b'Tuberculosis: No cases of active tuberculosis (TB) were reported in clinical trials Adverse reactions that occurred in Trials 1 and 2 in 1% of subjects in the OPZELURAand other bone measures [e.g., bone mineral content, peripheral quantitative with OPZELURA. Cases of active TB were reported in clinical trials of oral Janusgroup and none in the vehicle group were: neutropenia, allergic conjunctivitis, pyrexia,computed tomography, and x-ray analysis] occurred at doses5 mg/kg/day. When kinase inhibitors used to treat inflammatory conditions. Consider evaluating patientsseasonal allergy, herpes zoster, otitis externa, Staphylococcal infection, and administered starting at postnatal day 21 (the equivalent of a human 2-3 years of for latent and active TB infection prior to administration of OPZELURA. Duringacneiform dermatitis.age) at doses of 5 to 60 mg/kg/day, effects on body weight and bone occurred at OPZELURA use, monitor patients for the development of signs and symptoms of TB. DRUG INTERACTIONSdoses15 mg/kg/day, which were considered adverse at 60 mg/kg/day. Males were Viral Reactivation: Viral reactivation, including cases of herpes virus reactivation more severely affected than females in all age groups, and effects were generally Drug interaction studies with OPZELURA have not been conducted. Ruxolitinib ismore severe when administration was initiated earlier in the postnatal period. These OPZELURA (ruxolitinib) cream, for topical use (e.g., herpes zoster), were reported in clinical trials with Janus kinase inhibitors usedknown to be a substrate for cytochrome P450 3A4 (CYP3A4). Inhibitors of CYP3A4 findings were observed at systemic exposures that are at least 40% the MRHD Brief Summary of FULL PRESCRIBING INFORMATION to treat inflammatory conditions including OPZELURA. If a patient develops herpesmay increase ruxolitinib systemic concentrations whereas inducers of CYP3A4 mayclinical systemic exposure.zoster, consider interrupting OPZELURA treatment until the episode resolves. decrease ruxolitinib systemic concentrations. INDICATIONS AND USAGE: OPZELURA is indicated for the topical short-term Hepatitis B and C: The impact of Janus kinase inhibitors used to treat inflammatoryGeriatric Use: Of the 1249 total subjects with atopic dermatitis in clinical trials with and non-continuous chronic treatment of mild to moderate atopic dermatitis inconditions including OPZELURA on chronic viral hepatitis reactivation is unknown.Strong Inhibitors of CYP3A4: Avoid concomitant use of OPZELURA with strongOPZELURA, 115 were 65 years of age and older. No clinically meaningful differences non-immunocompromised patients 12 years of age and older whose disease is Patients with a history of hepatitis B or C infection were excluded from clinical trials. inhibitors of CYP3A4 as there is a potential to increase the systemic exposure ofin safety or effectiveness were observed between patients less than 65 years and not adequately controlled with topical prescription therapies or when those therapies ruxolitinib and could increase the risk of OPZELURA adverse reactions. patients 65 years and older.are not advisable. Hepatitis B viral load (HBV-DNA titer) increases, with or without associatedUSE IN SPECIFIC POPULATIONS PATIENT COUNSELING INFORMATIONelevations in alanine aminotransferase and aspartate aminotransferase, have been Limitation of Use: Use of OPZELURA in combination with therapeutic biologics, otherreported in patients with chronic HBV infections taking oral ruxolitinib. OPZELURAPregnancyAdvise the patient or caregivers to read the FDA-approved patient labeling JAK inhibitors or potent immunosuppressants such as azathioprine or cyclosporine initiation is not recommended in patients with active hepatitis B or hepatitis C. Pregnancy Exposure Registry: There will be a pregnancy registry that monitors(Medication Guide).is not recommended. Mortality: A higher rate of all-cause mortality, including sudden cardiovascularpregnancy outcomes in pregnant persons exposed to OPZELURA during pregnancy.Infections: Inform patients that they may be at increased risk for developing WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJORdeath was observed in clinical trials of oral Janus kinase inhibitors used to treatPregnant persons exposed to OPZELURA and healthcare providers should reportinfections, including serious infections, when taking Janus kinase inhibitors. Instruct ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS inflammatory conditions. Consider