Egyesült Államok - angol - NLM (National Library of Medicine)

wyeth pharmaceuticals llc, a subsidiary of pfizer inc. - sirolimus (unii: w36zg6ft64) (sirolimus - unii:w36zg6ft64) - sirolimus 1 mg in 1 ml - rapamune (sirolimus) is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. in patients at low-to moderate-immunologic risk , it is recommended that rapamune be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn 2 to 4 months after transplantation [see dosage and administration (2.2) ]. in patients at high-immunologic risk (defined as black recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high panel-reactive antibodies [pra; peak pra level >80%]), it is recommended that rapamune be used in combination with cyclosporine and corticosteroids for the first year following transplantation [see dosage and administration (2.3) , clinical studies (14.3) ]. cyclosporine withdrawal has not been studied in patients with banff grade 3 acute rejection or vascular rejection prior to cyclosporine withdrawal, those who are dialysis-dependent, those with serum creatinine >4.5 mg/dl, black patients, patients of multi-organ transplants, secondary transplants, or those with high levels of panel-reactive antibodies [see clinical studies (14.2) ]. in patients at high-immunologic risk , the safety and efficacy of rapamune used in combination with cyclosporine and corticosteroids has not been studied beyond one year; therefore after the first 12 months following transplantation, any adjustments to the immunosuppressive regimen should be considered on the basis of the clinical status of the patient [see clinical studies (14.3) ]. in pediatric patients , the safety and efficacy of rapamune have not been established in patients <13 years old, or in pediatric (<18 years) renal transplant patients considered at high-immunologic risk [see adverse reactions (6.5), clinical studies (14.6) ]. the safety and efficacy of de novo use of rapamune without cyclosporine have not been established in renal transplant patients [see warnings and precautions (5.12) ]. the safety and efficacy of conversion from calcineurin inhibitors to rapamune in maintenance renal transplant patients have not been established [see clinical studies (14.4) ]. rapamune (sirolimus) is indicated for the treatment of patients with lymphangioleiomyomatosis (lam). rapamune is contraindicated in patients with a hypersensitivity to rapamune [see warnings and precautions (5.4) ]. risk summary based on animal studies and the mechanism of action, rapamune can cause fetal harm when administered to a pregnant woman [see data, clinical pharmacology (12.1) ]. there are limited data on the use of sirolimus during pregnancy; however, these data are insufficient to inform a drug-associated risk of adverse developmental outcomes. in animal studies, sirolimus was embryo/fetotoxic in rats at sub-therapeutic doses [see data ]. advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 sirolimus crossed the placenta and was toxic to the conceptus. in rat embryo-fetal development studies, pregnant rats were administered sirolimus orally during the period of organogenesis (gestational day 6–15). sirolimus produced embryo-fetal lethality at 0.5 mg/kg (2.5-fold the clinical dose of 2 mg, on a body surface area basis) and reduced fetal weight at 1 mg/kg (5-fold the clinical dose of 2 mg). the no observed adverse effect level (noael) for fetal toxicity in rats was 0.1 mg/kg (0.5-fold the clinical dose of 2 mg). maternal toxicity (weight loss) was observed at 2 mg/kg (10-fold the clinical dose of 2 mg). the noael for maternal toxicity was 1 mg/kg. in combination with cyclosporine, rats had increased embryo-fetal mortality compared with sirolimus alone. in rabbit embryo-fetal development studies, pregnant rabbits were administered sirolimus orally during the period of organogenesis (gestational day 6–18). there were no effects on embryo-fetal development at doses up to 0.05 mg/kg (0.5-fold the clinical dose of 2 mg, on a body surface area basis); however, at doses of 0.05 mg/kg and above, the ability to sustain a successful pregnancy was impaired (i.e., embryo-fetal abortion or early resorption). maternal toxicity (decreased body weight) was observed at 0.05 mg/kg. the noael for maternal toxicity was 0.025 mg/kg (0.25-fold the clinical dose of 2 mg). in a pre- and post-natal development study in rats, pregnant females were dosed during gestation and lactation (gestational day 6 through lactation day 20). an increased incidence of dead pups, resulting in reduced live litter size, occurred at 0.5 mg/kg (2.5-fold the clinical dose of 2 mg/kg on a body surface area basis). at 0.1 mg/kg (0.5-fold the clinical dose of 2 mg), there were no adverse effects on offspring. sirolimus did not cause maternal toxicity or affect developmental parameters in the surviving offspring (morphological development, motor activity, learning, or fertility assessment) at 0.5 mg/kg, the highest dose tested. risk summary it is not known whether sirolimus is present in human milk. there are no data on its effects on the breastfed infant or milk production. the pharmacokinetic and safety profiles of sirolimus in infants are not known. sirolimus is present in the milk of lactating rats. there is potential for serious adverse effects from sirolimus in breastfed infants based on mechanism of action [see clinical pharmacology (12.1)]. