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genentech, inc. - tenecteplase (unii: wgd229o42w) (tenecteplase - unii:wgd229o42w) - tenecteplase 52.5 mg in 50 mg - tnkase® is indicated for use in the reduction of mortality associated with acute myocardial infarction (ami). treatment should be initiated as soon as possible after the onset of ami symptoms [see clinical studies (14.1)] . tnkase therapy in patients with acute myocardial infarction is contraindicated in the following situations because of an increased risk of bleeding [see warnings and precautions (5.1)] : - active internal bleeding - history of cerebrovascular accident - intracranial or intraspinal surgery or trauma within 2 months - intracranial neoplasm, arteriovenous malformation, or aneurysm - known bleeding diathesis - severe uncontrolled hypertension risk summary tnkase has been shown to elicit maternal and embryo toxicity in rabbits given multiple iv administrations. in rabbits administered 0.5, 1.5, and 5.0 mg/kg/day during organogenesis, vaginal hemorrhage resulted in maternal deaths. subsequent embryonic deaths were secondary to maternal hemorrhage and no fetal anomalies were observed. tnkase

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genentech, inc. - baloxavir marboxil (unii: 505cxm6ohg) (baloxavir - unii:4g86y4jt3f) - xofluza is indicated for treatment of acute uncomplicated influenza in patients 5 years of age and older who have been symptomatic for no more than 48 hours and who are otherwise healthy or at high risk of developing influenza-related complications1 [see clinical studies (14)]. xofluza is indicated for post-exposure prophylaxis of influenza in persons 5 years of age and older following contact with an individual who has influenza [see clinical studies (14.4)]. influenza viruses change over time, and factors such as the virus type or subtype, emergence of resistance, or changes in viral virulence could diminish the clinical benefit of antiviral drugs. consider available information on drug susceptibility patterns for circulating influenza virus strains when deciding whether to use xofluza [see warnings and precautions (5.2), microbiology (12.4) and clinical studies (14)] . xofluza is contraindicated in patients with a history of hypersensitivity to baloxavir marboxil or any of its ingredients. serious allergic reactions have included anaphylaxis, angioedema, urticaria, and erythema multiforme [see warnings and precautions (5.1)]. risk summary there are no adequate and well-controlled studies with xofluza in pregnant women to inform a drug-associated risk of adverse developmental outcomes. there are risks to the mother and fetus associated with influenza virus infection in pregnancy (see clinical considerations). in animal reproduction studies, no adverse developmental effects were observed in rats or rabbits with oral administration of baloxavir marboxil at exposures approximately 5 (rats) and 7 (rabbits) times the systemic baloxavir exposure at the maximum recommended human dose (mrhd) (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 defects, 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 pregnant women are at higher risk of severe complications from influenza, which may lead to adverse pregnancy and/or fetal outcomes, including maternal death, stillbirth, birth defects, preterm delivery, low birth weight, and small for gestational age. data animal data baloxavir marboxil was administered orally to pregnant rats (20, 200, or 1,000 mg/kg/day from gestation day 6 to 17) and rabbits (30, 100, or 1,000 mg/kg/day from gestation day 7 to 19). no adverse embryo-fetal effects were observed in rats up to the highest dose of baloxavir marboxil (1,000 mg/kg/day), resulting in systemic baloxavir exposure (auc) of approximately 5 times the exposure at the mrhd. in rabbits, fetal skeletal variations occurred at a maternally toxic dose (1,000 mg/kg/day) resulting in 2 abortions out of 19 pregnancies. no adverse maternal or embryo-fetal effects were observed in rabbits at the middle dose (100 mg/kg/day) resulting in systemic baloxavir exposure (auc) approximately 7 times the exposure at the mrhd. in the prenatal and postnatal development study in rats, baloxavir marboxil was administered orally at 20, 200, or 1,000 mg/kg/day from gestation day 6 to postpartum/lactation day 20. no significant effects were observed in the offspring at maternal systemic baloxavir exposure (auc) approximately 5 times the exposure at the mrhd. risk summary there are no data on the presence of baloxavir marboxil in human milk, the effects on the breastfed infant, or the effects on milk production. baloxavir and its related metabolites were present in the milk of lactating rats (see data) . the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for xofluza and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. data in a lactation study, baloxavir