the benefits and risks for the individual patientOPZELURA exposure by calling 1-855-463-3463. patients to tell their healthcare provider if they develop any signs or symptoms of an prior to initiating or continuing therapy with OPZELURA. Risk Summary: Available data from pregnancies reported in clinical trials withinfection. Advise patients that Janus kinase inhibitors increase the risk of herpes SERIOUS INFECTIONS Malignancy and Lymphoproliferative Disorders: Malignancies, includingOPZELURA are not sufficient to evaluate a drug-associated risk for major birthzoster, and some cases can be serious.Patients treated with oral Janus kinase inhibitors for inflammatory conditionslymphomas, were observed in clinical trials of oral Janus kinase inhibitors used todefects, miscarriage, or other adverse maternal or fetal outcomes. In animalMalignancies and Lymphoproliferative Disorders: Inform patients that Janus kinase are at risk for developing serious infections that may lead to hospitalization ortreat inflammatory conditions. Patients who are current or past smokers are atreproduction studies, oral administration of ruxolitinib to pregnant rats and rabbitsinhibitors may increase the risk for developing lymphomas and other malignancies death [see Warnings and Precautions and Adverse Reactions]. additional increased risk. Consider the benefits and risks for the individual patientduring the period of organogenesis resulted in adverse developmental outcomes atincluding skin cancer. Instruct patients to inform their health care provider if they Reported infections include: prior to initiating or continuing therapy with OPZELURA, particularly in patients withdoses associated with maternal toxicity. have ever had any type of cancer. Inform patients that periodic skin examinationsActive tuberculosis, which may present with pulmonary ora known malignancy (other than successfully treated non-melanoma skin cancers),The background risks of major birth defects and miscarriage for the indicatedshould be performed while using OPZELURA. extrapulmonary disease.patients who develop a malignancy, and patients who are current or past smokers. populations are unknown. All pregnancies carry some risk of birth defects, loss, orMajor Adverse Cardiovascular Events: Advise patients that events of major adverse Invasive fungal infections, including candidiasis and pneumocystosis.Non-melanoma Skin Cancers: Non-melanoma skin cancers including basal cell andother adverse outcomes. The background risk in the U.S. general population of majorcardiovascular events (MACE) including non-fatal myocardial infarction, non-fatal Bacterial, viral, and other infections due to opportunistic pathogens. squamous cell carcinoma have occurred in patients treated with OPZELURA. Performbirth defects and miscarriage is 2-4% and 15-20%, respectively. stroke, and cardiovascular death, have been reported in clinical studies with Janus Avoid use of OPZELURA in patients with an active, serious infection,periodic skin examinations during OPZELURA treatment and following treatment Data kinase inhibitors used to treat inflammatory conditions. Instruct all patients, including localized infections. If a serious infection develops, interruptas appropriate. Animal Data: Ruxolitinib was administered orally to pregnant rats or rabbits duringespecially current or past smokers or patients with other cardiovascular risk factors, OPZELURA until the infection is controlled. Major Adverse Cardiovascular Events (MACE): Major adverse cardiovascularthe period of organogenesis, at doses of 15, 30 or 60 mg/kg/day in rats and 10, 30to be alert for the development of signs and symptoms of cardiovascular events.The risks and benefits of treatment with OPZELURA should be carefullyevents (MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI),or 60 mg/kg/day in rabbits. There were no treatment-related malformations at anyThrombosis: Advise patients that events of DVT and PE have been reported in clinical considered prior to initiating therapy in patients with chronic or and non-fatal stroke were observed in clinical trials of Janus kinase inhibitors useddose. A decrease in fetal weight of approximately 9% was noted in rats at thestudies with Janus kinase inhibitors used to treat inflammatory conditions. Instruct recurrent infection. to treat inflammatory conditions. Consider the benefits and risks for the individualhighest and maternally toxic dose of 60 mg/kg/day. This dose resulted in systemicpatients to tell