Everolimus 5 mg Tablet, 28-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Kinase Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Everolimus (Afinitor) is used to treat advanced renal cell carcinoma (RCC; cancer that begins in the kidneys) that has already been treated unsuccessfully with other medications. Everolimus (Afinitor) is also used to treat a certain type of advanced breast cancer that has already been treated with at least one other medication. Everolimus (Afinitor) is also used to treat a certain type of cancer of the pancreas, stomach, intestines, or lungs that has spread or progressed and that cannot be treated with surgery. Everolimus (Afinitor) is also used to treat kidney tumors in people with tuberous s...
Read the full MedlinePlus article ↗- Great question. Think of a pathway inside cells that acts like a gas pedal for growth — in cancer and tuberous sclerosis, that pedal gets stuck down and cells grow out of control....
- What exactly is everolimus treating — how does it actually fight cancer or help with TSC?
- Yes — but the key isn't which you choose, it's being consistent. Food — especially a high-fat meal — can significantly lower the peak blood concentration of everolimus. That's not...
- Does it matter if I take everolimus with food or on an empty stomach?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Everolimus — tap one for details:
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII 3SY5LH9PMK
Anhydrous lactose is a milk sugar with no water content. It acts as a filler and binder in tablets and capsules, adding bulk and helping ingredients stick together.
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UNII 1P9D0Z171K
BHT is a synthetic antioxidant that prevents fats and oils in medicines from breaking down and becoming rancid. It helps keep the product stable and effective during storage.
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UNII 2S7830E561
Crospovidone is a synthetic polymer derived from povidone. It acts as a disintegrant, helping the tablet or capsule break apart quickly in the stomach so the active ingredient can be absorbed.
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UNII 0VUT3PMY82
Hypromellose 2910 is a plant-derived thickening agent made from cellulose. In medicines, it forms protective coatings on tablets or capsules, controls how fast the drug releases, and thickens liquid formulations.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
6 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $14.771 | $413.58 / 28 tablet |
| Medicaid paysCMS SDUD · 12 mo | $74.85 | $2,095.78 / 28 tablet |
| Medicare drug plans payPart D · Q2 2026 | $260.10 | $7,282.72 / 28 tablet |
| Medicare Part B allowsASP · J7527 | $1.163 / J7527 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Everolimus 5 mg 00054-0481-13 | Hikma | 30 tablets | $14.771 | AB | Availability likely | — |
| Everolimus 5 mgthis 00093-7767-24 | Teva | 28 tablets | $14.771 | AB | Availability likely | — |
| Torpenz 5 mg 00245-0823-04 | Upsher-Smith | 28 tablets | $14.771 | AB | Availability likely | — |
| Everolimus 5 mg 49884-0125-91 | Par | 28 tablets | $14.771 | — | Discontinued | — |
| Everolimus 5 mg 51991-0822-28 | Breckenridge | 28 tablets | $14.771 | AB | Availability likely | — |
| Everolimus 5 mg 70377-0011-22 | Biocon | 28 tablets | $14.771 | AB | Availability likely | — |
| Everolimus 5 mg 72603-0255-01 | NorthStar | 30 tablets | $14.771 | AB | Availability likely | — |
| Yulithira 5 mg 82249-0611-30 | CivicaScript, | 30 tablets | $14.771 | AB | Availability likely | — |
| Afinitor 5 mg 00078-0566-51 | Novartis | 28 tablets | — | AB | FDA listed | — |
| Everolimus 5 mg 63850-0059-01 | Natco | 28 tablets | — | AB | FDA listed | — |
| everolimus 5 mg 82293-0031-10 | Novugen | 28 tablets | — | AB | FDA listed | — |
| Everolimus 5 mg 60219-2281-02 | Amneal | 7 tablets | — | AB | FDA listed | — |
| Everolimus 5 mg 51991-0992-28 | Breckenridge | 7 tablets | — | AB | FDA listed | — |
| Afinitor Disperz 5 mg 00078-0628-51 | Novartis | 1 tablet | — | AB | FDA listed | — |
| Everolimus 5 mg 70377-0092-11 | Biocon | 28 tablets | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00093-7767-24 You're viewing this | 28 BLISTER PACK in 1 CARTON (0093-7767-24) / 1 TABLET in 1 BLISTER PACK (0093-7767-19) | 2020-06-10 | Active |
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Everolimus tablets are a kinase inhibitor indicated for the treatment of: Postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane after failure of treatment with letrozole or anastrozole. ( 1.1 ) Adults with progressive neuroendocrine tumors of pancreatic origin (PNET) and adults with progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic.