and its related metabolites were excreted in the milk of lactating rats administered baloxavir marboxil (1 mg/kg) on postpartum/lactation day 11, with peak milk concentration approximately 5 times that of maternal plasma concentrations occurring 2 hours post-dose. no effects of baloxavir marboxil on growth and postnatal development were observed in nursing pups at the highest oral dose tested in rats. maternal systemic exposure was approximately 5 times the baloxavir exposure in humans at the mrhd. treatment of acute uncomplicated influenza in adolescent subjects (≥ 12 years of age) the safety and effectiveness of xofluza for the treatment of acute uncomplicated influenza in adolescent subjects 12 years of age and older weighing at least 40 kg is supported by one randomized, double-blind, controlled trial in otherwise healthy subjects trial t0831 and one trial in subjects at high risk of developing influenza-related complications trial t0832 [see clinical studies (14.1)]. a total of 117 otherwise healthy adolescents 12 to17 years of age were randomized and received either xofluza (n=76) or placebo (n=41) in trial t0831; 38 adolescents 12 to 17 years of age at high risk for influenza complications were randomized and received either xofluza (n=21) or placebo (n=17) in trial t0832. the median time to alleviation of symptoms in influenza-infected adolescent subjects aged 12 to 17 years in trial t0831 was comparable to that observed in adults. in trial t0832, the median time to improvement of symptoms in the limited number of influenza-infected adolescent subjects aged 12 to 17 years was similar in the xofluza and placebo arms [see clinical studies (14.1)]. adverse events reported in adolescents in both trials were similar to those reported in adults [see adverse reactions (6.1)]. treatment of acute uncomplicated influenza in pediatric subjects (5 to < 12 years of age) the safety and effectiveness of xofluza in pediatric subjects 5 to less than 12 years of age is supported by one randomized, double-blind, controlled trial trial cp40563 with a primary endpoint of safety. in this trial, 118 pediatric subjects were randomized and treated in a 2:1 ratio and received either xofluza (n=79) or oseltamivir (n=39). efficacy was extrapolated from adults and adolescents based on comparable pk exposures in adults, adolescents and pediatric subjects 5 to less than 12 years of age. the median time to alleviation of signs and symptoms in influenza-infected subjects was comparable in the xofluza and oseltamivir arms. adverse events reported with xofluza in pediatric subjects were similar to those observed in adults and adolescents except for vomiting and diarrhea, which were both more commonly reported in pediatric subjects [see adverse reactions (6.1), clinical pharmacology (12.3), and clinical studies (14.1)]. post-exposure prophylaxis of influenza in pediatric and adolescent subjects (5 to < 18 years of age) the safety and effectiveness of xofluza for post-exposure prophylaxis in pediatric and adolescent subjects 5 to less than 18 years of age is supported by one randomized, double-blind, controlled trial conducted in japan trial t0834 [see clinical studies (14.3)]. subjects in this trial were randomized in a 1:1 ratio to receive xofluza or placebo. a total of 69 subjects from 5 to <18 years of age in trial t0834 received xofluza. the incidence of rt-pcr-confirmed symptomatic influenza in pediatric subjects 5 to <18 years of age was similar to that observed in adult subjects [see clinical pharmacology (12.3), and clinical studies (14.3)]. efficacy was extrapolated from adults based on comparable pk exposures in adults, adolescents and pediatric subjects 5 to <18 years of age. adverse events reported in pediatric and adolescent subjects were similar to those reported in adults in the same trial [see adverse reactions (6.1)]. pediatric subjects (< 5 years of age) the safety and effectiveness of xofluza for treatment and post-exposure prophylaxis of influenza in pediatric subjects less than 5 years of age have not been established [see warnings and precautions (5.2) and microbiology (12.4)]. the safety and effectiveness of xofluza in subjects 65 years of age and older has been established and is supported by one randomized, double-blind, controlled trial [see clinical studies (14.2)] . in trial t0832, of 730 xofluza-treated subjects at high risk of influenza-related complications, 209 (29%) subjects were 65 years of age and older. the median time to improvement of influenza symptoms in subjects 65 years of age and older was 70 hours in subjects who received xofluza (n=112) and 88 hours in those who received placebo (n=102). the safety profile observed for this population was similar to that reported in the overall trial population except for nausea, which was reported in 6% of elderly subjects compared to 1% of subjects from 18 to 64 years of age.