their healthcare provider if they develop any signs or symptoms ofpatient prior to initiating or continuing therapy with OPZELURA particularly inexposure approximately 22 times the clinical systemic exposure at the maximuma DVT or PE.Patients should be closely monitored for the development of signs andpatients who are current or past smokers and patients with other cardiovascular riskrecommended human dose (MRHD); the clinical systemic exposure from ruxolitinib symptoms of infection during and after treatment with OPZELURA [seefactors. Patients should be informed about the symptoms of serious cardiovascularcream, 1.5% applied twice daily to 25-40% body surface area is used for calculationThrombocytopenia, Anemia and Neutropenia: Advise patients of the risk of Warnings and Precautions]. events and the steps to take if these symptoms occur. of multiples of human exposure. In rabbits, lower fetal weights of approximately 8%thrombocytopenia, anemia, and neutropenia with OPZELURA. Instruct patients to tell and increased late resorptions were noted at the highest and maternally toxic dose their healthcare provider if they develop any signs or symptoms of thrombocytopenia, MORTALITY Thrombosis: Thrombosis, including deep venous thrombosis (DVT), pulmonaryanemia or neutropenia [see Warnings and Precautions]. Higher rate of all-cause mortality, including sudden cardiovascular deathembolism (PE) and arterial thrombosis, has been observed at an increased incidenceof 60 mg/kg/day. This dose resulted in systemic exposure approximately 70% the have been observed in patients treated with oral Janus kinase inhibitors in patients treated with oral Janus kinase inhibitors for inflammatory conditionsMRHD clinical systemic exposure. In a pre-and post-natal development study in rats,Administration Instructions: Advise patients or caregivers that OPZELURA is for for inflammatory conditions [see Warnings and Precautions]. compared to patients treated with placebo. Many of these adverse reactions werepregnant animals were dosed with ruxolitinib from implantation through lactation topical use only [see Dosage and Administration].MALIGNANCIES serious and some resulted in death. Thromboembolic events were observed inat doses up to 30 mg/kg/day. There were no drug-related adverse effects onAdvise patients to limit treatment to 60 grams per week.Lymphoma and other malignancies have been observed in patients treatedclinical trials with OPZELURA. There was no clear relationship between plateletembryofetal survival, postnatal growth, development parameters or offspringPregnancy: Inform patients to report their pregnancy to Incyte Corporationwith Janus kinase inhibitors for inflammatory conditions [see Warnings count elevations and thrombotic events. OPZELURA should be used with caution inreproductive function at the highest dose evaluated (3.1 times the MRHD clinical patients who may be at increased risk of thrombosis.systemic exposure). at 1-855-463-3463 [see Use in Specific Populations].and Precautions].Thrombocytopenia, Anemia and Neutropenia: Thrombocytopenia, anemia andLactation Lactation: Advise a patient not to breastfeed during treatment with OPZELURAMAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE) and for four weeks after the last dose [see Use in Specific Populations].Higher rate of MACE (including cardiovascular death, myocardial infarction,neutropenia were reported in the clinical trials with OPZELURA. Consider theRisk Summary: There are no data on the presence of ruxolitinib in human milk, the and stroke) has been observed in patients treated with Janus kinasebenefits and risks for individual patients who have a known history of these eventseffects on the breastfed child, or the effects on milk production. Ruxolitinib was inhibitors for inflammatory conditions [see Warnings and Precautions]. prior to initiating therapy with OPZELURA. Perform CBC monitoring as clinicallypresent in the milk of lactating rats. When a drug is present in animal milk, it is likelyManufactured for:indicated. If signs and/or symptoms of clinically significant thrombocytopenia,that the drug will be present in human milk. Because of the serious adverse findings THROMBOSIS anemia, and neutropenia occur, patients should discontinue OPZELURA. in adults, including risks of serious infections, thrombocytopenia, anemia, andIncyte CorporationThrombosis, including deep venous thrombosis, pulmonary embolism, andneutropenia, advise women not to breastfeed during treatment with