prior to, during and immediately after CIBINQO treatment. ( 5.7 )
5.1Serious Infections
The most frequent serious infections reported in clinical studies with CIBINQO for atopic dermatitis were herpes simplex, herpes zoster, and pneumonia [see Adverse Reactions (6.1) ] . Serious infections leading to hospitalization or death, including tuberculosis and bacterial, invasive fungal, viral, and other opportunistic infections, have occurred in patients receiving JAK inhibitors used to treat inflammatory conditions.
Avoid use of CIBINQO in patients with active, serious infection including localized infections. Consider the risks and benefits of treatment prior to initiating CIBINQO in patients:
with chronic or recurrent infection
who have been exposed to tuberculosis
with a history of a serious or an opportunistic infection
who have resided or traveled in areas of endemic tuberculosis or endemic mycoses
with underlying conditions that may predispose them to infection Closely monitor patients for the development of signs and symptoms of infection during and after treatment with CIBINQO. If a patient develops a serious or opportunistic infection, discontinue CIBINQO. Initiate complete diagnostic testing and appropriate antimicrobial therapy. The risks and benefits of treatment with CIBINQO should be carefully considered prior to reinitiating therapy with CIBINQO. Tuberculosis Evaluate and test patients for TB before starting CIBINQO therapy and consider yearly screening for patients in highly endemic areas for TB. CIBINQO is not recommended for use in patients with active TB. For patients with a new diagnosis of latent TB or prior untreated latent TB, or for patients with a negative test for latent TB but who are at high risk for TB infection, start preventive therapy for latent TB prior to initiation of CIBINQO. Monitor patients for the development of signs and symptoms of TB, including patients who were tested negative for latent TB infection prior to initiating therapy. Viral Reactivation Viral reactivation, including herpes virus reactivation (e.g., herpes zoster, herpes simplex), was reported in clinical trials with CIBINQO [see Adverse Reactions (6.1) ] . If a patient develops herpes zoster, consider interrupting CIBINQO until the episode resolves. Hepatitis B virus (HBV) reactivation has been reported in patients receiving JAK inhibitors. Perform viral hepatitis screening in accordance with clinical guidelines before starting therapy and monitor for reactivation during therapy with CIBINQO. CIBINQO is not recommended for use in patients with active hepatitis B or hepatitis C [see Clinical Pharmacology (12.3) ] . Monitor patients with inactive HBV for expression of HBV DNA during therapy with CIBINQO. If HBV DNA is detected during therapy with CIBINQO, consult a liver specialist.
5.2 Mortality In a large, randomized, postmarketing safety trial of another JAK inhibitor in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed in subjects treated with the JAK inhibitor compared with TNF blockers. CIBINQO is not approved for use in RA. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with CIBINQO.
5.3Malignancy and Lymphoproliferative Disorders
Malignancies, including non-melanoma skin cancer (NMSC), were observed in clinical trials with CIBINQO for atopic dermatitis [see Adverse Reactions (6.1) ] . Perform periodic skin examination for patients who are at increased risk for skin cancer. Exposure to sunlight and UV light should be limited by wearing protective clothing and using broad-spectrum sunscreen. Malignancies, including lymphomas, have occurred in patients receiving JAK inhibitors used to treat inflammatory conditions.
In a large, randomized, postmarketing safety trial of another JAK inhibitor in RA subjects, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed in subjects treated with the JAK inhibitor compared to those treated with TNF blockers. CIBINQO is not approved for use in RA. A higher rate of lymphomas was observed in subjects treated with the JAK inhibitor compared to those treated with TNF blockers.
A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. In this trial, current or past smokers had an additional increased risk of overall malignancies. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with CIBINQO, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy when on treatment, and patients who are current or past smokers.
5.4Major Adverse Cardiovascular Events
Major adverse cardiovascular events were reported in clinical trials of CIBINQO for atopic dermatitis [see Adverse Reactions (6.1) ]. In a large, randomized, postmarketing safety trial of another JAK inhibitor in RA subjects 50 years of age and older with at least one cardiovascular risk factor, a higher rate of major adverse cardiovascular events (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke was observed with the JAK inhibitor compared to those treated with TNF blockers.
