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Everolimus .5 mg Tablet, 60-count — NDC 72319-0015-02 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Everolimus .5 mg Tablet, 60-count — NDC 72319-015-02 (Billing 72319-0015-02)

by i3 Pharmaceuticals, LLC · 60 TABLET in 1 CONTAINER

This is a package of 60 tablets of Everolimus .5 mg Tablet from i3 Pharmaceuticals, LLC, marketed since Aug 2026 and currently FDA-listed. It is the main listing for this product, which comes in 2 package sizes.

NDC 72319-0015-02
🏷️ FDA NDC (as labeled) 72319-015-02 billing pads the product segment with a zero
This package
Contains60-count Pack sizes2 compare ↓
Main listing for product 72319-015 · Also comes in: 600 tablets 72319-015-60
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Sep 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 72319-015-02 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
72319 labeler · 015 product · 02 package
Package marketed since
Aug 7, 2026
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Barcode (UPC)
0372319015021, 0372319016103, 0372319017025, 0372319003608 +8 more
FDA record last changed
Sep 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 72319-015-02
Product NDC 72319-015
11-digit billing NDC 72319001502
RxCUI 977427, 977434, 977438, 2056895
UNII 9HW64Q8G6G
UPC 0372319015021, 0372319016103, 0372319017025, 0372319003608 +8 more
Application # ANDA219464
SPL Set ID be5da0fd-8fd4-4f84-a307-f270048d503c
Established class (EPC) Kinase Inhibitor; mTOR Inhibitor Immunosuppressant
Mechanism of action Protein Kinase Inhibitors; Cytochrome P450 3A4 Inhibitors; Cytochrome P450 2D6 Inhibitors; mTOR Inhibitors
Physiologic effect Decreased Immunologic Activity
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2026-08-07
Route ORAL
Dosage form TABLET
Substance EVEROLIMUS
TE code (Orange Book) AB · RLD · RS
Quick answers
  • RxCUI (RxNorm): 977427
Why two NDCs? The FDA registers this code as 72319-015-02 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 72319-0015-02. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Kinase Inhibitor class.

Pharmacologic class Kinase Inhibitor, mTOR Inhibitor Immunosuppressant
Drug family (ATC) Mammalian target of rapamycin (mTOR) kinase inhibitors, Mammalian target of rapamycin (mTOR) kinase inhibitors
How it works Protein Kinase Inhibitors, mTOR Inhibitors, Cytochrome P450 2D6 Inhibitors, Cytochrome P450 3A4 Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

📗 Our plain-language guide HelloPharmacist
  • It depends on the product. Afinitor, Yulithira and generic everolimus tablets treat certain cancers and tuberous sclerosis complex conditions. Zortress and generic transplant table...
  • Take it by mouth, the same way every time, either always with food or always without. The cancer and TSC products are usually once a day. The transplant products are usually twice...
  • Mouth sores are very common, along with infections, rash, tiredness, diarrhea, swelling and low appetite. Mention mouth sores early, since they can be managed. Call your doctor rig...
  • Check with me first. Many drugs change everolimus levels, including ketoconazole, clarithromycin, rifampin, St. John’s Wort and certain seizure medicines. Cannabidiol can raise lev...
📖 Read our full Everolimus guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

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 systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Try another pack size: 600 tablets
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
72319-0015-02 You're viewing this Main listing 60 TABLET in 1 CONTAINER 2026-08-07 — Active
72319-0015-60 72319-015-60 60 BLISTER PACK in 1 CARTON / 10 TABLET in 1 BLISTER PACK 2026-08-07 — Active

