Hoa Kỳ - Tiếng Anh - NLM (National Library of Medicine)

astrazeneca pharmaceuticals lp - durvalumab (unii: 28x28x9okv) (durvalumab - unii:28x28x9okv) - durvalumab 120 mg in 2.4 ml - imfinzi, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (es-sclc). imfinzi, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (btc). none. risk summary based on findings from animal studies and its mechanism of action, imfinzi can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no available data on the use of imfinzi in pregnant women. in animal reproduction studies, administration of durvalumab to pregnant cynomolgus monkeys from the confirmation of pregnancy through delivery at exposure levels approximately 6 to 20 times higher than those observed at the clinical dose of 10 mg/kg based on area under the curve (auc), resulted in an increase in premature delivery, fetal loss, and premature neonatal death (see data). human immunoglobulin g1 (igg1) is known to cross the placental barrier; therefore, durvalumab has the potential to be transmitted from the mother to the developing fetus. apprise 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 as reported in the literature, the pd-1/pd-l1 pathway plays a central role in preserving pregnancy by maintaining maternal immune tolerance to the fetus. in mouse allogeneic pregnancy models, disruption of pd-l1 signaling was shown to result in an increase in fetal loss. the effects of durvalumab on prenatal and postnatal development were evaluated in reproduction studies in cynomolgus monkeys. durvalumab was administered from the confirmation of pregnancy through delivery at exposure levels approximately 6 to 20 times higher than those observed at a clinical dose of 10 mg/kg (based on auc). administration of durvalumab resulted in premature delivery, fetal loss (abortion and stillbirth), and increase in neonatal deaths. durvalumab was detected in infant serum on postpartum day 1, indicating the presence of placental transfer of durvalumab. based on its mechanism of action, fetal exposure to durvalumab 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. risk summary there are no data on the presence of durvalumab in human milk, its effects on the breastfed child, or the effects on milk production. maternal igg is known to be present in human milk. the effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to imfinzi are unknown. durvalumab was present in the milk of lactating cynomolgus monkeys and was associated with premature neonatal death (see data ). because of the potential for adverse reactions in a breastfed child, advise women not to breastfeed during treatment with imfinzi and for 3 months after the last dose. refer to the prescribing information for the agents administered in combination with imfinzi for recommended duration to not breastfeed, as appropriate. data in lactating cynomolgus monkeys, durvalumab was present in breast milk at about 0.15% of maternal serum concentrations after administration of durvalumab from the confirmation of pregnancy through delivery at exposure levels approximately 6 to 20 times higher than those observed at the recommended clinical dose of 10 mg/kg (based on auc). administration of durvalumab resulted in premature neonatal death. pregnancy testing verify pregnancy status of females of reproductive potential prior to initiating treatment with imfinzi. contraception females imfinzi 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 imfinzi and for 3 months following the last dose of imfinzi. refer to the prescribing information for the agents administered in combination with imfinzi for recommended contraception duration, as appropriate. the safety and effectiveness of imfinzi have not been established in pediatric patients. of the 476 patients treated with imfinzi in the pacific study, 45% were 65 years or older, while 7.6% were 75 years or older. no overall differences in safety or effectiveness were observed between patients 65 years or older and younger patients. the pacific study did not include sufficient numbers of patients aged 75 years and over to determine whether they respond differently from younger patients. of the 265 patients with es-sclc treated with imfinzi in combination with chemotherapy 101 (38%) patients were 65 years or older and 19 (7.2%) patients were 75 years or older. there were no clinically meaningful differences in safety or efficacy between patients 65 years or older and younger patients. of the 330 patients with metastatic nsclc treated with imfinzi in combination with tremelimumab-actl and platinum-based chemotherapy, 143 (43%) patients were 65 years or older and 35 (11%) patients were 75 years or older. there were no clinically meaningful differences in safety or efficacy between patients 65 years or older and younger patients. of the 338 patients with btc treated with imfinzi in combination with chemotherapy in the topaz-1 study, 158 (47%) patients were 65 years or older and 38 (11%) patients were 75 years or older. no overall differences in safety or effectiveness of imfinzi have been observed between patients 65 years of age and older and younger adult patients. of the 393 patients with uhcc treated with imfinzi in combination with tremelimumab-actl, 50% of patients were 65 years of age or older and 13% of patients were 75 years of age or older. no overall differences in safety or effectiveness of imfinzi have been observed between patients 65 years of age and older and younger adult patients.

