الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - crizotinib (unii: 53ah36668s) (crizotinib - unii:53ah36668s) - crizotinib 250 mg - xalkori is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (nsclc) whose tumors are anaplastic lymphoma kinase (alk) or ros1-positive as detected by an fda-approved test [see dosage and administration (2.1)] . xalkori is indicated for the treatment of pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (alcl) that is alk-positive. limitations of use : the safety and efficacy of xalkori have not been established in older adults with relapsed or refractory, systemic alk-positive alcl. xalkori is indicated for the treatment of adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (imt) that is alk-positive. none. risk summary based on findings from animal studies and its mechanism of action, xalkori can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no available dat

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - eplerenone (unii: 6995v82d0b) (eplerenone - unii:6995v82d0b) - eplerenone 25 mg - inspra is indicated to improve survival of stable patients with symptomatic heart failure with reduced ejection fraction (≤40%) (hfref) after an acute myocardial infarction (mi). inspra is indicated for the treatment of hypertension, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular (cv) events, primarily strokes and mi. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes. control of high blood pressure should be part of comprehensive cv risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than one drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program's joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cv morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cv outcome benefit has been a reduction in the risk of stroke, but reductions in mi and cv mortality also have been seen regularly. elevated systolic or diastolic pressure causes increased cv risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. inspra may be used alone or in combination with other antihypertensive agents. for all patients inspra is contraindicated in all patients with: for patients treated for hypertension inspra is contraindicated for the treatment of hypertension in patients with: risk summary the available data from published case reports on eplerenone use during pregnancy are insufficient to establish a drug-associated risk of major birth defects, miscarriage, adverse maternal or fetal outcomes (see clinical considerations). in animal studies, no adverse developmental effects were observed when eplerenone was administered to pregnant rats and rabbits during organogenesis at exposures 32 and 31 times, respectively the human exposure at the 100 mg/day therapeutic dose. the estimated background risk of major birth defects and miscarriage for the indicated population are unknown. in the us 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 hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. pregnant women with hypertension should be carefully monitored and managed accordingly. pregnant women with heart failure are at increased risk for preterm birth. stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester. clinical classification of heart disease may worsen with pregnancy and lead to maternal death. closely monitor pregnant patients for destabilization of their heart failure. data animal data embryo-fetal development studies were conducted with doses up to 1000 mg/kg/day in rats and 300 mg/kg/day in rabbits (exposures up to 32 and 31 times the human auc for the 100 mg/day therapeutic dose, respectively) administered during organogenesis. no teratogenic effects were seen in rats or rabbits, although decreased rat fetal weights were observed, and decreased body weight in maternal rabbits and increased rabbit fetal resorptions and post-implantation loss were observed at the highest administered dosages. in a pre- and postnatal development study pregnant rats were administered eplerenone at doses up to 1000 mg/kg/day from gestation day 6 through lactation day 20. decreased pup weights were observed beginning at birth at 1000 mg/kg/day. risk summary there are no human data available on whether eplerenone is present in human milk, or has effects on breastfed infants or on milk production. eplerenone was present in the milk of lactating rats. when a drug is present in animal milk, it is likely that the drug will be present in human milk. infertility based on animal data, use of inspra may compromise male fertility. in mature rats, male fertility was decreased with eplerenone exposure at 17 times the 100 mg/day human therapeutic dose. reversibility of effects was not evaluated [see nonclinical toxicology (13.1)]. in a 10-week study of 304 hypertensive pediatric patients age 4 to 16 years treated with inspra up to 100 mg per day, doses that produced exposure similar to that in adults, inspra did not lower blood pressure effectively. in this study and in a 1-year pediatric safety study in 149 patients (age range 5 to 17 years), the incidence of reported adverse events was similar to that of adults. inspra has not been studied in hypertensive patients less than 4 years old because the study in older pediatric patients did not demonstrate effectiveness. inspra has not been studied in pediatric patients with heart failure. heart failure post-myocardial infarction of the total number of patients in ephesus, 3340 (50%) were 65 and over, while 1326 (20%) were 75 and over. patients greater than 75 years did not appear to benefit from the use of inspra [see clinical studies (14.1)]. no differences in overall incidence of adverse events were observed between elderly and younger patients. however, due to age-related decreases in creatinine clearance, the incidence of laboratory-documented hyperkalemia was increased in patients 65 and older [see warnings and precautions (5.1)]. hypertension of the total number of subjects in clinical hypertension studies of inspra, 1123 (23%) were 65 and over, while 212 (4%) were 75 and over. no overall differences in safety or effectiveness were observed between elderly subjects and younger subjects, however due to age-related decreases in creatine clearance, the risk of hyperkalemia may be increased [see warnings and precautions (5.1)] .

