Australia - English - Department of Health (Therapeutic Goods Administration)

astrazeneca pty ltd - anifrolumab, quantity: 300 mg - injection, concentrated - excipient ingredients: polysorbate 80; water for injections; trehalose dihydrate; histidine hydrochloride monohydrate; histidine; lysine hydrochloride - saphnelo (anifrolumab) is indicated as add on treatment of adult patients with moderate to severe, active systemic lupus erythematosus (sle), despite standard therapy.,the safety and efficacy of saphnelo have not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus.

United States - English - NLM (National Library of Medicine)

astrazeneca pharmaceuticals lp - anifrolumab (unii: 38rl9ae51q) (anifrolumab - unii:38rl9ae51q) - saphnelo (anifrolumab-fnia) is indicated for the treatment of adult patients with moderate to severe systemic lupus erythematosus (sle), who are receiving standard therapy [see clinical studies (14)] . limitations of use the efficacy of saphnelo has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. use of saphnelo is not recommended in these situations.                                                                 saphnelo is contraindicated in patients with a history of anaphylaxis with anifrolumab-fnia [see warnings and precautions (5.2)] . pregnancy exposure registry a pregnancy exposure registry monitors pregnancy outcomes in women exposed to saphnelo during pregnancy. for more information about the registry or to report a pregnancy while on saphnelo, contact astrazeneca at 1‑877‑693‑9268. risk summary the limited human data with saphnelo use in pregnant women are insufficient to inform on drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcome. monoclonal igg antibodies are known to be actively transported across the placenta as pregnancy progresses; therefore, anifrolumab-fnia exposure to the fetus may be greater during the third trimester of pregnancy. in an enhanced pre- and post-natal development study with pregnant cynomolgus monkeys that received intravenous administration of anifrolumab-fnia, there was no evidence of embryotoxicity or fetal malformations with exposures up to approximately 28‑times the exposure at the maximum recommended human dose (mrhd) on an area under curve (auc) basis (see data) . all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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. clinical considerations disease-associated maternal and/or embryo/fetal risk : pregnant women with sle are at increased risk of adverse pregnancy outcomes, including worsening of the underlying disease, premature birth, miscarriage, and intrauterine growth restriction. maternal lupus nephritis increases the risk of hypertension and preeclampsia/eclampsia. passage of maternal autoantibodies across the placenta may result in adverse neonatal outcomes, including neonatal lupus and congenital heart block. data animal data : in an enhanced pre- and post-natal development study, pregnant cynomolgus monkeys received anifrolumab-fnia at intravenous doses of 30 or 60 mg/kg once every 2 weeks from confirmation of pregnancy at gestation day 20, throughout the gestation period, and continuing until 1‑month post-partum (approximately lactation day 28). there was no evidence of anifrolumab-fnia related maternal toxicity, embryo-fetal toxicity, or post-natal developmental effects. no anifrolumab-fnia related effect on t-cell-dependent antibody response in the infants was noted up to day 180 after birth. the no observed adverse effect level (noael) for maternal and developmental toxicity was identified as 60 mg/kg (approximately 28‑times the mrhd on an auc basis). in the infants, mean serum concentrations of anifrolumab‑fnia on day 30 after birth increased with dose and were approximately 4.2% to 9.7% of the respective maternal concentrations. the anifrolumab-fnia concentrations in the infant serum were up to approximately 22‑times the concentrations in the maternal milk, suggesting that anifrolumab-fnia had transferred via the placenta. risk summary no data are available regarding the presence of saphnelo in human milk, the effects on the breastfed child, or the effects on milk production. anifrolumab-fnia was detected in the milk of female cynomolgus monkeys administered anifrolumab-fnia. due to species-species differences in lactation physiology, animal data may not reliably predict drug levels in humans. maternal igg is known to be present in human milk. if anifrolumab-fnia is transferred into human milk, the effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to anifrolumab-fnia are unknown. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for anifrolumab-fnia and any potential adverse effects on the breast-fed child from anifrolumab-fnia or from the underlying maternal condition. the safety and efficacy of saphnelo in pediatric patients less than 18 years of age have not been established. of the 664 patients with sle exposed to anifrolumab-fnia in clinical trials, 3% (n=20) were 65 and over. the number of patients aged 65 years of age and older was not sufficient to determine whether they respond differently from younger adult patients.

