SIROLIMUS tablet

Land: USA

Språk: engelsk

Kilde: NLM (National Library of Medicine)

Aktiv ingrediens:

SIROLIMUS (UNII: W36ZG6FT64) (SIROLIMUS - UNII:W36ZG6FT64)

Tilgjengelig fra:

American Health Packaging

INN (International Name):

SIROLIMUS

Sammensetning:

SIROLIMUS 1 mg

Administreringsrute:

ORAL

Resept typen:

PRESCRIPTION DRUG

Indikasjoner:

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that sirolimus tablets be used initially in a regimen with cyclosporine and corticosteroids; cyclosporine should be withdrawn 2 to 4 months after transplantation [see Dosage and Administration (2.2) ].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)].

Produkt oppsummering:

Since sirolimus is not absorbed through the skin, there are no special precautions. Do not use sirolimus tablets after the expiration date. The expiration date refers to the last day of that month. Sirolimus Tablets are available as follows: Sirolimus tablets should be stored at 20° to 25°C [USP Controlled Room Temperature] (68° to 77°F). FOR YOUR PROTECTION: Do not use if blister is torn or broken.

Autorisasjon status:

Abbreviated New Drug Application

Informasjon til brukeren

American Health Packaging
----------
MEDICATION GUIDE
8291521/0423
Sirolimus (sir-OH-li-mus) Tablets
What is the most important information I should know about sirolimus?
Sirolimus can cause serious side effects, including:
1.
Increased risk of getting infections. Serious infections can happen
including infections caused by
viruses, bacteria, and fungi (yeast). Your doctor may put you on
medicine to help prevent some of
these infections.
Call your doctor right away if you have symptoms of infection
including fever or chills while
taking sirolimus tablets.
2.
Increased risk of getting certain cancers. People who take sirolimus
have a higher risk of getting
lymphoma, and other cancers, especially skin cancer. Talk with your
doctor about your risk for
cancer.
Sirolimus has not been shown to be safe and effective in people who
have had liver or lung transplants.
Serious complications and death may happen in people who take
sirolimus after a liver or lung transplant.
You should not take sirolimus if you have had a liver or lung
transplant without talking with your doctor.
See the section “What are the possible side effects of sirolimus?”
for information about other side effects
of sirolimus.
What is sirolimus?
Sirolimus is a prescription medicine used to prevent rejection
(anti-rejection medicine) in people 13 years
of age and older who have received a kidney transplant. Rejection is
when your body’s immune system
recognizes the new organ as a “foreign” threat and attacks it.
Sirolimus is used with other medicines called cyclosporine (Gengraf,
Neoral, Sandimmune), and
corticosteroids. Your doctor will decide:
•
if sirolimus is right for you, and
•
how to best use it with cyclosporine and corticosteroids after your
transplant.
It is not known if sirolimus is safe and effective in children under
13 years of age.
Sirolimus is a prescription medicine also used to treat
lymphangioleiomyomatosis (LAM). LAM is a rare
progressive lung disease that affects predominantly women of
childbearing age.
Who should not t

Preparatomtale

SIROLIMUS- SIROLIMUS TABLET
AMERICAN HEALTH PACKAGING
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
SIROLIMUS TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR SIROLIMUS
TABLETS.
SIROLIMUS TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1999
WARNING: IMMUNOSUPPRESSION, USE IS NOT RECOMMENDED IN LIVER OR LUNG
TRANSPLANT PATIENTS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
INCREASED SUSCEPTIBILITY TO INFECTION AND THE POSSIBLE DEVELOPMENT OF
LYMPHOMA AND
OTHER MALIGNANCIES MAY RESULT FROM IMMUNOSUPPRESSION (5.1). ONLY
PHYSICIANS
EXPERIENCED IN IMMUNOSUPPRESSIVE THERAPY AND MANAGEMENT OF RENAL
TRANSPLANT
PATIENTS SHOULD USE SIROLIMUS FOR PROPHYLAXIS OF ORGAN REJECTION IN
PATIENTS RECEIVING
RENAL TRANSPLANTS.
THE SAFETY AND EFFICACY OF SIROLIMUS AS IMMUNOSUPPRESSIVE THERAPY HAVE
NOT BEEN
ESTABLISHED IN LIVER OR LUNG TRANSPLANT PATIENTS, AND THEREFORE, SUCH
USE IS NOT
RECOMMENDED (5.2, 5.3).
LIVER TRANSPLANTATION – EXCESS MORTALITY, GRAFT LOSS, AND HEPATIC
ARTERY THROMBOSIS
(5.2).
LUNG TRANSPLANTATION – BRONCHIAL ANASTOMOTIC DEHISCENCE (5.3).
RECENT MAJOR CHANGES
Warnings and Precautions, Cannabidiol Drug Interactions
(5.21)                8/2022
INDICATIONS AND USAGE
Sirolimus is an mTOR inhibitor immunosuppressant indicated for the
prophylaxis of organ rejection in
patients aged ≥13 years receiving renal transplants:
Patients at low-to moderate-immunologic risk: Use initially with
cyclosporine (CsA) and corticosteroids.
CsA withdrawal is recommended 2 to 4 months after transplantation
(1.1).
Patients at high-immunologic risk: Use in combination with CsA and
corticosteroids for the first 12
months following transplantation (1.1). Safety and efficacy of CsA
withdrawal has not been established
in high risk patients (1.1, 1.2, 14.3).
Sirolimus is an mTOR inhibitor indicated for the treatment of patients
with lymphangioleiomyomatosis
(1.3).
DOSAGE AND ADMINISTRATION
Renal Transplant