Pack size FAQ

What quantity is in this package?
This is a 60-count package — 60 tablet in 1 container.
How does this package differ from NDC 72319-0015-60?
Both are Everolimus .5 mg Tablet — the drug itself is identical. This page's package is the 60-count one, while NDC 72319-0015-60 is the 600 tablets package.
What NDC number is used to bill for this package of Everolimus .5 mg Tablet?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Everolimus .5 mg 70377-0070-11 Biocon 60 tablets $3.525 AB Availability likely —
Everolimus .5 mg 00054-0471-21 Hikma 60 tablets $3.525 AB Availability likely —
everolimus .5 mg 59651-0932-60 Aurobindo 60 tablets $3.525 AB Availability likely —
Everolimus .5 mg 49884-0159-02 Par 60 tablets $3.525 AB Availability likely —
Everolimus .5 mg 67877-0719-31 Ascend 60 tablets $3.525 AB Availability likely —
Zortress .5 mg 00078-0414-20 Novartis 60 tablets — AB FDA listed —
Everolimus .5 mg 63850-0063-02 Natco 60 tablets — AB FDA listed —
Everolimus .5 mgthis 72319-0015-02 i3 60 tablets — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2026
On the market since
Aug 2026
📍
2026
Currently FDA-listed
listed with the FDA
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

What it looks like

Color white
ShapeRound
Imprinti3;17
Size9 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • 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.
  • 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.
  • 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.
  • UNII 3NXW29V3WO
    Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
  • 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.

5 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — 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

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

Labeleri3 Pharmaceuticals, LLC
Application holderI3 PHARMACEUTICALS LLC
FDA applicationANDA219464 (ANDA)
Labeler code72319
First marketedAug 2026
Product typeHuman Prescription Drug
Portfolio19 products on file

More NDCs from i3 Pharmaceuticals, LLC labeler code 72319

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide 🧬 Pharmacokinetics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~2 min read ▾

WARNING: MALIGNANCIES and SERIOUS INFECTIONS; KIDNEY GRAFT THROMBOSIS; NEPHROTOXICITY; and MORTALITY IN HEART TRANSPLANTATION Malignancies and Serious Infections Only physicians experienced in immunosuppressive therapy and management of transplant patients should prescribe everolimus tablets. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient [see Warnings and Precautions (5.1)].

Increased susceptibility to infection and the possible development of malignancies, such as lymphoma and skin cancer, may result from immunosuppression [see Warnings and Precautions (5.2, 5.3)]. Kidney Graft Thrombosis An increased risk of kidney arterial and venous thrombosis, resulting in graft loss, was reported, mostly within the first 30 days posttransplantation [see Warnings and Precautions (5.4)]. Nephrotoxicity Increased nephrotoxicity can occur with use of standard doses of cyclosporine in combination with everolimus tablets.

Therefore, reduced doses of cyclosporine should be used in combination with everolimus tablets in order to reduce renal dysfunction. It is important to monitor the cyclosporine and everolimus whole blood trough concentrations [see Dosage and Administration (2.4, 2.5), Warnings and Precautions (5.6), Clinical Pharmacology (12.7, 12.8)]. Mortality in Heart Transplantation Increased mortality, often associated with serious infections, within the first three months posttransplantation was observed in a clinical trial of de novo heart transplant patients receiving immunosuppressive regimens with or without induction therapy.

Use in heart transplantation is not recommended [see Warnings and Precautions (5.7)]. 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 everolimus tablets ( 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 everolimus tablets 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 )

🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE Everolimus tablest 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 )

1.1Prophylaxis of Organ Rejection in Kidney Transplantation Everolimus tablets 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)]. Everolimus tablets 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)] .

1.2Prophylaxis of Organ Rejection in Liver Transplantation Everolimus tablets is indicated for the prophylaxis of allograft rejection in adult patients receiving a liver transplant. Everolimus tablets is to be administered no earlier than 30 days posttransplant concurrently in combination with reduced doses of tacrolimus and with corticosteroids [see Warnings and Precautions (5.5), Clinical Studies (14.2)] . TDM of everolimus and tacrolimus is recommended for all patients receiving these products [see Dosage and Administration (2.3, 2.5)] .

1.3Limitations of Use The safety and efficacy of everolimus tablets 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).

