Australia - English - Department of Health (Therapeutic Goods Administration)

bayer australia ltd - aflibercept, quantity: 40 mg/ml - injection, solution - excipient ingredients: monobasic sodium phosphate monohydrate; sodium chloride; dibasic sodium phosphate heptahydrate; sucrose; water for injections; polysorbate 20 - eylea (aflibercept) is indicated in adults for the treatment of: - neovascular (wet) age-related macular degeneration (wet amd) - visual impairment due to macular oedema secondary to central retinal vein occlusion (crvo) - diabetic macular oedema (dme) - visual impairment due to macular oedema secondary to branch retinal vein occlusion (brvo) - visual impairment due to myopic choroidal neovascularisation (myopic cnv)

Australia - English - Department of Health (Therapeutic Goods Administration)

bayer australia ltd - aflibercept, quantity: 40 mg/ml - injection, solution - excipient ingredients: monobasic sodium phosphate monohydrate; sucrose; polysorbate 20; sodium chloride; water for injections; dibasic sodium phosphate heptahydrate - eylea (aflibercept) is indicated in adults for the treatment of: - neovascular (wet) age-related macular degeneration (wet amd); - visual impairment due to macular oedema secondary to central retinal vein occlusion (crvo); - diabetic macular oedema (dme); - visual impairment due to macular oedema secondary to branch retinal vein occlusion (brvo); - visual impairment due to myopic choroidal neovascularisation (myopic cnv)

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

sanofi-aventis u.s. llc - aflibercept (unii: 15c2vl427d) (aflibercept - unii:15c2vl427d) - aflibercept 100 mg in 4 ml - zaltrap, in combination with fluorouracil, leucovorin, irinotecan-(folfiri), is indicated for the treatment of patients with metastatic colorectal cancer (mcrc) that is resistant to or has progressed following an oxaliplatin-containing regimen. none. risk summary based on findings from animal reproduction studies and its mechanism of action [see clinical pharmacology (12.1)] , zaltrap can cause fetal harm when administered to pregnant women. there is insufficient data in pregnant women exposed to zaltrap to assess the risks. administration of ziv-aflibercept during the period of organogenesis was embryotoxic and teratogenic in rabbits at exposure levels approximately 0.3 times the human exposure at the 4 mg per kg dose (see data) . advise pregnant women of the potential risk to a fetus. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. data animal data in pregnant rabbits, administration of ziv-aflibercept during the period of organogenesis resulted in an increase in postimplantation loss and external (including anasarca, umbilical hernia, diaphragmatic hernia and gastroschisis, cleft palate, ectrodactyly, and anal atresia), visceral (heart, great vessels, and arteries), and skeletal fetal malformations (including fused vertebrae, sternebrae, and ribs, supernumerary arches and ribs, and incomplete ossification) at doses greater than or equal to 3 mg per kg, administered once every 3 days (approximately 0.3 times the human exposure at the 4 mg per kg dose based on auc). risk summary there are no data on the presence of ziv-aflibercept in human milk, or the effects of ziv-aflibercept on the breastfed infant or on milk production. because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with zaltrap and for 1 month following the last dose. zaltrap can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)]. pregnancy testing verify the pregnancy status in females of reproductive potential prior to initiating zaltrap [see use in specific populations (8.1)] . contraception females based on data from animal studies and its mechanism of action, zaltrap can cause fetal harm when administered to pregnant women [see use in specific populations (8.1)] . advise female patients of reproductive potential to use effective contraception during treatment with zaltrap and for 3 months following the last dose. infertility advise female and male patients of reproductive potential that zaltrap may impair reproductive function and fertility [see nonclinical toxicology (13.1)] . the safety and effectiveness in pediatric patients have not been established. safety and efficacy were assessed, but not established in a dose-escalation, safety, and tolerability study (nct00622414) in 21 patients with solid tumors 2 to 21 years of age (median age 12.9). the mean elimination half-life of free ziv-aflibercept determined after the first dose in 8 pediatric patients aged 5 to 17 years was within the range of values previously observed in adults. the maximum tolerated dose based on body weight in these pediatric patients was lower than the dose known to be safe and effective in adults with mcrc. juvenile animal toxicity data weekly/every-two-weeks intravenous administration of ziv-aflibercept at dose of 3 mg per kg (approximately 0.6 times the human exposure at the 4 mg per kg dose based on auc) to growing young adult (sexually mature) cynomolgus monkeys for up to 6 months resulted in changes in the bone (effects on growth plate and the axial and appendicular skeleton), nasal cavity (atrophy/loss of the septum and/or turbinates), kidney (glomerulopathy with inflammation), ovary (decreased number of maturing follicles, granulosa cells, and/or theca cells), and adrenal gland (decreased vacuolation with inflammation). in another study in sexually immature cynomolgus monkeys (treated intravenously for 3 months), there were similar effects. the skeletal and nasal cavity effects were not reversible after a post-dosing recovery period. of the 611 patients with mcrc, patients treated with zaltrap/folfiri, 205 (34%) were 65 years or older, and 33 (5%) were 75 years or older. elderly patients (≥65 years of age) experienced higher incidences (≥5%) of diarrhea, dizziness, asthenia, weight decrease, and dehydration when compared to younger patients. monitor elderly patients more closely for diarrhea and dehydration [see warnings and precautions (5.9)]. the effect of zaltrap on overall survival was similar in patients <65 years old and ≥65 years old who received zaltrap/folfiri. no dosage modification is recommended for patients with renal impairment [see clinical pharmacology (12.3)] . no dosage modification is recommended for patients with mild (total bilirubin >1 to 1.5 times upper limit normal [uln] and any aspartate transaminase [ast]) and moderate (total bilirubin >1.5 to 3 times uln and any ast) hepatic impairment [see clinical pharmacology (12.3)] . zaltrap has not been studied in patients with severe hepatic impairment (total bilirubin >3 times uln and any ast).

