Cibinqo Drug Information

• 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 . 6.1 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) 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.

• 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) ] .

Pregnancy 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).

Pediatric Use The safety and effectiveness of CIBINQO in pediatric patients 12 years of age and older with atopic dermatitis have been established. In trials Trial-AD-1 and Trial-AD-2, 124 pediatric subjects 12 to less than 18 years old weighing 25 kg or more with moderate-to-severe atopic dermatitis were enrolled and randomized to receive either CIBINQO 100 mg (N=51), 200 mg (N=48), or matching placebo (N=25) in monotherapy. Additional 284 pediatric subjects 12 to less than 18 years of age weighing 25 kg or more with moderate-to-severe atopic dermatitis, were enrolled and randomized to receive either CIBINQO 100 mg (N=95) or 200 mg (N=94) or matching placebo (N=95) in combination with topical corticosteroids in Trial-AD-4. Efficacy and adverse reaction profile were comparable between the pediatric patients and adults . The safety and effectiveness of CIBINQO have not been established in pediatric patients below 12 years of age.

Juvenile Animal Toxicity Data In a juvenile animal toxicity study, abrocitinib was administered orally to juvenile rats at doses of 5, 25, and 75 mg/kg/day from postnatal day 10 (approximately equivalent to a human infant) through postnatal day 63 (approximately equivalent to an adolescent). Abrocitinib caused a reversible, dose‑related decrease in the primary spongiosa in the metaphysis of the proximal tibia and distal femur and adverse effects on bone development at all dose levels. Abrocitinib caused irreversible dose-related small or misshapen femoral heads at doses ≥5 mg/kg/day (0.8 times the MRHD based on AUC comparison); irreversibly decreased femur size and caused paw malrotation and limb impairment at doses ≥25 mg/kg/day (7.2 times the MRHD based on AUC comparison); and fractures at 75 mg/kg/day (27 times the MRHD based on AUC comparison). In a follow-up study, abrocitinib (25 mg/kg/day, at least 4.5 times the MRHD based on AUC comparison) was orally administered to juvenile rats from postnatal day (PND) 10, 15, 21, or 30 through PND day 63. Administration beginning PND 10 caused adverse macroscopic and microscopic bone findings consistent with the previous juvenile animal study. However, administration beginning PND 15 (approximately equivalent to a 6- to 12-month old infant) caused non-adverse reversible microscopic bone findings.

No bone findings were noted when administration began on PND 21 or 30 (approximately equivalent to 2- and 6-year old children, respectively).

is contraindicated in patients taking antiplatelet therapies, except for low-dose aspirin (≤81 mg daily), during the first 3 months of treatment. Antiplatelet therapies except for low-dose aspirin (≤81 mg daily), during the first 3 months of treatment.

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.