Birleşik Krallık - İngilizce - MHRA (Medicines & Healthcare Products Regulatory Agency)

daiichi sankyo uk ltd - olmesartan medoxomil; amlodipine besilate - oral tablet - 40mg ; 10mg

Birleşik Krallık - İngilizce - MHRA (Medicines & Healthcare Products Regulatory Agency)

daiichi sankyo uk ltd - olmesartan medoxomil; amlodipine besilate - oral tablet - 40mg ; 5mg

Birleşik Krallık - İngilizce - MHRA (Medicines & Healthcare Products Regulatory Agency)

daiichi sankyo uk ltd - olmesartan medoxomil; amlodipine besilate - oral tablet - 20mg ; 5mg

Birleşik Krallık - İngilizce - MHRA (Medicines & Healthcare Products Regulatory Agency)

daiichi sankyo uk ltd - olmesartan medoxomil; amlodipine besilate; hydrochlorothiazide - oral tablet - 20mg ; 5mg ; 12.5mg

Birleşik Krallık - İngilizce - MHRA (Medicines & Healthcare Products Regulatory Agency)

daiichi sankyo uk ltd - hydrochlorothiazide; amlodipine besilate; olmesartan medoxomil - oral tablet - 12.5mg ; 5mg ; 40mg

Birleşik Krallık - İngilizce - MHRA (Medicines & Healthcare Products Regulatory Agency)

daiichi sankyo uk ltd - amlodipine besilate; hydrochlorothiazide; olmesartan medoxomil - oral tablet - 10mg ; 12.5mg ; 40mg

Birleşik Krallık - İngilizce - MHRA (Medicines & Healthcare Products Regulatory Agency)

daiichi sankyo uk ltd - olmesartan medoxomil; amlodipine besilate; hydrochlorothiazide - oral tablet - 40mg ; 5mg ; 25mg

Birleşik Krallık - İngilizce - MHRA (Medicines & Healthcare Products Regulatory Agency)

daiichi sankyo uk ltd - olmesartan medoxomil; hydrochlorothiazide; amlodipine besilate - oral tablet - 40mg ; 25mg ; 10mg

ABD - İngilizce - NLM (National Library of Medicine)

