ABROCITINIB

Brand names: Cibinqo, CIBINQO

Boxed warning

WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, and THROMBOSIS WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE), and THROMBOSIS See full prescribing information for complete boxed warning. • Increased risk of serious bacterial, fungal, viral and opportunistic infections leading to hospitalization or death, including tuberculosis (TB). Discontinue treatment with CIBINQO if serious or opportunistic infection occurs. Test for latent TB before and during therapy; treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative latent TB test. ( 5.1 ) • Higher rate of all-cause mortality, including sudden cardiovascular death, with another JAK inhibitor vs. TNF blockers in rheumatoid arthritis (RA) patients. CIBINQO is not approved for use in RA patients. ( 5.2 ) • Malignancies have occurred with CIBINQO. Higher rate of lymphomas and lung cancers with another JAK inhibitor vs. TNF blockers in RA patients. ( 5.3 ) • MACE has occurred with CIBINQO. Higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke) with another JAK inhibitor vs. TNF blockers in RA patients. ( 5.4 ) • Thrombosis has occurred with CIBINQO. Increased incidence of pulmonary embolism, venous and arterial thrombosis with another JAK inhibitor vs. TNF blockers. ( 5.5 ) Serious Infections Patients treated with CIBINQO may be at increased risk for developing serious infections that may lead to hospitalization or death. The most frequent serious infections reported with CIBINQO were herpes simplex, herpes zoster, and pneumonia [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ] . If a serious or opportunistic infection develops, discontinue CIBINQO and control the infection. Reported infections from Janus kinase (JAK) inhibitors used to treat inflammatory conditions: • Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Test for latent TB before and during therapy; treat latent TB prior to use. Monitor all patients for active TB during treatment, even patients with initial negative latent TB test. • Invasive fungal infections, including cryptococcosis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease. • Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens. Avoid use of CIBINQO in patients with an active, serious infection including localized infections. The risks and benefits of treatment with CIBINQO should be carefully considered prior to initiating therapy in patients with chronic or recurrent infections. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with CIBINQO, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy [see Warnings and Precautions (5.1) ] . Mortality In a large, randomized, postmarketing safety study in rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular risk factor comparing another JAK inhibitor to TNF blocker treatment, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed with the JAK inhibitor. CIBINQO is not approved for use in RA patients [see Warnings and Precautions (5.2) ] . Malignancies Malignancies were reported in patients treated with CIBINQO. Lymphoma and other malignancies have been observed in patients receiving JAK inhibitors used to treat inflammatory conditions. In RA patients treated with another JAK inhibitor, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk [see Warnings and Precautions (5.3) ] . Major Adverse Cardiovascular Events Major adverse cardiovascular events were reported in patients treated with CIBINQO. In RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke), was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Discontinue CIBINQO in patients that have experienced a myocardial infarction or stroke [see Warnings and Precautions (5.4) ] . Thrombosis Deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients treated with CIBINQO. Thrombosis, including PE, DVT, 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 RA patients 50 years of age and older with at least one cardiovascular risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid CIBINQO in patients at risk. If symptoms of thrombosis occur, discontinue CIBINQO and treat appropriately [see Warnings and Precautions (5.5) ] .

Warnings

5 WARNINGS AND PRECAUTIONS • Hypoglycemia in Patients with Diabetes : Consider increased monitoring of blood glucose; advise diabetic patients to notify their healthcare provider if they develop signs and symptoms of hypoglycemia. ( 5.6 ) • Laboratory Abnormalities : Laboratory monitoring is recommended due to potential changes in platelets, lymphocytes, and lipids. ( 5.7 ) • Immunizations : Avoid use of live vaccines immediately prior to, during and immediately after CIBINQO treatment. ( 5.8 ) 5.1 Serious 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 patients with RA. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with CIBINQO. 5.3 Malignancy 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. 5.4 Major 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. 5.5 Thrombosis 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. 5.6 Hypoglycemia in Patients with Diabetes Hypoglycemia, including severe hypoglycemia, has been reported following initiation of JAK inhibitors in patients with diabetes. During treatment with CIBINQO, consider increased monitoring of blood glucose in patients with diabetes. Advise diabetic patients to notify their healthcare provider(s) if they develop signs or symptoms of hypoglycemia. 5.7 Laboratory 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 on cardiovascular morbidity and mortality has not been determined. 5.8 Immunizations Prior to initiating CIBINQO, complete all age-appropriate vaccinations as recommended by current immunization guidelines, including prophylactic herpes zoster vaccinations. Avoid vaccination with live vaccines immediately prior to, during and immediately after CIBINQO therapy.

