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eisai inc. - lenvatinib (unii: ee083865g2) (lenvatinib - unii:ee083865g2) - lenvatinib 10 mg - lenvima is indicated for the treatment of adult patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (dtc).  lenvima, in combination with pembrolizumab, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (rcc). lenvima, in combination with everolimus, is indicated for the treatment of adult patients with advanced rcc following one prior anti-angiogenic therapy. lenvima is indicated for the first-line treatment of patients with unresectable hepatocellular carcinoma (hcc). lenvima, in combination with pembrolizumab, is indicated for the treatment of patients with advanced endometrial carcinoma (ec) that is mismatch repair proficient (pmmr), as determined by an fda-approved test, or not microsatellite instability-high (msi-h), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation [see dosage and administration ( 2.1 )] . none. risk summary based on findings from animal studies and its mechanism of action, lenvima can cause fetal harm when administered to a pregnant woman [see clinical pharmacology ( 12.1 )] . in animal reproduction studies, oral administration of lenvatinib during organogenesis at doses below the recommended human doses resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits ( see data ) . there are no available human data informing the drug-associated risk. 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 an embryofetal development study, daily oral administration of lenvatinib mesylate at doses ≥0.3 mg/kg [approximately 0.14 times the recommended clinical dose of 24 mg based on body surface area (bsa)] to pregnant rats during organogenesis resulted in dose-related decreases in mean fetal body weight, delayed fetal ossifications, and dose-related increases in fetal external (parietal edema and tail abnormalities), visceral, and skeletal anomalies. greater than 80% post-implantation loss was observed at 1.0 mg/kg/day (approximately 0.5 times the recommended clinical dose of 24 mg based on bsa). daily oral administration of lenvatinib mesylate to pregnant rabbits during organogenesis resulted in fetal external (short tail), visceral (retroesophageal subclavian artery), and skeletal anomalies at doses greater than or equal to 0.03 mg/kg (approximately 0.03 times the recommended clinical dose of 24 mg based on bsa). at the 0.03 mg/kg dose, increased post-implantation loss, including 1 fetal death, was also observed. lenvatinib was abortifacient in rabbits, resulting in late abortions in approximately one-third of the rabbits treated at a dose level of 0.5 mg/kg/day (approximately 0.5 times the recommended clinical dose of 24 mg based on bsa). risk summary it is not known whether lenvima is present in human milk; however, lenvatinib and its metabolites are excreted in rat milk at concentrations higher than those in maternal plasma  ( see data ) . because of the potential for serious adverse reactions in breastfed children, advise women to discontinue breastfeeding during treatment with lenvima and for 1 week after the last dose. data animal data following administration of radiolabeled lenvatinib to lactating sprague dawley rats, lenvatinib-related radioactivity was approximately 2 times higher [based on area under the curve (auc)] in milk compared to maternal plasma. based on animal data and its mechanism of action, lenvima 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 lenvima [see use in specific populations ( 8.1 )]. contraception females advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with lenvima and for 30 days after the last dose. infertility lenvima may impair fertility in males and females of reproductive potential [ see nonclinical toxicology ( 13.1 )]. the safety and effectiveness of lenvima in pediatric patients have not been established. the safety and efficacy of lenvima alone and in combination were investigated but not established in four open label studies (nct02432274, nct04154189, nct04447755, nct03245151) in 232 patients aged 2 to <17 years with relapsed or refractory solid tumors, including osteosarcoma, ewing sarcoma, rhabdomyosarcoma, and high-grade glioma. hypothyroidism and pneumothorax were observed at a higher rate in pediatric patients compared to that of adult patients. the pharmacokinetics (pk) of lenvatinib in pediatric patients were within range of values previously observed in adults at the approved recommended dose of 24 mg. juvenile animal data daily oral administration of lenvatinib mesylate to juvenile rats for 8 weeks starting on postnatal day 21 (approximately equal to a human pediatric age of 2 years) resulted in growth retardation (decreased body weight gain, decreased food consumption, and decreases in the width and/or length of the femur and tibia) and secondary delays in physical development and reproductive organ immaturity at doses greater than or equal to 2 mg/kg (approximately 1.2 to 5 times the