إسرائيل - الإنجليزية - Ministry of Health

pfizer pfe pharmaceuticals israel ltd - linezolid - solution for infusion - linezolid 2 mg/ml - linezolid - linezolid - therapy is indicated only when an organism resistant to all other antibiotics is suspected. zyvoxid is indicated in adult and pediatric patients for the treatment of infections when known or suspected to be caused by susceptible organisms including those associated with concurrent bacteraemia such as: 1) pneumonia - community acquired and nosocomial pneumonia including multi drug resistant streptococcus pneumonia (mdrsp). 2) skin and soft tissue infections including diabetic foot infections. 3) enterococcal infections. combination therapy may be indicated if a concomitant gram negative pathogen is documented or suspected.

أستراليا - الإنجليزية - Department of Health (Therapeutic Goods Administration)

pfizer australia pty ltd - bupivacaine hydrochloride monohydrate, quantity: 5.27 mg/ml (equivalent: bupivacaine hydrochloride, qty 5 mg/ml); adrenaline (epinephrine) acid tartrate, quantity: 9.1 microgram/ml (equivalent: adrenaline (epinephrine), qty 5 microgram/ml) - injection, solution - excipient ingredients: water for injections; sodium chloride; sodium metabisulfite; citric acid; sodium citrate - pfizer bupivacaine with adrenaline injection is indicated for the production of local or regional anaesthesia and analgesia in individuals as follows;,surgical anaesthesia:,- epidural block for surgery,- field block (minor and major nerve blocks and infiltration),analgesia,- continuous epidural infusion or intermittent bolus epidural administration for analgesia in postoperative pain or labour pain,- field block (minor nerve block and infiltration),the choice of 2 strengths, 0.25%, and 0.5% makes it possible to vary the degree of motor blockade.

أستراليا - الإنجليزية - Department of Health (Therapeutic Goods Administration)

pfizer australia pty ltd - bupivacaine hydrochloride monohydrate, quantity: 2.64 mg/ml (equivalent: bupivacaine hydrochloride, qty 2.5 mg/ml); adrenaline (epinephrine) acid tartrate, quantity: 4.5 microgram/ml (equivalent: adrenaline (epinephrine), qty 2.5 microgram/ml) - injection, solution - excipient ingredients: sodium citrate; citric acid; sodium metabisulfite; water for injections; sodium chloride - pfizer bupivacaine with adrenaline is indicated for the production of local or regional anaesthesia and analgesia in individuals as follows;,surgical anaesthesia:,- epidural block for surgery,- field block (minor and major nerve blocks and infiltration),analgesia,- continuous epidural infusion or intermittent bolus epidural administration for analgesia in postoperative pain or labour pain,- field block (minor nerve block and infiltration),the choice of 2 strengths, 0.25%, and 0.5% makes it possible to vary the degree of motor blockade.

الاتحاد الأوروبي - الإنجليزية - EMA (European Medicines Agency)

pfizer europe ma eeig - pemetrexed disodium, pemetrexed disodium hemipentahydrate - carcinoma, non-small-cell lung; mesothelioma - antineoplastic agents - malignant pleural mesotheliomapemetrexed pfizer in combination with cisplatin is indicated for the treatment of chemotherapy naïve patients with unresectable malignant pleural mesothelioma.non-small cell lung cancerpemetrexed pfizer in combination with cisplatin is indicated for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.pemetrexed pfizer is indicated as monotherapy for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology in patients whose disease has not progressed immediately following platinum-based chemotherapy.pemetrexed pfizer is indicated as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-small cell lung cancer other than predominantly squamous cell histology.

