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ZORTRESS(everolimus)Tablets

2015-11-20 06:01:13 来源: 作者: 【大中小】浏览:444次评论:0条

HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use Zortress (everolimus) safely and effectively. See full prescribing information for Zortress. Tablets for oral administration. Initial U.S. Approval: 2010
WARNING: IMMUNOSUPPRESSION AND RENAL FUNCTION SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING • Only physicians experienced in immunosuppressive therapy and management of transplant patients should use everolimus. (5.1) • Increased susceptibility to infection and the possible development of malignancies may result from immunosuppression. (5.2, 5.3) • Reduced doses of cyclosporine are required for use in combination with everolimus in order to reduce nephrotoxicity. (5.8) • Increased incidence of kidney graft thrombosis. (5.5)
INDICATIONS AND USAGE
• Prophylaxis of organ rejection in adult patients at low-moderate immunologic risk receiving a kidney transplant. • Use in combination with basiliximab and concurrently with reduced doses of cyclosporine and corticosteroids. (1.1) • Use in patients at high immunologic risk is not established. (1.2) • Use for prophylaxis in organs other than kidney is not established. (1.2) • Safety and efficacy in pediatric patients (<18 years) has not been established. (1.2)
DOSAGE AND ADMINISTRATION
• Starting oral dose of 0.75 mg twice daily. Adjust maintenance dose to achieve everolimus trough concentrations within the 3-8 ng/mL target range. (2.1) Administer as soon as possible after transplantation. • Routine everolimus and cyclosporine therapeutic drug concentration monitoring is recommended. (2.2, 2.3) • Administer consistently with or without food (12) at the same time as cyclosporine. (2.4) • Moderate hepatic impairment: Reduce daily dose by half and monitor blood concentrations. (2.5)
DOSAGE FORMS AND STRENGTHS
Zortress is available as 0.25 mg, 0.5 mg, and 0.75 mg tablets. (3)
CONTRAINDICATIONS
• Patients with known hypersensitivity to everolimus, sirolimus, or to components of the drug product. (4)
WARNINGS AND PRECAUTIONS
• Lymphoma and Other Malignancies: Increased risk with all immunosuppressants; appears related to intensity and duration of use. Avoid prolonged exposure to UV light and sunlight. (5.2) • Serious infections: Increased risk of bacterial, viral, fungal and protozoal infections, including opportunistic infections: combination immunosuppression should be used with caution. (5.3) • Angioedema: Increased risk with concomitant ACE inhibitors; monitor for symptoms and treat promptly. (5.4) • Wound Healing/Fluid Accumulation: Increased risk for delayed wound healing. Monitor symptoms; treat promptly to minimize complications. (5.6) • Hyperlipidemia: Elevations of serum cholesterol and triglycerides are common. Monitoring is recommended; consider intervention including anti-lipid therapy. (5.7) • Proteinuria: Increased risk with higher trough concentrations; monitor urine protein. (5.9) • Polyoma Virus Infections: Risk of activation of latent viral infections; BK- virus associated nephropathy has been observed; consider reducing immunosuppression. (5.10) • Interactions with Strong Inhibitors and Inducers of CYP3A4: closely monitor everolimus trough concentrations with concomitant use. (5.11) • Non-Infectious Pneumonitis: Monitor for clinical symptoms or radiologic changes; fatal cases have occurred. Manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids. (5.12) • TMA/TTP/HUS: Concomitant use with cyclosporine may increase risk. Monitor for hematological changes or clinical symptoms. (5.13) • New Onset Diabetes After Transplantation: Blood glucose elevations may occur in dose related manner. Monitor serum glucose. (5.14) • Male Infertility: Azospermia or oligospermia may occur. (5.15, 13.1) • Immunizations: Live vaccines should be avoided. (5.16)
ADVERSE REACTIONS
The most common (incidence ≥20%) adverse events are: peripheral edema, constipation, hypertension, nausea, anemia, UTI, and hyperlipidemia. (6.2) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
CYP3A4 inhibitors and inducers: Strong-moderate inhibitors (e.g., cyclosporine, ketoconazole, erythromycin, verapamil) and inducers (e.g., rifampin) may affect everolimus concentrations. Blood concentration monitoring is recommended; consider dose adjustment of everolimus. (7)
USE IN SPECIFIC POPULATIONS
• Pregnancy: Based on animal data may cause fetal harm. (8.1) • Nursing Mothers: Discontinue drug or nursing taking into consideration importance of drug to mother. (8.3)
See 17 for PATIENT COUNSELING INFORMATION and the FDA-approved Medication Guide
Revised: 04/2010