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

bausch health us, llc - pegaptanib sodium (unii: 3hp012q0fh) (pegaptanib - unii:2h1pa8h1en) - pegaptanib sodium 3.47 mg in 1 ml - macugen® (pegaptanib sodium injection) is indicated for the treatment of neovascular (wet) age-related macular degeneration. macugen is contraindicated in patients with ocular or periocular infections. macugen is contraindicated in patients with known hypersensitivity to pegaptanib sodium or any other excipient in this product. teratogenic effects: pregnancy category b. pegaptanib produced no maternal toxicity and no evidence of teratogenicity or fetal mortality in mice at intravenous doses of up to 40 mg/kg/day (about 7,000 times the recommended human monocular ophthalmic dose of 0.3 mg/eye). pegaptanib crosses the placenta in mice. there are, however, no adequate and well-controlled studies in pregnant women. because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. it is not known whether pegaptanib is excreted in human milk. because many drugs are excreted in human milk, caution should be exercised when macugen is adm

European Union - English - EMA (European Medicines Agency)

pharmaswiss ceska republika s.r.o - pegaptanib - wet macular degeneration - ophthalmologicals - macugen is indicated for the treatment of neovascular (wet) age-related macular degeneration (amd).

Canada - English - Health Canada

pfizer canada ulc - pegaptanib - solution - 0.3mg - pegaptanib 0.3mg - eent drugs, miscellaneous

New Zealand - English - Medsafe (Medicines Safety Authority)

pfizer new zealand limited - pegaptanib sodium 3.47 mg/ml - solution for injection - 300 mcg/dose - active: pegaptanib sodium 3.47 mg/ml excipient: dibasic sodium phosphate heptahydrate monobasic sodium phosphate monohydrate sodium chloride water for injection

United Kingdom - English - MHRA (Medicines & Healthcare Products Regulatory Agency)

pfizer ltd - pegaptanib sodium - solution for injection - 3.33mg/1ml

India - English - Central Drugs Standard Control Organization

pfizer - pegaptanib sodium - vial - 0.3mg - vial

Singapore - English - HSA (Health Sciences Authority)