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - bosutinib monohydrate (unii: 844zje6i55) (bosutinib - unii:5018v4aez0) - bosutinib monohydrate 100 mg - bosulif is indicated for the treatment of: bosulif is contraindicated in patients with a history of hypersensitivity to bosulif. reactions have included anaphylaxis [see adverse reactions (6.1)] . risk summary based on findings from animal studies and its mechanism of action, bosulif can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no available data in pregnant women to inform the drug-associated risk. in animal reproduction studies conducted in rats and rabbits, oral administration of bosutinib during organogenesis caused adverse developmental outcomes, including structural abnormalities, embryo-fetal mortality, and alterations to growth at maternal exposures (auc) as low as 1.2 times the human exposure at the dose of 500 mg/day (see data ). advise pregnant women of the potential risk to a fetus. the 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 are 2–4% and 15–20%, respectively. data animal data in a rat fertility and early embryonic development study, bosutinib was administered orally to female rats for approximately 3 to 6 weeks, depending on day of mating (2 weeks prior to cohabitation with untreated breeder males until gestation day [gd] 7). increased embryonic resorptions occurred at greater than or equal to 10 mg/kg/day of bosutinib (1.6 and 1.2 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively), and decreased implantations and reduced number of viable embryos at 30 mg/kg/day of bosutinib (3.4 and 2.5 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively). in an embryo-fetal development study conducted in rabbits, bosutinib was administered orally to pregnant animals during the period of organogenesis at doses of 3, 10, and 30 mg/kg/day. at the maternally-toxic dose of 30 mg/kg/day of bosutinib, there were fetal anomalies (fused sternebrae, and 2 fetuses had various visceral observations), and an approximate 6% decrease in fetal body weight. the dose of 30 mg/kg/day resulted in exposures (auc) approximately 5.1 and 3.8 times the human exposures at the recommended doses of 400 and 500 mg/day, respectively. fetal exposure to bosutinib-derived radioactivity during pregnancy was demonstrated in a placental-transfer study in pregnant rats. in a rat pre- and postnatal development study, bosutinib was administered orally to pregnant animals during the period of organogenesis through lactation day 20 at doses of 10, 30, and 70 mg/kg/day. reduced number of pups born occurred at greater than or equal to 30 mg/kg/day bosutinib (3.4 and 2.5 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively), and increased incidence of total litter loss and decreased growth of offspring after birth occurred at 70 mg/kg/day bosutinib (6.9 and 5.1 times the human exposure at the recommended doses of 400 or 500 mg/day, respectively). risk summary no data are available regarding the presence of bosutinib or its metabolites in human milk or its effects on a breastfed child or on milk production. however, bosutinib is present in the milk of lactating rats. because of the potential for serious adverse reactions in a nursing child, breastfeeding is not recommended during treatment with bosulif and for 2 weeks after the last dose. animal data after a single radiolabeled bosutinib dose to lactating rats, radioactivity was present in the plasma of suckling offspring for 24 to 48 hours. based on findings from animal studies, bosulif can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . pregnancy females of reproductive potential should have a pregnancy test prior to starting treatment with bosulif. contraception females advise females of reproductive potential to use effective contraception (methods that result in less than 1% pregnancy rates) during treatment with bosulif and for 2 weeks after the last dose. infertility the risk of infertility in females or males of reproductive potential has not been studied in humans. based on findings from animal studies, bosulif may cause reduced fertility in females and males of reproductive potential [see nonclinical toxicology (13.1)] . the safety and effectiveness of bosulif have been established in pediatric patients 1 year of age and older with newly-diagnosed cp ph+ cml and cp ph+ cml that is resistant or intolerant to prior therapy. use of bosulif for these indications is based on data from bchild [nct04258943]. the study included pediatric patients with newly diagnosed cp ph+ cml in the following age groups: 2 patients 1 year of age to less than 6 years of age, 3 patients 6 years of age to less than 12 years of age, and 10 patients 12 years of age to less than 17 years of age. the study also included pediatric patients with cp ph+ cml that was resistant or intolerant to prior therapy in the following age groups: 4 patients 1 year of age to less than 6 years of age, 10 patients 6 years of age to less than 12 years of age, and 10 patients 12 years of