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

westminster pharmaceuticals, llc - posaconazole (unii: 6tk1g07bhz) (posaconazole - unii:6tk1g07bhz) - posaconazole delayed-release tablets are indicated for prophylaxis of invasive aspergillus and candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (hsct) recipients with graft-versus-host disease (gvhd) or those with hematologic malignancies with prolonged neutropenia from chemotherapy [see clinical studies (14.2) ] as follows: - posaconazole delayed-release tablets: adults and pediatric patients 13 years of age and older. additional pediatric use information is approved for merck sharp & dohme corp.’s noxafil (posaconazole) delayed-release tablets. however, due to merck sharp & dohme corp.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. posaconazole is contraindicated in persons with known hypersensitivity to posaconazole or other azole antifungal agents. posaconazole is contraindicated with sirolimus. concomitant administration of posaconaz

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

bryant ranch prepack - posaconazole (unii: 6tk1g07bhz) (posaconazole - unii:6tk1g07bhz) - posaconazole delayed-release tablets are indicated for the treatment of invasive aspergillosis in adults and pediatric patients 13 years of age and older. posaconazole is indicated for the prophylaxis of invasive aspergillus and candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (hsct) recipients with graft-versus-host disease (gvhd) or those with hematologic malignancies with prolonged neutropenia from chemotherapy [see clinical studies (14.1)] as follows: posaconazole delayed-release tablets : adults and pediatric patients 2 years of age and older who weigh greater than 40 kg posaconazole is contraindicated in persons with known hypersensitivity to posaconazole or other azole antifungal agents. posaconazole is contraindicated with sirolimus. concomitant administration of posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity [see drug interactions (7.1) and clinical pharmacology (12.3)] . posaconazole is contraindicated with cyp3a4 substrates that prolong the qt interval. concomitant administration of posaconazole with the cyp3a4 substrates, pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to qtc prolongation and cases of torsades de pointes [see warnings and precautions (5.2) and drug interactions (7.2)] . coadministration with the hmg-coa reductase inhibitors that are primarily metabolized through cyp3a4 (e.g., atorvastatin, lovastatin, and simvastatin) is contraindicated since increased plasma concentration of these drugs can lead to rhabdomyolysis [see drug interactions (7.3) and clinical pharmacology (12.3)] . posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [see drug interactions (7.4)] . coadministration of posaconazole with venetoclax at initiation and during the ramp-up phase is contraindicated in patients with chronic lymphocytic leukemia (cll) or small lymphocytic lymphoma (sll) due to the potential for increased risk of tumor lysis syndrome [see warnings and precautions (5.9) and drug interactions (7.15)]. risk summary based on findings from animal data, posaconazole may cause fetal harm when administered to pregnant women. available data for use of noxafil in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal reproduction studies, skeletal malformations (cranial malformations and missing ribs) and maternal toxicity (reduced food consumption and reduced body weight gain) were observed when posaconazole was dosed orally to pregnant rats during organogenesis at doses ≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of noxafil in healthy volunteers. in pregnant rabbits dosed orally during organogenesis, increased resorptions, reduced litter size, and reduced body weight gain of females were seen at doses 5 times the exposure achieved with the 400 mg twice daily oral suspension regimen. doses of ≥ 3 times the clinical exposure caused an increase in resorptions in these rabbits (see data) . based on animal 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 and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data posaconazole resulted in maternal toxicity (reduced food consumption and reduced body weight gain) and skeletal malformations (cranial malformations and missing ribs) when given orally to pregnant rats during organogenesis (gestational days 6 through 15) at doses ≥27 mg/kg (≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of drug in healthy volunteers). the no-effect dose for malformations and maternal toxicity in rats was 9 mg/kg, which is 0.7 times the exposure achieved with the 400 mg twice daily oral suspension regimen. no malformations were seen in rabbits dosed during organogenesis (gestational days 7 through 19) at doses up to 80 mg/kg (5 times the exposure achieved with the 400 mg twice daily oral suspension regimen). in the rabbit, the no-effect dose was 20 mg/kg, while high doses of 40 mg/kg and 80 mg/kg (3 or 5 times the clinical exposure) caused an increase in resorptions. in rabbits dosed at 80 mg/kg, a reduction in body weight gain of females and a reduction in litter size were seen. risk summary there are no data on the presence of posaconazole in human milk, the effects on the breastfed infant, or the effects on milk production. posaconazole is excreted in the milk of lactating rats. when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for