CIBINQO is not approved for use in RA. Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with CIBINQO, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur.
Discontinue CIBINQO in patients that have experienced a myocardial infarction or stroke.
5.5Thrombosis
Deep venous thrombosis (DVT) and pulmonary embolism (PE) were observed in subjects receiving CIBINQO in the clinical trials for atopic dermatitis [see Adverse Reactions (6.1) ] . Thrombosis, including DVT, PE, and arterial thrombosis have been reported in patients receiving JAK inhibitors used to treat inflammatory conditions. Many of these adverse reactions were serious and some resulted in death. In a large, randomized, postmarketing safety trial of another JAK inhibitor in RA subjects 50 years of age and older with at least one cardiovascular risk factor, higher rates of overall thrombosis, DVT, and PE were observed compared to those treated with TNF blockers.
CIBINQO is not approved for use in RA. Avoid CIBINQO in patients that may be at increased risk of thrombosis. If symptoms of thrombosis occur, discontinue CIBINQO and evaluate and treat patients appropriately.
5.6Laboratory Abnormalities Hematologic Abnormalities Treatment with
CIBINQO was associated with an increased incidence of thrombocytopenia and lymphopenia [see Adverse Reactions (6.1) ] . Prior to CIBINQO initiation, perform a CBC [see Dosage and Administration (2.1) ] . CBC evaluations are recommended at 4 weeks after initiation and 4 weeks after dose increase of CIBINQO. Discontinuation of CIBINQO therapy is required for certain laboratory abnormalities [see Dosage and Administration (2.6) ].
Lipid Elevations Dose-dependent increase in blood lipid parameters were reported in subjects treated with CIBINQO [see Adverse Reactions (6.1) ] . Lipid parameters should be assessed approximately 4 weeks following initiation of CIBINQO therapy and thereafter patients should be managed according to clinical guidelines for hyperlipidemia. The effect of these lipid parameter elevations
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Interactions
Strong inhibitors of CYP2C19: The recommended dosage is 50 mg once daily or 100 mg once daily for those patients who are not responding to 50 mg once daily. ( 2.5 , 7.1 )
Moderate to strong inhibitors of both CYP2C19 and CYP2C9, or strong CYP2C19 or CYP2C9 inducers: Avoid concomitant use. ( 7.1 )
P-gp substrate where small concentration changes may lead to serious or life-threatening toxicities: Monitor or titrate dosage of P-gp substrate. ( 7.2 )
7.1Effects of Other Drugs on
CIBINQO Table 4 includes drugs with clinically significant drug interactions affecting CIBINQO. Table 4. Clinically Significant Drug Interactions Affecting CIBINQO Strong CYP2C19 Inhibitors Clinical Impact Coadministration of CIBINQO with strong CYP2C19 inhibitors increases the combined exposure of abrocitinib and its two active metabolites, M1 and M2 which may increase the adverse reactions of CIBINQO [see Clinical Pharmacology (12.3) ].
Intervention Dosage reduction of CIBINQO is recommended when coadministered with strong CYP2C19 inhibitors [see Dosage and Administration (2.5) ]. Moderate to Strong Inhibitors of both CYP2C19 and CYP2C9 Clinical Impact Coadministration of CIBINQO with drugs that are moderate to strong inhibitors of both CYP2C19 and CYP2C9 increases the exposure of abrocitinib and its two active metabolites, M1 and M2 which may increase the adverse reactions of CIBINQO [ Clinical Pharmacology (12.3) ].
Intervention Avoid concomitant use of CIBINQO with drugs that are moderate to strong inhibitors of both CYP2C19 and CYP2C9 . Strong CYP2C19 or CYP2C9 Inducers Clinical Impact Coadministration of CIBINQO with strong CYP2C19 or CYP2C9 inducers decreases the combined exposure of abrocitinib and its two active metabolites, M1 and M2, which may result in loss of or reduced clinical response [see Clinical Pharmacology (12.3) ] .
Intervention Avoid concomitant use of CIBINQO with strong CYP2C19 or CYP2C9 inducers.