pfizer private limited - pegaptanib sodium - injection, solution - 0.3mg

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

sun pharmaceutical industries, inc. - pazopanib hydrochloride (unii: 33y9anm545) (pazopanib - unii:7rn5dr86ck) - pazopanib tablets are indicated for the treatment of adults with advanced renal cell carcinoma (rcc). pazopanib tablets are indicated for the treatment of adults with advanced soft tissue sarcoma (sts) who have received prior chemotherapy. limitations of use : the efficacy of pazopanib tablets for the treatment of patients with adipocytic sts or gastrointestinal stromal tumors has not been demonstrated. none. risk summary based on animal reproduction studies and its mechanism of action [see clinical pharmacology (12.1)] , pazopanib can cause fetal harm when administered to a pregnant woman. there are no available data on pazopanib use in pregnant women to evaluate for a drug-associated risk. in animal developmental and reproductive toxicology studies, oral administration of pazopanib to pregnant rats and rabbits throughout organogenesis resulted in teratogenicity, and abortion at systemic exposures lower than that observed at the mrhd of 800 mg/day (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. 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 in clinically recognized pregnancies and miscarriage is 2% to 4% and 15% to 20%, respectively. data animal data in a female fertility and early embryonic development study, female rats were administered oral pazopanib at least 15 days prior to mating and for 6 days after mating, which resulted in increased pre-implantation loss and early resorptions at dosages greater than or equal to 30 mg/kg/day (approximately 0.4-fold the auc at the mrhd of 800 mg/day). total litter resorption was seen at 300 mg/kg/day (approximately 0.8-fold the auc at the mrhd of 800 mg/day). postimplantation loss, embryolethality, and decreased fetal body weights were noted in females administered doses greater than or equal to 10 mg/kg/day (approximately 0.3-fold the auc at the mrhd of 800 mg/day). in embryo-fetal developmental toxicity studies in rats and rabbits, oral pazopanib was administered to pregnant animals during organogenesis. in rats, dose levels of greater than or equal to 3 mg/kg/day (approximately 0.1‑fold the auc at the mrhd of 800 mg/day) resulted in teratogenic effects, including cardiovascular malformations (retroesophageal subclavian artery, missing innominate artery, changes in the aortic arch), incomplete or absent ossification, increases in postimplantation loss, embryolethality and reduced fetal body weight. in rabbits, maternal toxicity, increased postimplantation loss and abortion were observed at doses greater than or equal to 30 mg/kg/day (approximately 0.007-fold the auc at the mrhd of 800 mg/day). in addition, severe maternal body weight loss and 100% litter loss were observed at doses greater than or equal to 100 mg/kg/day (0.02-fold the auc at the mrhd of 800 mg/day), while fetal weight was reduced at doses greater than or equal to 3 mg/kg/day (auc not calculated). risk summary there is no data on the presence of pazopanib or its metabolites in human milk or their effects on the breastfed infant or milk production. because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with pazopanib and for 2 weeks after the final dose. pazopanib can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)]. pregnancy testing verify pregnancy status of females of reproductive potential prior to starting treatment with pazopanib. contraception females advise females of reproductive potential to use effective contraception during treatment with pazopanib and for at least 2 weeks after the last dose. males advise males (including those who have had vasectomies) with female partners of reproductive potential to use condoms during treatment with pazopanib and for at least 2 weeks after the last dose. infertility based on findings from animal studies, pazopanib may impair fertility in females and males of reproductive potential while receiving treatment [see nonclinical toxicology (13.1)]. the safety and effectiveness of pazopanib in pediatric patients have not been established. pazopanib is not indicated for use in pediatric patients [see warnings and precautions (5.18)] . based on its mechanism of action, pazopanib may have severe effects on organ growth and maturation during early postnatal development. administration of pazopanib to juvenile rats < 21 days old resulted in toxicity to the lungs, liver, heart, and kidney and in death at doses significantly lower than the clinically recommended dose or doses tolerated in older animals (see juvenile animal toxicity data) . the safety and efficacy of pazopanib or an unapproved pazopanib formulation were investigated but not established in two open-label studies: a study in 37 pediatric patients 2 to < 17 years with recurrent or refractory solid tumors [nct00929903] and a study in 46 pediatric patients 1 year to < 17 years with refractory solid tumors, including sarcoma [nct01956669]. meaningful anti-tumor activity was not observed in these studies. juvenile animal toxicity data in rats, weaning occurs at day 21 postpartum which approximately equates to a human pediatric age of 2 years. in a juvenile animal toxicology study performed in rats, when animals were dosed from day 9 through day 14 postpartum (pre-weaning), pazopanib caused abnormal organ growth/maturation in the kidney, lung, liver, and heart at approximately 0.1-fold the auc in adults at the mrhd of 800 mg/day of pazopanib. at approximately 0.4-fold the auc in adults at the mrhd of 800 mg/day, pazopanib administration resulted in mortality. in repeat-dose toxicology studies in rats, including 4-week, 13-week, and 26-week administration, toxicities in bone, teeth, and nail beds were observed at doses greater than or equal to 3 mg/kg/day (approximately 0.07-fold the auc at the mrhd of 800 mg/day). doses of 300 mg/kg/day (approximately 0.8-fold the auc at the mrhd of 800 mg/day) were not tolerated in 13- and 26-week studies and animals required dose reductions due to body weight loss and morbidity. hypertrophy of epiphyseal growth plates, nail abnormalities (including broken, overgrown, or absent nails) and tooth abnormalities in growing incisor teeth (including excessively long, brittle, broken, and missing teeth, and dentine and enamel degeneration and thinning) were observed in rats at doses greater than or equal to 30 mg/kg/day (approximately 0.35-fold the auc at the mrhd of 800 mg/day) at 26 weeks, with the onset of tooth and nail bed alterations noted clinically after 4 to 6 weeks. similar findings were noted in repeat-dose studies in juvenile rats dosed with pazopanib beginning day 21 postpartum (post-weaning). in the post-weaning animals, the occurrence of changes in teeth and bones occurred earlier and with greater severity than in older animals. there was evidence of tooth degeneration and decreased bone growth at doses greater than or equal to 30 mg/kg (approximately 0.1- to 0.2-fold the auc at the mrhd of 800 mg/day). pazopanib exposure in juvenile rats was lower than that seen at the same dose levels in adult animals, based on comparative auc values. at pazopanib doses approximately 0.5- to 0.7-fold the auc at the mrhd of 800 mg/day, decreased bone growth in juvenile rats persisted even after the end of the dosing period. finally, despite lower pazopanib exposures than those reported in adult animals or adult humans, juvenile animals administered 300 mg/kg/dose pazopanib required dose reduction within 4 weeks of dosing initiation due to significant toxicity, although adult animals could tolerate this same dose for at least 3 times as long [see warnings and precautions (5.18)]. in pooled clinical trials with pazopanib, 30% of 2080 patients were aged ≥ 65 years. more patients ≥ 65 years had alt elevations > 3 times uln compared to patients < 65 years (23% versus 18%) [see warnings and precautions (5.1)]. in the rcc trials, 33% of 586 patients were aged ≥ 65 years. no overall differences in safety or effectiveness of pazopanib were observed between these patients and younger patients. in the sts trials, 24% of 382 patients were aged ≥ 65 years. patients aged ≥ 65 years had a higher incidence of grade 3 or 4 fatigue (19% versus 12% for patients aged <65 years), hypertension (10% versus 6%), decreased appetite (11% versus 2%), alt elevations (3% versus 2%) and ast elevations (4% versus 1%). in the randomized sts trial (veg110727), no overall differences in effectiveness of pazopanib were observed between patients aged ≥ 65 years and younger patients. no dose adjustment is recommended for patients with renal impairment. pazopanib has not been studied in patients with severe renal impairment or in patients undergoing peritoneal dialysis or hemodialysis. no dose adjustment is required in patients with mild hepatic impairment (either total bilirubin ≤ uln and alt > uln or bilirubin > 1 to 1.5 times uln and any alt value). pazopanib is not recommended in patients with moderate (total bilirubin > 1.5 to 3 times uln and any alt value) and severe (total bilirubin > 3 times uln and any alt value) hepatic impairment [see dosage and administration (2.3), clinical pharmacology (12.3)] .