posaconazole and any potential adverse effects on the breastfed child from posaconazole or from the underlying maternal condition. the safety and effectiveness of posaconazole oral suspension and posaconazole delayed-release tablets for the prophylaxis of invasive aspergillus and candida infections have been established in pediatric patients aged 2 and older who are at high risk of developing these infections due to being severely immunocompromised, such as hsct recipients with gvhd or those with hematologic malignancies with prolonged neutropenia from chemotherapy. the safety and effectiveness of posaconazole injection and posaconazole delayed-release tablets for the treatment of invasive aspergillosis have been established in pediatric patients aged 13 years and older. use of posaconazole in these age groups is supported by evidence from adequate and well-controlled studies of noxafil in adults and pediatric patients and additional pharmacokinetic and safety data in pediatric patients 2 years of age and older [see adverse reactions (6.1), clinical pharmacology (12.3), and clinical studies (14)] . the safety and effectiveness of posaconazole have not been established in pediatric patients younger than 2 years of age. no overall differences in the safety of noxafil delayed-release tablets and noxafil oral suspension were observed between geriatric patients and younger adult patients in the clinical trials; therefore, no dosage adjustment is recommended for any formulation of posaconazole in geriatric patients. no clinically meaningful differences in the pharmacokinetics of noxafil were observed in geriatric patients compared to younger adult patients during clinical trials [see clinical pharmacology (12.3)] . of the 230 patients treated with noxafil delayed-release tablets, 38 (17%) were greater than 65 years of age. of the 605 patients randomized to noxafil oral suspension in noxafil oral suspension study 1 and study 2, 63 (10%) were ≥65 years of age. in addition, 48 patients treated with greater than or equal to 800-mg/day noxafil oral suspension in another indication were ≥65 years of age. of the 288 patients randomized to noxafil injection/noxafil delayed-release tablets in the aspergillosis treatment study, 85 (29%) were ≥65 years of age. no overall differences in the pharmacokinetics and safety were observed between elderly and young subjects during clinical trials, but greater sensitivity of some older individuals cannot be ruled out. following single-dose administration of 400 mg of the noxafil oral suspension, there was no significant effect of mild (egfr: 50-80 ml/min/1.73 m2 , n=6) or moderate (egfr: 20-49 ml/min/1.73 m2 , n=6) renal impairment on posaconazole pharmacokinetics; therefore, no dose adjustment is required in patients with mild to moderate renal impairment. in subjects with severe renal impairment (egfr: <20 ml/min/1.73 m2 ), the mean plasma exposure (auc) was similar to that in patients with normal renal function (egfr: >80 ml/min/1.73 m2 ); however, the range of the auc estimates was highly variable (cv=96%) in these subjects with severe renal impairment as compared to that in the other renal impairment groups (cv<40%). due to the variability in exposure, patients with severe renal impairment should be monitored closely for breakthrough fungal infections [see dosage and administration (2)] . similar recommendations apply to posaconazole delayed-release tablets; however, a specific study has not been conducted with the posaconazole delayed-release tablets. after a single oral dose of noxafil oral suspension 400 mg, the mean auc was 43%, 27%, and 21% higher in subjects with mild (child-pugh class a, n=6), moderate (child-pugh class b, n=6), or severe (child-pugh class c, n=6) hepatic impairment, respectively, compared to subjects with normal hepatic function (n=18). compared to subjects with normal hepatic function, the mean cmax was 1% higher, 40% higher, and 34% lower in subjects with mild, moderate, or severe hepatic impairment, respectively. the mean apparent oral clearance (cl/f) was reduced by 18%, 36%, and 28% in subjects with mild, moderate, or severe hepatic impairment, respectively, compared to subjects with normal hepatic function. the elimination half-life (t½ ) was 27 hours, 39 hours, 27 hours, and 43 hours in subjects with normal hepatic function and mild, moderate, or severe hepatic impairment, respectively. it is recommended that no dose adjustment of posaconazole is needed in patients with mild to severe hepatic impairment (child-pugh class a, b, or c) [see dosage and administration (2) and warnings and precautions (5.4)] . similar recommendations apply to posaconazole delayed-release tablets; however, a specific study has not been conducted with the posaconazole delayed-release tablets. the pharmacokinetics of posaconazole are comparable in males and females. no adjustment in the dosage of posaconazole is necessary based on gender. the pharmacokinetic profile of posaconazole is not significantly affected by race. no adjustment in the dosage of posaconazole is necessary based on race. pharmacokinetic modeling suggests that patients weighing greater than 120 kg may have lower posaconazole plasma drug exposure. it is, therefore, suggested to closely monitor for breakthrough fungal infections particularly when using posaconazole oral suspension [see clinical pharmacology (12.3)] .