Hoa Kỳ - Tiếng Anh - NLM (National Library of Medicine)

astrazeneca pharmaceuticals lp - exenatide (unii: 9p1872d4ol) (exenatide - unii:9p1872d4ol) - exenatide 2 mg in 0.85 ml - bydureon bcise is indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus [see clinical studies (14)]. limitations of use bydureon bcise: bydureon bcise is contraindicated in patients with a: risk summary limited data with exenatide, the active ingredient in bydureon bcise, in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see clinical considerations) . based on animal reproduction studies, there may be risks to the fetus from exposure to bydureon bcise during pregnancy. bydureon bcise should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. animal reproduction studies identified increased adverse fetal and neonatal outcomes from exposure to exenatide extended-release during pregnancy or from exposure to exenatide during pregnancy and lactation, in association with maternal effects. in rats, exenatide extended-release, administered during the period of organogenesis, reduced fetal growth and produced skeletal ossification deficits at doses that approximate clinical exposures at the maximum recommended human dose (mrhd) of 2 mg/week. in mice, exenatide administered during gestation and lactation, caused increased neonatal deaths at doses that approximate clinical exposures at the mrhd (see data ). based on animal data, advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with an hba1c >7 and has been reported to be as high as 20-25% in women with hba1c >10. the estimated background risk of 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 2-4% and 15-20%, respectively. clinical considerations disease-associated maternal and/or embryofetal risk poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, 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 pregnant rats given subcutaneous doses of 0.3, 1, or 3 mg/kg exenatide extended-release every 3 days during organogenesis had systemic exposures 3-, 8-, and 19-times human exposure, respectively, at the mrhd of 2 mg/week bydureon bcise based on plasma exenatide exposure (auc) comparison. reduced fetal growth at all doses and skeletal ossification deficits at 1 and 3 mg/kg occurred at doses that decreased maternal food intake and body weight gain. in studies evaluating reproduction and development in pregnant mice and rabbits, maternal animals were administered exenatide, the active ingredient in bydureon bcise, by subcutaneous injection twice a day. differences in embryofetal developmental toxicity from subcutaneously injected exenatide extended-release and exenatide were not evaluated in mice, rats, or rabbits. in pregnant mice given 6, 68, 460, or 760 mcg/kg/day exenatide during fetal organogenesis, skeletal variations associated with slowed fetal growth, including changes in number of rib pairs or vertebral ossifications sites, and wavy ribs were observed at 760 mcg/kg/day, a dose that produced maternal toxicity and yielded systemic exposure 200-times the human exposure resulting from the mrhd of bydureon bcise based on auc comparison. in pregnant rabbits given 0.2, 2, 22, 156, or 260 mcg/kg/day exenatide during fetal organogenesis, irregular fetal skeletal ossifications were observed at 2 mcg/kg/day, a dose yielding systemic exposure up to 6-times the human exposure from the mrhd of bydureon bcise based on auc comparison. in maternal mice given 6, 68, or 760 mcg/kg/day exenatide from gestation day 6 through lactation day 20 (weaning), an increased number of neonatal deaths at 6 mcg/kg/day were observed on postpartum days 2 to 4 in dams given 6 mcg/kg/day, a dose yielding a systemic exposure equivalent to the human exposure from the mrhd of bydureon bcise based on auc comparison. risk summary there is no information regarding the presence of exenatide, in human milk, the effects of exenatide on the breastfed infant, or the effects of exenatide on milk production. exenatide, the active ingredient in bydureon bcise was present in the milk of lactating mice. however, due to species-specific differences in lactation physiology, the clinical relevance of these data is not clear (see data) . the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for exenatide and any potential adverse effects on the breastfed child from exenatide or from the underlying maternal condition. data in lactating mice subcutaneously injected twice a day with exenatide, the active ingredient in bydureon bcise, the concentration of exenatide in milk was up to 2.5% of the concentration in maternal plasma. the safety and effectiveness of bydureon bcise as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus have been established in pediatric patients aged 10 years and older. use of bydureon bcise for this indication is supported by a 24-week placebo-controlled trial with bydureon with 28-week open-label uncontrolled extension (trial 9) in 82 pediatric patients 10 years of age and older with type 2 diabetes, a pediatric pharmacokinetic study, and studies in adults with type 2 diabetes mellitus [see clinical pharmacology (12.3) and clinical studies (14.2, 14.3, 14.4, 14.6)] . safety and effectiveness of bydureon bcise have not been established in pediatric patients less than 10 years of age. in two comparator-controlled 28-week trials, bydureon bcise was studied in 74 patients (18%) who were at least 65 years of age and 10 (2.4%) patients who were at least 75 years of age. in these studies, no meaningful differences in safety and effectiveness were observed between patients ≥65 years of age and younger adult patients, but these studies did not include sufficient numbers of patients ≥75 years of age to determine whether they respond differently from younger adult patients. in a large cardiovascular outcomes trial [see clinical studies (14.5)] , bydureon was studied in 2,959 patients (40%) who were at least 65 years old and of those, 605 patients (8%) were at least 75 years old. use caution when initiating bydureon bcise in geriatric patients because they are more likely to have decreased kidney function [see use in specific populations (8.6)]. pharmacokinetic studies of adult patients with renal impairment who received bydureon bcise indicate that there is an increase in exenatide exposure in those with mild and moderate renal impairment as compared to patients with normal kidney function. bydureon bcise may induce nausea and vomiting with transient hypovolemia and may worsen kidney function in patients with renal impairment. monitor patients with mild renal impairment for adverse reactions that may lead to hypovolemia. bydureon bcise is not recommended for use in patients with egfr below 45 ml/min/1.73 m2 or end-stage renal disease. if bydureon bcise is used in patients with renal transplantation, closely monitor for adverse reactions that may lead to hypovolemia [see warnings and precautions (5.4) and clinical pharmacology (12.3)]. bydureon bcise® (by-dur-ee-on b-cise) (exenatide) extended-release injectable suspension for subcutaneous use once-weekly read the instructions for