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mylan institutional llc - zoledronic acid (unii: 6xc1pad3kf) (zoledronic acid anhydrous - unii:70hz18ph24) - zoledronic acid anhydrous 5 mg in 100 ml - zoledronic acid injection is indicated for treatment of paget's disease of bone in men and women. treatment is indicated in patients with paget’s disease of bone with elevations in serum alkaline phosphatase of two times or higher than the upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease [see clinical studies (14.5)] . zoledronic acid is contraindicated in patients with the following conditions: in female rats given daily subcutaneous doses of 0.01, 0.03, or 0.1 mg/kg, beginning 15 days before mating and continuing through gestation, parturition and lactation, dystocia and periparturient mortality were observed in pregnant rats allowed to deliver starting at 0.01 mg/kg/day (0.1 times the human 5 mg intravenous dose, based on auc). also, there was an increase in stillbirths and a decrease in neonate survival starting at 0.03 mg/kg/day (0.3 times the human 5 mg dose), while the number of viable newborns and pup body weig

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eugia us llc - zoledronic acid (unii: 6xc1pad3kf) (zoledronic acid anhydrous - unii:70hz18ph24) - zoledronic acid anhydrous 5 mg in 100 ml - zoledronic acid injection is indicated for treatment of paget’s disease of bone in men and women. treatment is indicated in patients with paget’s disease of bone with elevations in serum alkaline phosphatase of two times or higher than the upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease [see clinical studies (14.5) ] . zoledronic acid is contraindicated in patients with the following conditions: - hypocalcemia [see warnings and precautions (5.2) ] - creatinine clearance less than 35 ml/min and in those with evidence of acute renal impairment due to an increased risk of renal failure [see warnings and precautions (5.3) ] . - known hypersensitivity to zoledronic acid or any components of zoledronic acid injection. hypersensitivity reactions including urticaria, angioedema, and anaphylactic reaction/shock have been reported [see adverse reactions (6.2) ] . risk summary available data on the use of zoledronic acid in p

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gland pharma limited - zoledronic acid (unii: 6xc1pad3kf) (zoledronic acid anhydrous - unii:70hz18ph24) - zoledronic acid anhydrous 5 mg in 100 ml - zoledronic acid injection is indicated for treatment of osteoporosis in postmenopausal women. in postmenopausal women with osteoporosis, diagnosed by bone mineral density (bmd) or prevalent vertebral fracture, zoledronic acid injection reduces the incidence of fractures (hip, vertebral and non-vertebral osteoporosis-related fractures). in patients at high risk of fracture, defined as a recent low-trauma hip fracture, zoledronic acid injection reduces the incidence of new clinical fractures [see clinical studies (14.1)]. zoledronic acid injection is indicated for prevention of osteoporosis in postmenopausal women [see clinical studies (14.2)]. zoledronic acid injection is indicated for treatment to increase bone mass in men with osteoporosis [see clinical studies (14.3)]. zoledronic acid injection is indicated for the treatment and prevention of glucocorticoid-induced osteoporosis in men and women who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater

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fresenius kabi usa, llc - zoledronic acid (unii: 6xc1pad3kf) (zoledronic acid anhydrous - unii:70hz18ph24) - zoledronic acid anhydrous 5 mg in 100 ml - zoledronic acid injection is indicated for treatment of osteoporosis in postmenopausal women. in postmenopausal women with osteoporosis, diagnosed by bone mineral density (bmd) or prevalent vertebral fracture, zoledronic acid injection reduces the incidence of fractures (hip, vertebral and non-vertebral osteoporosis-related fractures). in patients at high risk of fracture, defined as a recent low-trauma hip fracture, zoledronic acid injection reduces the incidence of new clinical fractures [ see clinical studies (14.1) ]. zoledronic acid injection is indicated for prevention of osteoporosis in postmenopausal women [ see clinical studies (14.2) ]. zoledronic acid injection is indicated for treatment to increase bone mass in men with osteoporosis [ see clinical studies (14.3) ]. zoledronic acid injection is indicated for the treatment and prevention of glucocorticoid-induced osteoporosis in men and women who are either initiating or continuing systemic glucocorticoids i

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akorn - zoledronic acid (unii: 6xc1pad3kf) (zoledronic acid anhydrous - unii:70hz18ph24) - zoledronic acid anhydrous 5 mg in 100 ml - zoledronic acid injection is indicated for treatment of paget's disease of bone in men and women. treatment is indicated in patients with paget's disease of bone with elevations in serum alkaline phosphatase of two times or higher than the upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease [see clinical studies (14.5) ]. zoledronic acid injection is contraindicated in patients with the following conditions: - hypocalcemia [see warnings and precautions (5.2) ] - creatinine clearance less than 35 ml/min and in those with evidence of acute renal impairment due to an increased risk of renal failure [see warnings and precautions (5.3) ] - known hypersensitivity to zoledronic acid or any components of zoledronic acid injection. hypersensitivity reactions including urticaria, angioedema, and anaphylactic reaction/shock have been reported [see adverse reactions (6.2) ]. pregnancy category d [see warnings and precautions (5.6) ].