human exposure based on auc at the recommended clinical dose of 24 mg). decreased length of the femur and tibia persisted following 4 weeks of recovery. in general, the toxicologic profile of lenvatinib was similar between juvenile and adult rats, though toxicities including broken teeth at all dose levels and mortality at the 10 mg/kg/day dose level (attributed to primary duodenal lesions) occurred at earlier treatment time-points in juvenile rats. of the 261 patients with differentiated thyroid cancer (dtc) who received lenvima in select, 45% were ≥65 years of age and 11% were ≥75 years of age. no overall differences in safety or effectiveness were observed between these subjects and younger subjects. of the 352 patients with renal cell carcinoma (rcc) who received lenvima with pembrolizumab in clear, 45% were ≥65 years of age and 13% were ≥75 years of age. no overall differences in safety or effectiveness were observed between these elderly patients and younger patients.   of the 62 patients with rcc who received lenvima with everolimus in study 205, 36% were ≥65 years of age. conclusions are limited due to the small sample size, but there appeared to be no overall differences in safety or effectiveness between these subjects and younger subjects.  of the 476 patients with hepatocellular carcinoma (hcc) who received lenvima in reflect, 44% were ≥65 years of age and 12% were ≥75 years of age. no overall differences in safety or effectiveness were observed between patients ≥65 and younger subjects. patients ≥75 years of age showed reduced tolerability to lenvima. of 406 adult patients with endometrial carcinoma (ec) who were treated with lenvima in combination with pembrolizumab in study 309, 201 (50%) were 65 years and over. no overall differences in safety or effectiveness were observed between elderly patients and younger patients. no dose adjustment is recommended for patients with mild (clcr 60-89 ml/min) or moderate (clcr 30-59 ml/min) renal impairment. lenvatinib concentrations may increase in patients with dtc, rcc, or endometrial carcinoma and severe (clcr 15-29 ml/min) renal impairment. reduce the dose of lenvatinib for patients with rcc, dtc, or endometrial carcinoma and severe renal impairment [see dosage and administration   ( 2.7 )] . there is no recommended dose of lenvima for patients with hcc and severe renal impairment. lenvima has not been studied in patients with end stage renal disease [ see warnings and precautions ( 5.5 ) , clinical pharmacology ( 12.3 ) ] . no dose adjustment is recommended for patients with hcc and mild hepatic impairment (child-pugh a). there is no recommended dose for patients with hcc with moderate or severe hepatic impairment.  no dose adjustment is recommended for patients with dtc, rcc, or endometrial carcinoma and mild or moderate hepatic impairment (child-pugh a or b). lenvatinib concentrations may increase in patients with dtc, rcc, or endometrial carcinoma and severe hepatic impairment (child-pugh c). reduce the dose of lenvatinib for patients with dtc, rcc, or endometrial carcinoma and severe hepatic impairment [see dosage and administration ( 2.7 ) , clinical pharmacology ( 12.3 ) ] .

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pfizer laboratories div pfizer inc - axitinib (unii: c9lvq0yuxg) (axitinib - unii:c9lvq0yuxg) - axitinib 1 mg - inlyta in combination with avelumab is indicated for the first-line treatment of patients with advanced renal cell carcinoma (rcc). inlyta in combination with pembrolizumab is indicated for the first-line treatment of patients with advanced rcc. inlyta as a single agent is indicated for the treatment of advanced rcc after failure of one prior systemic therapy. none. risk summary based on findings in animal studies and its mechanism of action, inlyta can cause fetal harm when administered to a pregnant woman. there are no available human data to inform the drug-associated risk. in developmental toxicity studies, axitinib was teratogenic, embryotoxic and fetotoxic in mice at exposures lower than human exposures at the recommended starting dose (see data) . advise females of reproductive potential of the potential risk to a fetus. the background risk of major birth defects and miscarriage for the indicated populations are unknown. however, the background risk in the united states (u.s.) general population of major birth defects is 2%–4% and of miscarriage is 15%–20% of clinically recognized pregnancies. when inlyta is used in combination with avelumab or pembrolizumab, refer to the full prescribing information of avelumab or pembrolizumab for pregnancy information. data animal data oral axitinib administered twice daily to female mice prior to mating and through the first week of pregnancy caused an increase in post-implantation loss at all doses tested (≥15 mg/kg/dose, approximately 10 times the systemic exposure (auc) in patients at the recommended starting dose). in an embryo-fetal developmental toxicity study, pregnant mice received