7.2Effects of
CIBINQO on Other Drugs Table 5 includes clinically significant drug interactions affecting other drugs. Table 5. Clinically Significant Interactions Affecting Other Drugs P-gp Substrate Where Small Concentration Changes May Lead to Serious or Life-threatening Toxicities Clinical Impact Coadministration of CIBINQO with P-gp substrate increases plasma concentrations of P-gp substrates and may result in potential adverse reactions of the P-gp substrate where small concentration changes may lead to serious or life-threatening toxicities (e.g., digoxin) [see Clinical Pharmacology (12.3) ] .
Intervention Monitor appropriately or dose titrate P-gp substrate where small concentration changes may lead to serious or life-threatening toxicities when coadministered with CIBINQO . Antiplatelet Therapy Drugs Clinical Impact Coadministration of CIBINQO with antiplatelet therapy drugs may increase the risk of bleeding with thrombocytopenia [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.2) ]. Intervention Antiplatelet drugs, except for low-dose aspirin (≤81 mg daily), during the first 3 months of treatment are contraindicated with CIBINQO [see Contraindications (4) ] .
Pregnancy and breastfeeding
8.1Pregnancy Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to CIBINQO during pregnancy. Pregnant women exposed to CIBINQO and health care providers are encouraged to call 1-877-311-3770. Risk Summary Available data from pregnancies reported in clinical trials with CIBINQO are not sufficient to establish a drug‑associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
In animal reproduction studies, oral administration of abrocitinib to pregnant rats and rabbits during organogenesis at exposure 11 or 4 times the maximum recommended human dose (MRHD) based on AUC comparison, respectively, resulted in maternal dystocia and skeletal variations in rats and no adverse effects in rabbits ( see Data ). The background risks of major birth defects and miscarriage for the indicated population are unknown.
All pregnancies carry some risk of birth defects, loss, or other adverse outcomes. The background risks in the U.S. general population of major birth defects and miscarriages are 2–4% and 15–20% of clinically recognized pregnancies, respectively. Data Animal Data In an embryofetal development study, abrocitinib was administered orally to pregnant rats at doses of 10, 30, or 60 mg/kg/day during the period of organogenesis.
No fetal malformations were observed. Abrocitinib increased the incidence of skeletal variations of short 13 th ribs at 30 mg/kg/day (11 times the MRHD based on AUC comparison). Increased embryofetal lethality and additional skeletal variations (cervical arches with reduced ventral processes, thickened ribs, and unossified metatarsals) were noted at 60 mg/kg/day (17 times the MRHD based on AUC comparison). In an embryofetal development study, abrocitinib was administered orally to pregnant rabbits at doses of 10, 30, or 75 mg/kg/day during the period of organogenesis.
No abrocitinib-related maternal or developmental toxicity was noted at doses up to 75 mg/kg/day (4 times the MRHD based on AUC comparison). In a prenatal and postnatal development study, abrocitinib was administered orally to pregnant rats at doses of 10, 30, and 60 mg/kg/day beginning on gestation day 6 and continuing through lactation day 20. Dystocia with prolonged parturition and reduced offspring body weights were noted at 30 mg/kg/day (11 times the MRHD based on AUC comparison).
Postnatal survival was markedly decreased at 60 mg/kg/day (17 times the MRHD based on AUC comparison). No maternal toxicity was observed at 10 mg/kg/day (2.4 times the MRHD based on AUC comparison). No abrocitinib-related effects on postnatal developmental, neurobehavioral, or reproductive performance of offspring was noted at doses up to 30 mg/kg/day (11 times the MRHD based on AUC comparison).