use before you start using bydureon bcise. before using bydureon bcise, talk to your healthcare provider about how to use it the right way. caregivers should help children with mixing and injecting bydureon bcise. before you begin the autoinjector: before use supplies needed to give your injection: ● bydureon bcise autoinjector ● alcohol swab ● a clean, flat surface ● sharps container (see “disposal” instructions at the end of these instructions) step 1: prepare for injection a. let your autoinjector come to room temperature. remove 1 autoinjector from the refrigerator and rest it flat for 15 minutes. autoinjector can be kept at room temperature for up to 4 weeks. b. check the expiration date (labeled exp) printed on the autoinjector label. do not use the autoinjector past the expiration date. if the expiration date has passed, throw it away and get a new autoinjector. c. wash your hands. d. choose your injection site. you can inject into your stomach, thigh, or back of the upper arm, see figure d. each week you can use the same area of your body, but choose a different injection site in that area of your body. clean the area with an alcohol swab. figure d step 2: mix the medicine a. look in the window. you may see white medicine along the sides, bottom or top. this means the medicine is not mixed evenly. b. shake the autoinjector hard, in an up-and-down motion, until the medicine is mixed evenly and you do not see any white medicine along the sides, bottom or top. c. check the mix. hold the autoinjector up to the light and look through both sides and the bottom of the window. if not mixed well, repeat step 2 and check again. do not go to the next step unless your medicine is mixed well. to get a full dose, the medicine must be mixed well and look cloudy. if not mixed well, continue to shake hard. step 3: prepare the autoinjector important: after the medicine is fully mixed, you must complete the preparation steps right away , and inject to get the full dose. do not save it to use later. only unlock the autoinjector when you are ready to inject a. unlock the autoinjector. hold the autoinjector up straight with the orange cap toward the ceiling. turn the knob from the lock to the unlock position until you hear a click. b. while still holding the autoinjector straight up, firmly unscrew the orange cap. it is normal to see a few drops of liquid inside the cap. do not recap the autoinjector. throw away the cap. step 4: inject the dose a. inject and hold: b. make sure you received your full dose. after you receive your injection, you will see an orange rod in the window. after you lift the autoinjector from your skin, the green shield will move back up to lock over the needle. see the common questions and answers for what to do if you do not see the orange rod in the window after injection. step 4: inject the dose (continued) c. disposal. put your used autoinjector in a fda-cleared sharps disposal container right away after use. do not throw away (dispose of) loose needles and syringes into your household trash. if you do not have an fda-cleared sharps disposal container, you may use a household container that is: when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be state or local laws about how you should throw away used needles and syringes. for more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to fda’s website at: http://www.fda.gov/safesharpsdisposal. do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. do not recycle your used sharps disposal container. see “common questions and answers” for additional disposal information. please keep these instructions to use for your next dose. common questions and answers 1. where is the needle? the needle is attached to the autoinjector and covered by the orange cap. when you unscrew the orange cap, the green shield keeps the needle covered until you inject. for more information, please see figure n in step 3b in the instructions for use. 2. how do i know if the medicine is fully mixed? after shaking the autoinjector, look through both sides of the window. you should not see any white medicine along the bottom, top, or sides. if you see white medicine, it is unmixed. to mix, shake the autoinjector hard until the white medicine is no longer on the bottom, top, or sides. the medicine should look even throughout. 3. why do i need to hold the autoinjector upright while removing the orange cap? holding the autoinjector with the orange cap straight up helps prevent the medicine from leaking. it is normal to see a few drops of medicine inside the orange cap after you unscrew it. 4. why should i inject my medicine right away after mixing it? if you do not inject your medicine right away after mixing, the medicine may separate, and you will not get your full dose. you can re-mix your medicine if your autoinjector is in the locked position. however, after you unlock it, you must complete the preparation steps right away and inject to get the full dose. you cannot save it for later use. 5. how do i know i gave myself the full dose of medicine? to be sure you get your full dose, press and hold the autoinjector against your skin. you will feel the needle go into your skin. hold the needle against your skin for 15 seconds. this will allow enough time for all the medicine to go from the autoinjector to under your skin. after removing the needle, look for the orange rod in the window as a way to tell that the dose has been given. if the orange rod does not appear contact customer service at 1-800-236-9933. 6. why should i store my autoinjectors flat in the refrigerator? autoinjectors stored vertically (with the needle up or down) are more difficult to mix. the medicine can still be fully mixed, but it will take more shaking and more time. 7. what if i do not have an fda-cleared sharps disposal container? do not throw away (dispose of) the autoinjector in your household trash. if you do not have an fda-cleared sharps disposal container, you may use a household container that is: when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be state or local laws about how you should throw away used needles and autoinjectors. for more information about safe sharps disposal, and for specific information about sharps disposal in the state you live in, go to the fda’s website at: http://www.fda.gov/safesharpsdisposal. 8. what if i cannot unlock the autoinjector? review the instructions for use step 3 to make sure you are following the right instructions, then contact customer service, 1-800-236-9933 for help as needed. do not try to unlock with excessive force or tools. 9. what if i cannot remove the orange cap from the autoinjector? review the instructions for use step 3 to make sure you are following the right instructions. you should also check that the knob is fully in the unlocked position, then contact customer service, 1-800-236-9933 for help as needed. do not use tools or try to force the cap off. 10. for other questions about bydureon bcise: visit www.bydureonbcise.com. call customer service at 1-800-236-9933. how to store bydureon bcise autoinjector