oral doses of 0.15, 0.5 and 1.5 mg/kg/dose axitinib twice daily during the period of organogenesis. embryo-fetal toxicities observed in the absence of maternal toxicity included malformation (cleft palate) at 1.5 mg/kg/dose (approximately 0.5 times the auc in patients at the recommended starting dose) and variation in skeletal ossification at ≥0.5 mg/kg/dose (approximately 0.15 times the auc in patients at the recommended starting dose). risk summary there are no data on the presence of axitinib in human milk, or its effects on the breastfed child or on milk production. because of the potential for serious adverse reactions in a breastfed child from inlyta, advise lactating women not to breastfeed during treatment and for 2 weeks after the last dose. when inlyta is used in combination with avelumab or pembrolizumab, refer to the full prescribing information of avelumab or pembrolizumab for lactation information. based on findings in animal studies, inlyta can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)]. when inlyta is used in combination with avelumab or pembrolizumab, refer to the full prescribing information of avelumab or pembrolizumab for contraception information. pregnancy testing verify pregnancy status in females of reproductive potential prior to initiating treatment with inlyta. contraception females advise females of reproductive potential to use effective contraception during treatment with inlyta and for 1 week after the last dose. males based on findings in animal studies, advise males with female partners of reproductive potential to use effective contraception during treatment and for 1 week after the last dose. infertility females and males based on findings in animals, inlyta may impair fertility in females and males of reproductive potential [see nonclinical toxicology (13.1)] . the safety and efficacy of inlyta in pediatric patients have not been studied. juvenile animal toxicity data toxicities in bone and teeth were observed in immature mice and dogs administered oral axitinib twice daily for 1 month or longer. effects in bone consisted of thickened growth plates in mice and dogs at ≥15 mg/kg/dose (approximately 6 and 15 times, respectively, the systemic exposure (auc) in patients at the recommended starting dose). abnormalities in growing incisor teeth (including dental caries, malocclusions and broken and/or missing teeth) were observed in mice administered oral axitinib twice daily at ≥5 mg/kg/dose (approximately 1.5 times the auc in patients at the recommended starting dose). other toxicities of potential concern to pediatric patients have not been evaluated in juvenile animals. in a controlled clinical study with inlyta for the treatment of patients with rcc, 123/359 patients (34%) treated with inlyta were ≥65 years of age. although greater sensitivity in some older individuals cannot be ruled out, no overall differences were observed in the safety and effectiveness of inlyta between patients who were ≥65 years of age and younger. of the 434 patients randomized to inlyta 5 mg twice daily administered in combination with avelumab 10 mg/kg in the javelin renal 101 trial, 38% were 65 years or older and 8% were 75 years or older. no overall difference in safety or efficacy was reported between patients who were ≥65 years of age and younger. of the 432 patients randomized to inlyta 5 mg twice daily administered in combination with pembrolizumab 200 mg in the keynote-426 trial, 40% were 65 years or older. no overall difference in safety or efficacy was reported between patients who were ≥65 years of age and younger. no dosage adjustment is required in elderly patients [see dosage and administration (2.2), clinical pharmacology (12.3)] . in a dedicated hepatic impairment trial, compared to subjects with normal hepatic function, systemic exposure following a single dose of inlyta was similar in subjects with baseline mild hepatic impairment (child-pugh class a) and higher in subjects with baseline moderate hepatic impairment (child-pugh class b). no starting dose adjustment is required when administering inlyta to patients with mild hepatic impairment (child-pugh class a). a starting dose decrease is recommended when administering inlyta to patients with moderate hepatic impairment (child-pugh class b) [see dosage and administration (2.2), warnings and precautions (5.12), clinical pharmacology (12.3)] . inlyta has not been studied in subjects with severe hepatic impairment (child-pugh class c). no dedicated renal impairment trial for axitinib has been conducted. based on the population pharmacokinetic analyses, no significant difference in axitinib clearance was observed in patients with pre-existing mild to severe renal impairment (15 ml/min ≤creatinine clearance [clcr] <89 ml/min) [see clinical pharmacology (12.3)] . no starting dose adjustment is needed for patients with pre-existing mild to severe renal impairment. caution should be used in patients with end-stage renal disease (clcr <15 ml/min).

