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

pfizer australia pty ltd - sirolimus, quantity: 1 mg/ml - oral liquid, solution - excipient ingredients: polysorbate 80; propylene glycol; ethanol; ascorbyl palmitate; phosphatidyl choline; mono- and di- glycerides; soy fatty acids - indications as at 9 february 2004: rapamune is indicated for the prophylaxis of organ rejection in patients at mild to moderate immunological risk receiving renal transplants. therapeutic drug monitoring of sirolimus is required.

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

pfizer ltd - sirolimus - oral solution - 1mg/1ml

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

novartis pharmaceuticals uk ltd - ciclosporin - oral solution - 100mg/1ml

Israel - English - Ministry of Health

pfizer pharmaceuticals israel ltd - sirolimus - solution (oral) - sirolimus 1 mg/ml - sirolimus - sirolimus - rapamune is indicated for the prophylaxis of organ rejection in adult patients at low to moderate immunological risk receiving a renal transplant. it is recommended that rapamune be used initially in combination with cyclosporine microemulsion and corticosteroids for 2 to 3 months. rapamune may be continued as maintenance therapy with corticosteroids only if cyclosporine can be progressively discontinued.

Israel - English - Ministry of Health

pfizer pharmaceuticals israel ltd - sirolimus - solution (oral) - sirolimus 1 mg/ml - sirolimus - sirolimus - rapamune is indicated for the prophylaxis of organ rejection in adult patients at low to moderate immunological risk receiving a renal transplant. it is recommended that rapamune be used initially in combination with cyclosporine microemulsion and corticosteroids for 2 to 3 months. rapamune may be continued as maintenance therapy with corticosteroids only if cyclosporine can be progressively discontinued.

Singapore - English - HSA (Health Sciences Authority)

pfizer private limited - sirolimus - solution - 1 mg/ml - sirolimus 1 mg/ml

Israel - English - Ministry of Health

pfizer pharmaceuticals israel ltd - sirolimus - solution (oral) - sirolimus 1 mg/ml - sirolimus - rapamune is indicated for the prophylaxis of organ rejection in adult patients at low to moderate immunological risk receiving a renal transplant. it is recommended that rapamune be used initially in combination with cyclosporine microemulsion and corticosteroids for 2 to 3 months. rapamune may be continued as maintenance therapy with corticosteroids only if cyclosporine can be progressively discontinued.

Israel - English - Ministry of Health

novartis israel ltd - ciclosporin - solution - ciclosporin 100 mg/ml - cyclosporin - cyclosporin - prophylaxis of organ rejection in kidney liver heart allogenic transplants in conjunction with corticosteroids. may also be used in the treatment of chronic rejection in patients previously treated with other immuno-suppressive agents. bone marrow transplantation. endogenous uveitis. severe psoriasis above age 16 that did not respond to other treatment.atopic dermatitis in adults only up to 8 weeks for severe cases in which conventional therapy is ineffective or inappropriate. rheumatoid arthritis: severe cases in which standard treatments are ineffective or inappropriate. nephrotic syndrom type mcd (minimal change disease) in cases where conventional therapy has failed.

Malta - English - Medicines Authority

novartis ireland limited vista building, elm park, merrion road, ballsbridge, dublin 4,, ireland - ciclosporin - oral solution - ciclosporin 100 mg/ml - immunosuppressants

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

american health packaging - sirolimus (unii: w36zg6ft64) (sirolimus - unii:w36zg6ft64) - sirolimus 1 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 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)].