Brepocitinib
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, and THROMBOSIS SERIOUS INFECTIONS Patients treated with LISRAYA are at increased risk of developing serious bacterial, fungal, viral, and opportunistic infections that may lead to hospitalization or death. Reported infections with use of Janus kinase (JAK) inhibitors, including LISRAYA: Active tuberculosis (TB), which may present with pulmonary or extrapulmonary disease. Evaluate and test patients for latent and active TB infection prior to and during LISRAYA treatment. If positive, treat for TB.
Monitor all patients for active TB during treatment including patients who tested negative of a latent TB infection prior to LISRAYA treatment. Invasive fungal infections. 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 LISRAYA in patients with an active, serious infection, including localized infections. Consider the risks and benefits of LISRAYA in patients with chronic or recurrent infection prior to initiating treatment. Closely monitor patients for signs and symptoms of infection during and after treatment with LISRAYA.
If a serious infection occurs, interrupt LISRAYA treatment until the infection resolves or is adequately treated [see Warnings and Precautions ( 5.1 )] . MORTALITY A higher rate of all-cause mortality, including sudden cardiovascular death was observed with another Janus kinase (JAK) inhibitor when compared to tumor necrosis factor (TNF) blockers in patients with rheumatoid arthritis (RA) [see Warnings and Precautions ( 5.2 )]. LISRAYA is not approved for use in patients with RA. MALIGNANCY Malignancies have occurred in patients treated with LISRAYA.
A higher rate of malignancies (excluding non-melanoma skin cancer), lymphomas, and lung cancers was observed with another JAK inhibitor when compared to TNF blockers in patients with RA . LISRAYA is not approved for use in patients with RA. 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 (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) have occurred in patients treated with LISRAYA. A higher rate of MACE was observed with another JAK inhibitor when compared to TNF blockers in patients with RA.
LISRAYA is not approved for use in patients with RA. Patients who are current or past…
Dosing in kidney impairment
Renal Impairment The recommended dosage in patients with mild (eGFR: 60 to 89 mL/min) or moderate (eGFR: 30 to 59 mL/min) renal impairment is the same as in patients without renal impairment. LISRAYA is not recommended in patients with severe renal impairment (eGFR: < 30 mL/min).
Dosing in liver impairment
Hepatic Impairment The recommended dosage in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment is the same as in patients without hepatic impairment. LISRAYA has not been evaluated in patients with severe hepatic impairment (Child-Pugh C) and therefore, is not recommended in this population.
| Laboratory Measure | Action |
|---|---|
| Absolute Neutrophil Count (ANC) | Interrupt LISRAYA treatment if ANC is less than 1,000 cells/mm3; treatment may be restarted once ANC returns above this value |
| Absolute Lymphocyte Count (ALC) | Interrupt LISRAYA treatment if ALC is less than 500 cells/mm3; treatment may be restarted once ALC returns above this value |
| Hemoglobin (Hb) | Interrupt LISRAYA treatment if Hb is less than 8 g/dL; treatment may be restarted once Hb returns above this value |
| Hepatic transaminases (ALT/AST) | Interrupt LISRAYA treatment if drug-induced liver injury is suspected, until this diagnosis is excluded. |
Preparation and administration
Recommended Dosage and Administration The recommended dosage of LISRAYA is 30 mg once daily, administered orally with or without food [see Clinical Pharmacology] .
Drug interactions
Check brepocitinib against a medication listLabel text (4 paragraphs)
7 DRUG INTERACTIONS
7.1 Effects of Other Drugs on LISRAYA Smoking Smoking causes induction of CYP1A1 and CYP1A2 levels. The exposure of brepocitinib in current smokers is lower than in non-current smokers, and therefore, the effectiveness of LISRAYA may be reduced in smokers [see Clinical Pharmacology ( 12.3 )] .
7.2 Effects of LISRAYA on Other Drugs Substrates of P-gp and BCRP Brepocitinib is a P-gp and BCRP inhibitor. Concomitant use of LISRAYA with an orally administered P-gp or BCRP substrate may increase the systemic exposure of the P-gp or BCRP substrate [see Clinical Pharmacology ( 12.3 )]. Substrates of OCT2 or MATEs Transporters Brepocitinib inhibits renal uptake transporters, OCT2 and MATEs (MATE1, MATE2-K) [see Clinical Pharmacology ( 12.3 )] . Concomitant use of LISRAYA with drugs that are substrates of OCT2 and MATEs transporters may increase plasma concentrations of the substrates.
Closely monitor patients when LISRAYA is concomitantly used with drugs that are substrates of OCT2 or MATEs transporters for which minimal concentration changes in substrate plasma concentration may lead to serious adverse reactions.
Contraindications
4 CONTRAINDICATIONS LISRAYA is contraindicated in patients with a history of hypersensitivity reactions to brepocitinib or any of the excipients in LISRAYA [see Warnings and Precautions ( 5.6 )] . LISRAYA is contraindicated in patients with a history of hypersensitivity reactions to brepocitinib or any of the excipients in LISRAYA. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
LiverTox has no chapter for brepocitinib. Check the label's hepatic warnings.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings in animal studies, LISRAYA may cause fetal harm when administered to a pregnant woman. Available data from LISRAYA use in pregnant women are insufficient to establish a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, fetal skeletal malformations, and post-implantation loss were observed when brepocitinib was administered to pregnant rats and rabbits during the period of organogenesis at 1.6- and 3-times the exposure at the MRHD, respectively.
In a pre- and postnatal study in rats, brepocitinib did not cause adverse effects in maternal animals or offspring at exposures up to 5.5 times the MRHD. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15 % to 20%, respectively. There is a pregnancy safety study for LISRAYA.
If LISRAYA is administered during pregnancy, healthcare providers or patients should report LISRAYA exposure to Priovant Therapeutics by calling 1-800-511-9141 or by emailing contactcenter@priovant.com. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with dermatomyositis. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.
Data Animal Data In rat embryofetal developmental studies, pregnant rats were administered brepocitinib orally during the period of organogenesis. Skeletal malformations, early and late resorptions, post-implantation loss, and lower mean numbers of viable fetuses were observed with exposures 1.6 times the MRHD. No adverse effects were observed at 1.3 times the MRHD. In a rabbit embryofetal developmental study, pregnant rabbits were administered brepocitinib orally during the period of organogenesis. Increase of late resorptions, post-implantation loss, lower mean numbers of viable fetuses, and skeletal malformations were observed at 3 times the MRHD.
No developmental toxicity was observed in rabbits at 0.8 times the MRHD. In a pre- and postnatal development study, pregnant rats were administered brepocitinib orally from gestation day 6…
Breastfeeding (LactMed)
No information is available on the clinical use of brepocitinib during breastfeeding. Because of the potential for serious adverse reactions in the breastfed infant, including infections, GI perforation, and malignancy, breastfeeding is not recommended during treatment with brepocitinib and for 3 days after the last dose.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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