ZORTRESS- everolimus tablet

Země: Spojené státy

Jazyk: angličtina

Zdroj: NLM (National Library of Medicine)

Aktivní složka:

EVEROLIMUS (UNII: 9HW64Q8G6G) (EVEROLIMUS - UNII:9HW64Q8G6G)

Dostupné s:

Novartis Pharmaceuticals Corporation

INN (Mezinárodní Name):

EVEROLIMUS

Složení:

EVEROLIMUS 0.25 mg

Podání:

ORAL

Druh předpisu:

PRESCRIPTION DRUG

Terapeutické indikace:

Zortress is indicated for the prophylaxis of organ rejection in adult patients at low to moderate immunologic risk receiving a kidney transplant [ see Clinical Studies   (14.1)] . Zortress is to be administered in combination with basiliximab induction and concurrently with reduced doses of cyclosporine and with corticosteroids. Therapeutic drug monitoring (TDM) of everolimus and cyclosporine is recommended for all patients receiving these products [ see Dosage and Administration (2.2 , 2.3)] . Zortress is indicated for the prophylaxis of allograft rejection in adult patients receiving a liver transplant. Zortress is to be administered no earlier than 30 days posttransplant concurrently in combination with reduced doses of tacrolimus and with corticosteroids [ s ee Warnings and Precautions (5. 5 ) , Clinical Studies (14.2) ] . TDM of everolimus and tacrolimus is recommended for all patients receiving these products [ s ee Dosage and Administration (2.3 , 2.5)] . The safety and efficacy of Zortress has not been established in the following populations: - Kidney transplant patients at high immunologic risk. - Recipients of transplanted organs other than kidney and liver [see Warnings and Precautions (5.7)] . - Pediatric patients (less than 18 years). Zortress is contraindicated in patients with known hypersensitivity to everolimus, sirolimus, or to components of the drug product.  Risk Summary Based on animal studies and the mechanism of action [see Clinical Pharmacology (12.1)] , Zortress can cause fetal harm when administered to a pregnant woman. There are limited case reports of Zortress use in pregnant women; however, these reports are insufficient to inform a drug-associated risk of adverse developmental outcomes. Reproductive studies in animals have demonstrated that everolimus was maternally toxic in rabbits and caused embryo-fetal toxicities in rats and rabbits, at exposures near or below those achieved in human transplant patients. Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data Everolimus crossed the placenta and was toxic to the conceptus. Everolimus administered daily to pregnant rats by oral gavage at 0.1 mg/kg (approximately one tenth the exposure in humans administered the lowest starting dose of 0.75 mg twice daily), from before mating through organogenesis, resulted in increased preimplantation loss and embryonic resorptions. These effects occurred in the absence of maternal toxicities. Everolimus administered daily by oral gavage to pregnant rabbits during organogenesis resulted in abortions, maternal toxicity and lethality, and increased fetal resorptions. At these doses, exposure to everolimus (AUC) was approximately one-tenth-, one-half-, and one- and one-half-fold the exposures in humans administered the starting clinical dose, respectively. In a pre- and post-natal development study in rats, animals were dosed from implantation through lactation. At a dose of 0.1 mg/kg (0.6 mg/m2 ), there were no adverse effects on delivery and lactation or signs of maternal toxicity; however, there were reductions in body weight (up to 9% reduction) and in survival of offspring (~5%). There were no drug-related effects on the developmental parameters (morphological development, motor activity, learning, or fertility assessment) in the offspring. Risk Summary There is no data regarding the presence of Zortress in human milk, the effects on breastfed infants, or the effects on milk production. Everolimus and/or its metabolites are readily transferred into milk of lactating rats at a concentration 3.5 times higher than in maternal rat serum. In pre-post-natal and juvenile studies in rats, exposure to everolimus during the postnatal period caused developmental toxicity [see Use in Specific Populations (8.1), Nonclinical Toxicology (13.2)] . Advise lactating women not to breastfeed because of the potential for serious adverse reactions in infants exposed to everolimus. Contraception Females should not be pregnant or become pregnant while receiving Zortress. Advise females of reproductive potential that animal studies have been performed showing Zortress to be harmful to the mother and developing fetus [see Use in Specific Populations (8.1)] . Females of reproductive potential are recommended to use highly effective contraception methods while receiving Zortress and up to 8 weeks after treatment has been stopped. Infertility Females Amenorrhea occurred in female patients taking Zortress [see Adverse Reactions (6.2)] . Zortress may cause pre-implantation loss in females based on animal data [see Nonclinical Toxicology (13.1)] . Female fertility may be compromised by treatment with Zortress. Males Zortress treatment may impair fertility in males based on human [see Warnings and Precautions (5.18), Adverse Reactions (6.2, 6.3)] and animal findings [see Nonclinical Toxicology (13.1)] . The safe and effective use of Zortress in kidney or liver transplant patients younger than 18 years of age has not been established. There is limited clinical experience on the use of Zortress in patients of age 65 years or older. There is no evidence to suggest that elderly patients will require a different dosage recommendation from younger adult patients [ s ee C linical Pharmacology   ( 12. 5 ) ] . Everolimus whole blood trough concentrations should be closely monitored in patients with impaired hepatic function. For patients with mild hepatic impairment (Child-Pugh Class A), the dose should be reduced by approximately one-third of the normally recommended daily dose. For patients with moderate or severe hepatic impairment (Child-Pugh Class B or C), the initial daily dose should be reduced to approximately half of the normally recommended daily dose. Further dose adjustment and/or dose titration should be made if a patient’s whole blood trough concentration of everolimus, as measured by an LC/MS/MS assay, is not within the target trough concentration range of 3 to 8 ng/mL [ s ee Clinical Pharmacology (12. 6 )] . No dose adjustment is needed in patients with renal impairment [ s ee Clinical Pharmacology (12. 6 ) ] .