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

apotex corp. - pazopanib (unii: 7rn5dr86ck) (pazopanib - unii:7rn5dr86ck) - pazopanib tablets are indicated for the treatment of adults with advanced renal cell carcinoma (rcc). pazopanib tablets are indicated for the treatment of adults with advanced soft tissue sarcoma (sts) who have received prior chemotherapy. limitations of use : the efficacy of pazopanib tablets for the treatment of patients with adipocytic sts or gastrointestinal stromal tumors has not been demonstrated. none. risk summary based on animal reproduction studies and its mechanism of action [see clinical pharmacology (12.1)], pazopanib tablets can cause fetal harm when administered to a pregnant woman. there are no available data on pazopanib tablets use in pregnant women to evaluate for a drug-associated risk. in animal developmental and reproductive toxicology studies, oral administration of pazopanib to pregnant rats and rabbits throughout organogenesis resulted in teratogenicity, and abortion at systemic exposures lower than that observed at the mrhd of 800 mg/day (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. 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 in clinically recognized pregnancies and miscarriage is 2% to 4% and 15% to 20%, respectively. data animal data in a female fertility and early embryonic development study, female rats were administered oral pazopanib at least 15 days prior to mating and for 6 days after mating, which resulted in increased pre-implantation loss and early resorptions at dosages greater than or equal to 30 mg/kg/day (approximately 0.4-fold the auc at the mrhd of 800 mg/day). total litter resorption was seen at 300 mg/kg/day (approximately 0.8-fold the auc at the mrhd of 800 mg/day). postimplantation loss, embryolethality, and decreased fetal body weights were noted in females administered doses greater than or equal to 10 mg/kg/day (approximately 0.3-fold the auc at the mrhd of 800 mg/day). in embryo-fetal developmental toxicity studies in rats and rabbits, oral pazopanib was administered to pregnant animals during organogenesis. in rats, dose levels of greater than or equal to 3 mg/kg/day (approximately 0.1-fold the auc at the mrhd of 800 mg/day) resulted in teratogenic effects, including cardiovascular malformations (retroesophageal subclavian artery, missing innominate artery, changes in the aortic arch), incomplete or absent ossification, increases in postimplantation loss, embryolethality and reduced fetal body weight. in rabbits, maternal toxicity, increased postimplantation loss and abortion were observed at doses greater than or equal to 30 mg/kg/day (approximately 0.007-fold the auc at the mrhd of 800 mg/day). in addition, severe maternal body weight loss and 100% litter loss were observed at doses greater than or equal to 100 mg/kg/day (0.02-fold the auc at the mrhd of 800 mg/day), while fetal weight was reduced at doses greater than or equal to 3 mg/kg/day (auc not calculated). risk summary there is no data on the presence of pazopanib or its metabolites in human milk or their effects on the breastfed infant or milk production. because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with pazopanib tablets and for 2 weeks after the final dose. pazopanib tablets can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)). pregnancy testing verify pregnancy status of females of reproductive potential prior to starting treatment with pazopanib tablets. contraception females advise females of reproductive potential to use effective contraception during treatment with pazopanib tablets and for at least 2 weeks after the last dose. males advise males (including those who have had vasectomies) with female partners of reproductive potential to use condoms during treatment with pazopanib tablets and for at least 2 weeks after the last dose. infertility based on findings from animal studies, pazopanib tablets may impair fertility in females and males of reproductive potential while receiving treatment [see nonclinical toxicology (13.1) ]. the safety and effectiveness of pazopanib tablets in pediatric patients have not been established. pazopanib tablets are not indicated for use in pediatric patients [see warnings and precautions (5.18)] . based on its mechanism of action, pazopanib may have severe effects on organ growth and maturation during early postnatal development. administration of pazopanib to juvenile rats < 21 days old resulted in toxicity to the lungs, liver, heart, and kidney and in death at doses significantly lower than the clinically recommended dose or doses tolerated in older animals (see