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genentech, inc. - polatuzumab vedotin (unii: kg6vo684z6) (polatuzumab vedotin - unii:kg6vo684z6) - polivy in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (r-chp) is indicated for the treatment of adult patients who have previously untreated diffuse large b-cell lymphoma (dlbcl), not otherwise specified (nos) or high-grade b-cell lymphoma (hgbl) and who have an international prognostic index score of 2 or greater. polivy in combination with bendamustine and a rituximab product is indicated for the treatment of adult patients with relapsed or refractory dlbcl, nos, after at least two prior therapies. none. risk summary based on findings from animal studies and its mechanism of action [see clinical pharmacology (12.1)] , polivy can cause fetal harm. there are no available data in pregnant women to inform the drug-associated risk. in animal reproduction studies, administration of the small molecule component of polivy, mmae, to pregnant rats during organogenesis at exposures below the clinical exposure at the recommended dose of 1.8 mg/kg polivy every 21 days resulted in embryo-fetal mortality and structural abnormalities (see data) . advise a pregnant woman of the potential risks to a fetus. 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. data animal data no embryo-fetal development studies in animals have been performed with polatuzumab vedotin-piiq. in an embryo-fetal developmental study in pregnant rats, administration of two intravenous doses of mmae, the small molecule component of polivy, on gestational days 6 and 13 caused embryo-fetal mortality and structural abnormalities, including protruding tongue, malrotated limbs, gastroschisis, and agnathia compared to controls at a dose of 0.2 mg/kg (approximately 0.5-fold the human area under the curve [auc] at the recommended dose). risk summary there is no information regarding the presence of polatuzumab vedotin-piiq in human milk, the effects on the breastfed child, or milk production. because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with polivy and for 2 months after the last dose. polivy 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 prior to initiating polivy [see use in specific populations (8.1)] . contraception females advise females of reproductive potential to use effective contraception during treatment with polivy and for 3 months after the last dose [see nonclinical toxicology (13.1)] . males based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with polivy and for 5 months after the final dose [see nonclinical toxicity (13.1)] . infertility females based on findings in animal studies with mmae-containing antibody-drug conjugates (adcs), polivy may impair female fertility. the effect on fertility is reversible [see nonclinical toxicology (13.1)] . males based on findings from animal studies, polivy may impair male fertility. the reversibility of this effect is unknown [see nonclinical toxicology (13.1)] . safety and effectiveness of polivy have not been established in pediatric patients. among 435 patients treated with polivy plus r-chp in polarix, 227 (52%) were ≥65 years of age. no overall differences in safety or efficacy were observed between patients aged ≥65 years and younger patients. among 173 patients treated with polivy plus br in study go29365, 95 (55%) were ≥65 years of age. patients aged ≥65 had a numerically higher incidence of serious adverse reactions (64%) than patients aged <65 (53%). this study did not include sufficient numbers of patients to determine whether efficacy differed in patients aged ≥65 and younger patients. avoid the administration of polivy in patients with moderate or severe hepatic impairment (total bilirubin greater than 1.5 × uln and any ast). patients with moderate or severe hepatic impairment are likely to have increased exposure to mmae, which may increase the risk of adverse reactions. polivy has not been studied in patients with moderate or severe hepatic impairment [see clinical pharmacology (12.3) and warnings and precautions (5.7)]. no adjustment in the starting dose is required when administering polivy to patients with mild hepatic impairment (total bilirubin 1 to 1.5 × uln or ast greater than uln).

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genentech, inc. - oseltamivir phosphate (unii: 4a3o49ngez) (oseltamivir acid - unii:k6106lv5q8) - oseltamivir acid 30 mg - tamiflu is indicated for the treatment of acute, uncomplicated illness due to influenza a and b infection in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours. tamiflu is indicated for the prophylaxis of influenza a and b in patients 1 year and older. - tamiflu is not a substitute for early influenza vaccination on an annual basis as recommended by the centers for disease control and prevention advisory committee on immunization practices. - influenza viruses change over time. emergence of resistance substitutions could decrease drug effectiveness. other factors (for example, changes in viral virulence) might also diminish clinical benefit of antiviral drugs. prescribers should consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use tamiflu [see microbiology (12.4)] . - tamiflu is not recommended for patients with end-stage renal disease not undergoing dialysis [see dosage and administration (2.4) and use in specific populations (8.6)]. tamiflu is contraindicated in patients with known serious hypersensitivity to oseltamivir or any component of the product. severe allergic reactions have included anaphylaxis and serious skin reactions including toxic epidermal necrolysis, stevens-johnson