Adverse reactions
The following clinically significant adverse reactions are described elsewhere in the labeling:
Serious Infections [see Warnings and Precautions (5.1) ]
Mortality [see Warnings and Precautions (5.2) ]
Malignancy and Lymphoproliferative Disorders [see Warnings and Precautions (5.3) ]
Major Adverse Cardiovascular Events [see Warnings and Precautions (5.4) ]
Thrombosis [see Warnings and Precautions (5.5) ]
Laboratory Abnormalities [see Warnings and Precautions (5.6) ] Most common adverse events (≥1% with CIBINQO 100 mg) are nasopharyngitis, nausea, headache, herpes simplex, increased blood creatine phosphokinase, dizziness, urinary tract infection, fatigue, acne, vomiting, impetigo, oropharyngeal pain, hypertension, influenza, gastroenteritis, and dermatitis contact. ( 6.1 ) Most common adverse reactions (≥1% with CIBINQO 200 mg and greater than CIBINQO 100 mg) are nausea, headache, herpes simplex, increased blood creatine kinase, dizziness, urinary tract infection, acne, vomiting, gastroenteritis, upper abdominal pain, abdominal discomfort, herpes zoster, and thrombocytopenia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of CIBINQO was evaluated in four randomized, placebo-controlled clinical trials (2 monotherapy, 1 combination therapy with topical corticosteroid, and 1 dose-ranging) and one long-term extension trial in subjects with moderate to severe atopic dermatitis (AD).
A total of 1623 subjects with moderate to severe atopic dermatitis were treated with CIBINQO in these clinical trials representing 1428 patient-years of exposure. There were 634 subjects with at least 1 year of exposure to CIBINQO. In the placebo-controlled clinical trials, a total of 1198 subjects were exposed to CIBINQO with 608 subjects receiving CIBINQO 100 mg once daily and 590 subjects receiving CIBINQO 200 mg once daily for up to 16 weeks.
The median age of subjects was 33.0 years, 124 subjects (8.1%) were 12 to less than 18 years old and 94 subjects (6.1%) were 65 years of age or older. The majority of subjects were White (68.7%) and male (53.9%). Adverse reactions occurring at ≥1% in any of the treated groups and at a higher rate than in the placebo group are presented in Table 3. A total of 61 (5.1%) subjects treated with CIBINQO were discontinued from the trials due to adverse reactions.
The safety profile of CIBINQO in the monotherapy and the combination trial(s) were similar. Table 3. Adverse Reactions from Placebo-Controlled Trials Reported in ≥1% of CIBINQO Treated Subjects with Moderate to Severe Atopic Dermatitis and at Higher Rate than Placebo for up to 16 Weeks Weeks 0–16 CIBINQO 200 mg N=590 n (% Study size adjusted percentages ) CIBINQO 100 mg N=608 n (% ) Placebo N=342 n (% ) Nasopharyngitis 51 (8.7) 75 (12.4) 27 (7.9) Nausea 86 (14.5) 37 (6.0) 7 (2.1) Headache 46 (7.8) 36 (6.0) 12 (3.5) Herpes simplex Herpes simplex also includes oral herpes, ophthalmic herpes, herpes dermatitis, genital herpes. 25 (4.2) 20 (3.3) 6 (1.8) Increased blood creatine phosphokinase 17 (2.9) 14 (2.3) 5 (1.5) Dizziness 17 (2.9) 11 (1.8) 3 (0.9) Urinary tract infection 13 (2.2) 10 (1.7) 4 (1.2) Fatigue 8 (1.3) 10 (1.6) 2 (0.5) Acne 28 (4.7) 10 (1.6) 0 (0.0) Vomiting 19 (3.2) 9 (1.5) 3 (0.9) Impetigo 3 (0.5) 9 (1.5) 1 (0.3) Oropharyngeal pain 6 (1.0) 8 (1.4) 2 (0.6) Hypertension 5 (0.8) 7 (1.2) 2 (0.7) Influenza 6 (1.1) 7 (1.2) 0 (0.0) Gastroenteritis 8 (1.3) 7 (1.1) 2 (0.6) Dermatitis contact 3 (0.5) 6 (1.1) 1 (0.3) Abdominal pain upper 11 (1.9) 4 (0.6) 0 (0.0) Abdominal discomfort 7 (1.2) 3 (0.5) 1 (0.3) Herpes zoster 7 (1.2) 2 (0.3) 0 (0.0) Thrombocytopenia 9 (1.5) 0 (0.0) 0 (0.0) Specific Adverse Reactions Exposure adjusted incidence rates were adjusted by trial size for all the adverse reactions reported in this section.