Limitations of Use: Everolimus tablets are not indicated for the treatment of patients with functional carcinoid tumors. ( 1.2 ) 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 ) Everolimus tablets are a kinase inhibitor indicated for the treatment of adult and pediatric patients aged 1 year and older with TSC who have subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected. ( 1.5 )
1.1Hormone Receptor-Positive, HER2-Negative Breast Cancer Everolimus tablets are indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane, after failure of treatment with letrozole or anastrozole.
1.2Neuroendocrine Tumors (NET) Everolimus tablets are indicated for the treatment of adult patients with progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease. Everolimus tablets are indicated for the treatment of adult patients with progressive, well-differentiated, non-functional NET of gastrointestinal (GI) or lung origin with unresectable, locally advanced or metastatic disease. Limitations of Use: Everolimus tablets are not indicated for the treatment of patients with functional carcinoid tumors [see Clinical Studies ( 14.2 )] .
1.3Renal Cell Carcinoma (RCC) Everolimus tablets are indicated for the treatment of adult patients with advanced RCC after failure of treatment with sunitinib or sorafenib.
1.4Tuberous Sclerosis Complex (TSC)-Associated Renal Angiomyolipoma Everolimus tablets are indicated for the treatment of adult patients with renal angiomyolipoma and TSC, not requiring immediate surgery.
1.5Tuberous Sclerosis Complex (TSC)-Associated Subependymal Giant Cell Astrocytoma (SEGA) Everolimus tablets are indicated in adult and pediatric patients aged 1 year and older with TSC for the treatment of SEGA that requires therapeutic intervention but cannot be curatively resected.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Breast Cancer: 10 mg orally once daily. ( 2.2 ) NET: 10 mg orally once daily. ( 2.3 ) RCC: 10 mg orally once daily. ( 2.4 ) TSC-Associated Renal Angiomyolipoma: 10 mg orally once daily. ( 2.5 ) TSC-Associated SEGA: 4.5 mg/m 2 orally once daily; adjust dose to attain trough concentrations of 5 to 15 ng/mL. ( 2.6 , 2.8 )
2.2Recommended Dosage for Hormone Receptor-Positive, HER2-Negative Breast Cancer The recommended dosage of everolimus tablets is 10 mg orally once daily until disease progression or unacceptable toxicity.
2.3Recommended Dosage for Neuroendocrine Tumors (NET) The recommended dosage of everolimus tablets is 10 mg orally once daily until disease progression or unacceptable toxicity.
2.4Recommended Dosage for Renal Cell Carcinoma (RCC) The recommended dosage of everolimus tablets is 10 mg orally once daily until disease progression or unacceptable toxicity.
2.5Recommended Dosage for Tuberous Sclerosis Complex (TSC)-Associated Renal Angiomyolipoma The recommended dosage of everolimus tablets is 10 mg orally once daily until disease progression or unacceptable toxicity.
2.6Recommended Dosage for Tuberous Sclerosis Complex (TSC)-Associated Subependymal Giant Cell Astrocytoma (SEGA) The recommended starting dosage of everolimus tablets is 4.5 mg/m 2 orally once daily until disease progression or unacceptable toxicity [see Dosage and Administration ( 2.8 )] .
2.8Therapeutic Drug Monitoring (TDM) and Dose Titration for Tuberous Sclerosis Complex (TSC)-Associated Subependymal Giant Cell Astrocytoma (SEGA) Monitor everolimus whole blood trough concentrations at time points recommended in Table 1. Titrate the dose to attain trough concentrations of 5 ng/mL to 15 ng/mL. Adjust the dose using the following equation: New dose* = current dose x (target concentration divided by current concentration) *The maximum dose increment at any titration must not exceed 5 mg.