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

merck sharp & dohme llc - posaconazole (unii: 6tk1g07bhz) (posaconazole - unii:6tk1g07bhz) - posaconazole 40 mg in 1 ml - noxafil® injection and noxafil delayed-release tablets are indicated for the treatment of invasive aspergillosis in adults and pediatric patients 13 years of age and older. noxafil is indicated for the prophylaxis of invasive aspergillus and candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (hsct) recipients with graft-versus-host disease (gvhd) or those with hematologic malignancies with prolonged neutropenia from chemotherapy [see clinical studies (14.1)] as follows: - noxafil injection: adults and pediatric patients 2 years of age and older - noxafil delayed-release tablets: adults and pediatric patients 2 years of age and older who weigh greater than 40 kg - noxafil oral suspension: adults and pediatric patients 13 years of age and older - noxafil powdermix for delayed-release oral suspension: pediatric patients 2 years of age and older who weigh 40 kg or less noxafil oral susp

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

glenmark pharmaceuticals inc., usa - posaconazole (unii: 6tk1g07bhz) (posaconazole - unii:6tk1g07bhz) - posaconazole injection is indicated for the prophylaxis of invasive aspergillus and candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (hsct) recipients with graft-versus-host disease (gvhd) or those with hematologic malignancies with prolonged neutropenia from chemotherapy [see clinical studies (14.1)] as follows: pediatric use information is approved for merck sharp & dohme corp.’s noxafil (posaconazole) injection. however, due to merck sharp & dohme corp.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. posaconazole is contraindicated in persons with known hypersensitivity to posaconazole or other azole antifungal agents. posaconazole is contraindicated with sirolimus. concomitant administration of posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity [see drug interactions (7.1) and clinical pharmacology (12.3) ]. posaconazole is contraindicated with cyp3a4 substrates that prolong the qt interval. concomitant administration of posaconazole with the cyp3a4 substrates, pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to qtc prolongation and cases of torsades de pointes [see warnings and precautions (5.2) and drug interactions (7.2) ]. coadministration with the hmg-coa reductase inhibitors that are primarily metabolized through cyp3a4 (e.g., atorvastatin, lovastatin, and simvastatin) is contraindicated since increased plasma concentration of these drugs can lead to rhabdomyolysis [see drug interactions (7.3) and clinical pharmacology (12.3) ]. posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [see drug interactions (7.4) ]. coadministration of posaconazole with venetoclax at initiation and during the ramp-up phase is contraindicated in patients with chronic lymphocytic leukemia (cll) or small lymphocytic lymphoma (sll) due to the potential for increased risk of tumor lysis syndrome [see warnings and precautions (5.10) and drug interactions (7.16) ]. risk summary based on findings from animal data, posaconazole may cause fetal harm when administered to pregnant women. available data for use of posaconazole in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal reproduction studies, skeletal malformations (cranial malformations and missing ribs) and maternal toxicity (reduced food consumption and reduced body weight gain) were observed when posaconazole was dosed orally to pregnant rats during organogenesis at doses ≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of posaconazole in healthy volunteers. in pregnant rabbits dosed orally during organogenesis, increased resorptions, reduced litter size, and reduced body weight gain of females were seen at doses 5 times the exposure achieved with the 400 mg twice daily oral suspension regimen. doses of ≥ 3 times the clinical exposure caused an increase in resorptions in these rabbits (see data ). based on animal 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 and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data posaconazole resulted in maternal toxicity (reduced food consumption and reduced body weight gain) and skeletal malformations (cranial malformations and missing ribs) when given orally to pregnant rats during organogenesis (gestational days 6 through 15) at doses ≥27 mg/kg (≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of drug in healthy volunteers). the no-effect dose for malformations and maternal toxicity in rats was 9 mg/kg, which is 0.7 times the exposure achieved with the 400 mg twice daily oral suspension regimen. no malformations were seen in rabbits dosed during organogenesis (gestational days 7 through 19) at doses up to 80 mg/kg (5 times the exposure achieved with the 400 mg twice daily oral suspension regimen). in the rabbit, the no-effect dose was 20 mg/kg, while high doses of 40 mg/kg and 80 mg/kg (3 or 5 times the clinical exposure) caused an increase in resorptions. in rabbits dosed at 80 mg/kg, a reduction in body weight gain of females and a reduction in litter size were seen. risk summary there are no data on the presence of posaconazole in human milk, the effects on the breastfed infant, or the effects on milk production. posaconazole is excreted in the milk of lactating rats. when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for posaconazole and any potential adverse effects on the breastfed child from posaconazole or from the underlying maternal condition. the safety and effectiveness of posaconazole have not been established in pediatric patients younger than 2 years of age. pediatric use information is approved for merck sharp & dohme corp.’s noxafil (posaconazole) injection. however, due to merck sharp & dohme corp.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. no overall differences in the safety of posaconazole injection was observed between geriatric patients and younger adult patients in the clinical trials; therefore, no dosage adjustment is recommended for any formulation of posaconazole in geriatric patients. no clinically meaningful differences in the pharmacokinetics of posaconazole were observed in geriatric patients compared to younger adult patients during clinical trials [see clinical pharmacology (12.3) ]. of the 279 patients treated with posaconazole injection in the posaconazole injection study, 52 (19%) were greater than 65 years of age. no overall differences in the pharmacokinetics and safety were observed between elderly and young subjects during clinical trials, but greater sensitivity of some older individuals cannot be ruled out. posaconazole injection should be avoided in patients with moderate or severe renal impairment (egfr <50 ml/min), unless an assessment of the benefit/risk to the patient justifies the use of posaconazole injection. in patients with moderate or severe renal impairment (egfr <50 ml/min), receiving the posaconazole injection, accumulation of the intravenous vehicle, sbecd, is expected to occur. serum creatinine levels should be closely monitored in these patients, and, if increases occur, consideration should be given to changing to oral posaconazole therapy [see dosage and administration (2.9) and warnings and precautions (5.5) ]. after a single oral dose of noxafil® oral suspension 400 mg, the mean auc was 43%, 27%, and 21% higher in subjects with mild (child-pugh class a, n=6), moderate (child-pugh class b, n=6), or severe (child-pugh class c, n=6) hepatic impairment, respectively, compared to subjects with normal hepatic function (n=18). compared to subjects with normal hepatic function, the mean cmax was 1% higher, 40 % higher, and 34% lower in subjects with mild, moderate, or severe hepatic impairment, respectively. the mean apparent oral clearance (cl/f) was reduced by 18%, 36%, and 28% in subjects with mild, moderate, or severe hepatic impairment, respectively, compared to subjects with normal hepatic function. the elimination half-life (t½) was 27 hours, 39 hours, 27 hours, and 43 hours in subjects with normal hepatic function and mild, moderate, or severe hepatic impairment, respectively. it is recommended that no dose adjustment of posaconazole injection is needed in patients with mild to severe hepatic impairment (child-pugh class a, b, or c) [see dosage and administration (2) and warnings and precautions (5.4) ]. however, a specific study has not been conducted with posaconazole injection. the pharmacokinetics of posaconazole are comparable in males and females. no adjustment in the dosage of posaconazole injection is necessary based on gender. the pharmacokinetic profile of posaconazole is not significantly affected by race. no adjustment in the dosage of posaconazole injection is necessary based on race. pharmacokinetic modeling suggests that patients weighing greater than 120 kg may have lower posaconazole plasma drug exposure. it is, therefore, suggested to closely monitor for breakthrough fungal infections [see clinical pharmacology (12.3)].