age to less than 17 years of age [see adverse reactions (6.1) and clinical studies (14.3) ] . bsa-normalized apparent clearance in 27 pediatric patients aged 4 to <17 years (141.3 l/h/m2 ) was 29% higher than bsa-normalized apparent clearance in adult patients with cp ph+ cml (109.2 l/h/m2 ) [see clinical pharmacology (12.3)] . the recommended dosage of bosulif in pediatric patients is based on body-surface area (bsa) [see dosage and administration (2.1)]. the safety and effectiveness of bosulif in pediatric patients younger than 1 year of age with newly diagnosed cp ph+ cml, pediatric patients younger than 1 year of age with cp ph+ cml that is resistant or intolerant to prior therapy, and pediatric patients with ap ph+ cml or bp ph+ cml have not been established. in the single-arm study in patients with cml who were resistant or intolerant to prior therapy of bosulif in patients with ph+ cml, 20% were age 65 and over, 4% were 75 and over. of the 268 patients who received bosutinib in the study for newly diagnosed cml, 20% were age 65 and over, 5% were 75 and over. no overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. reduce the bosulif starting dose in patients with moderate (creatinine clearance [clcr ] 30 to 50 ml/min, estimated by cockcroft-gault (c-g)) and severe (clcr less than 30 ml/min, c-g) renal impairment at baseline. for patients who have declining renal function while on bosulif who cannot tolerate the starting dose, follow dose adjustment recommendations for toxicity [see dosage and administration (2.3, 2.5) and clinical pharmacology (12.3)] . bosulif has not been studied in patients undergoing hemodialysis. reduce the bosulif dosage in patients with hepatic impairment (child-pugh a, b, or c) [see dosage and administration (2.3, 2.5) and clinical pharmacology (12.3)]. bosulif® (bah-su-lif) (bosutinib) capsules this instructions for use contains information on how to prepare and give a dose of bosulif capsules by opening the capsules and mixing the contents with applesauce or yogurt for people who cannot swallow capsules whole. read this instructions for use before you prepare or give the first dose of bosulif, and each time you get a refill. ask your healthcare provider or pharmacist if you have any questions. important information you need to know before preparing a dose of bosulif capsules: preparing a dose of bosulif capsules: gather the following supplies: giving a dose of bosulif capsules: step 1: choose a clean, flat work surface. place all supplies on the work surface. step 2: wash and dry your hands well. step 3: put on disposable gloves step 4: get the prescribed number of bosulif capsule(s) needed to prepare the dose. step 5: add the amount of applesauce or yogurt needed for the prescribed dose to the container. dose amount of applesauce or yogurt 100 mg 10 ml (2 teaspoons) 150 mg 15 ml (3 teaspoons) 200 mg 20 ml (4 teaspoons) 250 mg 25 ml (5 teaspoons) 300 mg 30 ml (6 teaspoons) 350 mg 30 ml (6 teaspoons) 400 mg 35 ml (7 teaspoons) 450 mg 40 ml (8 teaspoons) 500 mg 45 ml (9 teaspoons) 550 mg 45 ml (9 teaspoons) 600 mg 50 ml (10 teaspoons) step 6: carefully open each of the bosulif capsule(s) needed for the dose and empty the entire contents into the applesauce or yogurt. mix the entire capsule contents with the applesauce or yogurt in the container. step 7: swallow all of the mixture right away, without chewing. step 8: dispose of (throw away) the empty bosulif capsule shell(s) in the household trash. step 9: wash teaspoon and the container with soap and warm water. step 10: remove disposable gloves and throw them away in the household trash. step 11: wash and dry your hands. how should i store bosulif capsules? keep bosulif and all medicines out of the reach of children. lab-0639-12.0 for more information, go to www.bosulif.com or www.pfizermedicalinformation.com or call 1-800-438-1985. this instructions for use has been approved by the u.s. food and drug administration. issued: 9 2023

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - amlodipine besylate (unii: 864v2q084h) (amlodipine - unii:1j444qc288), atorvastatin calcium trihydrate (unii: 48a5m73z4q) (atorvastatin - unii:a0jwa85v8f) - amlodipine 2.5 mg - caduet (amlodipine and atorvastatin) is indicated in patients for whom treatment with both amlodipine and atorvastatin is appropriate. amlodipine amlodipine is indicated for the treatment of hypertension, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including amlodipine. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than one drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program's joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. amlodipine may be used alone or in combination with other antihypertensive agents. chronic stable angina amlodipine is indicated for the symptomatic treatment of chronic stable angina. amlodipine may be used alone or in combination with other antianginal agents. vasospastic angina (prinzmetal's or variant angina) amlodipine is indicated for the treatment of confirmed or suspected vasospastic angina. amlodipine may be used as monotherapy or in combination with other antianginal agents. angiographically documented cad in patients with recently documented cad by angiography and without heart failure or an ejection fraction < 40%, amlodipine is indicated to reduce the risk of hospitalization for angina and to reduce the risk of a coronary revascularization procedure. atorvastatin therapy with hmg coa-reductase inhibitors (lipid-altering agents) should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease from hypercholesterolemia. drug therapy is recommended as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. in patients with coronary heart disease (chd) or multiple risk factors for chd, atorvastatin can be started simultaneously with diet restriction. in adult patients without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as age, smoking, hypertension, low high-density lipoprotein cholesterol (hdl-c), or a family history of early coronary heart disease, atorvastatin is indicated to: in adult patients with type 2 diabetes, and without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as retinopathy, albuminuria, smoking, or hypertension, atorvastatin is indicated to: in adult patients with clinically evident coronary heart disease, atorvastatin is indicated to: atorvastatin is indicated: atorvastatin has not been studied in conditions where the major lipoprotein abnormality is elevation of chylomicrons (fredrickson types i and v). risk summary caduet is contraindicated in women who are pregnant. atorvastatin atorvastatin is contraindicated for use in pregnant women since safety in pregnant women has not been established and there is no apparent benefit of lipid lowering drugs during pregnancy. because hmg-coa reductase inhibitors decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, atorvastatin may cause fetal harm when administered to a pregnant woman. caduet should be discontinued as soon as pregnancy is recognized [see contraindications (4)] . limited published data on the use of atorvastatin are insufficient to determine a drug-associated risk of major congenital malformations or miscarriage. in animal reproduction studies in rats and rabbits there was no evidence of embryo-fetal toxicity or congenital malformations at doses up to 30 and 20 times, respectively, the human exposure at the mrhd of 80 mg, based on body surface area (mg/m2 ). in rats administered atorvastatin during gestation and lactation, decreased postnatal growth and development was observed at doses ≥6 times the mrhd (see data ). amlodipine the limited available data based on post-marketing reports with amlodipine use in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. there are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy (see clinical considerations ). in animal reproduction studies, there was no evidence of adverse developmental effects when pregnant rats and rabbits were treated orally with amlodipine maleate during organogenesis at doses approximately 10 and 20-times mrhd, respectively. however for rats, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold). amlodipine has been shown to prolong both the gestation period and the duration of labor in rats at this dose (see data ). the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and post-partum hemorrhage). hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. pregnant women with hypertension should be carefully monitored and managed accordingly. data human data atorvastatin limited published data on atorvastatin calcium from observational studies, meta-analyses and case reports have not shown an increased risk of major congenital malformations or miscarriage. rare reports of congenital anomalies have been received following intrauterine exposure to other hmg-coa reductase inhibitors. in a review of approximately 100 prospectively followed pregnancies in women exposed to simvastatin or lovastatin, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed what would be expected in the general population. the number of cases is adequate to exclude a ≥3 to 4-fold increase in congenital anomalies over the background incidence. in 89% of the prospectively followed pregnancies, drug treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. animal data atorvastatin atorvastatin crosses the rat placenta and reaches a level in fetal liver equivalent to that of maternal plasma. when administered to pregnant rats and rabbits during organogenesis at oral doses up to 300 mg/kg/day and 100 mg/kg/day, respectively, atorvastatin was not teratogenic in rats at doses up to 300 mg/kg/day or in rabbits at doses up to 100 mg/kg/day. these doses resulted in multiples of about 30 times (rat) or 20 times (rabbit) the human exposure at the mrhd based on surface area (mg/m2 ). in rats, the maternally toxic dose of 300 mg/kg resulted in increased post-implantation loss and decreased fetal body weight. at the maternally toxic doses of 50 and 100 mg/kg/day in rabbits, there was increased