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par pharmaceutical companies, inc. - zoledronic acid (unii: 6xc1pad3kf) (zoledronic acid anhydrous - unii:70hz18ph24) - zoledronic acid anhydrous 5 mg in 100 ml - zoledronic acid injection is indicated for treatment of paget's disease of bone in men and women. treatment is indicated in patients with paget’s disease of bone with elevations in serum alkaline phosphatase of two times or higher than the upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease [see clinical studies (14.5) ]. zoledronic acid injection is contraindicated in patients with the following conditions: - hypocalcemia [see warnings and precautions (5.2) ] - creatinine clearance less than 35 ml/min and in those with evidence of acute renal impairment due to an increased risk of renal failure [see warnings and precautions (5.3) ]. - known hypersensitivity to zoledronic acid or any components of zoledronic acid injection. hypersensitivity reactions including urticaria, angioedema, and anaphylactic reaction/shock have been reported [see post-marketing experience (6.2) ]. pregnancy category d [see warnings and precautions

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breckenridge pharmaceutical, inc - zoledronic acid (unii: 6xc1pad3kf) (zoledronic acid anhydrous - unii:70hz18ph24) - zoledronic acid anhydrous 5 mg in 100 ml - zoledronic acid injection is indicated for treatment of paget's disease of bone in men and women. treatment is indicated in patients with paget’s disease of bone with elevations in serum alkaline phosphatase of two times or higher than the upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease [see clinical studies (14.5) ]. zoledronic acid injection is contraindicated in patients with the following conditions: - hypocalcemia [see warnings and precautions (5.2) ] - creatinine clearance less than 35 ml/min and in those with evidence of acute renal impairment due to an increased risk of renal failure [see warnings and precautions (5.3) ]. - known hypersensitivity to zoledronic acid or any components of zoledronic acid injection. hypersensitivity reactions including urticaria, angioedema, and anaphylactic reaction/shock have been reported [see adverse reactions (6.2) ]. pregnancy category d [see warnings and precautions (5.6) ].

