EVEROLIMUS tablet

البلد: الولايات المتحدة

اللغة: الإنجليزية

المصدر: NLM (National Library of Medicine)

العنصر النشط:

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

متاح من:

Hikma Pharmaceuticals USA Inc.

طريقة التعاطي:

ORAL

نوع الوصفة الطبية :

PRESCRIPTION DRUG

الخصائص العلاجية:

Everolimus is indicated for the treatment of adult patients with advanced RCC after failure of treatment with sunitinib or sorafenib. Everolimus is indicated for the treatment of adult patients with renal angiomyolipoma and TSC, not requiring immediate surgery. Everolimus is contraindicated in patients with clinically significant hypersensitivity to everolimus or to other rapamycin derivatives [see Warnings and Precautions (5.3)] . Risk Summary Based on animal studies and the mechanism of action [see Clinical Pharmacology (12.1)] , Everolimus can cause fetal harm when administered to a pregnant woman. There are limited case reports of Everolimus use in pregnant women; however, these reports are not sufficient to inform about risks of birth defects or miscarriage. In animal studies, everolimus caused embryo-fetal toxicities in rats when administered during the period of organogenesis at maternal exposures that were lower than human exposures at the recommended dose of Everolimus 10 mg orally once daily [see Data]. Advise pregnant women of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage is 2% to 4% and 15% to 20% of clinically recognized pregnancies, respectively. Data Animal Data: In animal reproductive studies, oral administration of everolimus to female rats before mating and through organogenesis induced embryo-fetal toxicities, including increased resorption, pre-implantation and post-implantation loss, decreased numbers of live fetuses, malformation (e.g., sternal cleft), and retarded skeletal development. These effects occurred in the absence of maternal toxicities. Embryo-fetal toxicities in rats occurred at doses ≥0.1 mg/kg (0.6 mg/m2 ) with resulting exposures of approximately 4% of the human exposure at the recommended dose of Everolimus 10 mg orally once daily based on area under the curve (AUC). In rabbits, embryo-toxicity evident as an increase in resorptions occurred at an oral dose of 0.8 mg/kg (9.6 mg/m2 ). The effect in rabbits occurred in the presence of maternal toxicities. In a pre- and post-natal development study in rats, animals were dosed from implantation through lactation. At the 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 from the control) and in survival of offspring (~5% died or missing). There were no drug-related effects on the developmental parameters (morphological development, motor activity, learning, or fertility assessment) in the offspring. Risk Summary There are no data on the presence of everolimus or its metabolites in human milk, the effects of everolimus on the breastfed infant or on milk production. Everolimus and its metabolites passed into the milk of lactating rats at a concentration 3.5 times higher than in maternal serum. Because of the potential for serious adverse reactions in breastfed infants from everolimus, advise women not to breastfeed during treatment with Everolimus and for 2 weeks after the last dose. Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to starting Everolimus [see Use in Specific Populations (8.1)] . Contraception Everolimus can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)] . Females: Advise female patients of reproductive potential to use effective contraception during treatment with Everolimus and for 8 weeks after the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Everolimus and for 4 weeks after the last dose. Infertility Females: Menstrual irregularities, secondary amenorrhea, and increases in luteinizing hormone (LH) and follicle stimulating hormone (FSH) occurred in female patients taking Everolimus. Based on these findings, Everolimus may impair fertility in female patients [see Adverse Reactions (6.1) and Nonclinical Toxicology (13.1)] . Males: Cases of reversible azoospermia have been reported in male patients taking Everolimus. In male rats, sperm motility, sperm count, plasma testosterone levels and fertility were diminished at AUC similar to those of the clinical dose of Everolimus 10 mg orally once daily. Based on these findings, Everolimus may impair fertility in male patients [see Nonclinical Toxicology (13.1)] . The safety and effectiveness of Everolimus in pediatric patients have not been established in: In RECORD-1, 41% of patients with renal cell carcinoma treated with Everolimus were ≥ 65 years of age, while 7% were ≥ 75 years of age. No overall differences in safety or effectiveness were observed between elderly and younger patients. Everolimus exposure may increase in patients with hepatic impairment [see Clinical Pharmacology (12.3)] . For patients with RCC and TSC-associated renal angiomyolipoma who have hepatic impairment, reduce the Everolimus dose as recommended [see Dosage and Administration (2.10)] .