OPZELURA 1801 Augustine Cut-offarterial thrombosis has been observed at an increased incidence in patientsLipid Elevations: Treatment with oral ruxolitinib has been associated with increasesand for approximately four weeks after the last dose (approximately 5 eliminationWilmington, DE 19803treated with oral Janus kinase inhibitors for inflammatory conditionsin lipid parameters including total cholesterol, low-density lipoprotein (LDL)half-lives). compared to placebo. Many of these adverse reactions were serious andcholesterol, and triglycerides.some resulted in death. Patients with symptoms of thrombosis should beADVERSE REACTIONS Data: Lactating rats were administered a single dose of [14C]-labeled ruxolitinibpromptly evaluated [see Warnings and Precautions]. (30 mg/kg) on postnatal Day 10, after which plasma and milk samples wereOPZELURA is a trademark of Incyte. All rights reserved.Clinical Trials Experience: Because clinical trials are conducted under widely varyingcollected for up to 24 hours. The AUC for total radioactivity in milk was approximatelyU.S. Patent Nos. 7598257; 8415362; 8722693; 8822481; WARNINGS AND PRECAUTIONSconditions, adverse reaction rates observed in the clinical trials of a drug cannot be13 times the maternal plasma AUC. Additional analysis showed the presence of9079912; 9974790; 10639310; 10610530; 10758543; 10869870directly compared to rates in the clinical trials of another drug and may not reflect theruxolitinib and several of its metabolites in milk, all at levels higher than those in 2021 Incyte Corporation. All rights reservedSerious Infections: Serious and sometimes fatal infections due to bacterial,rates observed in practice. In two double-blind, vehicle-controlled clinical trials (Trials 1maternal plasma. Issued: September 2021 PLR-ONA-00004mycobacterial, invasive fungal, viral, or other opportunistic pathogens have beenand 2), 499 subjects 12 years of age and older with atopic dermatitis were treated withPediatric Use: The safety and effectiveness of OPZELURA for the topical treatmentreported in patients receiving oral janus kinase inhibitors. Serious lower respiratoryOPZELURA twice daily for 8 weeks. In the OPZELURA group, 62% of subjects wereof atopic dermatitis have been established in pediatric patients aged 12 to 17 yearstract infections were reported in the clinical development program with topicalfemales, and 71% of subjects were White, 23% were Black, and 4% were Asian. Theof age with mild-to-moderate atopic dermatitis. Use of OPZELURA in this age groupruxolitinib. Avoid use of OPZELURA in patients with an active, serious infection,adverse reactions reported by1% of OPZELURA-treated subjects and at a greateris supported by evidence from Trials 1 and 2 which included 92 subjects aged 12 toincluding localized infections. Consider the risks and benefits of treatment prior toincidence than in the vehicle arm through week 8 are as follows for OPZELURA17 years. No clinically meaningful differences in safety or effectiveness were observed initiating OPZELURA in patients: with chronic or recurrent infection; with a history of(N=499) vs Vehicle (N=250), respectively: Subjects with any treatment emergentbetween adult and pediatric subjects. The safety and effectiveness of OPZELURAa serious or an opportunistic infection; who have been exposed to tuberculosis; whoadverse event (TEAE) 132 (27%) vs 83 (33%), Nasopharyngitis 13 (3%) vs 2 (1%),in pediatric patients younger than 12 years of age have not been established.have resided or traveled in areas of endemic tuberculosis or endemic mycoses; orBronchitis 4 (1%) vs 0 (0%), Ear infection 4 (1%) vs 0 (0%), Eosinophil count increasedwith underlying conditions that may predispose them to infection. Closely monitor4 (1%) vs 0 (0%), Urticaria 4 (1%) vs 0 (0%), Diarrhea 3 (1%) vs 1 (1%), Folliculitis Juvenile Animal Toxicity Data: Oral administration of ruxolitinib to juvenile rats patients for the development of signs and symptoms of infection during and after3 (1%) vs 0 (0%), Tonsillitis 3 (1%) vs 0 (0%), and Rhinorrhea 3 (1%) vs 1 (1%).resulted in effects on growth and bone measures. When administered starting at treatment with OPZELURA. Interrupt OPZELURA if a patient develops a seriouspostnatal day 7 (the equivalent of a human newborn) at doses of 1.5 to 75 mg/kg/day, infection, an opportunistic infection, or sepsis. Do not resume OPZELURA until theevidence of fractures occurred at doses30 mg/kg/day, and effects on body weight infection is controlled.'