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dr.reddy's laboratories ltd - zoledronic acid (unii: 6xc1pad3kf) (zoledronic acid anhydrous - unii:70hz18ph24) - zoledronic acid anhydrous 5 mg in 100 ml - zoledronic acid injection is indicated for treatment of paget's disease of bone in men and women. treatment is indicated in patients with paget’s disease of bone with elevations in serum alkaline phosphatase of two times or higher than the upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease [see clinical studies (14.5) ]. zoledronic acid injection is contraindicated in patients with the following conditions:   - hypocalcemia [see warnings and precautions (5.2) ] - creatinine clearance less than 35 ml/min and in those with evidence of acute renal impairment due to an increased risk of renal failure [see warnings and precautions (5.3) ]. - known hypersensitivity to zoledronic acid or any components of zoledronic acid injection. hypersensitivity reactions including urticaria, angioedema, and anaphylactic reaction/shock have been reported [see adverse reactions (6.2) ] . risk summary available data on the use of zoledronic acid in pregnant women are insufficient to inform a drug-associated risk of adverse maternal or fetal outcomes. discontinue zoledronic acid when pregnancy is recognized. in animal reproduction studies, daily subcutaneous administration of zoledronic acid to pregnant rats during organogenesis resulted in increases in fetal skeletal, visceral, and external malformations, decreases in postimplantation survival, and decreases in viable fetuses and fetal weight starting at doses equivalent to 2 times the recommended human 5 mg intravenous dose (based on auc). subcutaneous administration of zoledronic acid to rabbits during organogenesis did not cause adverse fetal effects at up to 0.4 times the human 5 mg intravenous dose (based on body surface area, mg/m2 ), but resulted in maternal mortality and abortion associated with hypocalcemia starting at doses equivalent to 0.04 times the human 5 mg intravenous dose. subcutaneous dosing of female rats from before mating through gestation and lactation and allowed to deliver caused maternal dystocia and periparturient mortality, increases in stillbirths and neonatal deaths, and reduced pup body weight starting at doses equivalent to 0.1 times the human 5 mg intravenous dose (based on auc). (see data). bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a period of years. the amount of bisphosphonate incorporated into adult bone, and available for release into the systemic circulation is directly related to the dose and duration of bisphosphonate use. consequently, based on the mechanism of action of bisphosphonates, there is a potential risk of fetal harm, predominantly skeletal, if a woman becomes pregnant after completing a course of bisphosphonate therapy. the impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on the risk has not been studied. the estimated background risk of major birth defects and miscarriage for the indicated populations 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 risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data in pregnant rats given daily subcutaneous doses of zoledronic acid of 0.1, 0.2, or 0.4 mg/kg during organogenesis, fetal skeletal, visceral, and external malformations, increases in pre-and post-implantation loss, and decreases in viable fetuses and fetal weight were observed at 0.2 and 0.4 mg/kg/day (equivalent to 2 and 4 times the human 5 mg intravenous dose, based on auc). adverse fetal skeletal effects at 0.4 mg/kg/day (4 times the human 5 mg dose) included unossified or incompletely ossified bones, thickened, curved or shortened bones, wavy ribs, and shortened jaw. other adverse fetal effects at this dose included reduced lens, rudimentary cerebellum, reduction or absence of liver lobes, reduction of lung lobes, vessel dilation, cleft palate, and edema. skeletal variations were observed in all groups starting at 0.1 mg/kg/day (1.2 times the human 5 mg dose). signs of maternal toxicity including reduced body weight and food consumption were observed at 0.4 mg/kg/day (4 times the human 5 mg dose). in pregnant rabbits given daily subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg during gestation no adverse fetal effects were observed up to 0.1 mg/kg/day (0.4 times the human 5 mg intravenous dose, based on body surface area, mg/m2 ). maternal mortality and abortion were observed in all dose groups (starting at 0.04 times the human 5 mg