juvenile animal toxicity data). the safety and efficacy of pazopanib tablets or an unapproved pazopanib formulation were investigated but not established in two open-label studies: a study in 37 pediatric patients 2 to < 17 years with recurrent or refractory solid tumors [nct00929903] and a study in 46 pediatric patients 1 year to < 17 years with refractory solid tumors, including sarcoma [nct01956669]. meaningful anti-tumor activity was not observed in these studies. juvenile animal toxicity data in rats, weaning occurs at day 21 postpartum which approximately equates to a human pediatric age of 2 years. in a juvenile animal toxicology study performed in rats, when animals were dosed from day 9 through day 14 postpartum (pre-weaning), pazopanib caused abnormal organ growth/maturation in the kidney, lung, liver, and heart at approximately 0.1-fold the auc in adults at the mrhd of 800 mg/day of pazopanib. at approximately 0.4-fold the auc in adults at the mrhd of 800 mg/day, pazopanib administration resulted in mortality. in repeat-dose toxicology studies in rats, including 4-week, 13-week, and 26-week administration, toxicities in bone, teeth, and nail beds were observed at doses greater than or equal to 3 mg/kg/day (approximately 0.07-fold the auc at the mrhd of 800 mg/day). doses of 300 mg/kg/day (approximately 0.8-fold the auc at the mrhd of 800 mg/day) were not tolerated in 13- and 26-week studies and animals required dose reductions due to body weight loss and morbidity. hypertrophy of epiphyseal growth plates, nail abnormalities (including broken, overgrown, or absent nails) and tooth abnormalities in growing incisor teeth (including excessively long, brittle, broken, and missing teeth, and dentine and enamel degeneration and thinning) were observed in rats at doses greater than or equal to 30 mg/kg/day (approximately 0.35-fold the auc at the mrhd of 800 mg/day) at 26 weeks, with the onset of tooth and nail bed alterations noted clinically after 4 to 6 weeks. similar findings were noted in repeat-dose studies in juvenile rats dosed with pazopanib beginning day 21 postpartum (post-weaning). in the post-weaning animals, the occurrence of changes in teeth and bones occurred earlier and with greater severity than in older animals. there was evidence of tooth degeneration and decreased bone growth at doses greater than or equal to 30 mg/kg (approximately 0.1- to 0.2-fold the auc at the mrhd of 800 mg/day). pazopanib exposure in juvenile rats was lower than that seen at the same dose levels in adult animals, based on comparative auc values. at pazopanib doses approximately 0.5- to 0.7-fold the auc at the mrhd of 800 mg/day, decreased bone growth in juvenile rats persisted even after the end of the dosing period. finally, despite lower pazopanib exposures than those reported in adult animals or adult humans, juvenile animals administered 300 mg/kg/dose pazopanib required dose reduction within 4 weeks of dosing initiation due to significant toxicity, although adult animals could tolerate this same dose for at least 3 times as long [see warnings and precautions (5.18)].  in pooled clinical trials with pazopanib tablets, 30% of 2,080 patients were aged ≥ 65 years. more patients ≥ 65 years had alt elevations > 3 x uln compared to patients < 65 years (23% versus 18%) [see warnings and precautions (5.1)]. in the rcc trials, 33% of 586 patients were aged ≥ 65 years. no overall differences in safety or effectiveness of pazopanib tablets were observed between these patients and younger patients. in the sts trials, 24% of 382 patients were aged ≥ 65 years. patients aged ≥ 65 years had a higher incidence of grade 3 or 4 fatigue (19% versus 12% for patients aged < 65 years), hypertension (10% versus 6%), decreased appetite (11% versus 2%), alt elevations (3% versus 2%) and ast elevations (4% versus 1%). in the randomized sts trial (veg110727), no overall differences in effectiveness of pazopanib tablets were observed between patients aged ≥ 65 years and younger patients. no dose adjustment is recommended for patients with renal impairment. pazopanib tablets have not been studied in patients with severe renal impairment or in patients undergoing peritoneal dialysis or hemodialysis. no dose adjustment is required in patients with mild hepatic impairment (either total bilirubin ≤ uln and alt > uln or bilirubin > 1 to 1.5 x uln and any alt value). pazopanib tablets are not recommended in patients with moderate (total bilirubin > 1.5 to 3 x uln and any alt value) and severe (total bilirubin > 3 x uln and any alt value) hepatic impairment [see dosage and administration (2.3), clinical pharmacology (12.3) ].