Multiple dose titrations may be required to attain the target trough concentration. When possible, use the same assay and laboratory for TDM throughout treatment. Table 1: Recommended Timing of Therapeutic Drug Monitoring Event When to Assess Trough Concentrations After Event Initiation of everolimus tablets 1 to 2 weeks Modification of everolimus tablets dose 1 to 2 weeks Initiation or discontinuation of moderate CYP3A inhibitor and P-gp inhibitor 2 weeks Initiation or discontinuation of cannabidiol oral solution 2 weeks Initiation or discontinuation of strong CYP3A inducer and P-gp inducer 2 weeks Change in hepatic function 2 weeks Stable dose with changing body surface area (BSA) Every 3 to 6 months Stable dose with stable BSA Every 6 to 12 months Abbreviation: P-gp, P-glycoprotein.
2.9Dosage Modifications for Adverse Reactions Table 2 summarizes recommendations for dosage modifications of everolimus tablets for the management of adverse reactions. Table 2: Recommended Dosage Modifications for Everolimus Tablets for Adverse Reactions Adverse Reaction Severity Dosage Modification Non-infectious pneumonitis [see Warnings and Precautions ( 5.1 )] Grade 2 Withhold until improvement to Grade 0 or 1. Resume at 50% of previous dose; change to every other day dosing if the reduced dose is lower than the lowest available strength.
Permanently discontinue if toxicity does not resolve or improve to Grade 1 within 4 weeks. Grade 3 Withhold until improvement to Grade 0 or 1. Resume at 50% of previous dose; change to every other day dosing if the reduced dose is lower than the lowest available strength.
If toxicity recurs at Grade 3, permanently discontinue. Grade 4 Permanently discontinue. Stomatitis [see Warnings and Precautions ( 5.5 )] Grade 2 Withhold until improvement to Grade 0 or 1.
Resume at same dose. If recurs at Grade 2, withhold until improvement to Grade 0 or 1. Resume at 50% of previous dose; change to every other day dosing if the reduced dose is lower than the lowest available strength.
Grade 3 Withhold until improvement to Gra…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS 2.5 mg tablet – White to slightly yellow, elongated tablets with a bevelled edge and no score, debossed with “TEVA” on one side and “7766” on the other side. 5 mg tablet – White to slightly yellow, elongated tablets with a bevelled edge and no score, debossed with “TEVA” on one side and “7767” on the other side. 7.5 mg tablet – White to slightly yellow, elongated tablets with a bevelled edge and no score, debossed with “TEVA” on one side and “7768” on the other side.
10 mg tablet – White to slightly yellow, elongated tablets with a bevelled edge and no score, debossed with “TEVA” on one side and “7769” on the other side. Everolimus tablets: 2.5 mg, 5 mg, 7.5 mg, and 10 mg tablets ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Everolimus is contraindicated in patients with clinically significant hypersensitivity to everolimus or to other rapamycin derivatives [see Warnings and Precautions ( 5.3 )] . Clinically significant hypersensitivity to everolimus or to other rapamycin derivatives. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS 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 not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of treatment after resolution of wound healing complications has not been established.
( 5.7 ) Geriatric Patients: Monitor and adjust dose for adverse reactions. ( 5.8 ) Metabolic Disorders: Monitor serum glucose and lipids prior to treatment and periodically thereafter. Withhold or permanently discontinue based on severity.
( 2.9 , 5.9 ) Myelosuppression: Monitor hematologic parameters prior to treatment and periodically thereafter. Withhold or permanently discontinue based on severity. ( 2.9 , 5.10 ) Risk of Infection or Reduced Immune Response with Vaccination: Avoid live vaccines and close contact with those who have received live vaccines.
Complete recommended childhood vaccinations prior to starting treatment. ( 5.11 ) Radiation Sensitization and Radiation Recall: Severe radiation reactions may occur. ( 5.12 , 6.2 ) Embryo-Fetal Toxicity: Can cause fetal harm.
Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.13 , 8.1 , 8.3 )
5.1Non-infectious Pneumonitis Non-infectious pneumonitis is a class effect of rapamycin derivatives. Non-infectious pneumonitis was reported in up to 19% of patients treated with everolimus in clinical trials, some cases were reported with pulmonary hypertension (including pulmonary arterial hypertension) as a secondary event. The incidence of Grade 3 and 4 non-infectious pneumonitis was up to 4% and up to 0.2%, respectively [see Adverse Reactions ( 6.1 )] .
Fatal outcomes have been observed. Consider a diagnosis of non-infectious pneumonitis in patients presenting with non-specific respiratory signs and symptoms. Consider opportunistic infections, such as pneumocystis jiroveci pneumonia (PJP) in the differential diagnosis.
