Ամերիկայի Միացյալ Նահանգներ - անգլերեն - NLM (National Library of Medicine)

amgen inc - denosumab (unii: 4eqz6yo2hi) (denosumab - unii:4eqz6yo2hi) - denosumab 60 mg in 1 ml - prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. in postmenopausal women with osteoporosis, prolia reduces the incidence of vertebral, nonvertebral, and hip fractures [see clinical studies (14.1)] . prolia is indicated for treatment to increase bone mass in men with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy [see clinical studies (14.2)] . prolia is indicated for the treatment of glucocorticoid-induced osteoporosis in men and women at high risk of fracture who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and expected to remain on glucocorticoids for at least 6 months. high risk of fracture is defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy [see clinical studies (14.3)] . prolia is indicated as a treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy (adt) for nonmetastatic prostate cancer. in these patients prolia also reduced the incidence of vertebral fractures [see clinical studies (14.4)] . prolia is indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer [see clinical studies (14.5)] . prolia is contraindicated in: - patients with hypocalcemia: pre-existing hypocalcemia must be corrected prior to initiating therapy with prolia [see warnings and precautions (5.1)] . - pregnant women: prolia may cause fetal harm when administered to a pregnant woman. in women of reproductive potential, pregnancy testing should be performed prior to initiating treatment with prolia [see use in specific populations (8.1)] . - patients with hypersensitivity to prolia: prolia is contraindicated in patients with a history of systemic hypersensitivity to any component of the product. reactions have included anaphylaxis, facial swelling, and urticaria [see warnings and precautions (5.3), adverse reactions (6.2)] . risk summary prolia is contraindicated for use in pregnant women because it may cause harm to a fetus. there are insufficient data with denosumab use in pregnant women to inform any drug-associated risks for adverse developmental outcomes. in utero denosumab exposure from cynomolgus monkeys dosed monthly with denosumab throughout pregnancy at a dose 50-fold higher than the recommended human dose based on body weight resulted in increased fetal loss, stillbirths, and postnatal mortality, and absent lymph nodes, abnormal bone growth, and decreased neonatal growth [see data] . data animal data the effects of denosumab on prenatal development have been studied in both cynomolgus monkeys and genetically engineered mice in which rank ligand (rankl) expression was turned off by gene removal (a "knockout mouse"). in cynomolgus monkeys dosed subcutaneously with denosumab throughout pregnancy starting at gestational day 20 and at a pharmacologically active dose 50-fold higher than the recommended human dose based on body weight, there was increased fetal loss during gestation, stillbirths, and postnatal mortality. other findings in offspring included absence of axillary, inguinal, mandibular, and mesenteric lymph nodes; abnormal bone growth, reduced bone strength, reduced hematopoiesis, dental dysplasia, and tooth malalignment; and decreased neonatal growth. at birth out to 1 month of age, infants had measurable blood levels of denosumab (22-621% of maternal levels). following a recovery period from birth out to 6 months of age, the effects on bone quality and strength returned to normal; there were no adverse effects on tooth eruption, though dental dysplasia was still apparent; axillary and inguinal lymph nodes remained absent, while mandibular and mesenteric lymph nodes were present, though small; and minimal to moderate mineralization in multiple tissues was seen in one recovery animal. there was no evidence of maternal harm prior to labor; adverse maternal effects occurred infrequently during labor. maternal mammary gland development was normal. there was no fetal noael (no observable adverse effect level) established for this study because only one dose of 50 mg/kg was evaluated. mammary gland histopathology at 6 months of age was normal in female offspring exposed to denosumab in utero ; however, development and lactation have not been fully evaluated. in rankl knockout mice, absence of rankl (the target of denosumab) also caused fetal lymph node agenesis and led to postnatal impairment of dentition and bone growth. pregnant rankl knockout mice showed altered maturation of the maternal mammary gland, leading to impaired lactation [see use in specific populations (8.2), nonclinical toxicology (13.2)] . the no effect dose for denosumab-induced teratogenicity is unknown. however, a cmax of 22.9 ng/ml was identified in cynomolgus monkeys as a level in which no biologic effects (noel) of denosumab were observed (no inhibition of rankl) [see clinical pharmacology (12.3)] . risk summary there is no information regarding the presence of denosumab