syndrome, and erythema multiforme [see warnings and precautions (5.1)] . risk summary there are no adequate and well-controlled studies with tamiflu in pregnant women to inform a drug-associated risk of adverse developmental outcomes. available published epidemiological data suggest that tamiflu, taken in any trimester, is not associated with an increased risk of birth defects. however, these studies individually are limited by small sample sizes, use of different comparison groups, and some lacked information on dose, which preclude a definitive assessment of the risk [see data and clinical pharmacology (12.3)] . in animal reproduction studies with oseltamivir, no adverse developmental effects were observed at clinically relevant exposures (see data) . the background risk of major birth defects and miscarriage for the indicated populations 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 is 2-4% and 15-20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk pregnant women are at higher risk of severe complications from influenza, which may lead to adverse pregnancy and/or fetal outcomes including maternal death, still births, birth defects, preterm delivery, low birth weight and small for gestational age. data human data published prospective and retrospective observational studies of more than 5,000 women exposed to tamiflu during pregnancy, including more than 1,000 women exposed in the first trimester, suggest that the observed rate of congenital malformations was not increased above the rate in the general comparison population, regardless of when therapy was administered during the gestational period. however, individually, none of these studies had adequate sample sizes and some lacked information on dose, which preclude a definitive assessment of the risk. animal data oseltamivir was administered orally during organogenesis to pregnant rats (at 50, 250, or 1500 mg/kg/day on gestation days 6 to 17) and rabbits (at 50, 150, or 500 mg/kg/day on gestation days 6 to 18). in rats, embryo-fetal effects consisting of an increased incidence of minor skeletal malformations were observed at a maternally toxic dose (1500 mg/kg/day), resulting in systemic drug exposures (based on auc for oseltamivir carboxylate) 190 times human exposures at the maximum recommended human dose (mrhd) of tamiflu (75 mg twice a day). in the rabbit study, embryo-fetal effects consisting of an increased incidence of minor skeletal abnormalities and variants were observed at maternally toxic doses (≥150 mg/kg/day) resulting in systemic exposures (based on auc for oseltamivir carboxylate) ≥8 times human exposures at the mrhd of tamiflu. in prenatal and postnatal development studies in rats, oseltamivir was administered orally (at 50, 250, 500, or 1500 mg/kg/day) from organogenesis through late gestation, delivery, and lactation (gestation day 6 to postpartum/lactation day 20). prolonged parturition duration and reduced offspring viability were observed at a maternally toxic dose (1500 mg/kg/day). no adverse maternal or offspring effects were observed at doses ≤500 mg/kg/day, resulting in systemic drug exposures (based on auc for oseltamivir carboxylate) 44 times human exposures at the mrhd of tamiflu. risk summary based on limited published data, oseltamivir and oseltamivir carboxylate have been shown to be present in human milk at low levels considered unlikely to lead to toxicity in the breastfed infant. postmarketing experience has not reported any information to suggest serious adverse effects of oseltamivir exposure via breast milk in infants. it is not known if oseltamivir affects human milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for tamiflu and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. treatment of influenza the safety and efficacy of tamiflu for the treatment of influenza in pediatric patients 2 weeks old to 17 years of age has been established [see dosage and administration (2.2), clinical pharmacology (12.3), and clinical studies (14.1)] and is based on: - 13 to 17 years of age: safety and efficacy in adolescent patients 13 to 17 years of age was supported by adequate and well-controlled trials in adults and adolescents and younger pediatric patients and safety data in adolescents treated with tamiflu in a study of treatment and prophylaxis. - 1 year to 12 years of age: safety and efficacy in pediatric patients 1 year to 12 years of age was supported by results of one double-blind, placebo-controlled trial in 452 pediatric patients with influenza in whom tamiflu 2 mg per kg twice daily or placebo was administered within 48 hours of symptom onset [see clinical studies (14.1)]. additional safety information was provided in a double-blind, placebo-controlled trial in pediatric patients 6 to 12 years of age with known asthma. efficacy could not be established in pediatric patients with asthma. - 2 weeks to less than 1 year of age: safety and efficacy in pediatric patients 2 weeks to less than 1 year of age is supported by adequate and well-controlled trials in adults and older pediatric patients and two open-label trials of tamiflu (2 to 3.5 mg per kg twice daily for 5 days) in 136 pediatric subjects 2 weeks to less than 1 year of age. in these two trials, the oseltamivir plasma concentrations in these subjects were similar to or higher than the oseltamivir plasma concentrations observed in older pediatric subjects and adults [see clinical pharmacology (12.3) and clinical studies (14.1)] . the safety and efficacy of tamiflu for treatment of influenza in pediatric patients less than 2 weeks of age have not been established. prophylaxis of