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Patients receiving everolimus tablets may require dose adjustments based on everolimus blood concentrations achieved, tolerability, individual response, change in concomitant medications and the clinical situation. Optimally, dose adjustments of everolimus tablets should be based on trough concentrations obtained 4 or 5 days after a previous dosing change. Dose adjustment is required if the trough concentration is below 3 ng/mL.

The total daily dose of everolimus tablets should be doubled using the available tablet strengths (0.25 mg, 0.5 mg, 0.75 mg, or 1 mg). Dose adjustment is also required if the trough concentration is greater than 8 ng/mL on 2 consecutive measures; the dose of everolimus tablets should be decreased by 0.25 mg twice daily [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)] . 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 mg twice daily starting 30 days after transplantation ( 2.2 ) Monitor Everolimus Concentrations : Adjust maintenance dose to achieve trough concentrations within the 3 to 8 ng/mL target range using LC/MS/MS assay method ( 2.1 , 2.2 , 2.3 ) Administer consistently with or without food at the same time as cyclosporine or tacrolimus ( 2.6 , 12.3 ) Mild Hepatic Impairment : Reduce initial daily dose by one-third ( 2.7 ) Moderate or Severe Hepatic Impairment : Reduce initial daily dose by one-half ( 2.7 , 12.6 )

2.1Dosage in Adult Kidney Transplant Patients An initial everolimus tablets dose of 0.75 mg orally twice daily (1.5 mg per day) is recommended for adult kidney transplant patients in combination with reduced-dose cyclosporine, administered as soon as possible after transplantation [see Dosage and Administration (2.3, 2.4), Clinical Studies (14.1)] . Oral prednisone should be initiated once oral medication is tolerated. Steroid doses may be further tapered on an individualized basis depending on the clinical status of patient and function of graft.

2.2Dosage in Adult Liver Transplant Patients Start everolimus tablets at least 30 days posttransplant. An initial dose of 1 mg orally twice daily (2 mg per day) is recommended for adult liver transplant patients in combination with reduced-dose tacrolimus [see Dosage and Administration (2.3, 2.5), Clinical Studies (14.2)] . Steroid doses may be further tapered on an individualized basis depending on the clinical status of patient and function of graft.

2.3Therapeutic Drug Monitoring (TDM) - Everolimus Routine everolimus whole blood therapeutic drug concentration monitoring is recommended for all patients. The recommended everolimus therapeutic range is 3 to 8 ng/mL [see Clinical Pharmacology (12.7)] . Careful attention should be made to clinical signs and symptoms, tissue biopsies, and laboratory parameters.

It is important to monitor everolimus blood concentrations, in patients with hepatic impairment, during concomitant administration of CYP3A4 inducers or inhibitors or cannabidiol, when switching cyclosporine formulations and/or when cyclosporine dosing is reduced according to recommended target concentrations [see Drug Interactions (7), Clinical Pharmacology (12.7, 12.8)] . There is an interaction of cyclosporine on everolimus, and consequently, everolimus concentrations may decrease if cyclosporine exposure is reduced.

There is little to no pharmacokinetic interaction of tacrolimus on everolimus, and thus, everolimus concentrations do not decrease if the tacrolimus exposure is reduced [see Drug Interactions (7.2)] . The everolimus recommended therapeutic range of 3 to 8 ng/mL is based on an LC/MS/MS assay method. Currently in clinical practice, everolimus whole blood trough concentrations may be measured by chromatographic or immunoassay methodologies.

