Israel - English - Ministry of Health

novo nordisk ltd., israel - semaglutide - tablets - semaglutide 14 mg - semaglutide - rybelsus is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus to improve glycaemic control as an adjunct to diet and exercise• as monotherapy when metformin is considered inappropriate due to intolerance or contraindications• in combination with other medicinal products for the treatment of diabetes.

Israel - English - Ministry of Health

novo nordisk ltd., israel - semaglutide - tablets - semaglutide 3 mg - semaglutide - rybelsus is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus to improve glycaemic control as an adjunct to diet and exercise• as monotherapy when metformin is considered inappropriate due to intolerance or contraindications• in combination with other medicinal products for the treatment of diabetes.

Israel - English - Ministry of Health

novo nordisk ltd., israel - semaglutide - tablets - semaglutide 7 mg - semaglutide - rybelsus is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus to improve glycaemic control as an adjunct to diet and exercise• as monotherapy when metformin is considered inappropriate due to intolerance or contraindications• in combination with other medicinal products for the treatment of diabetes.

Malta - English - Medicines Authority

uni-pharma kleon tsetis pharmaceutical laboratories s.a. 14th km national road athens - lamia 1, gr-145 64 kifissia, greece - lozenge - flurbiprofen 8.75 mg - throat preparations

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

janssen biotech, inc. - amivantamab (unii: 0jsr7z0nb6) (amivantamab - unii:0jsr7z0nb6) - rybrevant is indicated in combination with carboplatin and pemetrexed for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (nsclc) with epidermal growth factor receptor (egfr) exon 20 insertion mutations, as detected by an fda-approved test [see dosage and administration (2.2)] . rybrevant is indicated as a single agent for the treatment of adult patients with locally advanced or metastatic nsclc with egfr exon 20 insertion mutations, as detected by an fda-approved test [see dosage and administration (2.2)] , whose disease has progressed on or after platinum-based chemotherapy. none. risk summary based on the mechanism of action and findings in animal models, rybrevant can cause fetal harm when administered to a pregnant woman. there are no available data on the use of rybrevant in pregnant women or animal data to assess the risk of rybrevant in pregnancy. disruption or depletion of egfr in animal models resulted in impairment of embryo-fetal development including effects on placental, lung, cardiac, skin, and neural development. the absence of egfr or met signaling has resulted in embryo lethality, malformations, and post-natal death in animals ( 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 no animal studies have been conducted to evaluate the effects of amivantamab-vmjw on reproduction and fetal development; however, based on its mechanism of action, rybrevant can cause fetal harm or developmental anomalies. in mice, egfr is critically important in reproductive and developmental processes including blastocyst implantation, placental development, and embryo-fetal/postnatal survival and development. reduction or elimination of embryo-fetal or maternal egfr signaling can prevent implantation, can cause embryo-fetal loss during various stages of gestation (through effects on placental development) and can cause developmental anomalies and early death in surviving fetuses. adverse developmental outcomes were observed in multiple organs in embryos/neonates of mice with disrupted egfr signaling. similarly, knock out of met or its ligand hgf was embryonic lethal due to severe defects in placental development, and fetuses displayed defects in muscle development in multiple organs. human igg1 is known to cross the placenta; therefore, amivantamab-vmjw has the potential to be transmitted from the mother to the developing fetus. risk summary there are no data on the presence of amivantamab-vmjw in human milk, the effects on the breastfed child or on milk production. because of the potential for serious adverse reactions from rybrevant in breast-fed children, advise women not to breast-feed during treatment with rybrevant and for 3 months after the last dose. rybrevant can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)]. pregnancy testing verify pregnancy status of females of reproductive potential prior to initiating rybrevant. contraception females advise females of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of rybrevant. the safety and efficacy of rybrevant have not been established in pediatric patients. of the 151 patients with locally advanced or metastatic nsclc treated with rybrevant in combination with carboplatin and pemetrexed in the papillon study, 37% were ≥65 years of age and 8% were ≥75 years of age. of the 302 patients with locally advanced or metastatic nsclc treated with rybrevant as a single agent in the chrysalis study, 39% were ≥65 years of age and 11% were ≥75 years of age. no clinically important differences in safety or efficacy were observed between patients who were ≥65 years of age and younger patients.