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

eugia us llc - posaconazole (unii: 6tk1g07bhz) (posaconazole - unii:6tk1g07bhz) - posaconazole injection is indicated for the prophylaxis of invasive aspergillus and candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (hsct) recipients with graft-versus-host disease (gvhd) or those with hematologic malignancies with prolonged neutropenia from chemotherapy [see clinical studies (14.1)] as follows:    •   posaconazole injection: adults pediatric use information is approved for merck sharp & dohme corp.’s noxafil (posaconazole) injection. however, due to merck sharp & dohme corp.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. posaconazole is contraindicated in persons with known hypersensitivity to posaconazole or other azole antifungal agents. posaconazole is contraindicated with sirolimus. concomitant administration of posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity [see drug interactions (7.1) and clinical pharmacology (12.3)] . posaconazole is contraindicated with cyp3a4 substrates that prolong the qt interval. concomitant administration of posaconazole with the cyp3a4 substrates, pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to qtc prolongation and cases of torsades de pointes [see warnings and precautions (5.2) and drug interactions (7.2)] . coadministration with the hmg-coa reductase inhibitors that are primarily metabolized through cyp3a4 (e.g., atorvastatin, lovastatin, and simvastatin) is contraindicated since increased plasma concentration of these drugs can lead to rhabdomyolysis [see drug interactions (7.3) and clinical pharmacology (12.3)] . posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [see drug interactions (7.4)] . coadministration of posaconazole with venetoclax at initiation and during the ramp-up phase is contraindicated in patients with chronic lymphocytic leukemia (cll) or small lymphocytic lymphoma (sll) due to the potential for increased risk of tumor lysis syndrome [see warnings and precautions (5.10) and drug interactions (7.16)] . risk summary based on findings from animal data, posaconazole may cause fetal harm when administered to pregnant women. available data for use of posaconazole in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal reproduction studies, skeletal malformations (cranial malformations and missing ribs) and maternal toxicity (reduced food consumption and reduced body weight gain) were observed when posaconazole was dosed orally to pregnant rats during organogenesis at doses ≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of posaconazole in healthy volunteers. in pregnant rabbits dosed orally during organogenesis, increased resorptions, reduced litter size, and reduced body weight gain of females were seen at doses 5 times the exposure achieved with the 400 mg twice daily oral suspension regimen. doses of ≥ 3 times the clinical exposure caused an increase in resorptions in these rabbits (see data) . based on animal 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 and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data posaconazole resulted in maternal toxicity (reduced food consumption and reduced body weight gain) and skeletal malformations (cranial malformations and missing ribs) when given orally to pregnant rats during organogenesis (gestational days 6 through 15) at doses ≥27 mg/kg (≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of drug in healthy volunteers). the no-effect dose for malformations and maternal toxicity in rats was 9 mg/kg, which is 0.7 times the exposure achieved with the 400 mg twice daily oral suspension regimen. no malformations were seen in rabbits dosed during organogenesis (gestational days 7 through 19) at doses up to 80 mg/kg (5 times the exposure achieved with the 400 mg twice daily oral suspension regimen). in the rabbit, the no-effect dose was 20 mg/kg, while high doses of 40 mg/kg and 80 mg/kg (3 or 5 times the clinical exposure) caused an increase in resorptions. in rabbits dosed at 80 mg/kg, a reduction in body weight gain of females and a reduction in litter size were seen. risk summary there are no data on the presence of posaconazole in human milk, the effects on the breastfed infant, or the effects on milk production. posaconazole is excreted in the milk of lactating rats. when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for posaconazole and any potential adverse effects on the breastfed child from posaconazole or from the underlying maternal condition. the safety and effectiveness of posaconazole have not been established in pediatric patients younger than 2 years of age. pediatric use information is approved for merck sharp & dohme corp.’s noxafil (posaconazole) injection. however, due to merck sharp & dohme corp.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. no overall differences in the safety of posaconazole injection were observed between geriatric patients and younger adult patients in the clinical trials; therefore, no dosage adjustment is recommended for any formulation of posaconazole in geriatric patients. no clinically meaningful differences in the pharmacokinetics of posaconazole were observed in geriatric patients compared to younger adult patients during clinical trials [see clinical pharmacology (12.3)] . of the 279 patients treated with posaconazole injection in the posaconazole injection study, 52 (19%) were greater than 65 years of age. of the 288 patients randomized to posaconazole injection in the aspergillosis treatment study, 85 (29%) were ≥65 years of age.  no overall differences in the pharmacokinetics and safety were observed between elderly and young subjects during clinical trials, but greater sensitivity of some older individuals cannot be ruled out. posaconazole injection should be avoided in patients with moderate or severe renal impairment (egfr <50 ml/min), unless an assessment of the benefit/risk to the patient justifies the use of posaconazole injection. in patients with moderate or severe renal impairment (egfr <50 ml/min), receiving the posaconazole injection, accumulation of the intravenous vehicle, sbecd, is expected to occur. serum creatinine levels should be closely monitored in these patients, and, if increases occur, consideration should be given to changing to oral noxafil therapy [see dosage and administration (2.9) and warnings and precautions (5.5)] . after a single oral dose of noxafil oral suspension 400 mg, the mean auc was 43%, 27%, and 21% higher in subjects with mild (child-pugh class a, n=6), moderate (child-pugh class b, n=6), or severe (child-pugh class c, n=6) hepatic impairment, respectively, compared to subjects with normal hepatic function (n=18). compared to subjects with normal hepatic function, the mean cmax was 1% higher, 40% higher, and 34% lower in subjects with mild, moderate, or severe hepatic impairment, respectively. the mean apparent oral clearance (cl/f) was reduced by 18%, 36%, and 28% in subjects with mild, moderate, or severe hepatic impairment, respectively, compared to subjects with normal hepatic function. the elimination half-life (t½) was 27 hours, 39 hours, 27 hours, and 43 hours in subjects with normal hepatic function and mild, moderate, or severe hepatic impairment, respectively. it is recommended that no dose adjustment of noxafil oral suspension, noxafil delayed-release tablets, noxafil powdermix for delayed-release oral suspension, and posaconazole injection is needed in patients with mild to severe hepatic impairment (child-pugh class a, b, or c) [see  dosage and administration (2)  and warnings and precautions (5.4) ] . however, a specific study has not been conducted with, noxafil delayed-release tablets, noxafil powdermix for delayed-release oral suspension,  and posaconazole injection. the pharmacokinetics of posaconazole are comparable in males and females. no adjustment in the dosage of posaconazole is necessary based on gender. the pharmacokinetic profile of posaconazole is not significantly affected by race. no adjustment in the dosage of posaconazole is necessary based on race. pharmacokinetic modeling suggests that patients weighing greater than 120 kg may have lower posaconazole plasma drug exposure. it is, therefore, suggested to closely monitor for breakthrough fungal infections.