Because the measured everolimus whole blood trough concentrations depend on the assay used, individual patient sample concent… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 105 words ▾

3 DOSAGE FORMS AND STRENGTHS Everolimus tablets are available as 0.25 mg, 0.5 mg, 0.75 mg, and 1 mg tablets. Table 1. Description of Everolimus Tablets Dosage strength 0.25 mg 0.5 mg 0.75 mg 1 mg Appearance White to off-white, flat faced tablets with beveled edge Imprint “i3” on one side and “3” on the other side “i3” on one side and “15” on the other side “i3” on one side and “16” on the other side “i3” on one side and “17” on the other side Everolimus tablets is available as 0.25 mg, 0.5 mg, 0.75 mg, and 1 mg tablets ( 3 )

⛔ Contraindications 38 words ▾

4 CONTRAINDICATIONS Hypersensitivity to everolimus, sirolimus, or to components of the drug product ( 4 )

4.1Hypersensitivity Reactions Everolimus tablets is contraindicated in patients with known hypersensitivity to everolimus, sirolimus, or to components of the drug product.

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Angioedema [increased risk with concomitant angiotensin converting enzyme (ACE inhibitors)] : Monitor for symptoms and treat promptly ( 5.8 ) Delayed Wound Healing/Fluid Accumulation : Monitor symptoms; treat promptly to minimize complications ( 5.9 ) Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis : Monitor for symptoms or radiologic changes; manage by dose reduction or discontinuation until symptoms resolve; consider use of corticosteroids ( 5.10 ) Hyperlipidemia (elevations of serum cholesterol and triglycerides) : Monitor and consider anti-lipid therapy ( 5.11 ) Proteinuria (increased risk with higher trough concentrations) : Monitor urine protein ( 5.12 ) Polyoma Virus Infections (activation of latent viral infections; BK virus associated nephropathy) : Consider reducing immunosuppression ( 5.13 ) TMA/TTP/HUS (concomitant use with cyclosporine may increase risk) : Monitor for hematologic changes or symptoms ( 5.15 ) New Onset Diabetes After Transplantation : Monitor serum glucose ( 5.16 ) Male Infertility : Azoospermia or oligospermia may occur ( 5.18 , 13.1 ) Immunizations : Avoid live vaccines ( 5.19 ) Embryo-Fetal Toxicity : Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with everolimus tablets and for 8 weeks after final dose ( 5.17 , 8.1 , 8.3 )

5.1Management of Immunosuppression Only physicians experienced in management of systemic immunosuppressant therapy in transplantation should prescribe everolimus tablets. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for the maintenance therapy should have complete information requisite for the follow-up of the patient.

In limited data with the complete elimination of calcineurin inhibition (CNI), there was an increased risk of acute rejection.

5.2Lymphomas and Other Malignancies Patients receiving immunosuppressants, including everolimus tablets, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. As usual for patients with increased risk for skin cancer, exposure to sunlight and ultraviolet light should be limited by wearing protective clothing and using a sunscreen with a high protection factor.

5.3Serious Infections Patients receiving immunosuppressants, including everolimus tablets, are at increased risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections [see Warnings and Precautions (5.13), Adverse Reactions (6.1, 6.2)] . These infections may lead to serious, including fatal, outcomes. Because of the danger of over-immunosuppression, which can cause increased susceptibility to infection, combination immunosuppressant therapy should be used with caution.

Antimicrobial prophylaxis for Pneumocystis jiroveci ( carinii ) pneumonia and prophylaxis for cytomegalovirus (CMV) is recommended in transplant recipients.

5.4Kidney Graft Thrombosis An increased risk of kidney arterial and venous thrombosis, resulting in graft loss, has been reported, usually within the first 30 days posttransplantation [see Boxed Warning] .

5.5Hepatic Artery Thrombosis Mammalian target of rapamycin (mTOR) inhibitors are associated with an increase in hepatic artery thrombosis (HAT). Reported cases mostly have occurred within the first 30 days posttransplant and most also lead to graft loss or death. Therefore, everolimus tablets should not be administered earlier than 30 days after liver transplant.