Contraindications

4 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 (5.7) , 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 )

Overdose

10 OVERDOSAGE There is no experience regarding human overdosage with CIBINQO. There is no specific antidote for overdose with CIBINQO. In case of an overdose, call Poison Control Center at 1-800-222-1222 for latest recommendations.

Drug interactions

7 DRUG 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 ) 7.1 Effects 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. 7.2 Effects 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) ] .

Uses

1 INDICATIONS AND USAGE 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. Limitations of Use CIBINQO is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants. 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.

Dosage forms & strengths

TABLET, FILM COATED POWDER
ABROCITINIB 200 mg/1 ABROCITINIB 100 mg/1 ABROCITINIB 50 mg/1 ABROCITINIB 1 kg/kg
2 DOSAGE AND ADMINISTRATION • For recommended testing, evaluations, and procedures prior to CIBINQO initiation, see Full Prescribing Information. ( 2.1 ) • Recommended dosage is 100 mg orally once daily. ( 2.2 ) • 200 mg orally once daily is recommended for those patients who are not responding to 100 mg once daily. ( 2.2 ) • Moderate renal impairment: 50 mg once daily or 100 mg once daily for those patients who are not responding to 50 mg once daily. ( 2.3 ) • CYP2C19 poor metabolizer: 50 mg once daily or 100 mg once daily for those patients who are not responding to 50 mg once daily. ( 2.4 ) • For dosage modifications for certain adverse reactions, see Full Prescribing Information. ( 2.6 ) 2.1 Recommended Testing, Evaluations, and Procedures Prior to Treatment Initiation Perform the following tests and evaluations prior to CIBINQO initiation: • Tuberculosis (TB) infection evaluation – CIBINQO initiation is not recommended in patients with active TB. For patients with latent TB or those with a negative latent TB test who are at high risk for TB, start preventive therapy for latent TB prior to initiation of CIBINQO [see Warnings and Precautions (5.1) ] . • Viral hepatitis screening in accordance with clinical guidelines – CIBINQO initiation is not recommended in patients with active hepatitis B or hepatitis C [see Warnings and Precautions (5.1) ] . • A complete blood count (CBC) – CIBINQO initiation is not recommended in patients with a platelet count <150,000/mm 3 , an absolute lymphocyte count <500/mm 3 , an absolute neutrophil count <1,000/mm 3 , or a hemoglobin value <8 g/dL [see Warnings and Precautions (5.7) ] . Complete any necessary immunizations, including herpes zoster vaccinations, in agreement with current immunization guidelines prior to CIBINQO initiation [see Warnings and Precautions (5.8) ] . 2.2 Recommended Dosage The recommended dose is 100 mg once daily. If an adequate response is not achieved with CIBINQO 100 mg once daily, consider increasing the dosage to 200 mg once daily. Discontinue CIBINQO if an adequate response is not achieved with 200 mg once daily. Use the lowest efficacious dose to maintain response. CIBINQO can be used with or without topical corticosteroids. If a dose is missed, administer the dose as soon as possible unless it is less than 12 hours before the next dose, in which case skip the missed dose. Thereafter, resume dosing at the regular scheduled time. 2.3 Recommended Dosage in Patients with Renal Impairment or Hepatic Impairment Renal Impairment CIBINQO dosage recommendations for patients with renal impairment are provided in Table 1 [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . 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 [see Dosage and Administration (2.2) ] . Table 1. Dosage Recommendations in Patients with Renal Impairment Renal Impairment Stage Estimated Glomerular Filtration (eGFR) Glomerular filtration rate was estimated by the Modification of Diet in Renal Disease (MDRD) formula. Dosage Mild 60 – 89 mL/minute CIBINQO 100 mg once daily Moderate 30 – 59 mL/minute CIBINQO 50 mg once daily Severe Severe Renal Impairment and End-Stage Renal Disease include patients on renal replacement therapy. 15 – 29 mL/minute Not recommended for use End-Stage Renal Disease (ESRD) <15 mL/minute Hepatic Impairment CIBINQO is not recommended for use in patients with severe hepatic impairment [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ]. 2.4 Recommended Dosage in CYP2C19 Poor Metabolizers In patients who are known or suspected to be CYP2C19 poor metabolizers, the recommended dosage of CIBINQO is 50 mg once daily [see Use in Specific Populations (8.8) and Clinical Pharmacology (12.5) ]. If an adequate response is not achieved with CIBINQO 50 mg once daily, consider increasing the dosage to 100 mg once daily. Discontinue therapy if inadequate response is seen after dosage increase to 100 mg once daily . 2.5 Dosage Modifications due to Strong Inhibitors In patients taking strong inhibitors of cytochrome P450 (CYP) 2C19, reduce the dosage to 50 mg once daily [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . If an adequate response is not achieved with CIBINQO 50 mg daily, consider increasing the dosage to 100 mg once daily. Discontinue therapy if inadequate response is seen after dosage increase to 100 mg once daily. 2.6 Treatment Discontinuation due to Serious Infections or Hematologic Adverse Reactions Serious or Opportunistic Infections If a patient develops a serious or opportunistic infection, discontinue CIBINQO and control the infection. The risks and benefits of treatment with CIBINQO should be carefully considered prior to reinitiating therapy with CIBINQO [see Warnings and Precautions (5.1) ] . Hematologic Abnormalities Recommendations for CIBINQO discontinuation for laboratory abnormalities are summarized in Table 2. Table 2. Recommendations for CIBINQO Discontinuation for Hematologic Abnormalities Abbreviations: ALC=absolute lymphocyte count; ANC=absolute neutrophil count; CBC=complete blood count; Hb=hemoglobin Laboratory Measure Recommendation Platelet Count <50,000/mm 3 Discontinue CIBINQO and follow with CBC until >100,000/mm 3 ALC <500/mm 3 Treatment should be temporarily discontinued if ALC is less than 500 cells/mm 3 and may be restarted once ALC return above this value ANC <1,000/mm 3 Treatment should be temporarily discontinued if ANC is less than 1,000 cells/mm 3 and may be restarted once ANC return above this value Hb value <8 g/dL Treatment should be temporarily discontinued if Hb is less than 8 g/dL and may be restarted once Hb return above this value CBC evaluations are recommended at baseline, 4 weeks after treatment initiation and 4 weeks after dosage increase of CIBINQO. Laboratory evaluations may be extended for patients on chronic CIBINQO therapy who develop hematologic abnormalities [see Warnings and Precautions (5.7) ] . 2.7 Administration Instructions Administer CIBINQO with or without food at approximately the same time each day. Swallow CIBINQO tablets whole with water. Do not crush, split, or chew CIBINQO tablets.