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for rapamune and any potential adverse effects on the breastfed child from rapamune. contraception females should not be pregnant or become pregnant while receiving rapamune. advise females of reproductive potential that animal studies have been shown rapamune to be harmful to the developing fetus. females of reproductive potential are recommended to use highly effective contraceptive method. effective contraception must be initiated before rapamune therapy, during rapamune therapy, and for 12 weeks after rapamune therapy has been stopped [see warnings and precautions (5.15), use in specific populations (8.1) ]. infertility based on clinical findings and findings in animals, male and female fertility may be compromised by the treatment with rapamune [see adverse reactions (6.7), nonclinical toxicology (13.1) ]. ovarian cysts and menstrual disorders (including amenorrhea and menorrhagia) have been reported in females with the use of rapamune. azoospermia has been reported in males with the use of rapamune and has been reversible upon discontinuation of rapamune in most cases. renal transplant the safety and efficacy of rapamune in pediatric patients <13 years have not been established. the safety and efficacy of rapamune oral solution and rapamune tablets have been established for prophylaxis of organ rejection in renal transplantation in children ≥13 years judged to be at low- to moderate-immunologic risk. use of rapamune oral solution and rapamune tablets in this subpopulation of children ≥ 13 years is supported by evidence from adequate and well-controlled trials of rapamune oral solution in adults with additional pharmacokinetic data in pediatric renal transplantation patients [see clinical pharmacology (12.3) ]. safety and efficacy information from a controlled clinical trial in pediatric and adolescent (< 18 years of age) renal transplant patients judged to be at high-immunologic risk, defined as a history of one or more acute rejection episodes and/or the presence of chronic allograft nephropathy, do not support the chronic use of rapamune oral solution or tablets in combination with calcineurin inhibitors and corticosteroids, due to the higher incidence of lipid abnormalities and deterioration of renal function associated with these immunosuppressive regimens compared to calcineurin inhibitors, without increased benefit with respect to acute rejection, graft survival, or patient survival [see clinical studies (14.6) ]. lymphangioleiomyomatosis the safety and efficacy of rapamune in pediatric patients <18 years have not been established. clinical studies of rapamune oral solution or tablets did not include sufficient numbers of patients ≥65 years to determine whether they respond differently from younger patients. data pertaining to sirolimus trough concentrations suggest that dose adjustments based upon age in geriatric renal patients are not necessary. differences in responses between the elderly and younger patients have not been identified. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, or cardiac function, and of concomitant disease or other drug therapy. the maintenance dose of rapamune should be reduced in patients with hepatic impairment [see dosage and administration (2.7), clinical pharmacology (12.3) ]. dosage adjustment is not required in patients with renal impairment [see dosage and administration (2.8), clinical pharmacology (12.3) ]. rapamune / raap-a-mune/ (sirolimus) oral solution be sure that you read and understand the following instructions for the correct way to dilute and take rapamune oral solution. ask your pharmacist or doctor if you are not sure. important: each rapamune oral solution carton contains: you will also need: figure 1: opening the bottle 1. open the solution bottle. figure 2: inserting adapter 2. the first time you use a bottle of rapamune oral solution: figure 3: inserting syringe 3. use a new disposable amber oral syringe for each dose of rapamune oral solution. figure 4: withdrawing solution 4. withdraw the prescribed amount of rapamune oral solution: figure 5: capping syringe 5. if your doctor tells you to carry your medicine with you: figure 6: placing syringe in carrying case figure 7: emptying syringe into glass 6. taking a dose of rapamune oral solution: 7. always store the bottles of medication in the refrigerator. how should i store rapamune? keep rapamune and all medicines out of the reach of children. this instructions for use has been approved by the u.s. food and drug administration. lab-0579-6.0 revised: august 2022

