Cibinqo Drug Information

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: • 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. • Viral hepatitis screening in accordance with clinical guidelines – CIBINQO initiation is not recommended in patients with active hepatitis B or hepatitis C. • 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. Complete any necessary immunizations, including herpes zoster vaccinations, in agreement with current immunization guidelines prior to CIBINQO initiation.

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. 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. 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. Table 1.

Hepatic Impairment CIBINQO is not recommended for use in patients with severe hepatic impairment.

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. 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.

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. Hematologic Abnormalities Recommendations for CIBINQO discontinuation for laboratory abnormalities are summarized in Table 2.

Table 2. Recommendations for CIBINQO Discontinuation for Hematologic Abnormalities 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.

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.

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. 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 9 0 0 Specific Adverse Reactions Exposure adjusted incidence rates were adjusted by trial size for all the adverse reactions reported in this section. 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.

No thrombosis occurred in subjects treated with CIBINQO 100 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.

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. Most elevations were transient, there were no reported adverse reactions of rhabdomyolysis.

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.

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.

Intervention Dosage reduction of CIBINQO is recommended when coadministered with strong CYP2C19 inhibitors. 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. 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. Intervention Avoid concomitant use of CIBINQO with strong CYP2C19 or CYP2C9 inducers.

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). 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. Intervention Antiplatelet drugs, except for low-dose aspirin (≤81 mg daily), during the first 3 months of treatment are contraindicated with CIBINQO.

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). 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).

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. 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) 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).

CIBINQO is contraindicated in patients taking 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.