Abrocitinib

DAE Class; Rx

Common Brand Names; Cibinqo

• Dermatologics, JAK Inhibitors

Janus kinase (JAK) inhibitor; reversibly inhibits Janus kinase-1 (JAK1) by blocking adenosine triphosphate binding site

JAK-1 is essential for certain cytokines to elicit signals from various interleukins, cardiotrophin, neurotrophin, and interferons that are involved in inflammatory processes

Concomitant antiplatelet therapies, except for low-dose aspirin (≤81 mg qDay), during initial 3 months of treatment

>10%

Nausea (6-14.5%)

Nasopharyngitis (8.7-12.4%)

1-10%

Headache (6-7.8%)

Acne (1.6-4.7%)

Herpes simplex (3.3-4.2%)

Vomiting (1.5-3.2%)

Increased blood creatinine phosphokinase (2.3-2.9%)

Dizziness (1.8-2.9%)

Urinary tract infection (1.7-2.2%)

Upper abdominal pain (0.6-1.9%)

Fatigue (1.3-1.6%)

Impetigo (0.5-1.5%)

Thrombocytopenia (1.5%)

Oropharyngeal pain (1-1.4%)

Gastroenteritis (1.1-1.3%)

Influenza (1.1-1.2%)

Hypertension (0.8-1.2%)

Abdominal discomfort (0.5-1.2%)

Herpes zoster (0.3-1.2%)

Contact dermatitis (0.5-1.1%)

Black Box Warnings

Serious infection

• Increases risk for developing serious infections that may lead to hospitalization or death
• Most common serious infections reported were herpes simplex, herpes zoster, and pneumonia
• If serious opportunistic infection develops, discontinue therapy until infection controlled
• Avoid use with an active serious infection, including localized infections; carefully consider risks and benefits before initiating therapy in patients with chronic or recurrent infection
• Closely monitor for signs and symptoms of infection during and after treatment, including possible development of tuberculosis (TB) in patients who tested negative for latent TB infection before initiating therapy

• Reported infections include

  • Active TB, which may present with pulmonary or extrapulmonary disease; test for latent TB before use and during therapy; consider treating latent infection before use
  • Invasive fungal infections, including cryptococcosis and pneumocystosis
  • Bacterial, viral (including herpes zoster), and other infections due to opportunistic pathogens

Mortality

• Not approved for rheumatoid arthritis (RA)
• Patients with RA aged ≥50 years with at least 1 cardiovascular risk factor, in a comparison of another Janus kinase (JAK) inhibitor with TNF blockers, showed a higher rate of all-cause mortality, including sudden cardiovascular death, with the JAK inhibitor

Malignancies

• Lymphoma and other malignancies reported
• Higher rate of malignancies (excluding nonmelanoma skin cancer) observed
• Current or past smokers are at additional increased risk

Major adverse cardiovascular events (MACE)

• In patients with RA aged ≥50 years with at least 1 cardiovascular risk factor treated with another JAK inhibitor, a higher rate of MACE (defined as cardiovascular death, myocardial infarction, and stroke), was observed
• Patients who are current or past smokers are at additional increased risk
• Discontinue therapy if myocardial infarction or stroke occurs

Thrombosis

• Thrombosis, including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis reported
• Many of these adverse events were serious, and some resulted in death
• Avoid therapy in patients at risk
• If symptoms of thrombosis occur, discontinue therapy, and treat appropriately

Cautions

Malignancies reported; consider risks and benefits of treatment before initiating in patients with known malignancy, other than previously treated nonmelanoma skin cancer; screen for malignancies during treatment according to guidelines

Perform periodic skin examination for patients who are at increased risk for skin cancer; limit exposure to sun and ultraviolet (UV) light by wearing protective clothing and using broad-spectrum sunscreen

Higher rate of major adverse cardiovascular events (MACE; defined as cardiovascular death, myocardial infarction, and stroke) reported with another JAK inhibitor vs TNF blockers in RA patients

Thrombosis reported, including deep vein thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis; avoid therapy in patients who may be at increased risk of thrombosis

In patients with rheumatoid arthritis (RA) aged ≥50 years with at least 1 cardiovascular risk factor, a higher rate of all-cause mortality, including sudden cardiovascular death, was observed; not approved for RA

May cause neutropenia, lymphopenia, anemia, elevated lipids, or elevated liver enzymes; monitor for abnormal laboratory values, and assess the need to interrupt dosing

Pregnancy

Available postmarketing and published data reporting the use in pregnant women, are insufficient and confounded by concomitant use of other cytotoxic drugs, to evaluate for any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes

Lactation

Irinotecan and its metabolites are present in human milk; there is no information regarding effects of drug on breastfed infant, or on milk production; because of potential for serious adverse reactions from drug in breastfed child, advise lactating women not to breastfeed during treatment and for 7 days after final dose

Atopic Dermatitis

Indicated for refractory moderate-to-severe atopic dermatitis (AD) in patients aged ≥12 years whose disease is not adequately controlled with other systemic therapies, including biologics, or for whom those therapies are inadvisable

100 mg PO qDay

If adequate response not achieved, consider increasing to 200 mg qDay

Discontinue if adequate response not achieved with 200 mg/day

Use lowest efficacious dose to maintain response

Use with or without topical corticosteroids

Dosage Modifications

CYP2C19 poor metabolizers or coadministration with strong CYP2C19 inhibitors

• 50 mg qDay initially; if adequate response not achieved, may increase to 100 mg qDay
• Discontinue if inadequate response after dosage increase

Infection

• If serious or opportunistic infections develops, interrupt treatment until infection is controlled
• Carefully consider risks and benefits of treatment before reinitiating

Hematologic abnormalities

• Platelet count <50,000/mm³: Discontinue therapy and monitor until platelet count >100,000/mm³
• Absolute lymphocyte count (ALC) <500 cells/mm³: Interrupt therapy; may restart once ALC >500 cells/mm³
• Absolute neutrophil count (ANC) <1000 cells/mm³: Interrupt therapy; may restart once ANC >1000 cells/mm3
• Hemoglobin (Hb) <8 g/dL: Interrupt therapy; may restart once Hb >8 g/dL

Renal impairment

• Mild (eGFR 60-89 mL/min): No dosage adjustment necessary
• Moderate (eGFR 30-59 mL/min): 50 mg qDay initially; may double dose if adequate response not achieved
• Severe or end-stage renal disease (eGFR <29 mL/min): Not recommended
• Patients on renal replacement therapy: Not studied; not recommended

Hepatic impairment

• Mild or moderate (Child-Pugh A or B): No dose adjustment required
• Severe (Child-Pugh C): Not recommended

Abrocitinib