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u.s. pharmaceuticals - axitinib (unii: c9lvq0yuxg) (axitinib - unii:c9lvq0yuxg) - axitinib 5 mg - inlyta in combination with avelumab is indicated for the first-line treatment of patients with advanced renal cell carcinoma (rcc). inlyta in combination with pembrolizumab is indicated for the first-line treatment of patients with advanced rcc. inlyta as a single agent is indicated for the treatment of advanced rcc after failure of one prior systemic therapy. none. risk summary based on findings in animal studies and its mechanism of action, inlyta can cause fetal harm when administered to a pregnant woman. there are no available human data to inform the drug-associated risk. in developmental toxicity studies, axitinib was teratogenic, embryotoxic and fetotoxic in mice at exposures lower than human exposures at the recommended starting dose (see data) . advise females of reproductive potential of the potential risk to a fetus. the background risk of major birth defects and miscarriage for the indicated populations are unknown. however, the background risk in the united states (u.s.) general population of major birth defects is 2%–4% and of miscarriage is 15%–20% of clinically recognized pregnancies. when inlyta is used in combination with avelumab or pembrolizumab, refer to the full prescribing information of avelumab or pembrolizumab for pregnancy information. data animal data oral axitinib administered twice daily to female mice prior to mating and through the first week of pregnancy caused an increase in post-implantation loss at all doses tested (≥15 mg/kg/dose, approximately 10 times the systemic exposure (auc) in patients at the recommended starting dose). in an embryo-fetal developmental toxicity study, pregnant mice received oral doses of 0.15, 0.5 and 1.5 mg/kg/dose axitinib twice daily during the period of organogenesis. embryo-fetal toxicities observed in the absence of maternal toxicity included malformation (cleft palate) at 1.5 mg/kg/dose (approximately 0.5 times the auc in patients at the recommended starting dose) and variation in skeletal ossification at ≥0.5 mg/kg/dose (approximately 0.15 times the auc in patients at the recommended starting dose). risk summary there are no data on the presence of axitinib in human milk, or its effects on the breastfed child or on milk production. because of the potential for serious adverse reactions in a breastfed child from inlyta, advise lactating women not to breastfeed during treatment and for 2 weeks after the last dose. when inlyta is used in combination with avelumab or pembrolizumab, refer to the full prescribing information of avelumab or pembrolizumab for lactation information. based on findings in animal studies, inlyta can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)]. when inlyta is used in combination with avelumab or pembrolizumab, refer to the full prescribing information of avelumab or pembrolizumab for contraception information. pregnancy testing verify pregnancy status in females of reproductive potential prior to initiating treatment with inlyta. contraception females advise females of reproductive potential to use effective contraception during treatment with inlyta and for 1 week after the last dose. males based on findings in animal studies, advise males with female partners of reproductive potential to use effective contraception during treatment and for 1 week after the last dose. infertility females and males based on findings in animals, inlyta may impair fertility in females and males of reproductive potential [see nonclinical toxicology (13.1)] . the safety and efficacy of inlyta in pediatric patients have not been studied. juvenile animal toxicity data toxicities in bone and teeth were observed in immature mice and dogs administered oral axitinib twice daily for 1 month or longer. effects in bone consisted of thickened growth plates in mice and dogs at ≥15 mg/kg/dose (approximately 6 and 15 times, respectively, the systemic exposure (auc) in patients at the recommended starting dose). abnormalities in growing incisor teeth (including dental caries, malocclusions and broken and/or missing teeth) were observed in mice administered oral axitinib twice daily at ≥5 mg/kg/dose (approximately 1.5 times the auc in patients at the recommended starting dose). other toxicities of potential concern to pediatric patients have not been evaluated in juvenile animals. in a controlled clinical study with inlyta for the treatment of patients with rcc, 123/359 patients (34%) treated with inlyta were ≥65 years of age. although greater sensitivity in some older individuals cannot be ruled out, no overall differences were observed in the safety and effectiveness of inlyta between patients who were ≥65 years of age and younger. of the 434 patients randomized to inlyta 5 mg twice daily administered in combination with avelumab 10 mg/kg in the javelin renal 101 trial, 38% were 65 years or older and 8% were 75 years or older. no overall difference in safety or efficacy was reported between patients who were ≥65 years of age and younger. of the 432 patients randomized to inlyta 5 mg twice daily administered in combination with pembrolizumab 200 mg in the keynote-426 trial, 40% were 65 years or older. no overall difference in safety or efficacy was reported between patients who were ≥65 years of age and younger. no dosage adjustment is required in elderly patients [see dosage and administration (2.2), clinical pharmacology (12.3)] . in a dedicated hepatic impairment trial, compared to subjects with normal hepatic function, systemic exposure following a single dose of inlyta was similar in subjects with baseline mild hepatic impairment (child-pugh