daiichi sankyo inc. - edoxaban tosylate (unii: 32w99ue810) (edoxaban - unii:ndu3j18apo) - edoxaban 15 mg - savaysa is indicated to reduce the risk of stroke and systemic embolism (se) in patients with nonvalvular atrial fibrillation (nvaf). limitation of use for nvaf savaysa should not be used in patients with crcl > 95 ml/min because of an increased risk of ischemic stroke compared to warfarin [see dosage and administration (2.1), warnings and precautions (5.1) and clinical studies (14.1)] . savaysa is indicated for the treatment of deep vein thrombosis (dvt) and pulmonary embolism (pe) following 5 to 10 days of initial therapy with a parenteral anticoagulant. savaysa is contraindicated in patients with: - active pathological bleeding [see warnings and precautions (5.3) and adverse reactions (6.1)] . risk summary available data about savaysa use in pregnant women are insufficient to determine whether there are drug-associated risks for adverse developmental outcomes. in animal developmental studies, no adverse developmental effects were seen when edoxaban was administered orally to pregnant rats and rabbits during organogenesis at up to 16-times and 8-times, respectively, the human exposure, when based on body surface area and auc, respectively (see data) . the estimated 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 2-4% and 15-20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk pregnancy confers an increased risk of thromboembolism that is higher for women with underlying thromboembolic disease and certain high-risk pregnancy conditions. published data describe that women with a previous history of venous thrombosis are at high risk for recurrence during pregnancy. fetal/neonatal adverse reactions use of anticoagulants, including edoxaban, may increase the risk of bleeding in the fetus and neonate. monitor neonates for bleeding [see warnings and precautions (5.3)] . labor or delivery all patients receiving anticoagulants, including pregnant women, are at risk for bleeding. savaysa use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas. consider use of a shorter acting anticoagulant as delivery approaches [see warnings and precautions (5.3)] . data animal data embryo-fetal development studies were conducted in pregnant rats and rabbits during the period of organogenesis. in rats, no malformation was seen when edoxaban was administered orally at doses up to 300 mg/kg/day, or 49 times the human dose of 60 mg/day normalized to body surface area. increased post-implantation loss occurred at 300 mg/kg/day, but this effect may be secondary to the maternal vaginal hemorrhage seen at this dose. in rabbits, no malformation was seen at doses up to 600 mg/kg/day (49 times the human exposure at a dose of 60 mg/day when based on auc). embryo-fetal toxicities occurred at maternally toxic doses, and included absent or small fetal gallbladder at 600 mg/kg/day, and increased post-implantation loss, increased spontaneous abortion, and decreased live fetuses and fetal weight at doses equal to or greater than 200 mg/kg/day, which is equal to or greater than 20 times the human exposure. in a rat pre- and post-natal developmental study, edoxaban was administered orally during the period of organogenesis and through lactation day 20 at doses up to 30 mg/kg/day, which is up to 3 times the human exposure when based on auc. vaginal bleeding in pregnant rats and delayed avoidance response (a learning test) in female offspring were seen at 30 mg/kg/day. risk summary there are no data on the presence of edoxaban in human milk, or its effects on the breastfeeding infant or on milk production. edoxaban was present in rat milk. because of the potential for serious adverse reactions in nursing infants, including hemorrhage, advise patients that breastfeeding is not recommended during treatment with savaysa. females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician. the risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, identified with oral anticoagulants including savaysa should be assessed in females of reproductive potential and those with abnormal uterine bleeding. the safety and effectiveness of savaysa have not been established in pediatric patients with confirmed vte (pe and/or dvt). effectiveness was not demonstrated in an adequate and well-controlled study conducted in 145 savaysa-treated pediatric patients, from birth to less than 18 years of age with confirmed vte (pe and/or dvt), treated for 3 months up to a maximum of 12 months. of the total patients in the engage af-timi 48 study, 5182 (74%) were 65 years and older, while 2838 (41%) were 75 years and older. in hokusai vte, 1334 (32%) patients were 65 years and older, while 560 (14%) patients were 75 years and older. in the hokusai vte cancer study, 539 (52%) patients were 65 years and older and 176 (17%) were 75 years and older. in clinical trials the efficacy and safety of savaysa in elderly (65 years or older) and younger patients were similar [see adverse reactions (6.1), clinical pharmacology (12.3), and clinical studies (14)] . renal clearance accounts for approximately 50% of the total clearance of edoxaban. consequently, edoxaban blood levels are increased in patients with poor renal function compared to those with higher renal function. reduce savaysa dose to 30 mg once daily in patients with crcl 15-50 ml/min. there are limited clinical data with savaysa in patients with crcl < 15 ml/min; savaysa is therefore not recommended in these patients. hemodialysis does not significantly contribute to savaysa clearance [see dosage and administration (2.1, 2.2) and clinical pharmacology (12.3)] . as renal function improves and edoxaban blood levels decrease, the risk for ischemic stroke increases in patients with nvaf [see indications and usage (1.1), dosage and administration (2.1), and clinical studies (14.1)] . the use of savaysa in patients with moderate or severe hepatic impairment (child-pugh b and c) is not recommended as these patients may have intrinsic coagulation abnormalities. no dose reduction is required in patients with mild hepatic impairment (child-pugh a) [see clinical pharmacology (12.3)] . based on the clinical experience from the hokusai vte study, reduce savaysa dose to 30 mg in patients with body weight less than or equal to 60 kg [see dosage and administration (2.2) and clinical studies (14.2)] .