in human milk, the effects on the breastfed infant, or the effects on milk production. denosumab was detected in the maternal milk of cynomolgus monkeys up to 1 month after the last dose of denosumab (≤ 0.5% milk:serum ratio) and maternal mammary gland development was normal, with no impaired lactation. however, pregnant rankl knockout mice showed altered maturation of the maternal mammary gland, leading to impaired lactation [see use in specific populations (8.1), nonclinical toxicology (13.2)] . based on findings in animals, prolia can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . pregnancy testing verify the pregnancy status of females of reproductive potential prior to initiating prolia treatment. contraception females advise females of reproductive potential to use effective contraception during therapy, and for at least 5 months after the last dose of prolia. males denosumab was present at low concentrations (approximately 2% of serum exposure) in the seminal fluid of male subjects given prolia. following vaginal intercourse, the maximum amount of denosumab delivered to a female partner would result in exposures approximately 11000 times lower than the prescribed 60 mg subcutaneous dose, and at least 38 times lower than the noel in monkeys. therefore, male condom use would not be necessary as it is unlikely that a female partner or fetus would be exposed to pharmacologically relevant concentrations of denosumab via seminal fluid [see clinical pharmacology (12.3)] . the safety and effectiveness of prolia have not been established in pediatric patients. in one multicenter, open-label study conducted in 153 pediatric patients with osteogenesis imperfecta, aged 2 to 17 years, evaluating fracture risk reduction, efficacy was not established. hypercalcemia has been reported in pediatric patients with osteogenesis imperfecta treated with denosumab products, including prolia. some cases required hospitalization and were complicated by acute renal injury [see warnings and precautions (5.11)]. clinical studies in pediatric patients with osteogenesis imperfecta were terminated early due to the occurrence of life-threatening events and hospitalizations due to hypercalcemia. based on results from animal studies, prolia may negatively affect long-bone growth and dentition in pediatric patients below the age of 4 years. juvenile animal toxicity data treatment with prolia may impair long-bone growth in children with open growth plates and may inhibit eruption of dentition. in neonatal rats, inhibition of rankl (the target of prolia therapy) with a construct of osteoprotegerin bound to fc (opg-fc) at doses ≤ 10 mg/kg was associated with inhibition of bone growth and tooth eruption. adolescent primates treated with denosumab at doses 10 and 50 times (10 and 50 mg/kg dose) higher than the recommended human dose of 60 mg administered every 6 months, based on body weight (mg/kg), had abnormal growth plates, considered to be consistent with the pharmacological activity of denosumab [see nonclinical toxicology (13.2)]. cynomolgus monkeys exposed in utero to denosumab exhibited bone abnormalities, an absence of axillary, inguinal, mandibular, and mesenteric lymph nodes, reduced hematopoiesis, tooth malalignment, and decreased neonatal growth. some bone abnormalities recovered once exposure was ceased following birth; however, axillary, and inguinal lymph nodes remained absent 6 months post-birth [see use in specific populations (8.1)] . of the total number of patients in clinical studies of prolia, 9943 patients (76%) were ≥ 65 years old, while 3576 (27%) were ≥ 75 years old. of the patients in the osteoporosis study in men, 133 patients (55%) were ≥ 65 years old, while 39 patients (16%) were ≥ 75 years old. of the patients in the glucocorticoid-induced osteoporosis study, 355 patients (47%) were ≥ 65 years old, while 132 patients (17%) were ≥ 75 years old. no overall differences in safety or efficacy 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. no dose adjustment is necessary in patients with renal impairment. severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported postmarketing. in clinical studies, patients with advanced chronic kidney disease (i.e., egfr < 30 ml/min/1.73 m2 ), including dialysis-dependent patients, were at greater risk of developing hypocalcemia. the presence of underlying chronic kidney disease-mineral bone disorder (ckd-mbd, renal osteodystrophy) markedly increases the risk of hypocalcemia. concomitant use of calcimimetic drugs may also worsen hypocalcemia risk. consider the benefits and risks to the patient when administering prolia to patients with advanced chronic kidney disease. monitor calcium and mineral levels (phosphorus and magnesium). adequate intake of calcium and vitamin d is important in patients with advanced chronic kidney disease including dialysis-dependent patients [see dosage and administration (2.2),warnings and precautions (5.1), adverse reactions (6.1) and clinical pharmacology (12.3)] .