Advise patients to report promptly any new or worsening respiratory symptoms. Continue everolimus without dose alteration in patients who develop radiological changes suggestive of non-infectious pneumonitis and have few or no symptoms. Imaging appears to overestimate the incidence of clinical pneumonitis.
For Grade 2 to 4 non-infectious pneumonitis, withhold or permanently discontinue everolimus based on severity [see Dosage and Administration ( 2.9 )] . Corticosteroids may be indicated until clinical symptoms resolve. Administer prophylaxis for PJP when concomitant use of corticosteroids or other immunosuppressive agents are required.
The development of pneumonitis has been reported even at a reduced dose.
5.2Infections Everolimus has immunosuppressive properties and may predispose patients to bacterial, fungal, viral, or protozoal infections, including infections with opportunistic pathogens [see Adverse Reactions ( 6.1 )] . Localized and systemic infections, including pneumonia, mycobacterial infections, other bacterial infections, invasive fungal infections (e.g., aspergillosis, candidiasis, or PJP), and viral infections (e.g., reactivation of hepatitis B virus) have occurred. Some of these infections have been severe (e.g., sep…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Non-Infectious Pneumonitis [see Warnings and Precautions ( 5.1 )] Infections [see Warnings and Precautions ( 5.2 )] Severe Hypersensitivity Reactions [see Warnings and Precautions ( 5.3 )] Angioedema with Concomitant Use of ACE inhibitors [see Warnings and Precautions ( 5.4 )] Stomatitis [see Warnings and Precautions ( 5.5 )] Renal Failure [see Warnings and Precautions ( 5.6 )] Impaired Wound Healing [see Warnings and Precautions ( 5.7 )] Metabolic Disorders [see Warnings and Precautions ( 5.9 )] Myelosuppression [see Warnings and Precautions ( 5.10 )] Radiation Sensitization and Radiation Recall [see Warnings and Precautions ( 5.12 )] Breast cancer, NET, RCC: Most common adverse reactions (incidence ≥30%) include stomatitis, infections, rash, fatigue, diarrhea, edema, abdominal pain, nausea, fever, asthenia, cough, headache, and decreased appetite.
( 6.1 ) TSC-Associated Renal Angiomyolipoma: Most common adverse reaction (incidence ≥30%) is stomatitis. ( 6.1 ) TSC-Associated SEGA: Most common adverse reactions (incidence ≥30%) are stomatitis and respiratory tract infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice. Hormone Receptor-Positive, HER2-Negative Breast Cancer The safety of everolimus (10 mg orally once daily) in combination with exemestane (25 mg orally once daily) (n=485) vs. placebo in combination with exemestane (n=239) was evaluated in a randomized, controlled trial (BOLERO-2) in patients with advanced or metastatic hormone receptor-positive, HER2-negative breast cancer.
The median age of patients was 61 years (28 to 93 years), and 75% were white. The median follow-up was approximately 13 months. The most common adverse reactions (incidence ≥30%) were stomatitis, infections, rash, fatigue, diarrhea, and decreased appetite.
The most common Grade 3 to 4 adverse reactions (incidence ≥2%) were stomatitis, infections, hyperglycemia, fatigue, dyspnea, pneumonitis, and diarrhea. The most common laboratory abnormalities (incidence ≥50%) were hypercholesterolemia, hyperglycemia, increased aspartate transaminase (AST), anemia, leukopenia, thrombocytopenia, lymphopenia, increased alanine transaminase (ALT), and hypertriglyceridemia. The most common Grade 3 to 4 laboratory abnormalities (incidence ≥3%) were lymphopenia, hyperglycemia, anemia, hypokalemia, increased AST, increased ALT, and thrombocytopenia.
Fatal adverse reactions occurred in 2% of patients who received everolimus. The rate of adverse reactions resulting in permanent discontinuation was 24% for the everolimus arm. Dose adjustments (interruptions or reductions) occurred in 63% of patients in the everolimus arm.
Adverse reactions reported with an incidence of ≥10% for patients receiving everolimus vs. placebo are presented in Table 7. Laboratory abnormalities are presented in Table 8. The median duration of treatment with everolimus was 23.9 weeks; 33% were exposed to everolimus for a period of ≥32 weeks.