class a) and higher in subjects with baseline moderate hepatic impairment (child-pugh class b). no starting dose adjustment is required when administering inlyta to patients with mild hepatic impairment (child-pugh class a). a starting dose decrease is recommended when administering inlyta to patients with moderate hepatic impairment (child-pugh class b) [see dosage and administration (2.2), warnings and precautions (5.12), clinical pharmacology (12.3)] . inlyta has not been studied in subjects with severe hepatic impairment (child-pugh class c). no dedicated renal impairment trial for axitinib has been conducted. based on the population pharmacokinetic analyses, no significant difference in axitinib clearance was observed in patients with pre-existing mild to severe renal impairment (15 ml/min ≤creatinine clearance [clcr] <89 ml/min) [see clinical pharmacology (12.3)] . no starting dose adjustment is needed for patients with pre-existing mild to severe renal impairment. caution should be used in patients with end-stage renal disease (clcr <15 ml/min).

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seagen inc. - enfortumab vedotin (unii: dle8519rwm) (enfortumab vedotin - unii:dle8519rwm) - padcev® , in combination with pembrolizumab, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (muc). padcev, as a single agent, is indicated for the treatment of adult patients with locally advanced or muc who: none. risk summary based on the mechanism of action and findings in animals, padcev can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no available human data on padcev use in pregnant women to inform a drug-associated risk. in an animal reproduction study, administration of enfortumab vedotin-ejfv to pregnant rats during organogenesis caused maternal toxicity, embryo-fetal lethality, structural malformations and skeletal anomalies at maternal exposures similar to the exposures at the recommended human dose of 1.25 mg/kg (see data) . advise patients of the potential risk to the fetus. 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 a rat pilot embryo-fetal development study, administration of enfortumab vedotin-ejfv on gestation day 6 and 13 during the period of organogenesis resulted in a complete litter loss in all pregnant rats at the maternally toxic dose of 5 mg/kg (approximately 3 times the exposure at the recommended human dose). a dose of 2 mg/kg (similar to the exposure at the recommended human dose) resulted in maternal toxicity, embryo-fetal lethality and structural malformations that included gastroschisis, malrotated hindlimb, absent forepaw, malpositioned internal organs and fused cervical arch. additionally, skeletal anomalies (asymmetric, fused, incompletely ossified, and misshapen sternebrae, misshapen cervical arch, and unilateral ossification of the thoracic centra) and decreased fetal weight were observed. risk summary there are no data on the presence of enfortumab vedotin-ejfv in human milk, the effects on the breastfed child, or the effects on milk production. because of the potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during treatment with padcev and for 3 weeks after the last dose. pregnancy testing verify pregnancy status in females of reproductive potential prior to initiating padcev treatment [see use in specific populations (8.1)] . contraception females padcev 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 padcev and for 2 months after the last dose. males advise male patients with female partners of reproductive potential to use effective contraception during treatment with padcev and for 4 months after the last dose. infertility females based on findings in animal studies with mmae-containing antibody-drug conjugates (adcs), padcev may impair female fertility. the effect on fertility is reversible [see nonclinical toxicology (13.1)] . males based on findings from animal studies, padcev may impair male fertility [see nonclinical toxicology (13.1)] . safety and effectiveness of padcev in pediatric patients have not been established. of the 564 patients treated with padcev in combination with pembrolizumab, 44% (n=247) were 65-74 years and 26% (n=144) were 75 years or older. of the 720 patients treated with padcev as a single agent in clinical trials, 39% (n=282) were 65-74 years and 24% (n=170) were 75 years or older. no overall differences in effectiveness were observed between patients 65 years of age or older and younger patients. patients 75 years of age or older treated with padcev in combination with pembrolizumab experienced a higher incidence of fatal adverse reactions than younger patients. the incidence of fatal adverse reactions was 4% in patients younger than 75 and 7% in patients 75 years or older. patients 75 years of age or older treated with padcev as a single agent experienced a higher incidence of fatal adverse reactions than younger patients. the incidence of fatal adverse reactions was 6% in patients younger than 75 years, and 11% in patients 75 years or older. no significant difference was observed in the pharmacokinetics of padcev between patients 65 years and older and younger patients [see clinical pharmacology (12.3 )]. avoid the use of padcev in patients with moderate or severe hepatic impairment (total bilirubin >1.5 x uln and ast any). padcev has only been studied in a limited number of patients with moderate hepatic impairment (n=3) and has not been evaluated in patients with severe hepatic impairment [see clinical pharmacology (12.3)] . in another adc that contains mmae, the frequency of ≥ grade 3 adverse reactions and deaths was greater in patients with moderate (child-pugh b) or severe (child-pugh c) hepatic impairment compared to patients with normal hepatic function.