post-implantation loss, and at 100 mg/kg/day fetal body weights were decreased. in a study in pregnant rats administered atorvastatin calcium at doses equivalent to 20, 100, or 225 mg/kg/day, from gestation day 7 through to lactation day 20 (weaning), there was decreased survival at birth, postnatal day 4, weaning, and post-weaning in pups of mothers dosed with 225 mg/kg/day, a dose at which maternal toxicity was observed. pup body weight was decreased through postnatal day 21 at 100 mg/kg/day, and through postnatal day 91 at 225 mg/kg/day. pup development was delayed (rotarod performance at 100 mg/kg/day and acoustic startle at 225 mg/kg/day; pinnae detachment and eye-opening at 225 mg/kg/day). these doses of atorvastatin correspond to 6 times (100 mg/kg) and 22 times (225 mg/kg) the human exposure at the mrhd, based on auc. amlodipine no evidence of teratogenicity or other embryo/fetal toxicity was found when pregnant rats and rabbits were treated orally with amlodipine maleate at doses up to 10 mg amlodipine/kg/day (approximately 10 and 20 times the mrhd based on body surface area, respectively) during their respective periods of major organogenesis. however, for rats, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold) in rats receiving amlodipine maleate at a dose equivalent to 10 mg amlodipine/kg/day for 14 days before mating and throughout mating and gestation. amlodipine maleate has been shown to prolong both the gestation period and the duration of labor in rats at this dose. risk summary caduet is contraindicated during breastfeeding. atorvastatin atorvastatin use is contraindicated during breastfeeding [see contraindications (4)] . there is no available information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. it is not known whether atorvastatin is present in human milk, but it has been shown that another drug in this class passes into human milk and atorvastatin is present in rat milk. because of the potential for serious adverse reactions in a breastfed infant, advise women that breastfeeding is not recommended during treatment with caduet. amlodipine limited available data from a published clinical lactation study reports that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. no adverse effects of amlodipine on the breastfed infant have been observed. there is no available information on the effects of amlodipine on milk production. contraception atorvastatin may cause fetal harm when administered to a pregnant woman. advise females of reproductive potential to use effective contraception during treatment with caduet [see use in specific populations (8.1)] . the safety and effectiveness of caduet have not been established in pediatric populations. amlodipine amlodipine (2.5 to 5 mg daily) is effective in lowering blood pressure in patients 6 to 17 years [see clinical studies (14.1)] . the effect of amlodipine on blood pressure in patients less than 6 years of age is not known. atorvastatin heterozygous familial hypercholesterolemia (hefh) safety and effectiveness of atorvastatin have been established in patients 10 years to 17 years of age with hefh as an adjunct to diet to reduce total cholesterol, ldl-c, and apo b levels when, after an adequate trial of diet therapy, the following are present: use of atorvastatin for this indication is supported by evidence from [see dosage and administration (2), adverse reactions (6.1), clinical pharmacology (12.3), and clinical studies (14.11)] : advise postmenarchal girls of contraception recommendations, if appropriate for the patient [see use in specific populations (8.1)] . the long-term efficacy of atorvastatin therapy initiated in childhood to reduce morbidity and mortality in adulthood has not been established. the safety and efficacy of atorvastatin have not been established in pediatric patients younger than 10 years of age with hefh. homozygous familial hypercholesterolemia (hofh) clinical efficacy of atorvastatin with dosages up to 80 mg/day for 1 year was evaluated in an uncontrolled study of patients with hofh including 8 pediatric patients [see clinical studies (14.10)] . safety and effectiveness of caduet have not been established in geriatric populations. amlodipine clinical studies of amlodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. elderly patients have decreased clearance of amlodipine with a resulting increase of auc of approximately 40–60%, and a lower initial dose may be required [see dosage and administration (2)] . atorvastatin of the 39,828 patients who received atorvastatin in clinical studies, 15,813 (40%) were ≥ 65 years old and 2,800 (7%) were ≥ 75 years old. 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 patients, but greater sensitivity of some older adults cannot be ruled out. advanced age (≥ 65 years) is a predisposing factor for myopathy. caduet is contraindicated in patients with active liver disease which may include unexplained persistent elevations in hepatic transaminase levels [see contraindications (4) and clinical pharmacology (12.3)].