Table 7: Adverse Reactions Reported in ≥10% of Patients with Hormone Receptor-Positive Breast Cancer in BOLERO-2 Everolimus with Exemestane N=482 Placebo with Exemestane N=238 All Grades % Grade 3 to 4 % All Grades % Grade 3 to 4 % Gastrointestinal Stomatitis a 67 8 d 11
0.8 Diarrhea 33 2 18
0.8Nausea 29 0.4 28 1 Vomiting 17 1 12
0.8Constipation 14 0.4 d 13
0.4Dry mouth 11 0 7 0 General Fatigue 36 4 27 1 d Edema peripheral 19 1 d 6 0.4 d Pyrexia 15 0.2 d 7 0.4 d Asthenia 13 2 4 0 Infections Infections b 50 6 25 2 d Investigations Weight loss 25 1 d 6 0 Metabolism and nutrition Decreased appetite 30 1 d 12 0.4 d Hyperglycemia…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Strong CYP3A inhibitor and P-gp inhibitor : Avoid coadministration. ( 2.11 , 7.1 ) Moderate CYP3A inhibitor and P-gp inhibitor : Reduce the dosage as recommended. ( 2.11 , 7.1 ) Cannabidiol oral solution : Reduce the dosage as recommended. ( 2.11 , 7.1 ) Strong CYP3A inducer and P-gp inducer : Increase the dosage as recommended. ( 2.11 , 7.1 )
7.1Effect of Other Drugs on Everolimus Strong or Moderate CYP3A Inhibitor and P-gp Inhibitor Avoid the coadministration of a strong CYP3A inhibitor and P-gp inhibitor [see Dosage and Administration ( 2.11 ), Clinical Pharmacology ( 12.3 )] . Reduce the dosage for everolimus with a moderate CYP3A inhibitor and P-gp inhibitor as recommended [see Dosage and Administration ( 2.11 ), Clinical Pharmacology ( 12.3 )] . Cannabidiol Oral Solution Reduce the dosage of everolimus when coadministered with cannabidiol oral solution [see Dosage and Administration ( 2.11 )] .
Coadministration with cannabidiol oral solution increases everolimus exposure [see Clinical Pharmacology ( 12.3 )] , which may increase the risk of everolimus adverse reactions. The effects of other cannabidiol products on everolimus exposure are unknown. Strong CYP3A Inducer and P-gp Inducer Increase the dosage for everolimus with a strong CYP3A inducer and P-gp inducer as recommended [see Dosage and Administration ( 2.11 ), Clinical Pharmacology ( 12.3 )] .
7.2Effects of Combination Use of Angiotensin Converting Enzyme (ACE) Inhibitors Patients taking concomitant ACE inhibitors with everolimus may be at increased risk for angioedema. Avoid the concomitant use of ACE inhibitors with everolimus [see Warnings and Precautions ( 5.4 )] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS For breast cancer, NET, RCC, or TSC-associated renal angiomyolipoma patients with hepatic impairment , reduce the dose. ( 2.10 , 8.6 ) For patients with TSC-associated SEGA and severe hepatic impairment , reduce the starting dose and adjust dose to attain target trough concentrations. ( 2.8 , 2.10 , 8.6 )
8.1Pregnancy 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/m 2 ) 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/m 2 ), approximately 1.6 times the recommended dose of everolimus 10 mg orally once daily or the median dose administered to patients with tuberous sclerosis complex (TSC)-associated subependymal giant cell astrocytoma (SEGA).
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/m 2 ), 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.
8.2Lactation 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.
8.3Females and Males of Reproductive Potential 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 irregularit…
🤰 Pregnancy ▾
8.1Pregnancy 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/m 2 ) 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/m 2 ), approximately 1.6 times the recommended dose of everolimus 10 mg orally once daily or the median dose administered to patients with tuberous sclerosis complex (TSC)-associated subependymal giant cell astrocytoma (SEGA).
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/m 2 ), 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.
🧒 Pediatric Use ▾
8.4Pediatric Use TSC-Associated SEGA The safety and effectiveness of everolimus have been established in pediatric patients age 1 year and older with TSC-associated SEGA that requires therapeutic intervention but cannot be curatively resected. Use of everolimus for this indication is supported by evidence from a randomized, double-blind, placebo-controlled trial in adult and pediatric patients (EXIST-1); an open-label, single-arm trial in adult and pediatric patients (Study 2485); and additional pharmacokinetic data in pediatric patients [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), Clinical Studies ( 14.5 )] .