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athenex pharmaceutical division, llc. - pemetrexed disodium hemipentahydrate (unii: f4gsh45r4c) (pemetrexed - unii:04q9aiz7no) - pemetrexed for injection is indicated: - in combination with pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic non-squamous non-small cell lung cancer (nsclc), with no egfr or alk genomic tumor aberrations. in combination with pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic non-squamous non-small cell lung cancer (nsclc), with no egfr or alk genomic tumor aberrations. - in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous nsclc. - as a single agent for the maintenance treatment of patients with locally advanced or metastatic, non-squamous nsclc whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. - as a single agent for the treatment of patients with recurrent, metastatic non-squamous, nsclc after prior chemotherapy. limitations of use:

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ingenus pharmaceuticals, llc - pemetrexed disodium hemipentahydrate (unii: f4gsh45r4c) (pemetrexed - unii:04q9aiz7no) - pemetrexed for injection is indicated: - in combination with pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic non-squamous non-small cell lung cancer (nsclc), with no egfr or alk genomic tumor aberrations. - in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous nsclc. - as a single agent for the maintenance treatment of patients with locally advanced or metastatic, non-squamous nsclc whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. - as a single agent for the treatment of patients with recurrent, metastatic non-squamous, nsclc after prior chemotherapy. limitations of use: pemetrexed for injection is not indicated for the treatment of patients with squamous cell, non-small cell lung cancer [see clinical studies (14.1)]. pemetrexed for injection is indicated, in combination with cisplatin, for the initial treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery. pemetrexed for injection is contraindicated in patients with a history of severe hypersensitivity reaction to pemetrexed [see adverse reactions (6.1)]. risk summary based on findings from animal studies and its mechanism of action, pemetrexed for injection can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no available data on pemetrexed for injection use in pregnant women. in animal reproduction studies, intravenous administration of pemetrexed to pregnant mice during the period of organogenesis was teratogenic, resulting in developmental delays and malformations at doses lower than the recommended human dose of 500 mg/m2 [see data] . advise pregnant women of the potential risk to a fetus [see use in special populations (8.3)] . 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 pemetrexed was teratogenic in mice. daily dosing of pemetrexed by intravenous injection to pregnant mice during the period of organogenesis increased the incidence of fetal malformations (cleft palate; protruding tongue; enlarged or misshaped kidney; and fused lumbar vertebra) at doses (based on bsa) 0.03 times the human dose of 500 mg/m2 . at doses, based on bsa, greater than or equal to 0.0012 times the 500 mg/m2 human dose, pemetrexed administration resulted in dose-dependent increases in developmental delays (incomplete ossification of talus and skull bone; and decreased fetal weight). risk summary there is no information regarding the presence of pemetrexed or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. because of the potential for serious adverse reactions in breastfed infants from pemetrexed for injection, advise women not to breastfeed during treatment with pemetrexed for injection and for one week after the last dose. based on animal data pemetrexed for injection can cause malformations and developmental delays 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 initiating pemetrexed injection [see use in specific populations (8.1)] . contraception females because of the potential for genotoxicity, advise females of reproductive potential to use effective contraception during treatment with pemetrexed for injection and for 6 months after the last dose. males because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with pemetrexed for injection and for 3 months after the last dose [see nonclinical toxicology (13.1)] . infertilit y males pemetrexed for injection may impair fertility in males of reproductive potential. it is not known whether these effects on fertility are reversible [see nonclinical toxicology (13.1)] . the safety and effectiveness of pemetrexed for injection in pediatric patients have not been established. the safety and pharmacokinetics of pemetrexed for injection were evaluated in two clinical studies conducted in pediatric patients with recurrent solid tumors. (nct00070473 n=32 and