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

i3 pharmaceuticals, llc - posaconazole (unii: 6tk1g07bhz) (posaconazole - unii:6tk1g07bhz) - posaconazole delayed-release tablets are indicated for the prophylaxis of invasive aspergillus and candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (hsct) recipients with graft-versus-host disease (gvhd) or those with hematologic malignancies with prolonged neutropenia from chemotherapy [see clinical studies ( 14.2 )] as follows: • posaconazole delayed-release tablets: adults and pediatric patients 13 years of age and older. additional pediatric use information is approved for merck sharp & dohme corp.’s noxafil ® (posaconazole delayed-release tablets). however, due to merck sharp & dohme corp.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. posaconazole is contraindicated in persons with known hypersensitivity to posaconazole or other azole antifungal agents. posaconazole is contraindicated with sirolimus. concomitant adm

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

cardinal health 107, llc - posaconazole (unii: 6tk1g07bhz) (posaconazole - unii:6tk1g07bhz) - posaconazole is indicated for the prophylaxis of invasive aspergillus and candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (hsct) recipients with graft-versus-host disease (gvhd) or those with hematologic malignancies with prolonged neutropenia from chemotherapy [see clinical studies (14.1)] as follows: posaconazole delayed-release tablets: adults and pediatric patients 13 years of age and older. additional pediatric use information is approved for merck sharp & dohme corp.'s noxafil (posaconazole) delayed-release tablets. however, due to merck sharp & dohme corp.'s marketing exclusivity rights, this drug product is not labeled with that pediatric information. posaconazole is contraindicated in persons with known hypersensitivity to posaconazole or other azole antifungal agents. posaconazole is contraindicated with sirolimus. concomitant administration of posaconazole with sirolimus increas

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

merck sharp & dohme corp. - orbifloxacin (unii: 660932tpy6) (orbifloxacin - unii:660932tpy6), mometasone furoate (unii: 04201gdn4r) (mometasone - unii:8hr4qj6dw8), posaconazole (unii: 6tk1g07bhz) (posaconazole - unii:6tk1g07bhz) - indications: posatex® otic suspension is indicated for the treatment of otitis externa in dogs associated with susceptible strains of yeast (malassezia pachydermatis) and bacteria (coagulase positive staphylococci, pseudomonas aeruginosa , and enterococcus faecalis ). contraindications : posatex® otic suspension is contraindicated in dogs with known or suspected hypersensitivity to quinolones, mometasone furoate monohydrate, or posaconazole. do not use in dogs with known tympanic perforation (see precautions ).