5.6Everolimus Tablets and Calcineurin Inhibitor-Induced Nephrotoxicity In kidney transplant recipients, everolimus tablets with standard dose cyclosporine increases the risk of nephrotoxicity resulting in a lower glomerular filtration rate. Reduced d… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS Most common adverse reactions were as follows: Kidney Transplantation (incidence greater than or equal to 20%) : peripheral edema, constipation, hypertension, nausea, anemia, urinary tract infection (UTI), and hyperlipidemia ( 6.1 ) Liver Transplantation (incidence greater than 10%) : diarrhea, headache, peripheral edema, hypertension, nausea, pyrexia, abdominal pain, leukopenia, and hypercholesterolemia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact i3 Pharmaceuticals, LLC at 1-844-874-7353 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Serious and Otherwise Important Adverse Reactions The following adverse reactions are discussed in greater detail in other sections of the label. Hypersensitivity Reactions [see Contraindications (4.1)] Lymphomas and Other Malignancies [see Boxed Warning, Warnings and Precautions (5.2)] Serious Infections [see Warnings and Precautions (5.3)] Kidney Graft Thrombosis [see Warnings and Precautions (5.4)] Hepatic Artery Thrombosis [see Warnings and Precautions (5.5)] Everolimus tablets and Calcineurin Inhibitor-Induced Nephrotoxicity [see Warnings and Precautions (5.6)] Heart Transplantation [see Warnings and Precautions (5.7)] Angioedema [see Warnings and Precautions (5.8)] Wound Healing and Fluid Accumulation [see Warnings and Precautions (5.9)] Interstitial Lung Disease/Non-Infectious Pneumonitis [see Warnings and Precautions (5.10)] Hyperlipidemia [see Warnings and Precautions (5.11)] Proteinuria [see Warnings and Precautions (5.12)] Polyoma Virus Infections [see Warnings and Precautions (5.13)] Thrombotic Microangiopathy/Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome (TMA/TTP/HUS) [see Warnings and Precautions (5.15)] New Onset Diabetes After Transplant [see Warnings and Precautions (5.16)] Male Infertility [see Warnings and Precautions (5.18)]

6.2Clinical 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. Kidney Transplantation The data described below reflect exposure to everolimus tablets in an open-label, randomized trial of de novo kidney transplant patients of concentration-controlled everolimus at an initial everolimus tablets starting dose of 1.5 mg per day [target trough concentrations 3 to 8 ng/mL with reduced exposure cyclosporine (N = 274) compared to mycophenolic acid (N = 273) with standard exposure cyclosporine].

All patients received basiliximab induction therapy and corticosteroids. The population was between 18 and 70 years, more than 43% were 50 years of age or older (mean age was 46 years in the everolimus tablets group, 47 years control group); a majority of recipients were male (64% in the everolimus tablets group, 69% control group); and a majority of patients were Caucasian (70% in the everolimus tablets group, 69% control group). Demographic characteristics were comparable between treatment groups.

The most frequent diseases leading to transplantation were balanced between groups and included hypertension/nephrosclerosis, glomerulonephritis/glomerular disease and diabetes mellitus. Significantly more patients discontinued everolimus tablets 1.5 mg per day treatment (83/277, 30%) than discontinued the control regimen (60/277, 22%). Of those patients who prematurely discontinued treatment, most discontinuations were due to adverse reactions: 18% in the everolimus tablets group compared to 9% in the control group (p-value = 0.004).

This difference was more prominent between treatment groups among female patients. In those patients discontinuing study medication, adverse reactions were collected up to 7 days after study medication discontinuation and serious adverse reactions up to 30 days after study medication discontinuation. Discontinuation of everolimus tablets at a higher dose (3 mg per day) was 95/279, 34%, including 20% due to a… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Strong-moderate CYP3A4 inhibitors (e.g., cyclosporine, ketoconazole, erythromycin, verapamil) and CYP3A4 inducers (e.g., rifampin) may affect everolimus concentrations ( 7.1 ). Consider everolimus tablets dose adjustment ( 5.14 ) Therapeutic drug monitoring and dose reduction for everolimus tablets should be considered when everolimus tablets is coadministered with cannabidiol ( 5.22 , 7.13 )