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - misoprostol (unii: 0e43v0bb57) (misoprostol - unii:0e43v0bb57) - misoprostol 100 ug - cytotec (misoprostol) is indicated for reducing the risk of nsaid (nonsteroidal anti-inflammatory drugs, including aspirin)–induced gastric ulcers in patients at high risk of complications from gastric ulcer, e.g., the elderly and patients with concomitant debilitating disease, as well as patients at high risk of developing gastric ulceration, such as patients with a history of ulcer. cytotec has not been shown to reduce the risk of duodenal ulcers in patients taking nsaids. cytotec should be taken for the duration of nsaid therapy. cytotec has been shown to reduce the risk of gastric ulcers in controlled studies of 3 months' duration. it had no effect, compared to placebo, on gastrointestinal pain or discomfort associated with nsaid use. see boxed warnings. cytotec should not be taken by pregnant women to reduce the risk of ulcers induced by nonsteroidal anti-inflammatory drugs (nsaids). cytotec should not be taken by anyone with a history of allergy to prostaglandins.

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

pfizer laboratories div pfizer inc - palbociclib (unii: g9zf61le7g) (palbociclib - unii:g9zf61le7g) - palbociclib 75 mg - ibrance is indicated for the treatment of adult patients with hormone receptor (hr)-positive, human epidermal growth factor receptor 2 (her2)-negative advanced or metastatic breast cancer in combination with: none. risk summary based on findings from animal studies and its mechanism of action, ibrance can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no available data in pregnant women to inform the drug-associated risk. in animal reproduction studies, administration of palbociclib to pregnant rats and rabbits during organogenesis resulted in embryo-fetal toxicity at maternal exposures that were ≥4 times the human clinical exposure based on auc [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. 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 a fertility and early embryonic development study in female rats, palbociclib was administered orally for 15 days before mating through to day 7 of pregnancy, which did not cause embryo toxicity at doses up to 300 mg/kg/day with maternal systemic exposures approximately 4 times the human exposure (auc) at the recommended dose. in embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of palbociclib up to 300 mg/kg/day and 20 mg/kg/day, respectively, during the period of organogenesis. the maternally toxic dose of 300 mg/kg/day was fetotoxic in rats, resulting in reduced fetal body weights. at doses ≥100 mg/kg/day in rats, there was an increased incidence of a skeletal variation (increased incidence of a rib present at the seventh cervical vertebra). at the maternally toxic dose of 20 mg/kg/day in rabbits, there was an increased incidence of skeletal variations, including small phalanges in the forelimb. at 300 mg/kg/day in rats and 20 mg/kg/day in rabbits, the maternal systemic exposures were approximately 4 and 9 times the human exposure (auc) at the recommended dose, respectively. cdk4/6 double knockout mice have been reported to die in late stages of fetal development (gestation day 14.5 until birth) due to severe anemia. however, knockout mouse data may not be predictive of effects in humans due to differences in degree of target inhibition. risk summary there is no information regarding the presence of palbociclib in human milk, its effects on milk production, or the breastfed infant. because of the potential for serious adverse reactions in breastfed infants from ibrance, advise a lactating woman not to breastfeed during treatment with ibrance and for 3 weeks after the last dose. pregnancy testing based on animal studies, ibrance can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)]. females of reproductive potential should have a pregnancy test prior to starting treatment with ibrance. contraception females ibrance 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 ibrance and for at least 3 weeks 