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

novo nordisk - semaglutide (unii: 53axn4nnhx) (semaglutide - unii:53axn4nnhx) - rybelsus is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. limitations of use rybelsus is contraindicated in patients with: risk summary available data with rybelsus use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. there are clinical considerations regarding the risks of poorly controlled diabetes in pregnancy (see clinical considerations) . based on animal reproduction studies, there may be potential risks to the fetus from exposure to rybelsus during pregnancy. rybelsus should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. in pregnant rats administered semaglutide during organogenesis, embryofetal mortality, structural abnormalities and alterations to growth occurred at maternal exposures below the maximum recommended human dose (mrhd) based on auc. in rabbits and cynomolgus monkeys administered semaglutide during organogenesis, early pregnancy losses and structural abnormalities were observed at exposure below the mrhd (rabbit) and ≥10-fold the mrhd (monkey). these findings coincided with a marked maternal body weight loss in both animal species (see data) . the estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with an hba1c >7 and has been reported to be as high as 20 to 25% in women with a hba1c >10. 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 fetal risk poorly controlled diabetes during pregnancy increases the maternal risk for diabetic ketoacidosis, pre- eclampsia, spontaneous abortions, preterm delivery, and delivery complications. poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. data animal data in a combined fertility and embryofetal development study in rats, subcutaneous doses of 0.01, 0.03 and 0.09 mg/kg/day (0.2-, 0.7-, and 2.1-fold the mrhd) were administered to males for 4 weeks prior to and throughout mating and to females for 2 weeks prior to mating, and throughout organogenesis to gestation day 17. in parental animals, pharmacologically mediated reductions in body weight gain and food consumption were observed at all dose levels. in the offspring, reduced growth and fetuses with visceral (heart blood vessels) and skeletal (cranial bones, vertebra, ribs) abnormalities were observed at the human exposure. in an embryofetal development study in pregnant rabbits, subcutaneous doses of 0.0010, 0.0025 or 0.0075 mg/kg/day (0.06-, 0.6-, and 4.4-fold the mrhd) were administered throughout organogenesis from gestation day 6 to 19. pharmacologically mediated reductions in maternal body weight gain and food consumption were observed at all dose levels. early pregnancy losses and increased incidences of minor visceral (kidney, liver) and skeletal (sternebra) fetal abnormalities were observed at ≥0.0025 mg/kg/day, at clinically relevant exposures. in an embryofetal development study in pregnant cynomolgus monkeys, subcutaneous doses of 0.015, 0.075, and 0.15 mg/kg twice weekly (1.9-, 9.9-, and 29-fold the mrhd) were administered throughout organogenesis, from gestation day 16 to 50. pharmacologically mediated, marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with the occurrence of sporadic abnormalities (vertebra, sternebra, ribs) at ≥0.075 mg/kg twice weekly (> 9x human exposure). in a pre- and postnatal development study in pregnant cynomolgus monkeys, subcutaneous doses of 0.015, 0.075, and 0.15 mg/kg twice weekly (1.3-, 6.4-, and 14-fold the mrhd) were administered from gestation day 16 to 140. pharmacologically mediated marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with an increase in early pregnancy losses and led to delivery of slightly smaller offspring at ≥0.075 mg/kg twice weekly (> 6x human exposure). salcaprozate sodium (snac), an absorption enhancer in rybelsus, crosses the placenta and reaches fetal tissues in rats. in a pre- and postnatal development study in pregnant sprague dawley rats, snac was administered orally at 1,000 mg/kg/day (exposure levels were not measured) on gestation day 7 through lactation day 20. an increase in gestation length, an increase in the number of stillbirths and a decrease in pup viability were observed. risk summary there are no data on the presence of semaglutide in human milk, the effects on the breastfed infant, or the effects on milk production. semaglutide was present in the milk of lactating rats. snac and/or its metabolites concentrated in the milk of lactating rats. when a substance is present in animal milk, it is likely that the substance will be present in human milk (see data) . there are no data on the presence of snac in human milk. since the activity of ugt2b7, an enzyme involved in snac clearance, is lower in infants compared to adults, higher snac plasma levels may occur in neonates and infants. because of the unknown potential for serious adverse reactions in the breastfed infant due to the possible accumulation of snac from breastfeeding and because there are alternative formulations of semaglutide that can be used during lactation, advise patients that breastfeeding is not recommended during treatment with rybelsus. data in lactating rats, semaglutide was detected in milk at levels 3- to 12-fold lower than in maternal plasma. snac and/or its metabolites were detected in milk of lactating rats following a single maternal administration on lactation day 10. mean levels of snac and/or its metabolites in milk were approximately 2- to 12-fold higher than in maternal plasma. discontinue rybelsus in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide [see use in specific populations (8.1)] . the safety and effectiveness of rybelsus have not been established in pediatric patients. in the pool of glycemic control trials, 1229 (30%) rybelsus-treated patients were 65 years of age and over and 199 (5%) rybelsus-treated patients were 75 years of age and over [see clinical studies (14)] . in pioneer 6, the cardiovascular outcomes trial, 891 (56%) rybelsus-treated patients were 65 years of age and over and 200 (13%) rybelsus-treated patients were 75 years of age and over. no overall differences in safety or effectiveness for rybelsus have been observed between patients 65 years of age and older and younger adult patients. the safety and effectiveness of rybelsus was evaluated in a 26-week clinical study that included 324 patients with moderate renal impairment (egfr 30 to 59 ml/min/1.73m2 ) [see clinical studies (14.1)]. in patients with renal impairment including end-stage renal disease (esrd), no clinically relevant change in semaglutide pharmacokinetics (pk) was observed [see clinical pharmacology (12.3)] . no dose adjustment of rybelsus is recommended for patients with renal impairment. in a study in subjects with different degrees of hepatic impairment, no clinically relevant change in semaglutide pharmacokinetics (pk) was observed [see clinical pharmacology (12.3)] . no dose adjustment of rybelsus is recommended for patients with hepatic impairment.

Ireland - English - HPRA (Health Products Regulatory Authority)

teva pharma b.v. - candesartan cilexetil - tablets - 32 milligram

Ireland - English - HPRA (Health Products Regulatory Authority)

teva pharma b.v. - candesartan cilexetil - tablets - 16 milligram

Ireland - English - HPRA (Health Products Regulatory Authority)

teva pharma b.v. - candesartan cilexetil - tablets - 4 milligram

Ireland - English - HPRA (Health Products Regulatory Authority)

teva pharma b.v. - candesartan cilexetil - tablets - 8 milligram