All identified pills

Side effects

6 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 (5.7) ] 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 . 6.1 Clinical 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) [see Clinical Studies (14) ] 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 and 0 subjects treated with CIBINQO 100 mg or placebo. Both cases occurred in the first 4 weeks of exposure. Lipid Elevations In the placebo-controlled trials, for up to 16 weeks, there was a dose-related percent increase in low-density lipoprotein cholesterol (LDL-c), total cholesterol, and high-density lipoprotein cholesterol (HDL-c) relative to placebo at Week 4 which remained elevated through the final visit in the treatment period. Adverse reactions related to hyperlipidemia occurred in 1 subject (0.6 per 100 patient-years) exposed to CIBINQO 100 mg, 3 subjects (2.0 per 100 patient-years) exposed to CIBINQO 200 mg. Retinal Detachment In the placebo-controlled trials, for up to 16 weeks, retinal detachment occurred 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, retinal detachment occurred in 2 subjects (0.3 per 100 patient-years) treated with CIBINQO 100 mg. Creatine Phosphokinase Elevations (CPK) In the placebo-controlled trials, for up to 16 weeks, events of blood CPK increased were reported in 6 subjects (7.5 per 100 patient-years) treated with placebo, 11 subjects (6.9 per 100 patient-years) treated with 100 mg of CIBINQO and 19 subjects (12.3 per 100 patient-years) treated with 200 mg of CIBINQO. Most elevations were transient, there were no reported adverse reactions of rhabdomyolysis. Pediatric Subjects (12 to less than 18 years of age) The safety of CIBINQO was assessed in a trial of 284 subjects 12 to less than 18 years of age with moderate-to-severe atopic dermatitis (Trial-AD-4). The safety profile of CIBINQO in these subjects, assessed through the initial treatment period of 12 weeks and the long-term period (213 with at least 52 weeks of abrocitinib exposure), was comparable to the safety profile from trials in adults with atopic dermatitis.

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