Overall Infections In the placebo-controlled trials, for up to 16 weeks, overall infections were reported in 90 subjects (126.8 per 100 patient-years) treated with placebo, 211 subjects (168.8 per 100 patient-years) treated with CIBINQO 100 mg and 204 subjects (159.5 per 100 patient-years) treated with CIBINQO 200 mg. In all 5 clinical trials, including the long-term extension trial, overall infections were reported in 427 subjects (91.8 per 100 patient-years) treated with CIBINQO 100 mg and 394 subjects (103.2 per 100 patient-years) treated with CIBINQO 200 mg.
Serious Infections In the placebo-controlled trials, for up to 16 weeks, serious infections were reported in 2 subjects (2.6 per 100 patient-years) treated with placebo, 6 subjects (3.9 per 100 patient-years) treated with CIBINQO 100 mg, and 2 subjects (1.3 per 100 patient-years) treated with CIBINQO 200 mg. In all 5 clinical trials, including the long-term extension trial, serious infections were reported in 18 subjects (2.3 per 100 patient-years) treated with CIBINQO 100 mg and 16 subjects (2.3 per 100 patient-years) treated with CIBINQO 200 mg.
The most commonly reported serious infections were herpes simplex, herpes zoster, and pneumonia. Herpes Zoster In the placebo-controlled trials, for up to 16 weeks, opportunistic infections were generally cases of multidermatomal cutaneous herpes zoster. Herpes zoster was reported in 0 subjects treated with placebo, 3 subjects (1.9 per 100 patient-years) treated with CIBINQO 100 mg and 8 subjects (5.1 per 100 patient-years) treated with CIBINQO 200 mg.
In all 5 clinical trials, including the long-term extension trial, herpes zoster was reported in 16 subjects (2.0 per 100 patient-years) treated with CIBINQO 100 mg and 35 subjects (5.2 per 100 patient-years) treated with CIBINQO 200 mg. Malignancy In the placebo-controlled trials, for up to 16 weeks, no malignancy was reported in subjects treated with placebo or CIBINQO 100 mg and in 1 patient (0.65 per 100 patient-years) treated with CIBINQO 200 mg.
In all 5 clinical trials, including the long-term extension trial, malignancy was reported in 4 subjects (0.5 per 100 patient-years) treated with CIBINQO 100 mg and 2 subjects (0.3 per 100 patient-years) treated with CIBINQO 200 mg. Thrombosis In all clinical trials, including the long-term extension trial, pulmonary embolism was reported in 3 subjects (0.4 per 100 patient-years), who were treated with CIBINQO 200 mg.
Deep vein thrombosis was reported in 2 subjects (0.3 per 100 patient-years) who were treated with CIBINQO 200 mg. No thrombosis occurred in subjects treated with CIBINQO 100 mg. Major Adverse Cardiovascular Events In the placebo-controlled trials, for up to 16 weeks, major adverse cardiovascular event (MACE) was reported in 1 subject (0.6 per 100 patient-years) treated with CIBINQO 100 mg. In all 5 clinical trials, including the long-term extension trial, MACE was reported in 1 patient (0.1 per 100 patient-years) treated with CIBINQO 100 mg and 2 subjects (0.3 per 100 patient-years) treated with CIBINQO 200 mg.
Thrombocytopenia In the placebo-controlled trials, for up to 16 weeks, treatment with CIBINQO was associated with a dose-related decrease in platelet count. Maximum effects on platelets were observed within 4 weeks, after which the platelet count returned towards baseline despite continued therapy. In all 5 clinical trials, including the long-term extension trial, 6 subjects (0.9 per 100 patient-years) treated with CIBINQO 200 mg had adverse reactions of thrombocytopenia; no subjects treated with CIBINQO 100 mg had an adverse reaction of thrombocytopenia.
Lymphopenia In the placebo-controlled trials, for up to 16 weeks, confirmed ALC <500/mm 3 occurred in 2 subjects (1.2 per 100 patient-years) treated with CIBINQO 200 mg a
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
ABROCITINIB 50MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
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