Amerika Serikat - Inggris - NLM (National Library of Medicine)

daiichi sankyo inc. - pexidartinib hydrochloride (unii: ys6wai3xn7) (pexidartinib - unii:6783m2lv5x) - turalio is indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (tgct) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. none. risk summary based on findings from animal studies and its mechanism of action [see clinical pharmacology (12.1)] , turalio may cause embryo-fetal harm when administered to a pregnant woman. the available human data do not establish the presence or absence of major birth defects or miscarriage related to the use of turalio. oral administration of pexidartinib to pregnant animals during the period of organogenesis resulted in malformations, post-implantation loss, and abortion at maternal exposures that were approximately equal to the human exposure at the recommended dose of 800 mg (see data) . advise pregnant women of the potential risk to a fetus. 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. data animal data embryo-fetal development studies investigating the administration of pexidartinib during the period of organogenesis were conducted in rats and rabbits. in rats, pexidartinib resulted in increased post-implantation loss and fetal malformations including localized fetal edema, absence of kidney and ureter, abnormalities of the reproductive tract, and developmental variations including misshapen kidney, decreased skeletal ossification and higher mean litter proportions of slightly or moderately malaligned sternebrae at doses of 40 mg/kg (approximately equal to the human exposure at the recommended dose of 800 mg). in rabbits, administration of pexidartinib resulted in increased post-implantation loss, abortion, and fetal malformations including absence of kidney or ureter, rudimentary, misshapen or malpositioned kidney, rib abnormalities, and skeletal variations of accessory skull bones at doses of 60 mg/kg (approximately equal to the human exposure at the recommended dose of 800 mg). risk summary there are no data on the presence of pexidartinib or its metabolites in either human or animal milk or its effects on a breastfed child or on milk production. because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with turalio and for at least 1 week after the final dose. turalio may cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . pregnancy testing verify pregnancy status in females of reproductive potential prior to the initiation of turalio [see use in specific populations (8.1)] . contraception females advise females of reproductive potential to use effective non-hormonal contraception during treatment with turalio and for 1 month after the final dose. counsel patients to use non-hormonal method(s) of contraception, since turalio can render hormonal contraceptives ineffective [see drug interactions (7.3), nonclinical toxicology (13.1)] . males advise male patients with female partners of reproductive potential to use effective contraception during treatment with turalio and for 1 week after the final dose [see nonclinical toxicology (13.1)] . infertility based on findings from animal studies, turalio may impair both male and female fertility [see nonclinical toxicology (13.1)]. the safety and effectiveness of turalio in pediatric patients have not been established. clinical studies of turalio did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. reduce the dose when administering turalio to patients with mild to severe renal impairment (clcr 15 to 89 ml/min, estimated by cockcroft-gault [c-g]) [see dosage and administration (2.6), clinical pharmacology (12.3)] . no dosage adjustment is recommended for patients with mild hepatic impairment (total bilirubin less than or equal to upper limit of normal [uln] with ast greater than uln or total bilirubin greater than 1 and up to 1.5 times uln with any ast) [see clinical pharmacology (12.3)] . reduce the dosage of turalio for patients with moderate hepatic impairment (total bilirubin greater than 1.5 and up to 3 times uln, not due to gilbert's syndrome, with any ast) [see dosage and administration (2.7), clinical pharmacology (12.3)] . turalio has not been studied in patients with severe hepatic impairment (total bilirubin greater than 3 to 10 times uln and any ast).

Amerika Serikat - Inggris - 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 (ihc 3+ or ish 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 (ihc 3+ or ihc 2+/ish positive) gastric or gastroesophageal junction (gej) adenocarcinoma who have received a prior trastuzumab-based regimen. enhertu is indicated for the treatment of adult patients with unresectable or metastatic her2-positive (ihc 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options. this indication is approved under accelerated approval based on objective response rate and duration of response [see clinical studies (14.5)] . continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. 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 her2-positive or her2-low 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 her2-mutant unresectable or metastatic 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 her2-positive locally advanced or metastatic 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. of the 192 patients with her2-positive (ihc 3+) unresectable or metastatic solid tumors treated with enhertu 5.4 mg/kg in destiny-pantumor02, destiny-lung01 or destiny-crc02, 39% were 65 years or older and 9% 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)].

Amerika Serikat - Inggris - NLM (National Library of Medicine)

daiichi sankyo, inc. - prasugrel hydrochloride (unii: g89jq59i13) (prasugrel - unii:34k66tbt99) - effient® is indicated to reduce the rate of thrombotic cv events (including stent thrombosis) in patients with acute coronary syndrome (acs) who are to be managed with percutaneous coronary intervention (pci) as follows: - patients with unstable angina (ua) or non-st-elevation myocardial infarction (nstemi). - patients with st-elevation myocardial infarction (stemi) when managed with primary or delayed pci. effient has been shown to reduce the rate of a combined endpoint of cardiovascular death, nonfatal myocardial infarction (mi), or nonfatal stroke compared to clopidogrel. the difference between treatments was driven predominantly by mi, with no difference on strokes and little difference on cv death [see clinical studies (14)] . effient is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage (ich) [see warnings and precautions (5.1) and adverse reactions (6.1)] . effient is contraindicated in patients with a history of prior transient ischemic attac