dose). adverse maternal effects were associated with drug-induced hypocalcemia. in female rats given daily subcutaneous doses of 0.01, 0.03, or 0.1 mg/kg, beginning 15 days before mating and continuing through gestation, parturition and lactation, dystocia and periparturient mortality were observed in pregnant rats allowed to deliver starting at 0.01 mg/kg/day (0.1 times the human 5 mg intravenous dose, based on auc). also, there was an increase in stillbirths and a decrease in neonate survival starting at 0.03 mg/kg/day (0.3 times the human 5 mg dose), while the number of viable newborns and pup body weight on postnatal day 7 were decreased at 0.1 mg/kg/day (equivalent to the human 5 mg dose). maternal and neonatal deaths were considered related to drug-induced periparturient hypocalcemia. risk summary there are no data on the presence of zoledronic acid in human milk, the effects on the breastfed infant, or the effects on milk production. the developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for zoledronic acid and any potential adverse effects on the breast-fed child from zoledronic acid or from the underlying maternal condition. infertility there are no data available in humans. female fertility may be impaired based on animal studies demonstrating adverse effects of zoledronic acid on fertility parameters [see nonclinical toxicology (13.1)]. zoledronic acid injection is not indicated for use in children.   the safety and effectiveness of zoledronic acid was studied in a one-year active controlled trial of 152 pediatric subjects (74 receiving zoledronic acid). the enrolled population was subjects with severe osteogenesis imperfecta, aged 1 to 17 years, 55% male, 84% caucasian, with a mean lumbar spine bmd of 0.431 gm/cm2 , which is 2.7 standard deviations below the mean for age-matched controls (bmd z-score of -2.7). at one year, increases in bmd were observed in the zoledronic acid treatment group. however, changes in bmd in individual patients with severe osteogenesis imperfecta did not necessarily correlate with the risk for fracture or the incidence or severity of chronic bone pain. the adverse events observed with zoledronic acid use in children did not raise any new safety findings beyond those previously seen in adults treated for paget’s disease of bone including osteonecrosis of the jaw (onj) and renal impairment. however, adverse reactions seen more commonly in pediatric patients included pyrexia (61%), arthralgia (26%), hypocalcemia (22%) and headache (22%). these reactions, excluding arthralgia, occurred most frequently within three days after the first infusion and became less common with repeat dosing. no cases of onj or renal impairment were observed in this study. because of long-term retention in bone, zoledronic acid injection should only be used in children if the potential benefit outweighs the potential risk. plasma zoledronic acid concentration data was obtained from 10 patients with severe osteogenesis imperfecta (4 in the age group of 3 to 8 years and 6 in the age group of 9 to 17 years) infused with 0.05 mg/kg dose over 30 minutes. mean cmax and auc(0-last) was 167 ng/ml and 220 ng.h/ml respectively. the plasma concentration time profile of zoledronic acid in pediatric patients represent a multi-exponential decline, as observed in adult cancer patients at an approximately equivalent mg/kg dose. of the patients receiving zoledronic acid injection in the paget’s disease studies, 132 patients, were 65 years of age or over, while 68 patients, were at least 75 years of age. because decreased renal function occurs more commonly in the elderly, special care should be taken to monitor renal function. zoledronic acid injection is contraindicated in patients with creatinine clearance less than 35 ml/min and in those with evidence of acute renal impairment. there are no safety or efficacy data to support the adjustment of the zoledronic acid injection dose based on baseline renal function. therefore, no dosage adjustment is required in patients with a creatinine clearance of greater than or equal to 35 ml/min [see warnings and precautions (5.3) , clinical pharmacology (12.3) ]. risk of acute renal failure may increase with underlying renal disease and dehydration secondary to fever, sepsis, gastrointestinal losses, diuretic therapy, advanced age, etc. [see adverse reactions (6.2) ]. zoledronic acid injection is not metabolized in the liver. no clinical data are available for use of zoledronic acid injection in patients with hepatic impairment.