Ամերիկայի Միացյալ Նահանգներ - անգլերեն - NLM (National Library of Medicine)

amgen inc - epoetin (unii: 64fs3bfh5w) (erythropoietin - unii:64fs3bfh5w) - erythropoietin 2000 [iu] in 1 ml - epogen is indicated for the treatment of anemia due to chronic kidney disease (ckd), including patients on dialysis and not on dialysis to decrease the need for red blood cell (rbc) transfusion. epogen is indicated for the treatment of anemia due to zidovudine administered at ≤ 4200 mg/week in patients with hiv-infection with endogenous serum erythropoietin levels of ≤ 500 munits/ml. epogen is indicated for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of two additional months of planned chemotherapy. epogen is indicated to reduce the need for allogeneic rbc transfusions among patients with perioperative hemoglobin > 10 to ≤ 13 g/dl who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery. epogen is not indicated for patients who are willing to donate autologous blood pre-operatively. epogen has not been shown to improve quality of

Ամերիկայի Միացյալ Նահանգներ - անգլերեն - NLM (National Library of Medicine)

amgen inc - blinatumomab (unii: 4fr53sif3a) (blinatumomab - unii:4fr53sif3a) - blinatumomab 12.5 ug in 1 ml - blincyto is indicated for the treatment of cd19-positive b-cell precursor acute lymphoblastic leukemia (all) in first or second complete remission with minimal residual disease (mrd) greater than or equal to 0.1% in adult and pediatric patients. blincyto is indicated for the treatment of relapsed or refractory cd19-positive b-cell precursor acute lymphoblastic leukemia (all) in adult and pediatric patients. blincyto is contraindicated in patients with known hypersensitivity to blinatumomab or to any component of the product formulation. risk summary based on its mechanism of action, blincyto may cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no available data on the use of blincyto in pregnant women to evaluate for a drug-associated risk. in animal reproduction studies, a murine surrogate molecule administered to pregnant mice crossed the placental barrier (see data) . blinatumomab causes t-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. in addition, based on expression of cd19 on b-cells and the finding of b-cell depletion in non-pregnant animals, blinatumomab can cause b-cell lymphocytopenia in infants exposed to blinatumomab in-utero. 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. clinical considerations fetal/neonatal adverse reactions due to the potential for b-cell lymphocytopenia in infants following exposure to blincyto in utero , the infant's b lymphocytes should be monitored before the initiation of live virus vaccination [see warnings and precautions (5.11)] . data animal data animal reproduction studies have not been conducted with blinatumomab. in embryo-fetal developmental toxicity studies, a murine surrogate molecule was administered intravenously to pregnant mice during the period of organogenesis. the surrogate molecule crossed the placental barrier and did not cause embryo-fetal toxicity or teratogenicity. the expected depletions of b and t cells were observed in the pregnant mice, but hematological effects were not assessed in fetuses. risk summary there is no information regarding the presence of blinatumomab in human milk, the effects on the breastfed infant, or the effects on milk production. because many drugs are excreted in human milk and because of the potential for serious adverse reactions in breastfed infants from blincyto, including b-cell lymphocytopenia, advise patients not to breastfeed during treatment with blincyto and for 48 hours after the last dose. blincyto may cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . pregnancy testing verify the pregnancy status of females of reproductive potential prior to initiating blincyto treatment. contraception females advise females of reproductive potential to use effective contraception during treatment with blincyto and for 48 hours after the last dose. minimal residual disease (mrd)-positive b-cell precursor all the safety and efficacy of blincyto for the treatment of cd19-positive b-cell precursor acute lymphoblastic leukemia (all) in first or second complete remission with minimal residual disease (mrd) greater than or equal to 0.1% have been established in pediatric patients. use of blincyto is supported by evidence from two randomized, controlled trials (study aall1331 nct02101853 and study 20120215 nct02393859) in pediatric subjects with first relapsed b-cell precursor all. both studies included pediatric patients with mrd-positive b-cell precursor all. the studies included pediatric patients treated with blincyto in the following age groups: 6 infants (1 month up to less than 2 years), 165 children (2 years up to less than 12 years), and 70 adolescents (12 years to less than 17 years). in general, the adverse reactions in blincyto-treated pediatric patients were similar in type to those seen in adult patients with mrd-positive all [see adverse reactions (6.1)] , and no differences in safety were observed between the different pediatric age subgroups. relapsed or refractory b-cell precursor all the safety and efficacy of blincyto have been established in pediatric patients with relapsed or refractory b-cell precursor all. use of blincyto is supported by a single-arm trial in pediatric patients with relapsed or refractory b-cell precursor all. this study included pediatric patients in the following age groups: 10 infants (1 month up to less than 2 years), 40 children (2 years up to less than 12 years), and 20 adolescents (12 years to less than 18 years). no differences in efficacy were observed between the different age subgroups [see clinical studies (14.2)] . in general, the adverse reactions in blincyto-treated pediatric patients with relapsed or refractory all were similar in type to those seen in adult patients with relapsed or refractory b-cell precursor all [see adverse reactions (6.1)] . adverse reactions that were observed more frequently (≥ 10% difference) in the pediatric population compared to the adult population were pyrexia (80% vs. 61%), hypertension (26% vs. 8%), anemia (41% vs. 24%), infusion-related reaction (49% vs. 34%), thrombocytopenia (34% vs. 21%), leukopenia (24% vs. 11%), and weight increased (17% vs. 6%). in pediatric patients less than 2 years old (infants) with relapsed or refractory all, the incidence of neurologic toxicities was not significantly different than for the other age groups, but its manifestations were different; the only event terms reported were agitation, headache, insomnia, somnolence, and irritability. infants also had an increased incidence of hypokalemia (50%) compared to other pediatric age cohorts (15-20%) or adults (17%). benzyl alcohol toxicity in neonates serious and fatal adverse reactions, including "gasping syndrome," can occur in very low birth weight (vlbw) neonates born weighing less than 1500 g, and early preterm neonates (infants born less than 34 weeks gestational age) treated with benzyl alcohol-preserved drugs intravenously. the "gasping syndrome" is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. in these cases, benzyl alcohol dosages of 99 to 234 mg/kg/day produced high concentrations of benzyl alcohol and its metabolite in the blood and urine (blood concentration of benzyl alcohol were 0.61 to 1.378 mmol/l). additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. the minimum amount of benzyl alcohol at which serious adverse reactions may occur in neonates is not known [see warnings and precautions (5.12)] . use the preservative-free formulations of blincyto where possible in neonates. when prescribing blincyto (with preservative) in neonatal patients, consider the combined daily metabolic load of benzyl alcohol from all sources including blincyto (with preservative). the blincyto 7-day bag (with preservative) contains 7.4 mg of benzyl alcohol per ml [see warnings and precautions (5.12)] . benzyl alcohol administration may contribute to metabolic acidosis in pediatric patients, particularly those with immaturity of the metabolic pathway for alcohol, or those with underlying conditions or receiving concomitant medications that could predispose to acid base imbalance. monitor these patients during use of blincyto (with preservative) for new or worsening metabolic acidosis. of the total number of patients with all treated in clinical studies of blincyto, approximately 12% were 65 and over, while 2% were 75 and older. 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. however, elderly patients experienced a higher rate of serious infections and neurological toxicities, including cognitive disorder, encephalopathy, and confusion [see warnings and precautions (5.2, 5.3)] .

