Safety and Tolerability

Important Safety Information

WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS

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.

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 or those who have resided or traveled in areas of endemic tuberculosis or endemic mycoses.

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.

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.

Viral reactivation, including herpes virus reactivation (eg, herpes zoster, herpes simplex), was reported in clinical studies with CIBINQO. If a patient develops herpes zoster, consider interrupting CIBINQO until the episode resolves. Hepatitis B virus reactivation has been reported in patients receiving JAK inhibitors. Perform viral hepatitis screening and monitoring for reactivation in accordance with clinical guidelines before starting therapy and during therapy with CIBINQO. CIBINQO is not recommended for use in patients with active hepatitis B or hepatitis C.

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.

MALIGNANCIES
Malignancies, including non-melanoma skin cancer (NMSC), were reported in patients treated with CIBINQO. Lymphoma and other malignancies have been observed in patients receiving JAK inhibitors used to treat inflammatory conditions. 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.

In a large, randomized postmarketing safety study of another JAK inhibitor in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer [NMSC]) was observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. CIBINQO is not approved for use in RA patients. A higher rate of lymphomas was observed in patients 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. 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 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.

MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE)
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. CIBINQO is not approved for use in RA patients. Patients who are current or past smokers are at additional increased risk. Discontinue CIBINQO in patients that have experienced a myocardial infarction or stroke.

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.

THROMBOSIS
Deep vein 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 overall thrombosis, DVT, and PE were observed when compared with TNF blockers. CIBINQO is not approved for use in RA patients.

Avoid CIBINQO in patients that may be at increased risk of thrombosis. If symptoms of thrombosis occur, discontinue CIBINQO and treat patients appropriately.

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

LABORATORY ABNORMALITIES
Hematologic Abnormalities: Treatment with CIBINQO was associated with an increased incidence of thrombocytopenia and lymphopenia. Prior to CIBINQO initiation, perform a complete blood count (CBC). 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.

Lipid Elevations: Dose-dependent increase in blood lipid parameters were reported in patients treated with CIBINQO. 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.

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.

RENAL IMPAIRMENT
Avoid use in patients with severe renal impairment or end stage renal disease, including those on renal replacement therapy.

HEPATIC IMPAIRMENT
Avoid use in patients with severe hepatic impairment.

ADVERSE REACTIONS
Most common adverse reactions (≥1%) in subjects receiving 100 mg and 200 mg include: nasopharyngitis, nausea, headache, herpes simplex, increased blood creatine phosphokinase, dizziness, urinary tract infection, fatigue, acne, vomiting, oropharyngeal pain, influenza, gastroenteritis.

Most common adverse reactions (≥1%) in subjects receiving either 100 mg or 200 mg also include: impetigo, hypertension, contact dermatitis, upper abdominal pain, abdominal discomfort, herpes zoster, and thrombocytopenia.

Inform patients that retinal detachment has been reported in CIBINQO clinical trials. Advise patients to immediately inform their healthcare provider if they develop any sudden changes in vision.

DRUG INTERACTIONS
Monitor appropriately or dose titrate P-gp substrate where small concentration changes may lead to serious or life-threatening toxicities when coadministered with CIBINQO. See Prescribing Information for clinically relevant drug interactions.

USE IN PREGNANCY
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. Advise females of reproductive potential that CIBINQO may impair fertility.

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 or visit CIBINQOPregnancyRegistry.com.

LACTATION
Advise women not to breastfeed during treatment with CIBINQO and for one day after the last dose.

Please see full Prescribing Information, including BOXED WARNING, and Medication Guide.

INDICATION

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 with other immunosuppressants.