influenza the safety and efficacy of tamiflu for the prophylaxis of influenza in pediatric patients 1 year to 17 years old has been established [see dosage and administration (2.3), clinical pharmacology (12.3), and clinical studies (14.2)] and is based on: - 13 to 17 years of age: prophylaxis in adolescent patients 13 to 17 years of age is supported by one randomized, placebo-controlled post-exposure household prophylaxis trial of tamiflu 75 mg taken orally once daily for 7 days in household contacts including 207 adolescents [see clinical studies (14.2)]. - 1 year to 12 years of age: tamiflu for prophylaxis in pediatric patients 1 year to 12 years of age is supported by one randomized, open-label, post-exposure household prophylaxis trial including pediatric subjects 1 year to 12 years of age who received 30 to 60 mg of tamiflu for oral suspension (supplied as powder) taken orally once daily for 10 days [see clinical studies (14.2)]. additional safety information was provided in a 6-week seasonal prophylaxis (community outbreak) safety study in 49 patients 1 year to 12 years of age. the safety and efficacy of tamiflu for prophylaxis of influenza have not been established for pediatric patients less than 1 year of age. treatment of influenza of the 4,765 adults in clinical trials of tamiflu for the treatment of influenza, 948 (20%) were 65 years and older, while 329 (7%) were 75 years and older. in three double-blind, placebo-controlled trials in the treatment of influenza in patients at least 65 years old, that enrolled 741 subjects (374 received placebo and 362 received tamiflu), no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects [see clinical studies (14.1)] . prophylaxis of influenza of the 4,603 adults in clinical trials of tamiflu for the prophylaxis of influenza, 1,046 (23%) were 65 years and older, while 719 (16%) were 75 years and older. in a randomized, placebo-controlled trial in elderly residents of nursing homes who took tamiflu for up to 42 days for the prophylaxis of influenza (tamiflu n=276, placebo n=272), no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects [see clinical studies (14.2)] . patients with renal impairment had higher blood levels of oseltamivir carboxylate compared to patients with normal renal function which may increase the risk of tamiflu-associated adverse reactions. therefore, dosage adjustment is recommended for patients with a serum creatinine clearance between 10 and 60 ml/minute and for patients with end-stage renal disease (esrd) undergoing routine hemodialysis or continuous peritoneal dialysis treatment [see dosage and administration (2.4)]. tamiflu is not recommended for patients with esrd not undergoing dialysis [see indications and usage (1.3) and clinical pharmacology (12.3)] . no dosage adjustment is required in patients with mild to moderate hepatic impairment. the safety and pharmacokinetics in patients with severe hepatic impairment have not been evaluated [see clinical pharmacology (12.3)] . efficacy of tamiflu in the treatment of influenza in patients with chronic cardiac disease and/or respiratory disease was evaluated in one randomized, placebo-controlled clinical trial. efficacy in this population, as measured by time to alleviation of all symptoms, was not established, but no new safety signals were identified [see clinical studies (14.1) ]. no clinical trial data are available regarding treatment of influenza in patients with any medical condition sufficiently severe or unstable to be considered at imminent risk of requiring hospitalization. efficacy of tamiflu for the treatment or prophylaxis of influenza has not been established in immunocompromised patients [see clinical studies (14.2)] . safety of tamiflu has been demonstrated for up to 12 weeks for prophylaxis of influenza in immunocompromised patients [see adverse reactions (6.1)]. how do i give a dose of tamiflu for oral suspension? step 1. shake the tamiflu for oral suspension bottle well before each use. step 2. open the bottle by pushing downward on the child resistant bottle cap and twisting it in the direction of the arrow. step 3. measure the oral suspension with an appropriate oral dosing dispenser to be sure you get the correct dose. contact your pharmacist if you do not have an appropriate oral dosing dispenser. step 4. give the full contents of oral dosing dispenser directly into the mouth. step 5. close the bottle with the child-resistant bottle cap after each use. step 6. rinse oral dosing dispenser under running tap water and allow to air dry after each use. how do i mix the contents of tamiflu capsules with sweetened liquids, if directed by my healthcare provider or pharmacist? you will need: - the prescribed dose of tamiflu capsules - a small bowl - sweetened liquid, such as chocolate syrup (regular or sugar-free), corn syrup, caramel topping, or light brown sugar (dissolved in water) step 1. open the contents of the prescribed dose of tamiflu capsules into a small bowl. step 2. add a small amount of the sweetened liquid to the capsule contents. step 3. stir the mixture and give the entire dose of tamiflu.

Ηνωμένες Πολιτείες - Αγγλικά - NLM (National Library of Medicine)