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

fresensius kabi usa, llc - posaconazole (unii: 6tk1g07bhz) (posaconazole - unii:6tk1g07bhz) - posaconazole injection is indicated for the treatment of invasive aspergillosis in adults and pediatric patients 13 years of age and older. posaconazole is indicated for the prophylaxis of invasive aspergillus and candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (hsct) recipients with graft-versus- host disease (gvhd) or those with hematologic malignancies with prolonged neutropenia from chemotherapy [see clinical studies (14.1)] as follows: - posaconazole injection: adults and pediatric patients 2 years of age and older posaconazole is contraindicated in persons with known hypersensitivity to posaconazole or other azole antifungal agents. posaconazole is contraindicated with sirolimus. concomitant administration of posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity [see drug interactions (7.1) and clinical pharmacology (12.3)] . posaconazole is contraindicated with cyp3a4 substrates that prolong the qt interval. concomitant administration of posaconazole with the cyp3a4 substrates, pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to qtc prolongation and cases of torsades de pointes [see warnings and precautions (5.2) and drug interactions (7.2)] . coadministration with the hmg-coa reductase inhibitors that are primarily metabolized through cyp3a4 (e.g., atorvastatin, lovastatin, and simvastatin) is contraindicated since increased plasma concentration of these drugs can lead to rhabdomyolysis [see drug interactions (7.3) and clinical pharmacology (12.3)] . posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [see drug interactions (7.4)] . coadministration of posaconzole with venetoclax at initiation and during the ramp-up phase is contraindicated in patients with chronic lymphocytic leukemia (cll) or small lymphocytic lymphoma (sll) due to the potential for increased risk of tumor lysis syndrome [see warnings and precautions (5.10) and drug interactions (7.16)]. risk summary based on findings from animal data, posaconazole may cause fetal harm when administered to pregnant women. available data for use of posaconazole in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal reproduction studies, skeletal malformations (cranial malformations and missing ribs) and maternal toxicity (reduced food consumption and reduced body weight gain) were observed when posaconazole was dosed orally to pregnant rats during organogenesis at doses ≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of posaconazole in healthy volunteers. in pregnant rabbits dosed orally during organogenesis, increased resorptions, reduced litter size, and reduced body weight gain of females were seen at doses 5 times the exposure achieved with the 400 mg twice daily oral suspension regimen. doses of ≥ 3 times the clinical exposure caused an increase in resorptions in these rabbits (see data) . based on animal 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 and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data posaconazole resulted in maternal toxicity (reduced food consumption and reduced body weight gain) and skeletal malformations (cranial malformations and missing ribs) when given orally to pregnant rats during organogenesis (gestational days 6 through 15) at doses ≥27 mg/kg (≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of drug in healthy volunteers). the no-effect dose for malformations and maternal toxicity in rats was 9 mg/kg, which is 0.7 times the exposure achieved with the 400 mg twice daily oral suspension regimen. no malformations were seen in rabbits dosed during organogenesis (gestational days 7 through 19) at doses up to 80 mg/kg (5 times the exposure achieved with the 400 mg twice daily oral suspension regimen). in the rabbit, the no-effect dose was 20 mg/kg, while high doses of 40 mg/kg and 80 mg/kg (3 or 5 times the clinical exposure) caused an increase in resorptions. in rabbits dosed at 80 mg/kg, a reduction in body weight gain of females and a reduction in litter size were seen. risk summary there are no data on the presence of posaconazole in human milk, the effects on the breastfed infant, or the effects on milk production. posaconazole is excreted in the milk of lactating rats. when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for posaconazole and any potential adverse effects on the breastfed child from posaconazole or from the underlying maternal condition. the safety and effectiveness of posaconazole injection for the prophylaxis of invasive aspergillus and candida infections have been established in pediatric patients aged 2 and older who are at high risk of developing these infections due to being severely immunocompromised, such as hsct recipients with gvhd or those with hematologic malignancies with prolonged neutropenia from chemotherapy. the safety and effectiveness of posaconazole injection for the treatment of invasive aspergillosis have been established in pediatric patients aged 13 years and older. use of posaconazole in these age groups is supported by evidence from adequate and well-controlled studies of posaconazole in adult and pediatric patients and additional pharmacokinetic and safety data in pediatric patients 2 years of age and older [see adverse reactions (6.1), clinical pharmacology (12.3) and clinical studies (14)] . the safety and effectiveness of posaconazole have not been established in pediatric patients younger than 2 years of age. no overall differences in the safety of posaconazole injection were observed between geriatric patients and younger adult patients in the clinical trials; therefore, no dosage adjustment is recommended for any formulation of posaconazole in geriatric patients. no clinically meaningful differences in the pharmacokinetics of posaconazole were observed in geriatric patients compared to younger adult patients during clinical trials [see clinical pharmacology (12.3)] . of the 279 patients treated with posaconazole injection in the posaconazole injection study, 52 (19%) were greater than 65 years of age. of the 230 patients treated with noxafil® delayed-release tablets , 38 (17%) were greater than 65 years of age. of the 288 patients randomized to posaconazole injection/ noxafil® delayed-release tablets in the aspergillosis treatment study, 85 (29%) were ≥65 years of age. no overall differences in the pharmacokinetics and safety were observed between elderly and young subjects during clinical trials, but greater sensitivity of some older individuals cannot be ruled out. posaconazole injection should be avoided in patients with moderate or severe renal impairment (egfr <50 ml/min), unless an assessment of the benefit/risk to the patient justifies the use of posaconazole injection. in patients with moderate or severe renal impairment (egfr <50 ml/min), receiving the posaconazole injection, accumulation of the intravenous vehicle, sbecd, is expected to occur. serum creatinine levels should be closely monitored in these patients, and, if increases occur, consideration should be given to changing to oral posaconazole therapy [see dosage and administration (2.9) and warnings and precautions (5.5)] . it is recommended that no dose adjustment of posaconazole injection is needed in patients with mild to severe hepatic impairment (child-pugh class a, b, or c) [see dosage and administration (2) and warnings and precautions (5.4)] . however, a specific study has not been conducted with posaconazole injection. the pharmacokinetics of posaconazole are comparable in males and females. no adjustment in the dosage of posaconazole is necessary based on gender. the pharmacokinetic profile of posaconazole is not significantly affected by race. no adjustment in the dosage of posaconazole is necessary based on race. pharmacokinetic modeling suggests that patients weighing greater than 120 kg may have lower posaconazole plasma drug exposure. it is, therefore, suggested to closely monitor for breakthrough fungal infections.