ABD - İngilizce - NLM (National Library of Medicine)

daiichi sankyo inc. - trastuzumab deruxtecan (unii: 5384hk7574) (trastuzumab deruxtecan - unii:5384hk7574) - enhertu is indicated for the treatment of adult patients with unresectable or metastatic her2-positive breast cancer who have received a prior anti-her2-based regimen either: - in the metastatic setting, or - in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy. enhertu is indicated for the treatment of adult patients with unresectable or metastatic her2-low (ihc 1+ or ihc 2+/ish-) breast cancer, as determined by an fda-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy [see dosage and administration (2.1)] . enhertu is indicated for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (nsclc) whose tumors have activating her2 (erbb2) mutations, as detected by an fda-approved test, and who have received a prior systemic therapy. this indication is approved under accelerated approval based on objective response rate and duration of response [see clinical studies (14.3)] . continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. enhertu is indicated for the treatment of adult patients with locally advanced or metastatic her2-positive gastric or gastroesophageal junction (gej) adenocarcinoma who have received a prior trastuzumab-based regimen. none. risk summary based on its mechanism of action, enhertu can cause fetal harm when administered to a pregnant woman. there are no available data on the use of enhertu in pregnant women. in postmarketing reports, use of a her2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death (see data ). based on its mechanism of action, the topoisomerase inhibitor component of enhertu, dxd, can also cause embryo-fetal harm when administered to a pregnant woman because it is genotoxic and targets actively dividing cells [see clinical pharmacology (12.1), nonclinical toxicology (13.1)] . advise patients of the potential risks to a fetus. there are clinical considerations if enhertu is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of enhertu (see clinical considerations ). the estimated 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. clinical considerations fetal/neonatal adverse reactions monitor women who received enhertu during pregnancy or within 7 months prior to conception for oligohydramnios. if oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care. data human data there are no available data on the use of enhertu in pregnant women. in postmarketing reports in pregnant women receiving a her2-directed antibody, cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death have been reported. these case reports described oligohydramnios in pregnant women who received a her2-directed antibody either alone or in combination with chemotherapy. in some case reports, amniotic fluid index increased after use of a her2-directed antibody was stopped. animal data there were no animal reproductive or developmental toxicity studies conducted with fam-trastuzumab deruxtecan-nxki. risk summary there is no data regarding the presence of fam-trastuzumab deruxtecan-nxki in human milk, the effects on the breastfed child, or the effects on milk production. because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with enhertu and for 7 months after the last dose. pregnancy testing verify pregnancy status of females of reproductive potential prior to initiation of enhertu. contraception females enhertu 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 enhertu and for 7 months after the last dose. males because of the potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment with enhertu and for 4 months after the last dose [see nonclinical toxicology (13.1)] . infertility based on findings in animal toxicity studies, enhertu may impair male reproductive function and fertility [see nonclinical toxicology (13.1)] . safety and effectiveness of enhertu have not been established in pediatric patients. of the 1287 patients with breast cancer treated with enhertu 5.4 mg/kg, 22% were 65 years or older and 3.8% were 75 years or older. no overall differences in efficacy within clinical studies were observed between patients ≥65 years of age compared to younger patients. there was a higher incidence of grade 3-4 adverse reactions observed in patients aged 65 years or older (59%) as compared to younger patients (49%)., of the 101 patients with unresectable or metastatic her2-mutant nsclc treated with enhertu 5.4 mg/kg, 40% were 65 years or older and 8% were 75 years or older. no overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. of the 125 patients with locally advanced or metastatic her2-positive gastric or gej adenocarcinoma treated with enhertu 6.4 mg/kg in destiny-gastric01, 56% were 65 years or older and 14% were 75 years or older. no overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. no dose adjustment of enhertu is required in patients with mild (creatinine clearance [clcr] ≥60 and <90 ml/min) or moderate (clcr ≥30 and <60 ml/min) renal impairment [see clinical pharmacology (12.3)] . a higher incidence of grade 1 and 2 ild/pneumonitis has been observed in patients with moderate renal impairment [see warnings and precautions (5.1)]. monitor patients with moderate renal impairment more frequently. the recommended dosage of enhertu has not been established for patients with severe renal impairment (clcr <30 ml/min) [see clinical pharmacology (12.3)]. no dose adjustment of enhertu is required in patients with mild (total bilirubin ≤uln and any ast >uln or total bilirubin >1 to 1.5 times uln and any ast) or moderate (total bilirubin >1.5 to 3 times uln and any ast) hepatic impairment. in patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor, dxd [see dosage and administration (2.3)]. the recommended dosage of enhertu has not been established for patients with severe hepatic impairment (total bilirubin >3 times uln and any ast) [see clinical pharmacology (12.3)].