Israel - English - Ministry of Health

astrazeneca (israel) ltd - anifrolumab - concentrate for solution for infusion - anifrolumab 150 mg/ml - anifrolumab - saphnelo is indicated for the treatment of adult patients with moderate to severe systemic lupus erythematosus (sle), who are receiving standard therapy.limitations of usethe efficacy of saphnelo has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. use of saphnelo is not recommended in these situations.

European Union - English - EMA (European Medicines Agency)

astrazeneca ab - anifrolumab - lupus erythematosus, systemic - immunosuppressants - saphnelo is indicated as an add-on therapy for the treatment of adult patients with moderate to severe, active autoantibody-positive systemic lupus erythematosus (sle), despite standard therapy.,

Malaysia - English - NPRA (National Pharmaceutical Regulatory Agency, Bahagian Regulatori Farmasi Negara)

astrazeneca sdn. bhd. - anifrolumab -

Canada - English - Health Canada

astrazeneca canada inc - anifrolumab - solution - 150mg - anifrolumab 150mg

Saudi Arabia - English - SFDA (Saudi Food and Drug Authority)- الهيئة العامة للغذاء والدواء

astrazeneca ab, sweden - anifrolumab - concentrate for solution for infusion - 150 mg/ml,

Japan - English - すりの適正使用協議会 RAD-AR Council, Japan

astrazeneca k.k - anifrolumab(genetical recombination) - injection

European Union - English - EMA (European Medicines Agency)

bristol-myers squibb pharma eeig - nivolumab - carcinoma, non-small-cell lung - antineoplastic and immunomodulating agents, monoclonal antibodies - nivolumab bms is indicated for the treatment of locally advanced or metastatic squamous non-small cell lung cancer (nsclc) after prior chemotherapy in adults.

United States - English - NLM (National Library of Medicine)