Egyesült Államok - angol - NLM (National Library of Medicine)

remedyrepack inc. - sirolimus (unii: w36zg6ft64) (sirolimus - unii:w36zg6ft64) - sirolimus tablets are indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. in patients at low- to moderate-immunologic risk , it is recommended that sirolimus tablets be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn 2 to 4 months after transplantation [see dosage and administration ( 2.2) ].  in patients at high-immunologic risk  (defined as black recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high panel-reactive antibodies [pra; peak pra level > 80%]), it is recommended that sirolimus tablets be used in combination with cyclosporine and corticosteroids for the first year following transplantation [see dosage and administration ( 2.3 ), clinical studies ( 14.3) ]. cyclosporine withdrawal has not been studied in patients with banff grade 3 acute rejection or vascular rejection prior to cyclosporine withdrawal, those who are dialysis-dependent, those with serum creatinine >4.5 mg/dl, black patients, patients of multi-organ transplants, secondary transplants, or those with high levels of panel-reactive antibodies [see clinical studies (14.2) ].  in patients at high-immunologic risk, the safety and efficacy of sirolimus tablets used in combination with cyclosporine and corticosteroids has not been studied beyond one year; therefore after the first 12 months following transplantation, any adjustments to the immunosuppressive regimen should be considered on the basis of the clinical status of the patient [see clinical studies ( 14.3) ].  in pediatric patients ,  the safety and efficacy of sirolimus tablets have not been established in patients <13 years old, or in pediatric (<18 years) renal transplant patients considered at high- immunologic risk [see adverse reactions ( 6.5), clinical studies ( 14.6) ]. the safety and efficacy of de novo use of sirolimus tablets without cyclosporine have not been established in renal transplant patients [see  warnings and precautions ( 5.12) ]. the safety and efficacy of  conversion from calcineurin inhibitors to sirolimus tablets in maintenance renal transplant patients have not been established [see clinical studies ( 14.4) ]. sirolimus is indicated for the treatment of patients with lymphangioleiomyomatosis (lam). sirolimus is contraindicated in patients with a hypersensitivity to sirolimus [see warnings and precautions (5.4) ]. risk summary based on animal studies and the mechanism of action, sirolimus can cause fetal harm when administered to a pregnant woman [see data , clinical pharmacology ( 12.1) ]. there are limited data on the use of sirolimus during pregnancy; however, these data are insufficient to inform a drug-associated risk of adverse developmental outcomes. in animal studies, sirolimus was embryo/fetotoxic in rats at sub-therapeutic doses [ see data ]. advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 sirolimus crossed the placenta and was toxic to the conceptus. in rat embryo-fetal development studies, pregnant rats were administered sirolimus orally during the period of organogenesis (gestational day 6 to 15). sirolimus produced embryo-fetal lethality at 0.5 mg/kg (2.5-fold the clinical dose of 2 mg, on a body surface area basis) and reduced fetal weight at 1 mg/kg (5-fold the clinical dose of 2 mg). the no observed adverse effect level (noael) for fetal toxicity in rats was 0.1 mg/kg (0.5-fold the clinical dose of 2 mg). maternal toxicity (weight loss) was observed at 2 mg/kg (10-fold the clinical dose of 2 mg). the noael for maternal toxicity was 1 mg/kg. in combination with cyclosporine, rats had increased embryo-fetal mortality compared with sirolimus alone. in rabbit embryo-fetal development studies, pregnant rabbits were administered sirolimus orally during the period of organogenesis (gestational day 6 to 18). there were no effects on embryo-fetal development at doses up to 0.05 mg/kg (0.5-fold the clinical dose of 2 mg, on a body surface area basis); however, at doses of 0.05 mg/kg and above, the ability to sustain a successful pregnancy was impaired (i.e., embryo-fetal abortion or early resorption). maternal toxicity (decreased body weight) was observed at 0.05 mg/kg. the noael for maternal toxicity was 0.025 mg/kg (0.25-fold the clinical dose of 2 mg). in a pre- and post-natal development study in rats, pregnant females were dosed during gestation and lactation (gestational day 6 through lactation day 20). an increased incidence of dead pups, resulting in reduced live litter size, occurred at 0.5 mg/kg (2.5-fold the clinical dose of 2 mg/kg on a body surface area basis). at 0.1 mg/kg (0.5-fold the clinical dose of 2 mg), there were no adverse effects on offspring. sirolimus did not cause maternal toxicity or affect developmental parameters in the surviving offspring (morphological development, motor activity, learning, or fertility assessment) at 0.5 mg/kg, the highest dose tested. risk summary it is not known whether sirolimus is present in human milk. there are no data on its effects on the breastfed infant or milk production. the pharmacokinetic and safety profiles of sirolimus in infants are not known. sirolimus is present in the milk of lactating rats. there is potential for serious adverse effects from sirolimus in breastfed infants based on mechanism of action [see clinical pharmacology ( 12.1) ]. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for sirolimus and any potential adverse effects on the breastfed child from sirolimus. contraception females should not be pregnant or become pregnant while receiving sirolimus. advise females of reproductive potential that animal studies have been shown sirolimus to be harmful to the developing fetus. females of reproductive potential are recommended to use highly effective contraceptive method. effective contraception must be initiated before sirolimus therapy, during sirolimus therapy, and for 12 weeks after sirolimus therapy has been stopped [see warnings and precautions ( 5.15), use in specific populations ( 8.1) ]. infertility based on clinical findings and findings in animals, male and female fertility may be compromised by the treatment with sirolimus [ see adverse reactions ( 6.7), nonclinical toxicology ( 13.1) ]. ovarian cysts and menstrual disorders (including amenorrhea and menorrhagia) have been reported in females with the use of sirolimus. azoospermia has been reported in males with the use of sirolimus and has been reversible upon discontinuation of sirolimus in most cases. renal transplant the safety and efficacy of sirolimus in pediatric patients <13 years have not been established.   the safety and efficacy of sirolimus oral solution and sirolimus tablets have been established for prophylaxis of organ rejection in renal transplantation in children ≥13 years judged to be at low- to moderate-immunologic risk. use of sirolimus oral solution and sirolimus tablets in this subpopulation of children ≥13 years is supported by evidence from adequate and well-controlled trials of sirolimus oral solution in adults with additional pharmacokinetic data in pediatric renal transplantation patients [see clinical pharmacology (12.3) ].  safety and efficacy information from a controlled clinical trial in pediatric and adolescent (<18 years of age) renal transplant patients judged to be at high-immunologic risk, defined as a history of one or more acute rejection episodes and/or the presence of chronic allograft nephropathy, do not support the chronic use of sirolimus oral solution or tablets in combination with calcineurin inhibitors and corticosteroids, due to the higher incidence of lipid abnormalities and deterioration of renal function associated with these immunosuppressive regimens compared to calcineurin inhibitors, without increased benefit with respect to acute rejection, graft survival, or patient survival [see clinical studies (14.6) ]. lymphangioleiomyomatosis the safety and efficacy of sirolimus in pediatric patients <18 years have not been established. clinical studies of sirolimus oral solution or tablets did not include sufficient numbers of patients ≥65 years to determine whether they respond differently from younger patients. data pertaining to sirolimus trough concentrations suggest that dose adjustments based upon age in geriatric renal patients are not necessary. differences in responses between the elderly and younger patients have not been identified. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, or cardiac function, and of concomitant disease or other drug therapy. the maintenance dose of sirolimus should be reduced in patients with hepatic impairment [see dosage and administration (2.7), clinical pharmacology (12.3) ]. dosage adjustment is not required in patients with renal impairment [see dosage and administration (2.8),clinical pharmacology (12.3) ].