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

regeneron pharmaceuticals, inc. - aflibercept (unii: 15c2vl427d) (aflibercept - unii:15c2vl427d) - aflibercept 40 mg in 1 ml - eylea is indicated for the treatment of: eylea is contraindicated in patients with ocular or periocular infections. eylea is contraindicated in patients with active intraocular inflammation. eylea is contraindicated in patients with known hypersensitivity to aflibercept or any of the excipients in eylea. hypersensitivity reactions may manifest as rash, pruritus, urticaria, severe anaphylactic/anaphylactoid reactions, or severe intraocular inflammation. risk summary adequate and well-controlled studies with eylea have not been conducted in pregnant women. aflibercept produced adverse embryofetal effects in rabbits, including external, visceral, and skeletal malformations. a fetal no observed adverse effect level (noael) was not identified. at the lowest dose shown to produce adverse embryofetal effects, systemic exposures (based on auc for free aflibercept) were approximately 6 times higher than auc values observed in humans after a single intravitreal treatment at the recommended clinical dose [see animal data]. animal reproduction studies are not always predictive of human response, and it is not known whether eylea can cause fetal harm when administered to a pregnant woman. based on the anti-vegf mechanism of action for aflibercept [see clinical pharmacology (12.1)], treatment with eylea may pose a risk to human embryofetal development. eylea should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. the 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 two embryofetal development studies, aflibercept produced adverse embryofetal effects when administered every three days during organogenesis to pregnant rabbits at intravenous doses ≥3 mg per kg, or every six days during organogenesis at subcutaneous doses ≥0.1 mg per kg. adverse embryofetal effects included increased incidences of postimplantation loss and fetal malformations, including anasarca, umbilical hernia, diaphragmatic hernia, gastroschisis, cleft palate, ectrodactyly, intestinal atresia, spina bifida, encephalomeningocele, heart and major vessel defects, and skeletal malformations (fused vertebrae, sternebrae, and ribs; supernumerary vertebral arches and ribs; and incomplete ossification). the maternal no observed adverse effect level (noael) in these studies was 3 mg per kg. aflibercept produced fetal malformations at all doses assessed in rabbits and the fetal noael was not identified. at the lowest dose shown to produce adverse embryofetal effects in rabbits (0.1 mg per kg), systemic exposure (auc) of free aflibercept was approximately 6 times higher than systemic exposure (auc) observed in adult patients after a single intravitreal dose of 2 mg. risk summary there is no information regarding the presence of aflibercept in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production/excretion. because many drugs are excreted in human milk, and because the potential for absorption and harm to infant growth and development exists, eylea is not recommended during breastfeeding. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for eylea and any potential adverse effects on the breastfed child from eylea. contraception females of reproductive potential are advised to use effective contraception prior to the initial dose, during treatment, and for at least 3 months after the last intravitreal injection of eylea. infertility there are no data regarding the effects of eylea on human fertility. aflibercept adversely affected female and male reproductive systems in cynomolgus monkeys when administered by intravenous injection at a dose approximately 1500 times higher than the systemic level observed in adult patients with an intravitreal dose of 2 mg. a no observed adverse effect level (noael) was not identified. these findings were reversible within 20 weeks after cessation of treatment [see nonclinical toxicology (13.1)]. the safety and effectiveness of eylea have been demonstrated in two clinical studies of pre-term infants with rop. these two studies randomized pre-term infants between initial treatment with eylea or laser. efficacy of each treatment is supported by the demonstration of a clinical course which was better than would have been expected without treatment [see dosage and administration (2.9), adverse reactions (6.1), clinical pharmacology (12.3) and clinical studies (14.6)] . in the clinical studies, approximately 76% (2049/2701) of patients randomized to treatment with eylea were ≥65 years of age and approximately 46% (1250/2701) were ≥75 years of age. no significant differences in efficacy or safety were seen with increasing age in these studies.

Australia - English - Department of Health (Therapeutic Goods Administration)

sanofi-aventis australia pty ltd - aflibercept -

Australia - English - Department of Health (Therapeutic Goods Administration)

sanofi-aventis australia pty ltd - aflibercept -

Australia - English - Department of Health (Therapeutic Goods Administration)

sanofi-aventis australia pty ltd - aflibercept -

Australia - English - Department of Health (Therapeutic Goods Administration)

sanofi-aventis australia pty ltd - aflibercept -

Australia - English - Department of Health (Therapeutic Goods Administration)

sanofi-aventis australia pty ltd - aflibercept -

Australia - English - Department of Health (Therapeutic Goods Administration)

sanofi-aventis australia pty ltd - aflibercept -