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

bryant ranch prepack - posaconazole (unii: 6tk1g07bhz) (posaconazole - unii:6tk1g07bhz) - posaconazole delayed-release tablets are indicated for the prophylaxis of invasive aspergillus and candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (hsct) recipients with graft-versus-host disease (gvhd) or those with hematologic malignancies with prolonged neutropenia from chemotherapy [see clinical studies ( 14.2 )] as follows: • posaconazole delayed-release tablets: adults and pediatric patients 13 years of age and older. additional pediatric use information is approved for merck sharp & dohme corp.’s noxafil ® (posaconazole delayed-release tablets). however, due to merck sharp & dohme corp.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. posaconazole is contraindicated in persons with known hypersensitivity to posaconazole or other azole antifungal agents. posaconazole is contraindicated with sirolimus. concomitant administration of posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity [see drug interactions ( 7.1 ) and clinical pharmacology ( 12.3 )] . posaconazole is contraindicated with cyp3a4 substrates that prolong the qt interval. concomitant administration of posaconazole with the cyp3a4 substrates, pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to qtc prolongation and cases of torsades de pointes [see warnings and precautions ( 5.2 ) and drug interactions ( 7.2 )]. coadministration with the hmg-coa reductase inhibitors that are primarily metabolized through cyp3a4 (e.g., atorvastatin, lovastatin, and simvastatin) is contraindicated since increased plasma concentration of these drugs can lead to rhabdomyolysis [see drug interactions ( 7.3 ) and clinical pharmacology ( 12.3 )] . posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [see drug interactions ( 7.4 )]. coadministration of posaconazole with venetoclax at initiation and during the ramp-up phase is contraindicated in patients with chronic lymphocytic leukemia (cll) or small lymphocytic lymphoma (sll) due to the potential for increased risk of tumor lysis syndrome [see warnings and precautions ( 5.10) and drug interactions ( 7.16)]. risk summary based on findings from animal data, posaconazole may cause fetal harm when administered to pregnant women. available data for use of posaconazole in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal reproduction studies, skeletal malformations (cranial malformations and missing ribs) and maternal toxicity (reduced food consumption and reduced body weight gain) were observed when posaconazole was dosed orally to pregnant rats during organogenesis at doses ≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of posaconazole in healthy volunteers. in pregnant rabbits dosed orally during organogenesis, increased resorptions, reduced litter size, and reduced body weight gain of females were seen at doses 5 times the exposure achieved with the 400 mg twice daily oral suspension regimen. doses of ≥3 times the clinical exposure caused an increase in resorptions in these rabbits (see data). based on animal 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 and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data posaconazole resulted in maternal toxicity (reduced food consumption and reduced body weight gain) and skeletal malformations (cranial malformations and missing ribs) when given orally to pregnant rats during organogenesis (gestational days 6 through 15) at doses ≥27 mg/kg (≥1.4 times the 400 mg twice daily oral suspension regimen based on steady-state plasma concentrations of drug in healthy volunteers). the no effect dose for malformations and maternal toxicity in rats was 9 mg/kg, which is 0.7 times the exposure achieved with the 400 mg twice daily oral suspension regimen. no malformations were seen in rabbits dosed during organogenesis (gestational days 7 through 19) at doses up to 80 mg/kg (5 times the exposure achieved with the 400 mg twice daily oral suspension regimen). in the rabbit, the no-effect dose was 20 mg/kg, while high doses of 40 mg/kg and 80 mg/kg (3 or 5 times the clinical exposure) caused an increase in resorptions. in rabbits dosed at 80 mg/kg, a reduction in body weight gain of females and a reduction in litter size were seen. risk summary there are no data on the presence of posaconazole in human milk, the effects on the breastfed infant, or the effects on milk production. posaconazole is excreted in the milk of lactating rats. when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for posaconazole and any potential adverse effects on the breastfed child from posaconazole or from the underlying maternal condition. the