Egyesült Államok - angol - NLM (National Library of Medicine)

almaject, inc. - temsirolimus (unii: 624kn6gm2t) (temsirolimus - unii:624kn6gm2t) - temsirolimus injection is indicated for the treatment of advanced renal cell carcinoma. temsirolimus injection is contraindicated in patients with bilirubin >1.5xuln [see warnings and precautions (5.2)] . risk summary based on findings in animal studies and its mechanism of action, temsirolimus can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . although there are no data on the use of temsirolimus injection in pregnant women, there are limited data on the use of sirolimus, the active metabolite of temsirolimus, during pregnancy; however, these data are insufficient to inform a drug-associated risk of adverse developmental outcomes. in animal reproductive studies, oral daily administration of temsirolimus to pregnant rats and rabbits during organogenesis caused adverse embryo-fetal effects at approximately 0.04 and 0.12 times the auc in patients at the recommended dose, respectively (see data) . advise pregnant women of the potential hazard 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 2-4% and 15-20%, respectively. data animal data temsirolimus administered daily as an oral formulation throughout organogenesis caused adverse embryo-fetal effects in rats and rabbits at human sub-therapeutic exposures. embryo-fetal adverse effects in rats consisted of reduced fetal weight and reduced ossifications, and in rabbits included reduced fetal weight, omphalocele, bifurcated sternabrae, notched ribs, and incomplete ossifications. in rats, the adverse embryo-fetal effects were observed at the oral dose of 2.7 mg/m2 /day (approximately 0.04-fold the auc in patients with cancer at the human recommended dose). in rabbits, the adverse embryo-fetal effects were observed at the oral dose of ≥7.2 mg/m2 /day (approximately 0.12-fold the auc in patients with cancer at the recommended human dose). risk summary there is no information regarding the presence of temsirolimus or its metabolites in human milk, or their effects on the breastfed child or milk production. trace amounts of sirolimus, the active metabolite of temsirolimus, were present in milk from lactating rats administered sirolimus. because of the potential for serious adverse reactions in a breastfed child from temsirolimus injection, advise a lactating woman not to breastfeed during treatment with temsirolimus injection and for 3 weeks after the final dose. contraception females temsirolimus injection can cause fetal harm when administered to a pregnant woman [see use in specific population (8.1)] . advise females of reproductive potential to use effective contraception during treatment with temsirolimus injection and for 3 months after the last dose. males advise males with partners of reproductive potential to use effective contraception during treatment with temsirolimus injection and for 3 months after the last dose [see nonclinical toxicology (13.1)] . infertility based on the findings in animal fertility studies, male and female fertility may be compromised by the treatment with temsirolimus injection. it is not known if the effects on fertility in animal studies were reversible [see nonclinical toxicology (13.1)] . limited data are available on the use of temsirolimus in pediatric patients. the effectiveness of temsirolimus in pediatric patients with advanced recurrent/refractory solid tumors has not been established. temsirolimus injection was studied in 71 patients (59 patients ages 1 to 17 years and 12 patients ages 18 to 21 years) with relapsed/refractory solid tumors in a phase 1-2 safety and exploratory pharmacodynamic study. in phase 1, 19 pediatric patients with advanced recurrent/refractory solid tumors received temsirolimus injection at doses ranging from 10 mg/m2 to 150 mg/m2 as a 60-minute intravenous infusion once weekly in three-week cycles. in phase 2, 52 pediatric patients with recurrent/relapsed neuroblastoma, rhabdomyosarcoma, or high grade glioma received temsirolimus injection at a weekly dose of 75 mg/m2 . one of 19 patients with neuroblastoma achieved a partial response. there were no objective responses in pediatric patients with recurrent/relapsed rhabdomyosarcoma or high grade glioma. adverse reactions associated with temsirolimus injection were similar to those observed in adults. the most common adverse reactions (≥20%) in pediatric patients receiving the 75 mg/m2 dose included thrombocytopenia, infections, asthenia/fatigue, fever, pain, leukopenia, rash, anemia, hyperlipidemia, increased cough, stomatitis, anorexia, increased plasma levels of alanine aminotransferase and aspartate aminotransferase, hypercholesterolemia, hyperglycemia, abdominal pain, headache, arthralgia, upper respiratory infection, nausea and vomiting, neutropenia, hypokalemia, and hypophosphatemia. pharmacokinetics: in phase 1 of the above mentioned pediatric trial, the single-dose and multiple-dose total systemic exposure (auc) of temsirolimus and sirolimus were less than dose-proportional over the dose range of 10 to 150 mg/m2 . in the phase 2 portion, the multiple-dose (day 1, cycle 2) pharmacokinetics of temsirolimus injection 75 mg/m2 were characterized in an additional 35 patients ages 28 days to 21 years (median age of 8 years). the geometric mean body surface adjusted clearance of temsirolimus and sirolimus was 9.45 l/h/m2 and 9.26 l/h/m2 , respectively. the mean elimination half-life of temsirolimus and sirolimus was 31 hours and 44 hours, respectively. the exposure (aucss) to temsirolimus and sirolimus was approximately 6-fold and 2-fold higher, respectively than the exposure in adult patients receiving a 25 mg intravenous infusion. clinical studies of temsirolimus injection did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. based on the results of a phase 3 study, elderly patients may be more likely to experience certain adverse reactions including diarrhea, edema, and pneumonia [see warnings and precautions (5.16)] . no clinical studies were conducted with temsirolimus injection in patients with decreased renal function. less than 5% of total radioactivity was excreted in the urine following a 25 mg intravenous dose of [14 c]-labeled temsirolimus in healthy subjects. renal impairment is not expected to markedly influence drug exposure, and no dosage adjustment of temsirolimus injection is recommended in patients with renal impairment. temsirolimus injection has not been studied in patients undergoing hemodialysis. temsirolimus injection was evaluated in a dose escalation phase 1 study in 110 patients with normal or varying degrees of hepatic impairment as defined by ast and bilirubin levels and patients with liver transplant (table 3). patients with moderate and severe hepatic impairment had increased rates of adverse reactions and deaths, including deaths due to progressive disease, during the study (table 3). temsirolimus injection is contraindicated in patients with bilirubin >1.5xuln [see contraindications (4), and warnings and precautions (5.2)] . use caution when treating patients with mild hepatic impairment. if temsirolimus injection must be given in patients with mild hepatic impairment (bilirubin >1-1.5xuln or ast >uln but bilirubin ≤uln), reduce the dose of temsirolimus injection to 15 mg/week [see dosage and administration (2.4)] . because there is a need for dosage adjustment based upon hepatic function, assessment of ast and bilirubin levels is recommended before initiation of temsirolimus injection and periodically thereafter.