nct00520936 n=72). patients in both studies received concomitant vitamin b12 and folic acid supplementation and dexamethasone. no tumor responses were observed. adverse reactions observed in pediatric patients were similar to those observed in adults. single-dose pharmacokinetics of pemetrexed for injection were evaluated in 22 patients age 4 to 18 years enrolled in nct00070473 were within range of values in adults. of the 3,946 patients enrolled in clinical studies of pemetrexed for injection, 34% were 65 and over and 4% were 75 and over. no overall differences in effectiveness were observed between these patients and younger patients. the incidences of grade 3-4 anemia, fatigue, thrombocytopenia, hypertension, and neutropenia were higher in patients 65 years of age and older as compared to younger patients: in at least one of five randomized clinical trials. [see adverse reactions (6.1) and clinical studies (14.1, 14.2)]. pemetrexed for injection is primarily excreted by the kidneys. decreased renal function results in reduced clearance and greater exposure (auc) to pemetrexed for injection compared with patients with normal renal function [warnings and precautions (5.2, 5.6) and clinical pharmacology (12.3)] . no dose is recommended for patients with creatinine clearance less than 45 ml/min [see dosage and administration (2.3)].

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zydus pharmaceuticals usa inc. - pemetrexed disodium (unii: 2pku919ba9) (pemetrexed - unii:04q9aiz7no) - pemetrexed for injection, usp is indicated: - in combination with pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic non-squamous nsclc, with no egfr or alk genomic tumor aberrations. - in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous, non-small cell lung cancer (nsclc). - as a single agent for the maintenance treatment of patients with locally advanced or metastatic, non-squamous nsclc whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. - as a single agent for the treatment of patients with recurrent, metastatic non-squamous, nsclc after prior chemotherapy. limitations of use : pemetrexed for injection, usp is not indicated for the treatment of patients with squamous cell, non-small cell lung cancer [see clinical studies (14.1)]. pemetrexed for injection, usp is indicated, in combination with cisplatin, for

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

eugia us llc - pemetrexed disodium hemipentahydrate (unii: f4gsh45r4c) (pemetrexed - unii:04q9aiz7no) - pemetrexed for injection is indicated: • in combination with pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic non-squamous non-small cell lung cancer (nsclc), with no egfr or alk genomic tumor aberrations. • in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous nsclc. • as a single agent for the maintenance treatment of patients with locally advanced or metastatic, non-squamous nsclc whose disease has not progressed after four cycles of  platinum-based first-line chemotherapy. • as a single agent for the treatment of patients with recurrent, metastatic non-squamous, nsclc after prior chemotherapy. limitations of use : pemetrexed for injection is not indicated for the treatment of patients with squamous cell, non-small cell lung cancer [see clinical studies (14.1)] . pemetrexed for injection is indicated, in combination with cisplatin, for the initial treatment of patients with malignant pleural

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

fresenius kabi usa, llc - pemetrexed disodium (unii: 2pku919ba9) (pemetrexed - unii:04q9aiz7no) - pemetrexed for injection is indicated: - in combination with pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic non-squamous non-small cell lung cancer (nsclc), with no egfr or alk genomic tumor aberrations. - in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous nsclc. - as a single agent for the maintenance treatment of patients with locally advanced or metastatic, non-squamous nsclc whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. - as a single agent for the treatment of patients with recurrent, metastatic non-squamous, nsclc after prior chemotherapy. limitations of use: pemetrexed for injection is not indicated for the treatment of patients with squamous cell, non-small cell lung cancer [see clinical studies (14.1)]. pemetrexed for injection is indicated, in combination with cisplatin, for the initial treatment of patients with malignant pleural mesothelioma whose disease is unresectable or who are otherwise not candidates for curative surgery. pemetrexed for injection is contraindicated in patients with a history of severe hypersensitivity reaction to pemetrexed [see adverse reactions (6.1)]. risk summary based on findings from animal studies and its mechanism of action, pemetrexed for injection can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no available data on pemetrexed for injection use in pregnant women. in animal reproduction studies, intravenous administration of pemetrexed to pregnant mice during the period of organogenesis was teratogenic, resulting in developmental delays and malformations at doses lower than the recommended human dose of 500 mg/m2 [see data] . advise pregnant women of the potential risk to a fetus [see use in special populations (8.3)] . 