Dosage & Administration
Cibinqo Prescribing Information
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:
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- 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.
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- Invasive fungal infections, including cryptococcosis and pneumocystosis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
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- 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)].
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.
Recommended Testing, Evaluations, and Procedures Prior to Treatment Initiation
Perform the following tests and evaluations prior to CIBINQO initiation:
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- 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)].
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- 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)].
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- A complete blood count (CBC) – CIBINQO initiation is 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 <8 g/dL [see Warnings and Precautions (5.6)].
Complete any necessary immunizations, including herpes zoster vaccinations, in agreement with current immunization guidelines prior to CIBINQO initiation [see Warnings and Precautions (5.7)].
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.
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)].
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Renal Impairment Stage | Estimated Glomerular Filtration (eGFR) * | Dosage |
Mild | 60 – 89 mL/minute | CIBINQO 100 mg once daily |
Moderate | 30 – 59 mL/minute | CIBINQO 50 mg once daily |
Severe † | 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)].
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.
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.
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.
| Abbreviations: ALC=absolute lymphocyte count; ANC=absolute neutrophil count; CBC=complete blood count; Hb=hemoglobin | |
Laboratory Measure | Recommendation |
Platelet Count <50,000/mm3 | Discontinue CIBINQO and follow with CBC until >100,000/mm3 |
ALC <500/mm3 | Treatment should be temporarily discontinued if ALC is less than 500 cells/mm3 and may be restarted once ALC return above this value |
ANC <1,000/mm3 | Treatment should be temporarily discontinued if ANC is less than 1,000 cells/mm3 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 (5.6)].
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.
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- 50 mg: Pink, oval, film-coated tablet debossed with "PFE" on one side and "ABR 50" on the other.
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- 100 mg: Pink, round, film-coated tablet debossed with "PFE" on one side and "ABR 100" on the other.
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- 200 mg: Pink, oval, film-coated tablet debossed with "PFE" on one side and "ABR 200" on the other.
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 13th 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).
Lactation
Risk Summary
There are no data on the presence of abrocitinib in human milk, the effects on the breast-fed infant, or the effects on milk production. Abrocitinib was secreted in milk of lactating rats (see Data). When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the serious adverse findings in adults, including risks of serious infections, malignancy, and thrombosis, advise women not to breastfeed during treatment with CIBINQO and for one day after the last dose (approximately 5–6 elimination half-lives).
Data
Animal Data
Lactating female rats were orally administered a single dose of 10 mg/kg abrocitinib on lactation day 12. Abrocitinib AUC was approximately 5 times greater in milk than in plasma.
Females and Males of Reproductive Potential
Infertility
Females
Based on the findings in rats, oral administration of CIBINQO may impair female fertility. Impaired fertility in female rats was reversible 1 month after cessation of abrocitinib oral administration [see Nonclinical Toxicology (13.1)].
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 [see Clinical Studies (14) and Adverse Reactions (6.1)].
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).
Geriatric Use
A total of 145 (4.6%) subjects 65 years of age and older, while 25 (0.8%) were 75 years of age and older, were enrolled in CIBINQO clinical trials. Clinical trials of CIBINQO did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.
A higher proportion of subjects 65 years of age and older discontinued from clinical trials compared to younger subjects. Among all subjects exposed to CIBINQO, including the long-term extension trial, confirmed ALC <500/mm3 occurred only in subjects 65 years of age and older. A higher proportion of subjects 65 years of age and older had platelet counts <75,000/mm3. The incidence rate of herpes zoster in subjects 65 years of age and older treated with CIBINQO (7.40 per 100 patient-years) was higher than that of subjects 18 to less than 65 years of age (3.44 per 100 patient-years).
Renal Impairment
In patients with severe (eGFR <30 mL/min) and moderate (eGFR 30–59 mL/min) renal impairment, the combined exposure (AUCinf,u) of abrocitinib and its two active metabolites, M1 and M2, is increased compared to patients with normal renal function (eGFR ≥90 mL/min) [see Clinical Pharmacology (12.3)]. This may increase the risk of adverse reactions such as infections.
CIBINQO is not recommended for use in patients with severe renal impairment and ESRD including those on renal replacement therapy [see Dosage and Administration (2.3)].
A dosage reduction in patients with moderate renal impairment is recommended. No dosage adjustment is required in patients with mild renal impairment (eGFR 60–89 mL/min) [see Dosage and Administration (2.3)].
CIBINQO has not been studied in subjects on renal replacement therapy. In Phase 3 clinical trials, CIBINQO was not evaluated in subjects with atopic dermatitis with baseline creatinine clearance values less than 40 mL/min.
Hepatic Impairment
Avoid use of CIBINQO in patients with severe (Child Pugh C) hepatic impairment. In clinical trials, CIBINQO was not evaluated in subjects with severe (Child Pugh C) hepatic impairment.
Dosage adjustment is not required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment based on similar combined exposure (AUCinf,u) of abrocitinib and its two active metabolites, M1 and M2 compared to patients with normal hepatic function [see Clinical Pharmacology (12.3)].
CYP2C19 Poor Metabolizers
In patients who are CYP2C19 poor metabolizers, the AUC of abrocitinib is increased compared to CYP2C19 normal metabolizers due to reduced metabolic clearance. Dosage reduction of CIBINQO is recommended in patients who are known or suspected to be CYP2C19 poor metabolizers based on genotype or previous history/experience with other CYP2C19 substrates [see Dosage and Administration (2.4) and Clinical Pharmacology (12.5)].
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)].