The safety and effectiveness of everolimus have not been established in pediatric patients less than 1 year of age with TSC-associated SEGA. In EXIST-1, the incidence of infections and serious infections were reported at a higher frequency in patients <6 years of age. Ninety-six percent of 23 everolimus-treated patients <6 years had at least one infection compared to 67% of 55 everolimus-treated patients ≥6 years.
Thirty-five percent of 23 everolimus-treated patients <6 years of age had at least 1 serious infection compared to 7% of 55 everolimus-treated patients ≥6 years. Although a conclusive determination cannot be made due to the limited number of patients and lack of a comparator arm in the open label follow-up periods of EXIST-1 and Study 2485, everolimus did not appear to adversely impact growth and pubertal development in the 115 pediatric patients treated with everolimus for a median duration of 4.1 years. Other Indications The safety and effectiveness of everolimus in pediatric patients have not been established in: Hormone receptor-positive, HER2-negative breast cancer Neuroendocrine tumors (NET) Renal cell carcinoma (RCC) TSC-associated renal angiomyolipoma
🧓 Geriatric Use ▾
8.5Geriatric Use In BOLERO-2, 40% of patients with breast cancer treated with everolimus were ≥65 years of age, while 15% were ≥75 years of age. No overall differences in effectiveness were observed between elderly and younger patients. The incidence of deaths due to any cause within 28 days of the last everolimus dose was 6% in patients ≥65 years of age compared to 2% in patients <65 years of age.
Adverse reactions leading to permanent treatment discontinuation occurred in 33% of patients ≥65 years of age compared to 17% in patients <65 years of age. 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. In RADIANT-3, 30% of patients with PNET 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), a serine-threonine kinase, downstream of the PI3K/AKT pathway. The mTOR pathway is dysregulated in several human cancers and in tuberous sclerosis complex (TSC). Everolimus binds to an intracellular protein, FKBP-12, resulting in an inhibitory complex formation with mTOR complex 1 (mTORC1) and thus inhibition of mTOR kinase activity.
Everolimus reduced the activity of S6 ribosomal protein kinase (S6K1) and eukaryotic initiation factor 4E-binding protein (4E-BP1), downstream effectors of mTOR, involved in protein synthesis. S6K1 is a substrate of mTORC1 and phosphorylates the activation domain 1 of the estrogen receptor which results in ligand-independent activation of the receptor. In addition, everolimus inhibited the expression of hypoxia-inducible factor (e.g., HIF-1) and reduced the expression of vascular endothelial growth factor (VEGF).
Inhibition of mTOR by everolimus has been shown to reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and/or in vivo studies. Constitutive activation of the PI3K/Akt/mTOR pathway can contribute to endocrine resistance in breast cancer. In vitro studies show that estrogen-dependent and HER2+ breast cancer cells are sensitive to the inhibitory effects of everolimus, and that combination treatment with everolimus and Akt, HER2, or aromatase inhibitors enhances the anti-tumor activity of everolimus in a synergistic manner.
Two regulators of mTORC1 signaling are the oncogene suppressors tuberin-sclerosis complexes 1 and 2 ( TSC1 , TSC2 ). Loss or inactivation of either TSC1 or TSC2 leads to activation of downstream signaling. In TSC, a genetic disorder, inactivating mutations in either the TSC1 or the TSC2 gene lead to hamartoma formation throughout the body as well as seizures and epileptogenesis.
Overactivation of mTOR results in neuronal dysplasia, aberrant axonogenesis and dendrite formation, increased excitatory synaptic currents, reduced myelination, and disruption of the cortical laminar structure causing abnormalities in neuronal development and function. Treatment with an mTOR inhibitor in animal models of mTOR dysregulation in the brain resulted in seizure suppression, prevention of the development of new-onset seizures, and prevention of premature death.
12.2Pharmacodynamics Exposure-Response Relationship In patients with TSC-associated subependymal giant cell astrocytoma (SEGA), the magnitude of the reduction in SEGA volume was correlated with the everolimus trough concentration. Cardiac Electrophysiology In a randomized, placebo-controlled, cross-over study, 59 healthy subjects received a single oral dose of everolimus (20 mg and 50 mg) and placebo. Everolimus at single doses up to 50 mg did not prolong the QT/QTc interval.