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 pemetrexed was teratogenic in mice. daily dosing of pemetrexed by intravenous injection to pregnant mice during the period of organogenesis increased the incidence of fetal malformations (cleft palate; protruding tongue; enlarged or misshaped kidney; and fused lumbar vertebra) at doses (based on bsa) 0.03 times the human dose of 500 mg/m2 . at doses, based on bsa, greater than or equal to 0.0012 times the 500 mg/m2 human dose, pemetrexed administration resulted in dose-dependent increases in developmental delays (incomplete ossification of talus and skull bone; and decreased fetal weight). risk summary there is no information regarding the presence of pemetrexed or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. because of the potential for serious adverse reactions in breastfed infants from pemetrexed for injection, advise women not to breastfeed during treatment with pemetrexed for injection and for one week after the last dose. based on animal data pemetrexed for injection can cause malformations and developmental delays 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 initiating pemetrexed injection [see use in specific populations (8.1)] . contraception females because of the potential for genotoxicity, advise females of reproductive potential to use effective contraception during treatment with pemetrexed for injection and for 6 months after the last dose. males because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with pemetrexed for injection and for 3 months after the last dose [see nonclinical toxicology (13.1)] . infertility males pemetrexed for injection may impair fertility in males of reproductive potential. it is not known whether these effects on fertility are reversible [see nonclinical toxicology (13.1)] . the safety and effectiveness of pemetrexed for injection in pediatric patients have not been established. the safety and pharmacokinetics of pemetrexed for injection were evaluated in two clinical studies conducted in pediatric patients with recurrent solid tumors (nct00070473 n=32 and nct00520936 n=72). patients in both studies received concomitant vitamin b12 and folic acid supplementation and dexamethasone. no tumor responses were observed. adverse reactions observed in pediatric patients were similar to those observed in adults. single-dose pharmacokinetics of pemetrexed for injection were evaluated in 22 patients age 4 to 18 years enrolled in nct00070473 were within range of values in adults. of the 3,946 patients enrolled in clinical studies of pemetrexed for injection, 34% were 65 and over and 4% were 75 and over. no overall differences in effectiveness were observed between these patients and younger patients. the incidences of grade 3-4 anemia, fatigue, thrombocytopenia, hypertension, and neutropenia were higher in patients 65 years of age and older as compared to younger patients: in at least one of five randomized clinical trials. [see adverse reactions (6.1) and clinical studies (14.1, 14.2)]. pemetrexed for injection is primarily excreted by the kidneys. decreased renal function results in reduced clearance and greater exposure (auc) to pemetrexed for injection compared with patients with normal renal function [see warnings and precautions (5.2, 5.6) and clinical pharmacology (12.3)] . no dose is recommended for patients with creatinine clearance less than 45 ml/min [see dosage and administration (2.3)].

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

accord healthcare inc. - pemetrexed disodium hemipentahydrate (unii: f4gsh45r4c) (pemetrexed - unii:04q9aiz7no) - pemetrexed for injection is indicated: - in combination with pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic non-squamous non-small cell lung cancer (nsclc), with no egfr or alk genomic tumor aberrations. - in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous, nsclc. - as a single agent for the maintenance treatment of patients with locally advanced or metastatic, non-squamous nsclc whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. - as a single agent for the treatment of patients with recurrent, metastatic non-squamous, nsclc after prior chemotherapy. limitations of use: pemetrexed for injection is not indicated for the treatment of patients with squamous cell, non-small cell lung cancer [see clinical studies ( 14.1)]. pemetrexed for injection is indicated, in combination with cisplatin