safety and effectiveness of posaconazole delayed-release tablets for the prophylaxis of invasive aspergillus and candida infections have been established in pediatric patients aged 13 years and older who are at high risk of developing these infections due to being severely immunocompromised, such as hsct recipients with gvhd or those with hematologic malignancies with prolonged neutropenia from chemotherapy. use of posaconazole in these age groups is supported by evidence from adequate and well-controlled studies of posaconazole in adult and pediatric patients and additional pharmacokinetic and safety data in pediatric patients 13 years of age and older [see adverse reactions ( 6.1 ), clinical pharmacology ( 12.3 ) and clinical studies ( 14 )]. the safety and effectiveness of posaconazole have not been established in pediatric patients younger than 2 years of age. additional pediatric use information is approved for merck sharp & dohme corp.’s noxafil ® (posaconazole delayed-release tablets). however, due to merck sharp & dohme corp.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.  no overall differences in the safety of posaconazole delayed-release tablets were observed between geriatric patients and younger adult patients in the clinical trials; therefore, no dosage adjustment is recommended for any formulation of posaconazole in geriatric patients. no clinically meaningful differences in the pharmacokinetics of posaconazole were observed in geriatric patients compared to younger adult patients during clinical trials [see clinical pharmacology ( 12.3 )]. of the 230 patients treated with posaconazole delayed-release tablets, 38 (17%) were greater than 65 years of age.  no overall differences in the pharmacokinetics and safety were observed between elderly and young subjects during clinical trials, but greater sensitivity of some older individuals cannot be ruled out. following single-dose administration of 400 mg of the noxafil ® oral suspension, there was no significant effect of mild (egfr: 50-80 ml/min/1.73 m 2 , n=6) or moderate (egfr: 20-49 ml/min/1.73 m 2 , n=6) renal impairment on posaconazole pharmacokinetics; therefore, no dose adjustment is required in patients with mild to moderate renal impairment. in subjects with severe renal impairment (egfr: <20 ml/min/1.73 m 2 ), the mean plasma exposure (auc) was similar to that in patients with normal renal function (egfr: >80 ml/min/1.73 m 2 ); however, the range of the auc estimates was highly variable (cv=96%) in these subjects with severe renal impairment as compared to that in the other renal impairment groups (cv<40%). due to the variability in exposure, patients with severe renal impairment should be monitored closely for breakthrough fungal infections [see dosage and administration ( 2 )] . similar recommendations apply to posaconazole delayed-release tablets; however, a specific study has not been conducted with the posaconazole delayed-release tablets. after a single oral dose of noxafil ® oral suspension 400 mg, the mean auc was 43%, 27%, and 21% higher in subjects with mild (child-pugh class a, n=6), moderate (child-pugh class b, n=6), or severe (child-pugh class c, n=6) hepatic impairment, respectively, compared to subjects with normal hepatic function (n=18). compared to subjects with normal hepatic function, the mean c max was 1% higher, 40% higher, and 34% lower in subjects with mild, moderate, or severe hepatic impairment, respectively. the mean apparent oral clearance (cl/f) was reduced by 18%, 36%, and 28% in subjects with mild, moderate, or severe hepatic impairment, respectively, compared to subjects with normal hepatic function. the elimination half-life (t ½ ) was 27 hours, 39 hours, 27 hours, and 43 hours in subjects with normal hepatic function and mild, moderate, or severe hepatic impairment, respectively.   it is recommended that no dose adjustment of posaconazole delayed-release tablets is needed in patients with mild to severe hepatic impairment (child-pugh class a, b, or c) [see dosage and administration ( 2 ) and warnings and precautions ( 5.4 )] . however, a specific study has not been conducted with posaconazole delayed-release tablets. the pharmacokinetics of posaconazole are comparable in males and females. no adjustment in the dosage of posaconazole is necessary based on gender. the pharmacokinetic profile of posaconazole is not significantly affected by race. no adjustment in the dosage of posaconazole is necessary based on race. pharmacokinetic modeling suggests that patients weighing greater than 120 kg may have lower posaconazole plasma drug exposure. it is, therefore, suggested to closely monitor for breakthrough fungal infections.