e.r. squibb & sons, l.l.c. - nivolumab (unii: 31yo63lbsn) (nivolumab - unii:31yo63lbsn) - nivolumab 10 mg in 1 ml - opdivo, as a single agent or in combination with ipilimumab, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma. opdivo is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected stage iib, stage iic, stage iii, or stage iv melanoma . opdivo, in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (nsclc). opdivo, in combination with ipilimumab, is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma. opdivo is indicated for the treatment of adult patients with classical hodgkin lymphoma (chl) that has relapsed or progressed after: this indication is approved under accelerated approval based on overall response rate [see clinical studies (14.7)] . continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. opdivo is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (scchn) with disease progression on or after platinum-based therapy. opdivo is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (uc) who are at high risk of recurrence after undergoing radical resection of uc [see clinical studies (14.9)]. opdivo, in combination with cisplatin and gemcitabine, is indicated for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma. opdivo is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who: opdivo, as a single agent or in combination with ipilimumab, is indicated for the treatment of adult and pediatric patients 12 years and older with microsatellite instability-high (msi-h) or mismatch repair deficient (dmmr) metastatic colorectal cancer (crc) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. this indication is approved under accelerated approval based on overall response rate and duration of response [see clinical studies (14.10)] . continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. opdivo, in combination with ipilimumab, is indicated for the treatment of adult patients with hepatocellular carcinoma (hcc) who have been previously treated with sorafenib. this indication is approved under accelerated approval based on overall response rate and duration of response [see clinical studies (14.11)] . continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. opdivo, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. none. based on data from animal studies and its mechanism of action [see clinical pharmacology (12.1)] , opdivo can cause fetal harm when administered to a pregnant woman. in animal reproduction studies, administration of nivolumab to cynomolgus monkeys from the onset of organogenesis through delivery resulted in increased abortion and premature infant death (see data) . human igg4 is known to cross the placental barrier and nivolumab is an immunoglobulin g4 (igg4); therefore, nivolumab has the potential to be transmitted from the mother to the developing fetus. the effects of opdivo are likely to be greater during the second and third trimesters of pregnancy. there are no available data on opdivo use in pregnant women to evaluate a drug-associated risk. advise pregnant women of the potential risk to a fetus. the background risk in the u.s. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. animal data a central function of the pd-1/pd-l1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. blockade of pd-l1 signaling has been shown in murine models of pregnancy to disrupt tolerance to the fetus and to increase fetal loss. the effects of nivolumab on prenatal and postnatal development were evaluated in monkeys that received nivolumab twice weekly from the onset of organogenesis through delivery, at exposure levels of between 9 and 42 times higher than those observed at the clinical dose of 3 mg/kg (based on auc). nivolumab administration resulted in a non-dose-related increase in spontaneous abortion and increased neonatal death. based on its mechanism of action, fetal exposure to nivolumab may increase the risk of developing immune-mediated disorders or altering the normal immune response and immune-mediated disorders have been reported in pd-1 knockout mice. in surviving infants (18 of 32 compared to 11 of 16 vehicle-exposed infants) of cynomolgus monkeys treated with nivolumab, there were no apparent malformations and no effects on neurobehavioral, immunological, or clinical pathology parameters throughout the 6-month postnatal period. there are no data on the presence of nivolumab in human milk, the effects on the breastfed child, or the effects on milk production. because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for 5 months after the last dose of opdivo. verify the pregnancy status of females of reproductive potential prior to initiating opdivo [see use in specific populations (8.1)] . opdivo can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . advise females of reproductive potential to use effective contraception during treatment with opdivo and for 5 months following the last dose. the safety and effectiveness of opdivo have been established in pediatric patients aged 12 years and older for the following indications: as a single agent and in combination with ipilimumab for the treatment of unresectable or metastatic melanoma, as a single agent for the adjuvant treatment of completely resected stage iib, stage iic, stage iii, or stage iv melanoma and, as a single agent or in combination with ipilimumab for the treatment of msi-h or dmmr mcrc that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. use of opdivo for these indications is supported by evidence from adequate and well-controlled studies in adults with melanoma or msi-h or dmmr mcrc and additional pharmacokinetic data in pediatric patients. nivolumab exposure in pediatric patients 12 years and older is comparable to that of adults and the courses of melanoma and msi-h or dmmr mcrc are similar in pediatric patients aged 12 years and older to that of adults to allow extrapolation of safety and efficacy [see adverse reactions (6.1), clinical pharmacology (12.3) , clinical studies (14.1 , 14.10)] . the safety and effectiveness of opdivo have not been established for pediatric patients younger than 12 years old with melanoma or msi-h or dmmr mcrc. the safety and effectiveness of opdivo have not been established in pediatric patients with non-small cell lung cancer, malignant pleural mesothelioma, advanced renal cell carcinoma, classical hodgkin lymphoma, squamous cell carcinoma of the head and neck, urothelial carcinoma, hepatocellular carcinoma, esophageal cancer, gastric cancer, gastroesophageal cancer and esophageal adenocarcinoma. single agent of 3569 patients with melanoma, nsclc, renal cell carcinoma, urothelial carcinoma, escc, and esophageal or gastroesophageal junction cancer who were randomized to single agent