7.1Interactions With Strong Inhibitors or Inducers of CYP3A4 and P-glycoprotein Everolimus is mainly metabolized by CYP3A4 in the liver and to some extent in the intestinal wall and is a substrate for the multidrug efflux pump, P-glycoprotein (P-gp). Therefore, absorption and subsequent elimination of systemically absorbed everolimus may be influenced by medicinal products that affect CYP3A4 and/or P-gp. Concurrent treatment with strong inhibitors (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, boceprevir, telaprevir) and inducers (e.g., rifampin, rifabutin) of CYP3A4 is not recommended.

Inhibitors of P-gp (e.g., digoxin, cyclosporine) may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations. In vitro , everolimus was a competitive inhibitor of CYP3A4 and of CYP2D6, potentially increasing the concentrations of medicinal products eliminated by these enzymes. Thus, caution should be exercised when coadministering everolimus tablets with CYP3A4 and CYP2D6 substrates with a narrow therapeutic index [see Dosage and Administration (2.3)] .

All in vivo interaction studies were conducted without concomitant cyclosporine. Pharmacokinetic interactions between everolimus tablets and concomitantly administered drugs are discussed below. Drug interaction studies have not been conducted with drugs other than those described below.

7.2Cyclosporine (CYP3A4/P-gp Inhibitor and CYP3A4 Substrate) The steady-state C max and area under the curve (AUC) estimates of everolimus were significantly increased by coadministration of single dose cyclosporine [see Clinical Pharmacology (12.5)] . Dose adjustment of everolimus tablets might be needed if the cyclosporine dose is altered [see Dosage and Administration (2.3)] . Everolimus tablets had a clinically minor influence on cyclosporine pharmacokinetics in transplant patients receiving cyclosporine (Neoral).

7.3Ketoconazole and Other Strong CYP3A4 Inhibitors Multiple-dose ketoconazole administration to healthy volunteers significantly increased single dose estimates of everolimus C max , AUC, and half-life. It is recommended that strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, boceprevir, telaprevir) should not be coadministered with everolimus tablets [see Warnings and Precautions (5.14), Clinical Pharmacology (12.5)] .

7.4Erythromycin (Moderate CYP3A4 Inhibitor) Multiple-dose erythromycin administration to healthy volunteers significantly increased single dose estimates of everolimus C max , AUC, and half-life. If erythromycin is coadministered, everolimus blood concentrations should be monitored and a dose adjustment made as necessary [see Clinical Pharmacology (12.5)] .

7.5Verapamil (CYP3A4 and P-gp Substrate) Multiple-dose verapamil administration to healthy volunteers significantly increased single dose estimates of everolimus C max and AUC. Everolimus half-life was not changed. If verapamil is coadministered, everolimus blood concentrations should be monitored and a dose adjustment made as necessary [see Clinical Pharmacology (12.5)] .

7.6Atorvastatin (CYP3A4 Substrate) and Pravastatin (P-gp Substrate) Single-dose administration of everolimus tablets with either atorvastatin or pravastatin to healthy subjects did not influence the pharmacokinetics of atorvastatin, pravastatin and everolimus, as well as total HMG-CoA reductase bioreactivity in plasma to a clinically relevant extent. However, these results cannot be extrapolat… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy : Based on animal data, may cause maternal and fetal harm ( 8.1 ) Lactation : Breastfeeding not recommended ( 8.2 ) Females and Males of Reproductive Potential : May impair fertility ( 8.1 , 8.3 , 13.1 )

8.1Pregnancy Risk Summary Based on animal studies and the mechanism of action [see Clinical Pharmacology (12.1)], everolimus tablets can cause fetal harm when administered to a pregnant woman. There are limited case reports of everolimus tablets 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/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) 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.

8.2Lactation Risk Summary There is no data regarding the presence of everolimus tablets 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.