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 ibrance and for 3 months after the last dose [see nonclinical toxicology (13.1)] . infertility males based on animal studies, ibrance may impair fertility in males of reproductive potential [see nonclinical toxicology (13.1)] . the safety and efficacy of ibrance in pediatric patients have not been studied. altered glucose metabolism (glycosuria, hyperglycemia, decreased insulin) associated with changes in the pancreas (islet cell vacuolation), eye (cataracts, lens degeneration), kidney (tubule vacuolation, chronic progressive nephropathy) and adipose tissue (atrophy) were identified in a 27 week repeat-dose toxicology study in rats that were immature at the beginning of the studies and were most prevalent in males at oral palbociclib doses ≥30 mg/kg/day (approximately 11 times the adult human exposure [auc] at the recommended dose). some of these findings (glycosuria/hyperglycemia, pancreatic islet cell vacuolation, and kidney tubule vacuolation) were present with lower incidence and severity in a 15 week repeat-dose toxicology study in immature rats. altered glucose metabolism or associated changes in the pancreas, eye, kidney and adipose tissue were not identified in a 27-week repeat-dose toxicology study in rats that were mature at the beginning of the study and in dogs in repeat-dose toxicology studies up to 39 weeks duration. toxicities in teeth independent of altered glucose metabolism were observed in rats. administration of 100 mg/kg palbociclib for 27 weeks (approximately 15 times the adult human exposure [auc] at the recommended dose) resulted in abnormalities in growing incisor teeth (discolored, ameloblast degeneration/necrosis, mononuclear cell infiltrate). other toxicities of potential concern to pediatric patients have not been evaluated in juvenile animals. of 444 patients who received ibrance in paloma-2, 181 patients (41%) were ≥65 years of age and 48 patients (11%) were ≥75 years of age. of 347 patients who received ibrance in paloma-3, 86 patients (25%) were ≥65 years of age and 27 patients (8%) were ≥75 years of age. no overall differences in safety or effectiveness of ibrance were observed between these patients and younger patients. no dose adjustment is required in patients with mild or moderate hepatic impairment (child-pugh classes a and b). for patients with severe hepatic impairment (child-pugh class c), the recommended dose of ibrance is 75 mg once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete cycle of 28 days [see dosage and administration (2.2)] . based on a pharmacokinetic trial in subjects with varying degrees of hepatic function, the palbociclib unbound exposure (unbound aucinf ) decreased by 17% in subjects with mild hepatic impairment (child-pugh class a), and increased by 34% and 77% in subjects with moderate (child-pugh class b) and severe (child-pugh class c) hepatic impairment, respectively, relative to subjects with normal hepatic function. peak palbociclib unbound exposure (unbound cmax ) increased by 7%, 38% and 72% for mild, moderate and severe hepatic impairment, respectively, relative to subjects with normal hepatic function [see clinical pharmacology (12.3)] . review the full prescribing information for the aromatase inhibitor or fulvestrant for dose modifications related to hepatic impairment. no dose adjustment is required in patients with mild, moderate, or severe renal impairment (crcl >15 ml/min). based on a pharmacokinetic trial in subjects with varying degrees of renal function, the total palbociclib exposure (aucinf ) increased by 39%, 42%, and 31% with mild (60 ml/min ≤ crcl <90 ml/min), moderate (30 ml/min ≤ crcl <60 ml/min), and severe (crcl <30 ml/min) renal impairment, respectively, relative to subjects with normal renal function. peak palbociclib exposure (cmax ) increased by 17%, 12%, and 15% for mild, moderate, and severe renal impairment, respectively, relative to subjects with normal renal function. the pharmacokinetics of palbociclib have not been studied in patients requiring hemodialysis [see clinical pharmacology (12.3)] .