Přehled produktů:

Zortress (everolimus) tablets are packed in child-resistant blisters. Each strength is available in boxes of 60 tablets (6 blister strips of 10 tablets each). Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Protect from light and moisture.

Stav Autorizace:

New Drug Application

Informace pro uživatele

Novartis Pharmaceuticals Corporation
----------
This Medication Guide has been approved by the U.S. Food and
Drug Administration.
Revised: February 2024
MEDICATION GUIDE
ZORTRESS [ZOR-tres]
(everolimus)
tablets, for oral use
What is the most important information I should know about ZORTRESS?
ZORTRESS can cause serious side effects, including:
•
Increased risk of getting certain cancers. People who take ZORTRESS
have a higher chance of
getting lymphoma and other cancers, especially skin cancer. Talk to
your doctor about your risk
for cancer.
•
Increased risk of serious infections. ZORTRESS weakens the body’s
immune system and affects
your ability to fight infections. Serious infections can happen with
ZORTRESS that may lead to
death. People taking ZORTRESS have a higher chance of getting
infections caused by viruses,
bacteria, and fungi (yeast).
•
Call your doctor if you have symptoms of infection, including fever or
chills.
•
Blood clot in the blood vessels of your transplanted kidney. If this
happens, it usually occurs
within the first 30 days after your kidney transplant. Tell your
doctor right away if you:
•
have pain in your groin, lower back, side or stomach (abdomen)
•
make less urine or you do not pass any urine
•
have blood in your urine or dark colored urine (tea-colored)
•
have fever, nausea, or vomiting
•
Serious problems with your transplanted kidney (nephrotoxicity). You
will need to start with a
lower dose of cyclosporine when you take it with ZORTRESS. Your doctor
should do regular
blood tests to check your levels of both ZORTRESS and cyclosporine.
•
Increased risk of death that can be related to infection, in people
who have had a heart transplant.
You should not take ZORTRESS without talking to your doctor if you
have had a heart
transplant.
See the section “What are the possible side effects of ZORTRESS?”
for information about other serious
side effects.
What is ZORTRESS?
ZORTRESS is a prescription medicine used to prevent transplant
rejection (antirejection medicine)

Charakteristika produktu

ZORTRESS- EVEROLIMUS TABLET
NOVARTIS PHARMACEUTICALS CORPORATION
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ZORTRESS SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR ZORTRESS.
ZORTRESS (EVEROLIMUS) TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2010
WARNING: MALIGNANCIES AND SERIOUS INFECTIONS;
KIDNEY GRAFT THROMBOSIS; NEPHROTOXICITY; AND
MORTALITY IN HEART TRANSPLANTATION
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
ONLY PHYSICIANS EXPERIENCED IN IMMUNOSUPPRESSIVE THERAPY AND
MANAGEMENT OF
TRANSPLANT PATIENTS SHOULD USE ZORTRESS (5.1)
INCREASED SUSCEPTIBILITY TO INFECTION AND THE POSSIBLE DEVELOPMENT OF
MALIGNANCIES
MAY RESULT FROM IMMUNOSUPPRESSION (5.2, 5.3)
INCREASED INCIDENCE OF KIDNEY GRAFT THROMBOSIS (5.4)
REDUCED DOSES OF CYCLOSPORINE ARE REQUIRED FOR USE IN COMBINATION WITH
ZORTRESS IN
ORDER TO REDUCE NEPHROTOXICITY (2.4, 2.5, 5.6, 12.7, 12.8)
INCREASED MORTALITY IN A HEART TRANSPLANT CLINICAL TRIAL. USE IN HEART
TRANSPLANTATION IS
NOT RECOMMENDED (5.7)
RECENT MAJOR CHANGES
Warnings and Precautions, Cannabidiol Drug Interactions (5.22)
9/2023
INDICATIONS AND USAGE
Zortress is an mTOR inhibitor immunosuppressant indicated for the
prophylaxis of organ rejection in adult
patients:
Kidney Transplant: at low-moderate immunologic risk. Use in
combination with basiliximab, cyclosporine
(reduced doses) and corticosteroids (1.1)
Liver Transplant: Administer no earlier than 30 days posttransplant.
Use in combination with tacrolimus
(reduced doses) and corticosteroids (1.2, 5.5)
Limitations of Use: Safety and efficacy have not been established in
the following:
Kidney transplant patients at high immunologic risk (1.3)
Recipients of transplanted organs other than kidney or liver (1.3,
5.7)
Pediatric patients (less than 18 years) (1.3)
DOSAGE AND ADMINISTRATION
Kidney Transplantation: starting oral dose of 0.75 mg twice daily as
soon as possible after
transplantation (2.1)
Liver Transplantation: starting oral dose of 1