Egyesült Államok - angol - NLM (National Library of Medicine)

gland pharma limited - temsirolimus (unii: 624kn6gm2t) (temsirolimus - unii:624kn6gm2t) - temsirolimus injection is indicated for the treatment of advanced renal cell carcinoma. temsirolimus injection is contraindicated in patients with bilirubin >1.5×uln [see warnings and precautions (5.2) ]. risk summary based on findings in animal studies and its mechanism of action, temsirolimus can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)]. although there are no data on the use of temsirolimus injection in pregnant women, there are limited data on the use of sirolimus, the active metabolite of temsirolimus, during pregnancy; however, these data are insufficient to inform a drug-associated risk of adverse developmental outcomes. in animal reproductive studies, oral daily administration of temsirolimus to pregnant rats and rabbits during organogenesis caused adverse embryo-fetal effects at approximately 0.04 and 0.12 times the auc in patients at the recommended dose, respectively (see data). advise pregnant women of the potential hazard to a fetus. the est

Egyesült Államok - angol - NLM (National Library of Medicine)

vistapharm, llc - sirolimus (unii: w36zg6ft64) (sirolimus - unii:w36zg6ft64) - sirolimus oral solution is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. in patients at low-to moderate-immunologic risk , it is recommended that sirolimus oral solution be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn 2 to 4 months after transplantation [see dosage and administration (2.2) ]. in patients at high-immunologic risk (defined as black recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high panel-reactive antibodies [pra; peak pra level > 80%]), it is recommended that sirolimus oral solution be used in combination with cyclosporine and corticosteroids for the first year following transplantation [see dosage and administration (2.3), clinical studies (14.3) ]. cyclosporine withdrawal has not been studied in patients with banff grade 3 acute rejection or vascular rejection prior to cyclosporine withdrawal, those who are dialysis-dependent, those with serum creatinine > 4.5 mg/dl, black patients, patients of multi-organ transplants, secondary transplants, or those with high levels of panel-reactive antibodies [see clinical studies (14.2) ]. in patients at high-immunologic risk , the safety and efficacy of sirolimus oral solution used in combination with cyclosporine and corticosteroids has not been studied beyond one year; therefore after the first 12 months following transplantation, any adjustments to the immunosuppressive regimen should be considered on the basis of the clinical status of the patient [see clinical studies (14.3) ]. in pediatric patients , the safety and efficacy of sirolimus oral solution have not been established in patients < 13 years old, or in pediatric (< 18 years) renal transplant patients considered at high-immunologic risk [see adverse reactions (6.5), clinical studies (14.6) ]. the safety and efficacy of de novo use of sirolimus oral solution without cyclosporine have not been established in renal transplant patients [see warnings and precautions (5.12) ]. the safety and efficacy of conversion from calcineurin inhibitors to sirolimus oral solution  in maintenance renal transplantpatients have not been established [see clinical studies (14.4) ]. sirolimus oral solution is contraindicated in patients with a hypersensitivity to sirolimus [see warnings and precautions (5.4) ]. risk summary based on animal studies and the mechanism of action, sirolimus can cause fetal harm when administered to a pregnant woman [see data, clinical pharmacology (12.1) ]. there are limited data on the use of sirolimus during pregnancy; however, these data are insufficient to inform a drug-associated risk of adverse developmental outcomes. in animal studies, sirolimus was embryo/fetotoxic in rats at sub-therapeutic doses [see data ]. advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 sirolimus crossed the placenta and was toxic to the conceptus. in rat embryo-fetal development studies, pregnant rats were administered sirolimus orally during the period of organogenesis (gestational day 6-15). sirolimus produced embryo-fetal lethality at 0.5 mg/kg (2.5-fold the clinical dose of 2 mg, on a body surface area basis) and reduced fetal weight at 1 mg/kg (5-fold the clinical dose of 2 mg). the no observed adverse effect level (noael) for fetal toxicity in rats was 0.1 mg/kg (0.5-fold the clinical dose of 2 mg). maternal toxicity (weight loss) was observed at 2 mg/kg (10-fold the clinical dose of 2 mg). the noael for maternal toxicity was 1 mg/kg. in combination with cyclosporine, rats had increased embryo-fetal mortality compared with sirolimus alone. in rabbit embryo-fetal development studies, pregnant rabbits were administered sirolimus orally during the period of organogenesis (gestational day 6-18). there were no effects on embryo-fetal