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dr.reddy's laboratories inc - zoledronic acid (unii: 6xc1pad3kf) (zoledronic acid anhydrous - unii:70hz18ph24) - zoledronic acid anhydrous 5 mg in 100 ml - zoledronic acid injection is indicated for treatment of paget's disease of bone in men and women. treatment is indicated in patients with paget’s disease of bone with elevations in serum alkaline phosphatase of two times or higher than the upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease [see clinical studies (14.5) ]. zoledronic acid injection is contraindicated in patients with the following conditions:   - hypocalcemia [see warnings and precautions (5.2) ] - creatinine clearance less than 35 ml/min and in those with evidence of acute renal impairment due to an increased risk of renal failure [see warnings and precautions (5.3) ]. - known hypersensitivity to zoledronic acid or any components of zoledronic acid injection. hypersensitivity reactions including urticaria, angioedema, and anaphylactic reaction/shock have been reported [see adverse reactions (6.2) ] . pregnancy category d [see warnings and precautions (5.

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

dr. reddy's laboratories limited - zoledronic acid (unii: 6xc1pad3kf) (zoledronic acid anhydrous - unii:70hz18ph24) - zoledronic acid anhydrous 4 mg in 5 ml - zoledronic acid injection is indicated for the treatment of hypercalcemia of malignancy defined as an albumin­-corrected calcium (cca) of greater than or equal to 12 mg/dl [3.0 mmol/l] using the formula: cca in mg/dl=ca in mg/dl + 0.8 (4.0 g/dl - patient albumin [g/dl]). zoledronic acid injection is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy. prostate cancer should have progressed after treatment with at least one hormonal therapy. limitations of use the safety and efficacy of zoledronic acid injection in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions have not been established. hy persensitivity to zoledronic acid or any components of zoledronic acid injection hypersensitivity reactions including rare cases of urticaria and angioedema, and very rare cases of anaphylactic reaction/shock have been reported [see adverse reactions (6.2) ]. risk summary based on findings from animal studies and its mechanism of action, zoledronic acid 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 zoledronic acid to pregnant rats during organogenesis resulted in fetal malformations and embryo-fetal lethality at maternal exposures that were ≥ 2.4 times the human clinical exposure based on auc (see data). bisphosphonates, such as zoledronic acid, are incorporated into the bone matrix, from where they are gradually released over periods of weeks to years. there may be a risk of fetal harm (e.g., skeletal and other abnormalities) if a woman becomes pregnant after completing a course of bisphosphonate therapy. advise pregnant women and females of reproductive potential of the potential risk to a fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the u.s. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. data animal data in female rats given subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg/day beginning 15 days before mating and continuing through gestation, the number of stillbirths was increased and survival of neonates was decreased in the mid- and high-dose groups (greater than or equal to 0.2 times the human systemic exposure following an intravenous dose of 4 mg, based on an auc comparison).   adverse maternal effects were observed in all dose groups (with a systemic exposure of greater than or equal to 0.07 times the human systemic exposure following an intravenous dose of 4 mg, based on an auc comparison) and included dystocia and periparturient mortality in pregnant rats allowed to deliver. maternal mortality may have been related to drug-induced inhibition of skeletal calcium mobilization, resulting in periparturient hypocalcemia. this appears to be a bisphosphonate-class effect.   in pregnant rats given a subcutaneous dose of zoledronic acid of 0.1, 0.2, or 0.4 mg/kg/day during gestation, adverse fetal effects were observed in the mid- and high-dose groups (with systemic exposures of 2.4 and 4.8 times, respectively, the human systemic exposure following an intravenous dose of 4 mg, based on an auc comparison). these adverse effects included increases in pre- and postimplantation losses, decreases in viable fetuses, and fetal skeletal, visceral, and external malformations. fetal skeletal effects observed in the high-dose group included unossified or incompletely ossified bones, thickened, curved, or shortened bones, wavy ribs, and shortened jaw. other adverse fetal effects observed in the high-dose group included reduced lens, rudimentary cerebellum, reduction or absence of liver lobes, reduction of lung lobes, vessel dilation, cleft palate, and edema. skeletal variations were also observed in the low-dose group at 0.1 mg/kg/day (with systemic exposure of 1.2 times the human systemic exposure following an intravenous dose of 4 mg, based on an auc comparison). signs of maternal toxicity were observed in the high-dose group and included reduced body weights and food consumption, indicating that maximal exposure levels were achieved in this study.   in pregnant rabbits given subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg/day during gestation (less than or equal to 0.5 times the human intravenous dose of 4 mg, based on a comparison of relative body surface areas), no adverse fetal effects were observed. maternal mortality and abortion occurred in all treatment groups (at doses greater than or equal to 0.05 times the human intravenous dose of 4 mg, based on a comparison of relative body surface areas). adverse maternal effects were associated with, and may have been caused by, drug-induced hypocalcemia. risk summary after administration of zoledronic acid, it is not known whether zoledronic acid is present in human milk, or whether it affects milk production or the breastfed child. zoledronic acid binds to bone long term and may be released over periods of weeks to years. because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during and after zoledronic acid treatment. pregnancy testing verify pregnancy status of females of reproductive potential prior to initiation of zoledronic acid.   contraception   females zoledronic acid can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1) ].   zoledronic acid binds to bone long term and may be released over periods of weeks to years. advise females of reproductive potential to use effective contraception during and after zoledronic acid treatment.   infertility females based on animal studies, zometa may impair fertility in females of reproductive potential [see nonclinical toxicology (13.1)].   zoledronic acid injection is not indicated for use in children. the safety and effectiveness of zoledronic acid was studied in a one-year, active-controlled trial of 152 pediatric subjects (74 receiving zoledronic acid). the enrolled population was subjects with severe osteogenesis imperfecta, aged 1 to 17 years, 55% male, 84% caucasian, with a mean lumbar spine bone mineral density (bmd)  of 0.431 gm/cm2 , which is 2.7 standard deviations below the mean for age-matched controls (bmd z-score of -2.7). at one year, increases in bmd were observed in the zoledronic acid treatment group. however, changes in bmd in individual patients with severe osteogenesis imperfecta did not necessarily correlate with the risk for fracture or the incidence or severity of chronic bone pain. the adverse events observed with zoledronic acid injection use in children did not raise any new safety findings beyond those previously seen in adults treated for hypercalcemia of malignancy or bone metastases. however, adverse reactions seen more commonly in pediatric patients included pyrexia (61%), arthralgia (26%), hypocalcemia (22%) and headache (22%). these reactions, excluding arthralgia, occurred most frequently within 3 days after the first infusion and became less common with repeat dosing. because of long-term retention in bone, zoledronic acid injection should only be used in children if the potential benefit outweighs the potential risk. plasma zoledronic acid concentration data was obtained from 10 patients with severe osteogenesis imperfecta (4 in the age group of 3 to 8 years and 6 in the age group of 9 to 17 years) infused with 0.05 mg/kg dose over 30 min. mean cmax and auc(0-last) was 167 ng/ml and 220 ng•h/ml, respectively. the plasma concentration time profile of zoledronic acid in pediatric patients represent a multi-exponential decline, as observed in adult cancer patients at an approximately equivalent mg/kg dose. clinical studies of zoledronic acid injection in hypercalcemia of malignancy included 34 patients who were 65 years of age or older. no significant differences in response rate or adverse reactions were seen in geriatric patients receiving zoledronic acid injection as compared to younger patients. controlled clinical studies of zoledronic acid injection in the treatment of multiple myeloma and bone metastases of solid tumors in patients over age 65 revealed similar efficacy and safety in older and younger patients. because decreased renal function occurs more commonly in the elderly, special care should be taken to monitor renal function.