Amerika Serikat - Inggris - NLM (National Library of Medicine)

daiichi sankyo, inc. - pexidartinib hydrochloride (unii: ys6wai3xn7) (pexidartinib - unii:6783m2lv5x) - turalio is indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (tgct) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. none. risk summary based on findings from animal studies and its mechanism of action [see clinical pharmacology (12.1)] , turalio may cause embryo-fetal harm when administered to a pregnant woman. the available human data do not establish the presence or absence of major birth defects or miscarriage related to the use of turalio. oral administration of pexidartinib to pregnant animals during the period of organogenesis resulted in malformations, post-implantation loss, and abortion at maternal exposures that were approximately equal to the human exposure at the recommended dose (see data) . advise pregnant women of the potential risk to a fetus. 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 1

Amerika Serikat - Inggris - NLM (National Library of Medicine)

daiichi sankyo inc. - quizartinib dihydrochloride (unii: wk7q6ziz10) (quizartinib - unii:7la4o6q0d3) - vanflyta is indicated in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (aml) that is flt3 internal tandem duplication (itd)-positive as detected by an fda-approved test [see dosage and administration (2.1) and clinical studies (14)] . limitations of use vanflyta is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (hsct); improvement in overall survival with vanflyta in this setting has not been demonstrated [see clinical studies (14)] . vanflyta is contraindicated in patients with severe hypokalemia, severe hypomagnesemia, long qt syndrome, or in patients with a history of ventricular arrhythmias or torsades de pointes [see warnings and precautions (5.1)]. risk summary based on findings from animal studies and its mechanism of action, vanflyta can cause embryo-fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no available data on vanflyta use in pregnant women to evaluate for a drug-associated risk. in animal reproduction studies, oral administration of quizartinib to pregnant rats during organogenesis resulted in adverse developmental outcomes including structural abnormalities and alterations to growth at maternal exposures approximately 3 times those in patients at the maximum recommended human dose (mrhd) of 53 mg/day (see data ). advise pregnant women of the potential risk to a fetus. the background risk in the u.s. general population of major birth defects is 2-4%, and of miscarriage is 15-20% of clinically recognized pregnancies. data animal data in an embryo-fetal development study in rats, pregnant animals received oral doses of quizartinib of 0, 0.6, 2, or 6 mg/kg/day during the period of organogenesis. administration of quizartinib at the dose of 6 mg/kg/day was associated with adverse developmental outcomes including structural abnormalities (anasarca and edema) and alterations to growth (lower fetal weights and effects on skeletal ossification). at this dose, the maternal systemic exposures (auc) were approximately 3 times the human exposure at the mrhd of 53 mg/day. risk summary there are no data on the presence of quizartinib or its metabolites in human milk, or the effects on the breastfed child or milk production. because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with vanflyta and for one month after the last dose. vanflyta can cause embryo-fetal harm when administered to pregnant women [see use in specific populations (8.1)] . pregnancy testing verify pregnancy status in females of reproductive potential within seven days before starting treatment with vanflyta. contraception females advise female patients of reproductive potential to use effective contraception during treatment with vanflyta and for 7 months after the last dose. males based on genotoxicity findings, advise male patients with female partners of reproductive potential to use effective contraception during treatment with vanflyta and for 4 months after the last dose [see nonclinical toxicology (13.1)] . infertility females based on findings from animal studies, vanflyta may impair female fertility. these effects on fertility were reversible [see nonclinical toxicology (13.1)] . males based on findings from animal studies, vanflyta may impair male fertility. these effects on fertility were reversible [see nonclinical toxicology (13.1)]. safety and effectiveness of vanflyta have not been established in pediatric patients. there were 533 patients with newly diagnosed aml in the clinical study; of the total number of vanflyta-treated patients, 69 (26%) were 65 years of age and older, while 1 (0.4%) was 75 years of age [see clinical studies (14)] . no overall differences in safety or efficacy were observed between patients 65 years of age and older and younger adult patients. no dosage adjustment is recommended in patients with mild to moderate renal impairment (i.e., estimated creatinine clearance [clcr] by cockcroft-gault equation: clcr 30 to 89 ml/min). vanflyta has not been studied in patients with severe renal impairment (clcr <30 ml/min) [see clinical pharmacology (12.3)] . no dosage adjustment is recommended in patients with mild hepatic impairment (child-pugh class a or total bilirubin ≤ upper limit of normal [uln] and aspartate aminotransferase [ast] >uln, or total bilirubin >1 to 1.5 times uln and any value for ast) or moderate hepatic impairment (child-pugh class b or total bilirubin >1.5 to 3 times uln and any value for ast). vanflyta has not been studied in patients with severe (child-pugh class c or total bilirubin >3 times uln and any value for ast) hepatic impairment [see clinical pharmacology (12.3)] .

Amerika Serikat - Inggris - NLM (National Library of Medicine)

daiichi sankyo - olmesartan medoxomil (unii: 6m97xtv3hd) (olmesartan - unii:8w1iqp3u10) - tablet, film coated - 5 mg - benicar® is indicated for the treatment of hypertension. it may be used alone or in combination with other antihypertensive agents. benicar® is contraindicated in patients who are hypersensitive to any component of this product.

Inggris - Inggris - MHRA (Medicines & Healthcare Products Regulatory Agency)

daiichi sankyo uk ltd - raloxifene hydrochloride - tablet - 60mg

Inggris - Inggris - MHRA (Medicines & Healthcare Products Regulatory Agency)

daiichi sankyo uk ltd - olmesartan medoxomil - oral tablet - 20mg

Inggris - Inggris - MHRA (Medicines & Healthcare Products Regulatory Agency)

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

Inggris - Inggris - MHRA (Medicines & Healthcare Products Regulatory Agency)

daiichi sankyo uk ltd - hydrochlorothiazide; olmesartan medoxomil - oral tablet - 25mg ; 20mg