genentech, inc. - ranibizumab (unii: zl1r02vt79) (ranibizumab - unii:zl1r02vt79) - ranibizumab 10 mg in 1 ml - lucentis is indicated for the treatment of patients with:           lucentis is contraindicated in patients with ocular or periocular infections. lucentis is contraindicated in patients with known hypersensitivity to ranibizumab or any of the excipients in lucentis. hypersensitivity reactions may manifest as severe intraocular inflammation. risk summary there are no adequate and well-controlled studies of lucentis administration in pregnant women. administration of ranibizumab to pregnant monkeys throughout the period of organogenesis resulted in a low incidence of skeletal abnormalities at intravitreal doses 13-times the predicted human exposure (based on maximal serum trough levels [cmax ]) after a single eye treatment at the recommended clinical dose. no skeletal abnormalities were observed at serum trough levels equivalent to the predicted human exposure after a single eye treatment at the recommended clinical dose [see animal data] . animal reproduction studies are not always predictive of human response, and it is not known whether ranibizumab can cause fetal harm when administered to a pregnant woman. based on the anti-vegf mechanism of action for ranibizumab [see clinical pharmacology (12.1)] , treatment with lucentis may pose a risk to human embryofetal development. lucentis should be given to a pregnant woman only if clearly needed. data animal data an embryo-fetal developmental toxicity study was performed on pregnant cynomolgus monkeys. pregnant animals received intravitreal injections of ranibizumab every 14 days starting on day 20 of gestation, until day 62 at doses of 0, 0.125, and 1 mg/eye. skeletal abnormalities including incomplete and/or irregular ossification of bones in the skull, vertebral column, and hindlimbs and shortened supernumerary ribs were seen at a low incidence in fetuses from animals treated with 1 mg/eye of ranibizumab. the 1 mg/eye dose resulted in trough serum ranibizumab levels up to 13 times higher than predicted cmax levels with single eye treatment in humans. no skeletal abnormalities were seen at the lower dose of 0.125 mg/eye, a dose which resulted in trough exposures equivalent to single eye treatment in humans. no effect on the weight or structure of the placenta, maternal toxicity, or embryotoxicity was observed. risk summary there are no data available on the presence of ranibizumab in human milk, the effects of ranibizumab on the breastfed infant or the effects of ranibizumab on milk production/excretion. because many drugs are excreted in human milk, and because the potential for absorption and harm to infant growth and development exists, caution should be exercised when lucentis is administered to a nursing woman. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for lucentis and any potential adverse effects on the breastfed child from ranibizumab. infertility no studies on the effects of ranibizumab on fertility have been conducted and it is not known whether ranibizumab can affect reproduction capacity. based on the anti-vegf mechanism of action for ranibizumab, treatment with lucentis may pose a risk to reproductive capacity. the safety and effectiveness of lucentis in pediatric patients have not been established. in the clinical studies, approximately 76% (2449 of 3227) of patients randomized to treatment with lucentis were ≥ 65 years of age and approximately 51% (1644 of 3227) were ≥ 75 years of age [see clinical studies (14)]. no notable differences in efficacy or safety were seen with increasing age in these studies. age did not have a significant effect on systemic exposure.

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genentech, inc. - alteplase (unii: 1rxs4ue564) (alteplase - unii:1rxs4ue564) - alteplase 50 mg in 50 ml - activase is indicated for the treatment of acute ischemic stroke. exclude intracranial hemorrhage as the primary cause of stroke signs and symptoms prior to initiation of treatment [see contraindications (4.1)] . initiate treatment as soon as possible but within 3 hours after symptom onset. activase is indicated for use in acute myocardial infarction (ami) for the reduction of mortality and reduction of the incidence of heart failure. limitation of use: the risk of stroke may outweigh the benefit produced by thrombolytic therapy in patients whose ami puts them at low risk for death or heart failure. activase is indicated for the lysis of acute massive pulmonary embolism, defined as: - acute pulmonary emboli obstructing blood flow to a lobe or multiple lung segments. - acute pulmonary emboli accompanied by unstable hemodynamics, e.g., failure to maintain blood pressure without supportive measures. do not administer activase to treat acute ischemic stroke in the following situations in which the risk of bleedi

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genentech, inc. - capecitabine (unii: 6804dj8z9u) (capecitabine - unii:6804dj8z9u) - capecitabine 150 mg - xeloda is indicated for the: - adjuvant treatment of patients with stage iii colon cancer as a single agent or as a component of a combination chemotherapy regimen. - perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy. - treatment of patients with unresectable or metastatic colorectal cancer as a single agent or as a component of a combination chemotherapy regimen. xeloda is indicated for the: - treatment of patients with advanced or metastatic breast cancer as a single agent if an anthracycline- or taxane-containing chemotherapy is not indicated. - treatment of patients with advanced or metastatic breast cancer in combination with docetaxel after disease progression on prior anthracycline-containing chemotherapy. xeloda is indicated for the: - treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen. - treatment of adults with her2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease as a component of a combination regimen. xeloda is indicated for the adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen. xeloda is contraindicated in patients with history of severe hypersensitivity reaction to fluorouracil or capecitabine [see adverse reactions (6.1)] . risk summary based on findings in animal reproduction studies and its mechanism of action [see clinical pharmacology (12.1)] , xeloda can cause fetal harm when administered to a pregnant woman. available human data with xeloda use in pregnant women is not sufficient to inform the drug-associated risk. in animal reproduction studies, administration of capecitabine to pregnant animals during the period of organogenesis caused embryolethality and teratogenicity in mice and embryolethality in monkeys at 0.2 and 0.6 times the exposure (auc) in patients receiving the recommended dose of 1,250 mg/m2 twice daily, respectively (see data) . advise pregnant women of the potential risk to a fetus. 