ملخص المنتج:

Everolimus Tablets 2.5 mg tablets are supplied as a white to off white, uniform to lightly speckled, capsule-shaped, flat-face, beveled edge tablet with “54 [space] 391” debossed on one side and plain on the other side. NDC 0054-0480-13: Bottle of 30 Tablets NDC 0054-0480-22: Bottle of 90 Tablets NDC 0054-0480-14: Blister Pack of 28 Tablets 5 mg tablets are supplied as a white to off white, uniform to lightly speckled, capsule-shaped, flat-face, beveled edge tablet with “54 [space] 451” debossed on one side and plain on the other side. NDC 0054-0481-13: Bottle of 30 Tablets NDC 0054-0481-22: Bottle of 90 Tablets NDC 0054-0481-14: Blister Pack of 28 Tablets 7.5 mg tablets are supplied as a white to off white, uniform to lightly speckled, capsule-shaped, flat-face, beveled edge tablet with “54 [space] 627” debossed on one side and plain on the other side. NDC 0054-0497-13: Bottle of 30 Tablets NDC 0054-0497-22: Bottle of 90 Tablets NDC 0054-0497-14: Blister Pack of 28 Tablets 10 mg tablets are supplied as a white to off white, uniform to lightly speckled, capsule-shaped, flat-face, beveled edge tablet with “54 [space] 701” debossed on one side and plain on the other side. NDC 0054-0482-13: Bottle of 30 Tablets NDC 0054-0482-22: Bottle of 90 Tablets NDC 0054-0482-14: Blister Pack of 28 Tablets Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature]. Store in the original container; protect from light and moisture. Follow special handling and disposal procedures for anticancer pharmaceuticals.1

الوضع إذن:

Abbreviated New Drug Application

خصائص المنتج

EVEROLIMUS- EVEROLIMUS TABLET
HIKMA PHARMACEUTICALS USA INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
EVEROLIMUS TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
EVEROLIMUS TABLETS.
EVEROLIMUS TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2009
INDICATIONS AND USAGE
Everolimus is a kinase inhibitor indicated for the treatment of:
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DOSAGE AND ADMINISTRATION
Modify the dose for patients with hepatic impairment or for patients
taking drugs that inhibit or induce P-
glycoprotein (P-gp) and CYP3A4. (2.1)
RCC:
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TSC-Associated Renal Angiomyolipoma:
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DOSAGE FORMS AND STRENGTHS
Everolimus Tablets: 2.5 mg, 5 mg, 7.5 mg, and 10 mg tablets. (3)
CONTRAINDICATIONS
Clinically significant hypersensitivity to everolimus or to other
rapamycin derivatives. (4)
WARNINGS AND PRECAUTIONS
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Adults with advanced renal cell carcinoma (RCC) after failure of
treatment with sunitinib or sorafenib.
(1.3)
Adults with renal angiomyolipoma and tuberous sclerosis complex (TSC),
not requiring immediate
surgery. (1.4)
10 mg orally once daily (2.4)
10 mg orally once daily. (2.5)
Non-infectious Pneumonitis: Monitor for clinical symptoms or
radiological changes. Withhold or
permanently discontinue based on severity. (2.9, 5.1)
Infections: Monitor for signs and symptoms of infection. Withhold or
permanently discontinue based
on severity. (2.9, 5.2)
Severe Hypersensitivity Reactions: Permanently discontinue for
clinically significant hypersensitivity.
(5.3)
Angioedema: Patients taking concomitant angiotensin-converting-enzyme
(ACE) inhibitors may be at
increased risk for angioedema. Permanently discontinue for angioedema.
(5.4, 7.2)
Stomatitis: Initiate dexamethasone alcohol-free mouthwash when
starting treatment. (5.5, 6.1)
Renal Failure: Monitor renal function prior to treatment and
periodically thereafter. (5.6)
Risk of Impaired Wound Healing: Withhold for at least 1 week prior to
elective surgery. Do