development at doses up to 0.05 mg/kg (0.5-fold the clinical dose of 2 mg, on a body surface area basis); however, at doses of 0.05 mg/kg and above, the ability to sustain a successful pregnancy was impaired (i.e., embryo-fetal abortion or early resorption). maternal toxicity (decreased body weight) was observed at 0.05 mg/kg. the noael for maternal toxicity was 0.025 mg/kg (0.25-fold the clinical dose of 2 mg). in a pre-and post-natal development study in rats, pregnant females were dosed during gestation and lactation (gestational day 6 through lactation day 20). an increased incidence of dead pups, resulting in reduced live litter size, occurred at 0.5 mg/kg (2.5-fold the clinical dose of 2 mg/kg on a body surface area basis). at 0.1 mg/kg (0.5-fold the clinical dose of 2 mg), there were no adverse effects on offspring. sirolimus did not cause maternal toxicity or affect developmental parameters in the surviving offspring (morphological development, motor activity, learning, or fertility assessment) at 0.5 mg/kg, the highest dose tested. risk summary it is not known whether sirolimus is present in human milk. there are no data on its effects on the breastfed infant or milk production. the pharmacokinetic and safety profiles of sirolimus in infants are not known. sirolimus is present in the milk of lactating rats. there is potential for serious adverse effects from sirolimus in breastfed infants based on mechanism of action [see clinical pharmacology (12.1) ]. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for sirolimus and any potential adverse effects on the breastfed child from sirolimus. contraception females should not be pregnant or become pregnant while receiving sirolimus. advise females of reproductive potential that animal studies have been shown sirolimus to be harmful to the developing fetus. females of reproductive potential are recommended to use highly effective contraceptive method. effective contraception must be initiated before sirolimus therapy, during sirolimus therapy, and for 12 weeks after sirolimus therapy has been stopped [see warnings and precautions (5.15), use in specific populations (8.1) ]. infertility based on clinical findings and findings in animals, male and female fertility may be compromised by the treatment with sirolimus [see adverse reactions (6.7), nonclinical toxicology (13.1) ]. ovarian cysts and menstrual disorders (including amenorrhea and menorrhagia) have been reported in females with the use of sirolimus. azoospermia has been reported in males with the use of sirolimus and has been reversible upon discontinuation of sirolimus in most cases. renal transplant the safety and efficacy of sirolimus in pediatric patients < 13 years have not been established. the safety and efficacy of sirolimus oral solution have been established for prophylaxis of organ rejection in renal transplantation in children ≥ 13 years judged to be at low- to moderate-immunologic risk. use of sirolimus oral solution in this subpopulation of children ≥ 13 years is supported by evidence from adequate and well-controlled trials of sirolimus oral solution in adults with additional pharmacokinetic data in pediatric renal transplantation patients [see clinical pharmacology (12.3) ]. safety and efficacy information from a controlled clinical trial in pediatric and adolescent (< 18 years of age) renal transplant patients judged to be at high-immunologic risk, defined as a history of one or more acute rejection episodes and/or the presence of chronic allograft nephropathy, do not support the chronic use of sirolimus oral solution in combination with calcineurin inhibitors and corticosteroids, due to the higher incidence of lipid abnormalities and deterioration of renal function associated with these immunosuppressive regimens compared to calcineurin inhibitors, without increased benefit with respect to acute rejection, graft survival, or patient survival [see clinical studies (14.6) ]. clinical studies of sirolimus oral solution did not include sufficient numbers of patients ≥ 65 years to determine whether they respond differently from younger patients. data pertaining to sirolimus trough concentrations suggest that dose adjustments based upon age in geriatric renal patients are not necessary. differences in responses between the elderly and younger patients have not been identified. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, or cardiac function, and of concomitant disease or other drug therapy. the maintenance dose of sirolimus should be reduced in patients with hepatic impairment [see dosage and administration (2.7), clinical pharmacology (12.3) ]. dosage adjustment is not required in patients with renal impairment [see dosage and administration (2.8), clinical pharmacology (12.3) ]. sirolimus (sir-oh-li-mus) oral solution be sure that you read and understand the following instructions for the correct way to dilute and take sirolimus oral solution. ask your pharmacist or doctor if you are not sure. important: - always keep the bottle in an upright position. - you may store sirolimus oral solution that is in a syringe at room temperature up to 77°f (25°c) or in the refrigerator at 36°f to 46°f (2°c to 8°c) for up to 24 hours. see “how should i store sirolimus oral solution?” at the end of these instructions for use. - sirolimus oral solution can develop a slight haze when it is refrigerated. if this happens, bring the sirolimus oral solution to room temperature and then gently shake the bottle until the haze goes away. - only use a glass or plastic cup to dilute sirolimus oral solution. - if you are a caregiver, do not let sirolimus oral solution come in contact with your skin or eyes. if you get the oral solution on your skin, wash the area well with soap and water. if you get the oral solution in your eyes, rinse with plain water. - if you spill sirolimus oral solution, dry the area with a dry paper towel and then wipe the area with a wet paper towel. throw away the paper towels in the trash and wash your hands well with soap and water. each sirolimus oral solution carton contains: a) a 2 oz. (60 ml fill) amber glass bottle of sirolimus (concentration of 1 mg/ml) b) 1 oral syringe adapter for fitting into the neck of the bottle c) enough disposable amber oral syringes and caps for daily dosing d) 1 carrying case you will also need: - glass or plastic cup - 6 oz. of water or orange juice only. 1. opening the solution bottle. - remove the safety cap by pushing down and turning counterclockwise (figure 1). 2. the first time you use a bottle of sirolimus oral solution: - insert the oral syringe adapter (plastic tube with stopper) tightly into the bottle until it is even with the top of the bottle (figure 2). - do not remove the oral syringe adapter from the bottle once inserted.  3. use a new disposable amber oral syringe for each dose of sirolimus oral solution. - fully push down (depress) on the plunger of the disposable amber oral syringe. - then, tightly insert the oral syringe into the opening in the adapter (figure 3). 4. withdraw the prescribed amount of sirolimus oral solution: - gently pull back the plunger of the syringe until the level of the oral solution is even with the marking on the syringe for your prescribed dose. - always keep the bottle in an upright position. - if bubbles form within the oral solution in the syringe, empty the syringe into the bottle and repeat step 4 (figure 4). - you may need to repeat step 4 more than once to draw up your prescribed dose. 5. if your doctor tells you to carry your medicine with you: - each dose of sirolimus oral solution should be placed in an oral syringe. place a cap securely on each syringe. the cap should snap into place (figure 5). figure 6: placing syringe in carrying case - place the capped syringe in the enclosed carrying case (figure 6). if you need more than 1 carrying case, talk with your doctor or pharmacist. - see `how should i store sirolimus oral solution? ' for storage instructions. figure 7: emptying syringe into glass 6. taking a dose of sirolimus oral solution: - choose a clean flat work surface. place a clean paper towel on the work surface. wash and dry your hands. - empty the syringe into a glass or plastic cup containing at least 2 ounces (1/4 cup, 60 ml) of water or orange juice, stir vigorously for 1 minute and drink right away (figure 7). - if more than 1 syringe is needed for your prescribed dose, empty the oral solution from each syringe into the same glass or plastic cup of water or orange juice. - refill the container with at least 4 ounces (1/2 cup, 120 ml) of water or orange juice, stir vigorously again and drink the rinse solution.do not mix sirolimus oral solution with apple juice, grapefruit juice, or other liquids. only glass or plastic cups should be used to mix sirolimus oral solution. - the syringe and cap should be used only one time and then thrown away. - throw away the paper towel and clean the work surface. wash your hands. 7. always store the bottles of medication in the refrigerator. how should i store sirolimus oral solution? - store bottles of sirolimus oral solution in the refrigerator at 36°f to 46°f (2°c to 8°c) - protect from light - store sirolimus oral solution that is in a syringe at room temperature up to 77°f (25°c) or in the refrigerator at 36°f to 46°f (2°c to 8°c) for up to 24 hours - if necessary, bottles of sirolimus oral solution can be stored at room temperature up to 77°f (25°c) for up to 15 days - when a bottle of sirolimus oral solution is opened, it should be used within 1 month - use any diluted sirolimus oral solution right away keep sirolimus oral solution and all medicines out of the reach of children. this instructions for use has been approved by the u.s. food and drug administration. manufactured by: novitium pharma llc 70 lake drive, east windsor new jersey 08520 distributed by: vistapharm, inc. largo, fl 33771 usa trademarks are the property of their respective owners. revised: april, 2022 lb4062-05