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. data animal data oral administration of capecitabine to pregnant mice during the period of organogenesis at a dose of 198 mg/kg/day caused malformations and embryo lethality. in separate pharmacokinetic studies, this dose in mice produced 5'-dfur auc values that were approximately 0.2 times the auc values in patients administered the recommended daily dose. malformations in mice included cleft palate, anophthalmia, microphthalmia, oligodactyly, polydactyly, syndactyly, kinky tail and dilation of cerebral ventricles. oral administration of capecitabine to pregnant monkeys during the period of organogenesis at a dose of 90 mg/kg/day, caused fetal lethality. this dose produced 5'-dfur auc values that were approximately 0.6 times the auc values in patients administered the recommended daily dose. risk summary there is no information regarding the presence of capecitabine or its metabolites in human milk, or on its effects on milk production or the breastfed child. capecitabine metabolites were present in the milk of lactating mice (see data) . because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with xeloda and for 1 week after the last dose. data lactating mice given a single oral dose of capecitabine excreted significant amounts of capecitabine metabolites into the milk. xeloda can 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 initiating xeloda. contraception females advise females of reproductive potential to use effective contraception during treatment with xeloda and for 6 months after the last dose. males based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with xeloda and for 3 months after the last dose [see nonclinical toxicology (13.1)]. infertility based on animal studies, xeloda may impair fertility in females and males of reproductive potential [see nonclinical toxicology (13.1)] . the safety and effectiveness of xeloda in pediatric patients have not been established. safety and effectiveness were assessed, but not established in two single arm studies in 56 pediatric patients aged 3 months to <17 years with newly diagnosed gliomas. in both trials, pediatric patients received an investigational pediatric formulation of capecitabine concomitantly with and following completion of radiation therapy (total dose of 5580 cgy in 180 cgy fractions). the relative bioavailability of the investigational formulation to xeloda was similar. the adverse reaction profile was consistent with that of adults, with the exception of laboratory abnormalities which occurred more commonly in pediatric patients. the most frequently reported laboratory abnormalities (per-patient incidence ≥ 40%) were increased alt (75%), lymphocytopenia (73%), hypokalemia (68%), thrombocytopenia (57%), hypoalbuminemia (55%), neutropenia (50%), low hematocrit (50%), hypocalcemia (48%), hypophosphatemia (45%) and hyponatremia (45%). of 7938 patients with colorectal cancer who were treated with xeloda, 33% were older than 65 years. of the 4536 patients with metastatic breast cancer who were treated with xeloda, 18% were older than 65 years. of 1951 patients with gastric, esophageal, or gastrointestinal junction cancer who were treated with xeloda, 26% were older than 65 years. of 364 patients with pancreatic cancer who received adjuvant treatment with xeloda, 47% were 65 years or older. no overall differences in efficacy were observed comparing older versus younger patients with colorectal cancer, gastric, esophageal or gastrointestinal junction cancer, or pancreatic cancer using the approved recommended dosages and treatment regimens. older patients experience increased gastrointestinal toxicity due to xeloda compared to younger patients. deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil [see drug interactions (7.1)]. the exposure of capecitabine and its inactive metabolites (5-dfur and fbal) increases in patients with clcr <50 ml/min as determined by cockcroft-gault [see clinical pharmacology (12.3)] . reduce the dosage for patients with clcr of 30 to 50 ml/min [see dosage and administration (2.6)] . there is limited experience with xeloda in patients with clcr <30 ml/min, and a dosage has not been established in those patients. if no treatment alternative exists, xeloda could be administered to such patients on an individual basis applying a reduced starting dose, close monitoring of a patient's clinical and biochemical data and dose modifications guided by observed adverse reactions. the exposure of capecitabine increases in patients with mild to moderate hepatic impairment. the effect of severe hepatic impairment on the safety and pharmacokinetics of xeloda is unknown [see clinical pharmacology (12.3)]. monitor patients with hepatic impairment more frequently for adverse reactions.