Ամերիկայի Միացյալ Նահանգներ - անգլերեն - NLM (National Library of Medicine)

amgen inc - romosozumab (unii: 3vhf2zd92j) (romosozumab - unii:3vhf2zd92j) - evenity is indicated for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy.  the anabolic effect of evenity wanes after 12 monthly doses of therapy. therefore, the duration of evenity use should be limited to 12 monthly doses. if osteoporosis therapy remains warranted, continued therapy with an anti-resorptive agent should be considered [see dosage and administration ( 2.2 ) and clinical studies ( 14.1 )] . evenity is contraindicated in patients with: - hypocalcemia. pre-existing hypocalcemia must be corrected prior to initiating therapy with evenity [ see warnings and precautions ( 5.3 ) , adverse reactions ( 6.1 ) and use in specific populations ( 8.7 )] . - a history of systemic hypersensitivity to romosozumab or to any component of the product formulation. reactions have included angioedema, erythema m

Մալայզիա - անգլերեն - NPRA (National Pharmaceutical Regulatory Agency, Bahagian Regulatori Farmasi Negara)

amgen biopharmaceuticals malaysia sdn bhd - denosumab -

Մալայզիա - անգլերեն - NPRA (National Pharmaceutical Regulatory Agency, Bahagian Regulatori Farmasi Negara)

amgen biopharmaceuticals malaysia sdn bhd - denosumab -

Մալայզիա - անգլերեն - NPRA (National Pharmaceutical Regulatory Agency, Bahagian Regulatori Farmasi Negara)

amgen biopharmaceuticals malaysia sdn bhd - panitumumab -

Մալայզիա - անգլերեն - NPRA (National Pharmaceutical Regulatory Agency, Bahagian Regulatori Farmasi Negara)

amgen biopharmaceuticals malaysia sdn bhd - recombinant human granulocyte colony-stimulating factor (filgrastim) -

Մալայզիա - անգլերեն - NPRA (National Pharmaceutical Regulatory Agency, Bahagian Regulatori Farmasi Negara)

amgen biopharmaceuticals malaysia sdn bhd - recombinant human granulocyte colony-stimulating factor (filgrastim) -

Մալայզիա - անգլերեն - NPRA (National Pharmaceutical Regulatory Agency, Bahagian Regulatori Farmasi Negara)

amgen biopharmaceuticals malaysia sdn bhd - pegfilgrastim -