12.3Pharmacokinetics Absorption After administration of everolimus in patients with advanced solid tumors, peak everolimus concentrations are reached 1 to 2 hours after administration of oral doses ranging from 5 mg to 70 mg. Following single doses, C max is dose-proportional with daily dosing between 5 mg and 10 mg. With single doses of 20 mg and higher, the increase in C max is less than dose-proportional; however, AUC shows dose-proportionality over the 5 mg to 70 mg dose range.
Steady-state was achieved within 2 weeks following once-daily dosing. In patients with TSC-associated SEGA, everolimus C min was approximately dose-proportional within the dose range from 1.35 mg/m 2 to 14.4 mg/m 2 . Effect of Food: In healthy subjects, a high-fat meal (containing approximately 1,000 calories and 55 grams of fat) reduced systemic exposure to everolimus 10 mg (as measured by AUC) by 22% and the peak blood concentration C max by 54%.
Light-fat meals (containing approximately 500 calories and 20 grams of fat) reduced AUC by 32% and C max by 42%. Distribution The blood-to-plasma ratio of everolimus, which is concentration-dependent…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), a serine-threonine kinase, downstream of the PI3K/AKT pathway. The mTOR pathway is dysregulated in several human cancers and in tuberous sclerosis complex (TSC). Everolimus binds to an intracellular protein, FKBP-12, resulting in an inhibitory complex formation with mTOR complex 1 (mTORC1) and thus inhibition of mTOR kinase activity.
Everolimus reduced the activity of S6 ribosomal protein kinase (S6K1) and eukaryotic initiation factor 4E-binding protein (4E-BP1), downstream effectors of mTOR, involved in protein synthesis. S6K1 is a substrate of mTORC1 and phosphorylates the activation domain 1 of the estrogen receptor which results in ligand-independent activation of the receptor. In addition, everolimus inhibited the expression of hypoxia-inducible factor (e.g., HIF-1) and reduced the expression of vascular endothelial growth factor (VEGF).
Inhibition of mTOR by everolimus has been shown to reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and/or in vivo studies. Constitutive activation of the PI3K/Akt/mTOR pathway can contribute to endocrine resistance in breast cancer. In vitro studies show that estrogen-dependent and HER2+ breast cancer cells are sensitive to the inhibitory effects of everolimus, and that combination treatment with everolimus and Akt, HER2, or aromatase inhibitors enhances the anti-tumor activity of everolimus in a synergistic manner.
Two regulators of mTORC1 signaling are the oncogene suppressors tuberin-sclerosis complexes 1 and 2 ( TSC1 , TSC2 ). Loss or inactivation of either TSC1 or TSC2 leads to activation of downstream signaling. In TSC, a genetic disorder, inactivating mutations in either the TSC1 or the TSC2 gene lead to hamartoma formation throughout the body as well as seizures and epileptogenesis.
Overactivation of mTOR results in neuronal dysplasia, aberrant axonogenesis and dendrite formation, increased excitatory synaptic currents, reduced myelination, and disruption of the cortical laminar structure causing abnormalities in neuronal development and function. Treatment with an mTOR inhibitor in animal models of mTOR dysregulation in the brain resulted in seizure suppression, prevention of the development of new-onset seizures, and prevention of premature death.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Everolimus Tablets 2.5 mg tablets White to slightly yellow, elongated tablets with a bevelled edge and no score debossed with “TEVA” on one side and “7766” on the other side; available in: NDC 0093-7766-24 – Carton containing 4 blister cards of 7 tablets each (28 tablets total). 5 mg tablets White to slightly yellow, elongated tablets with a bevelled edge and no score debossed with “TEVA” on one side and “7767” on the other side; available in: NDC 0093-7767-24 – Carton containing 4 blister cards of 7 tablets each (28 tablets total).
7.5mg tablets White to slightly yellow, elongated tablets with a bevelled edge and no score debossed with “TEVA” on one side and “7768” on the other side; available in: NDC 0093-7768-24 – Carton containing 4 blister cards of 7 tablets each (28 tablets total). 10 mg tablets White to slightly yellow, elongated tablets with a bevelled edge and no score debossed with “TEVA” on one side and “7769” on the other side; available in: NDC 0093-7769-24 – Carton containing 4 blister cards of 7 tablets each (28 tablets total). 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. Keep this and all drugs out of the reach of children. Follow special handling and disposal procedures for anti-cancer pharmaceuticals.