opdivo in clinical studies, 41% were 65 years and over and 10% were 75 years and over. no overall differences in safety or effectiveness were observed between elderly patients and younger patients [see clinical studies (14.1, 14.2, 14.4, 14.6, 14.9, 14.12)]. in patients with chl, recurrent head and neck scc, or dmmr or msi-h metastatic crc (mcrc) who were treated with single agent opdivo in clinical studies did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients [see clinical studies (14.7, 14.8, 14.10)]. in combination with ipilimumab of the 314 patients with melanoma who were randomized to opdivo in combination with ipilimumab, 41% were 65 years or older and 11% were 75 years or older. no overall differences in safety or effectiveness were reported between elderly patients and younger patients [see clinical studies (14.1)]. of the 576 patients with nsclc who were randomized to opdivo in combination with ipilimumab, 48% were 65 years or older and 10% were 75 years or older. no overall difference in safety was reported between older patients and younger patients; however, there was a higher discontinuation rate due to adverse reactions in patients aged 75 years or older (29%) relative to all patients who received opdivo with ipilimumab (18%). of the 396 patients in the primary efficacy population (pd-l1 ≥1%) randomized to opdivo in combination with ipilimumab, the hazard ratio for overall survival was 0.70 (95% ci: 0.55, 0.89) in the 199 patients younger than 65 years compared to 0.91 (95% ci: 0.72, 1.15) in the 197 patients 65 years or older [see clinical studies (14.3)]. of the 303 patients with malignant pleural mesothelioma who were randomized to opdivo in combination with ipilimumab, 77% were 65 years old or older and 26% were 75 years or older. no overall difference in safety was reported between older patients and younger patients; however, there were higher rates of serious adverse reactions and discontinuation due to adverse reactions in patients aged 75 years or older (68% and 35%, respectively) relative to all patients who received opdivo with ipilimumab (54% and 28%, respectively). for patients aged 75 years or older who received chemotherapy, the rate of serious adverse reactions was 34% and the discontinuation rate due to adverse reactions was 26% relative to 28% and 19% respectively for all patients. the hazard ratio for overall survival was 0.76 (95% ci: 0.52, 1.11) in the 71 patients younger than 65 years compared to 0.74 (95% ci: 0.59, 0.93) in the 232 patients 65 years or older randomized to opdivo in combination with ipilimumab [see clinical studies (14.5)]. of the 550 patients with renal cell carcinoma who were randomized to opdivo in combination with ipilimumab, 38% were 65 years or older and 8% were 75 years or older. no overall difference in safety was reported between elderly patients and younger patients. in elderly patients with intermediate or poor risk, no overall difference in effectiveness was reported [see clinical studies (14.6)]. of the 49 patients with hepatocellular carcinoma who were treated with opdivo in combination with ipilimumab, 29% were between 65 years and 74 years of age and 8% were 75 years or older. clinical studies of opdivo in combination with ipilimumab did not include sufficient numbers of patients with hepatocellular carcinoma aged 65 and over to determine whether they respond differently from younger patients [see clinical studies (14.11)]. of the 325 patients with escc who were randomized to opdivo in combination with ipilimumab, 43% were 65 years old or older and 7% were 75 years or older. no overall difference in safety was reported between older patients and younger patients; however, there was a higher discontinuation rate due to adverse reactions in patients aged 75 years or older (38%) relative to all patients who received opdivo with ipilimumab (23%). for patients aged 75 years or older who received chemotherapy, the discontinuation rate due to adverse reactions was 33% relative to 23% for all patients [see clinical studies (14.12)]. in combination with platinum-containing chemotherapy of the 179 patients with nsclc who were randomized to opdivo in combination with platinum-doublet chemotherapy, 48% were 65 years old or older and 6% were 75 years old or older. no overall differences in safety or effectiveness were reported between patients older and younger than 65 years [see clinical studies (14.3)]. of the 1,110 patients with escc, gc, gejc, or eac who were randomized to opdivo in combination with fluoropyrimidine- and platinum-containing chemotherapy), 42% were 65 years or older and 10% were 75 years or older. no overall difference in safety was reported between elderly patients and younger patients [see clinical studies (14.12, 14.13)] . of the 304 patients with uc who were treated with opdivo in combination with gemcitabine and platinum-doublet chemotherapy, 40% were 65 years or older and 11% were 75 years or older. no overall differences in safety or effectiveness were observed between patients 65 years of age and over and younger patients. clinical studies of opdivo with platinum-doublet chemotherapy did not include sufficient numbers of patients aged 75 years and over to determine whether safety and effectiveness differs compared to younger patients. [see clinical studies (14.9)]. in combination with ipilimumab and platinum-doublet chemotherapy of the 361 patients with nsclc who were randomized to opdivo in combination with ipilimumab and platinum-doublet chemotherapy, 51% were 65 years or older and 10% were 75 years or older. no overall difference in safety was reported between older patients and younger patients; however, there was a higher discontinuation rate due to adverse reactions in patients aged 75 years or older (43%) relative to all patients who received opdivo with ipilimumab and chemotherapy (24%). for patients aged 75 years or older who received chemotherapy only, the discontinuation rate due to adverse reactions was 16% relative to all patients who had a discontinuation rate of 13%. based on an updated analysis for overall survival, of the 361 patients randomized to opdivo in combination with ipilimumab and platinum-doublet chemotherapy, the hazard ratio for overall survival was 0.61 (95% ci: 0.47, 0.80) in the 176 patients younger than 65 years compared to 0.73 (95% ci: 0.56, 0.95) in the 185 patients 65 years or older [see clinical studies (14.4)]. in combination with cabozantinib of the 320 patients with renal cell carcinoma who were treated with opdivo in combination with cabozantinib, 41% were 65 years or older and 9% were 75 years or older. no overall difference in safety was reported between elderly patients and younger patients [see clinical studies (14.6)].