Egyesült Államok - angol - NLM (National Library of Medicine)

ascend laboratories, llc - sirolimus (unii: w36zg6ft64) (sirolimus - unii:w36zg6ft64) - sirolimus is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. in patients at low-to moderate-immunologic risk , it is recommended that sirolimus tablets be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn 2 to 4 months after transplantation [see dosage and administration (2.2)]. in patients at high-immunologic risk (defined as black recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high panel-reactive antibodies [pra; peak pra level > 80%]), it is recommended that sirolimus tablets be used in combination with cyclosporine and corticosteroids for the first year following transplantation [see dosage and administration (2.3), clinical studies (14.3)]. cyclosporine withdrawal has not been studied in patients with banff grade 3 acute rejection or vascular rejection prior to cyclosporine withdrawal, those who are dial

Egyesült Államok - angol - NLM (National Library of Medicine)

zydus lifesciences limited - sirolimus (unii: w36zg6ft64) (sirolimus - unii:w36zg6ft64) - sirolimus 0.5 mg - sirolimus tablets are indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. in patients at low- to moderate-immunologic risk, it is recommended that sirolimus tablets be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn 2 to 4 months after transplantation [see dosage and administration (2.2) ]. in patients at high-immunologic risk (defined as black recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high panel-reactive antibodies [pra; peak pra level > 80%]), it is recommended that sirolimus tablets be used in combination with cyclosporine and corticosteroids for the first year following transplantation [see dosage and administration (2.3), clinical studies (14.3) ]. cyclosporine withdrawal has not been studied in patients with banff grade 3 acute rejection or vascular rejection prior to cyclosporine withdrawal, those who are

Szlovénia - szlovén - JAZMP (Javna agencija RS za zdravila in medicinske pripomočke)

temsirolimus - koncentrat in vehikel za raztopino za infundiranje - temsirolimus 30 mg / 1 viala - temsirolimus

Egyesült Államok - angol - NLM (National Library of Medicine)

apotex corp - sirolimus (unii: w36zg6ft64) (sirolimus - unii:w36zg6ft64) - sirolimus oral solution is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. in patients at low-to moderate-immunologic risk , it is recommended that sirolimus oral solution be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn 2 to 4 months after transplantation [see dosage and administration (2.2) ]. in patients at high-immunologic risk (defined as black recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high panel-reactive antibodies [pra; peak pra level > 80%]), it is recommended that sirolimus oral solution be used in combination with cyclosporine and corticosteroids for the first year following transplantation [see dosage and administration (2.3) , clinical studies (14.3) ]. cyclosporine withdrawal has not been studied in patients with banff grade 3 acute rejection or vascular rejection prior to cyclosporine withdraw

Egyesült Államok - angol - NLM (National Library of Medicine)

major pharmaceuticals - sirolimus (unii: w36zg6ft64) (sirolimus - unii:w36zg6ft64) - sirolimus tablets are indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. in patients at low-to moderate-immunologic risk , it is recommended that sirolimus tablets be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn 2 to 4 months after transplantation [see dosage and administration (2.2) ]. in patients at high-immunologic risk (defined as black recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high panel-reactive antibodies [pra; peak pra level > 80%]), it is recommended that sirolimus tablets be used in combination with cyclosporine and corticosteroids for the first year following transplantation [see dosage and administration (2.3), clinical studies (14.3) ]. cyclosporine withdrawal has not been studied in patients with banff grade 3 acute rejection or vascular rejection prior to cyclosporine withdrawal, those who are d