Úc - Tiếng Anh - Department of Health (Therapeutic Goods Administration)

astrazeneca pty ltd - water for injections -

Úc - Tiếng Anh - Department of Health (Therapeutic Goods Administration)

astrazeneca pty ltd - water for injections -

Úc - Tiếng Anh - Department of Health (Therapeutic Goods Administration)

astrazeneca pty ltd - sodium chloride -

Úc - Tiếng Anh - Department of Health (Therapeutic Goods Administration)

astrazeneca pty ltd - sodium chloride -

Úc - Tiếng Anh - Department of Health (Therapeutic Goods Administration)

juno pharmaceuticals pty ltd - suxamethonium chloride -

Úc - Tiếng Anh - Department of Health (Therapeutic Goods Administration)

juno pharmaceuticals pty ltd - sodium chloride, quantity: 200 mg/ml - injection, concentrated - excipient ingredients: water for injections; sodium hydroxide; hydrochloric acid - indications as at 19 february 1993 : as an additive to parenteral fluids in patients who have specific electrolyte needs. as a sclerosing agent for small symptomatic varicose veins.

Úc - Tiếng Anh - Department of Health (Therapeutic Goods Administration)

juno pharmaceuticals pty ltd - neostigmine methylsulfate -

Úc - Tiếng Anh - Department of Health (Therapeutic Goods Administration)

juno pharmaceuticals pty ltd - pancuronium bromide, quantity: 2 mg/ml - injection, solution - excipient ingredients: water for injections; sodium acetate; sodium chloride; acetic acid; sodium hydroxide - indiactions as at 1 january 1991: 1. as an adjunct to surgical anaesthesia to induce skeletal muscle relaxation to facilitate operative manipulations. the necessary conditions for intubation can be achieved with pancuronium bromide alone or following suxamethonium. 2. pancuronium bromide is also indicated to promote mechanical ventilation by reducing or eliminating spontaneous breathing effort in intensive care patients.