Ηνωμένες Πολιτείες - Αγγλικά - NLM (National Library of Medicine)

genentech, inc. - tenecteplase (unii: wgd229o42w) (tenecteplase - unii:wgd229o42w) - tnkase® is indicated to reduce the risk of death associated with acute st elevation myocardial infarction (stemi). tnkase is contraindicated in patients with [see warnings and precautions (5.1)] : - active internal bleeding - history of cerebrovascular accident - intracranial or intraspinal surgery or trauma within 2 months - intracranial neoplasm, arteriovenous malformation, or aneurysm - known bleeding diathesis - severe uncontrolled hypertension risk summary there are risks to the mother and fetus from acute st elevation myocardial infarction, which is a medical emergency in pregnancy and can be fatal if left untreated (see clinical considerations). published data consisting of a small number of case reports involving the use of related thrombolytic agents in pregnant women have not identified an increased risk of major birth defects. there are no data on the use of tenecteplase during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outco

Ηνωμένες Πολιτείες - Αγγλικά - NLM (National Library of Medicine)

genentech, inc. - pralsetinib (unii: 1wpe73o1wv) (pralsetinib - unii:1wpe73o1wv) - gavreto is indicated for the treatment of adult patients with metastatic ret fusion-positive non-small cell lung cancer (nsclc) as detected by an fda approved test. gavreto is indicated for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic ret fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). this indication is approved under accelerated approval based on overall response rate and duration of response [see clinical studies (14.2)] . continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). none. risk summary based on findings from animal studies and its mechanism of action, gavreto can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)]. there are no available data on gavreto use in pregnant women to inform drug-associated risk. oral administration of pralsetinib to pregnant rats during the period of organogenesis resulted in malformations and embryolethality at maternal exposures below the human exposure at the clinical dose of 400 mg once daily (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 2-4% and 15-20%, respectively. data animal data in an embryo-fetal development study, once daily oral administration of pralsetinib to pregnant rats during the period of organogenesis resulted in 100% post-implantation loss at dose levels ≥ 20 mg/kg (approximately 1.8 times the human exposure based on area under the curve [auc] at the clinical dose of 400 mg). post-implantation loss also occurred at the 10 mg/kg dose level (approximately 0.6 times the human exposure based on auc at the clinical dose of 400 mg). once daily oral administration of pralsetinib at dose levels ≥ 5 mg/kg (approximately 0.2 times the human auc at the clinical dose of 400 mg) resulted in an increase in visceral malformations and variations (absent or small kidney and ureter, absent uterine horn, malpositioned kidney or testis, retroesophageal aortic arch) and skeletal malformations and variations (vertebral and rib anomalies and reduced ossification). risk summary there are no data on the presence of pralsetinib or its metabolites in human milk or their effects on either the breastfed child or on milk production. because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with gavreto and for 1 week after the last dose. based on animal data, gavreto can cause embryolethality and malformations at doses resulting in exposures below the human exposure at the clinical dose of 400 mg daily [see use in specific populations (8.1)]. pregnancy testing verify pregnancy status of females of reproductive potential prior to initiating gavreto [see use in specific populations (8.1)]. contraception gavreto can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)]. females advise females of reproductive potential to use effective non-hormonal contraception during treatment with gavreto and for 2 weeks after the last dose. gavreto may render hormonal contraceptives ineffective. males advise males with female partners of reproductive potential to use effective contraception during treatment with gavreto and for 1 week after the last dose. infertility based on histopathological findings in the reproductive tissues of male and female rats and a dedicated fertility study in which animals of both sexes were treated and mated to each other, gavreto may impair fertility [see nonclinical toxicology (13.1)]. the safety and effectiveness of gavreto have been established in pediatric patients aged 12 years and older for ret fusion-positive thyroid cancer. use of gavreto in this age group is supported by evidence from an adequate and well-controlled study of gavreto in adults with additional population pharmacokinetic data demonstrating that age and body weight had no clinically meaningful effect on the pharmacokinetics of pralsetinib, that the exposure of pralsetinib is expected to be similar between adults and pediatric patients age 12 years and older, and that the course of ret fusion-positive thyroid cancer is sufficiently similar in adults and pediatric patients to allow extrapolation of data in adults to pediatric patients [see adverse reactions (6.1), clinical pharmacology (12.3), and clinical studies (14.2)]. the safety and effectiveness of gavreto have not been established in pediatric patients with ret fusion-positive nsclc or in pediatric patients younger than 12 years old with ret fusion-positive thyroid cancer. animal toxicity data in a 4-week repeat-dose toxicology study in non-human primates, physeal dysplasia in the femur occurred at doses resulting in exposures similar to the human exposure (auc) at the clinical dose of 400 mg. in rats there were findings of increased physeal thickness in the femur and sternum as well as tooth (incisor) abnormalities (fractures, dentin matrix alteration, ameloblast/odontoblast degeneration, necrosis) in both 4- and 13-week studies at doses resulting in exposures similar to the human exposure (auc) at the clinical dose of 400 mg. recovery was not assessed in the 13-week toxicology study, but increased physeal thickness in the femur and incisor degeneration did not show evidence of complete recovery in the 28-day rat study. monitor growth plates in adolescent patients with open growth plates. consider interrupting or discontinuing therapy based on the severity of any growth plate abnormalities and based on an individual risk-benefit assessment. of the 540 patients in arrow who received the recommended dose of gavreto at 400 mg once daily, 31% were 65 years or and over, while 7% were 75 years and over. no overall differences in pharmacokinetics (pk), safety or effectiveness were observed between patients aged 65 years or older and younger patients. no dose adjustment is required for patients with mild (total bilirubin ≤ uln and ast > uln or total bilirubin > 1 to 1.5 × uln and any ast), moderate (total bilirubin > 1.5 to 3 × uln and any ast) or severe (total bilirubin > 3 × uln and any ast) hepatic impairment.

Παναμάς - Αγγλικά - Ministerio de Salud (Dirección Nacional de Farmacia Y Drogas)

genentech, inc - dornasa alfa - dornasa alfa....2.50 mg