1
📋 Description ▾
11 DESCRIPTION Everolimus tablets are a kinase inhibitor. The chemical name of everolimus, USP is (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-dihydroxy-12-{(1R)-2-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]-1-methylethyl}-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-aza-tricyclo[30.3.1.0 4,9 ]hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentaone. The molecular formula is C 53 H 83 NO 14 and the molecular weight is 958.2.
The structural formula is: Everolimus tablets for oral administration contain 2.5 mg, 5 mg, 7.5 mg, or 10 mg of everolimus, USP and the following inactive ingredients: butylated hydroxytoluene, crospovidone, hypromellose 2910, lactose anhydrous, lactose monohydrate, and magnesium stearate. 1
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information ). Non-infectious Pneumonitis Advise patients of the risk of developing non-infectious pneumonitis and to immediately report any new or worsening respiratory symptoms to their healthcare provider [see Warnings and Precautions ( 5.1 )] . Infections Advise patients that they are more susceptible to infections and that they should immediately report any signs or symptoms of infections to their healthcare provider [see Warnings and Precautions ( 5.2 )] .
Hypersensitivity Reactions Advise patients of the risk of clinically significant hypersensitivity reactions and to promptly contact their healthcare provider or seek emergency care for signs of hypersensitivity reaction, including rash, itching, hives, difficulty breathing or swallowing, flushing, chest pain, or dizziness [see Contraindications (4), Warnings and Precautions ( 5.3 )] . Angioedema with Concomitant Use of ACE Inhibitors Advise patients to avoid ACE inhibitors and to promptly contact their healthcare provider or seek emergency care for signs or symptoms of angioedema [see Warnings and Precautions ( 5.4 )] .
Stomatitis Advise patients of the risk of stomatitis and to use alcohol-free mouthwashes during treatment [see Warnings and Precautions ( 5.5 )] . Renal Impairment Advise patients of the risk of developing kidney failure and the need to monitor their kidney function periodically during treatment [see Warnings and Precautions ( 5.6 )] . Risk of Impaired Wound Healing Advise patients that everolimus tablets may impair wound healing.
Advise patients to inform their healthcare provider of any planned surgical procedure [see Warnings and Precautions ( 5.7 )] . Geriatric Patients Inform patients that in a study conducted in patients with breast cancer, the incidence of deaths and adverse reactions leading to permanent discontinuation was higher in patients ≥65 years compared to patients <65 years [see Warnings and Precautions ( 5.8 ), Use in Specific Populations ( 8.5 )] . Metabolic Disorders Advise patients of the risk of metabolic disorders and the need to monitor glucose and lipids periodically during therapy [see Warnings and Precautions ( 5.9 )] .
Myelosuppression Advise patients of the risk of myelosuppression and the need to monitor CBCs periodically during therapy [see Warnings and Precautions ( 5.10 )] . Risk of Infection or Reduced Immune Response with Vaccination Advise patients to avoid the use of live vaccines and close contact with those who have received live vaccines [see Warnings and Precautions ( 5.11 )] . Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception during treatment and for 8 weeks after the last dose. Advise patients to inform their healthcare provider of a known or suspected pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 4 weeks after the last dose [see Warnings and Precautions ( 5.13 ), Use in Specific Populations ( 8.1 , 8.3 )] .
Radiation Sensitization and Radiation Recall Radiation sensitization and recall can occur in patients treated with radiation prior to, during, or subsequent to everolimus treatment. Advise patients to inform their healthcare provider if they have had or are planning to receive radiation therapy [see Warnings and Precautions ( 5.12 )] . Lactation Advise women not to breastfeed during treatment with everolimus and for 2 weeks after the last dose [see Use in Specific Populations ( 8.2 )] .
Infertility Advise males and females of reproductive potential of the potential risk for impaired fertility [see Use in Specific Populations ( 8.3 )] . Brands listed are the trademarks of their respective owners. Manufactured In Croatia By: Pliva Hrvatska d.o.o.
Zagreb, Croatia Manufactured For: Teva Pharmaceuticals Parsippan…