8.3Females and Males of Reproductive Potential Contraception Females should not be pregnant or become pregnant while receiving everolimus tablets. Advise females of reproductive potential that animal studies have been performed showing everolimus tablets 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 everolimus tablets and up to 8 weeks after treatment has been stopped.

Infertility Females Amenorrhea occurred in female patients taking everolimus tablets [see Adverse Reactions (6.2)]. Everolimus tablets may cause preimplantation loss in females based on animal data [see Nonclinical Toxicology (13.1)]. Female fertility may be compromised by treatment with everolimus tablets.

Males Everolimus t… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Based on animal studies and the mechanism of action [see Clinical Pharmacology (12.1)], everolimus tablets can cause fetal harm when administered to a pregnant woman. There are limited case reports of everolimus tablets 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/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) 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.

🧒 Pediatric Use 27 words ▾

8.4Pediatric Use The safe and effective use of everolimus tablets in kidney or liver transplant patients younger than 18 years of age has not been established.

🧓 Geriatric Use 46 words ▾

8.5Geriatric Use There is limited clinical experience on the use of everolimus tablets 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 [see Clinical Pharmacology (12.5)] .

🆘 Overdosage 127 words ▾

10 OVERDOSAGE Reported experience with overdose in humans is very limited. There is a single case of an accidental ingestion of 1.5 mg everolimus in a 2-year-old child where no adverse reactions were observed. Single doses up to 25 mg have been administered to transplant patients with acceptable acute tolerability.

Single doses up to 70 mg (without cyclosporine) have been given with acceptable acute tolerability. General supportive measures should be followed in all cases of overdose. Everolimus is not considered dialyzable to any relevant degree (less than 10% of everolimus removed within 6 hours of hemodialysis).

In animal studies, everolimus showed a low acute toxic potential. No lethality or severe toxicity was observed after single oral doses of 2000 mg/kg (limit test) in either mice or rats.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Everolimus inhibits antigenic and interleukin (IL-2 and IL-15) stimulated activation and proliferation of T and B lymphocytes. In cells, everolimus binds to a cytoplasmic protein, the FK506 Binding Protein-12 (FKBP-12), to form an immunosuppressive complex (everolimus: FKBP-12) that binds to and inhibits the mammalian target of rapamycin (mTOR), a key regulatory kinase. In the presence of everolimus phosphorylation of p70 S6 ribosomal protein kinase (p70S6K), a substrate of mTOR, is inhibited.

Consequently, phosphorylation of the ribosomal S6 protein and subsequent protein synthesis and cell proliferation are inhibited. The everolimus: FKBP-12 complex has no effect on calcineurin activity. In rats and nonhuman primate models, everolimus effectively reduces kidney allograft rejection resulting in prolonged graft survival.

12.3Pharmacokinetics Everolimus pharmacokinetics have been characterized after oral administration of single and multiple doses to adult kidney transplant patients, hepatically-impaired patients, and healthy subjects. Absorption After oral dosing, peak everolimus concentrations occur 1 to 2 hours post dose. Over the dose range of 0.5 mg to 2 mg twice daily, everolimus C max and AUC are dose proportional in transplant patients at steady-state.

Food Effect In 24 healthy subjects, a high-fat breakfast (44.5 g fat) reduced everolimus C max by 60%, delayed T max by a median 1.3 hours, and reduced AUC by 16% compared with a fasting administration. To minimize variability, everolimus should be taken consistently with or without food [see Dosage and Administration (2.6)] . Distribution The blood-to-plasma ratio of everolimus is concentration dependent ranging from 17% to 73% over the range of 5 ng/mL to 5000 ng/mL.

Plasma protein binding is approximately 74% in healthy subjects and in patients with moderate hepatic impairment. The apparent distribution volume associated with the terminal phase (Vz/F) from a single-dose pharmacokinetic study in maintenance kidney transplant patients is 342 to 107 L (range: 128 to 589 L). Elimination Metabolism Everolimus is a substrate of CYP3A4 and P-gp.

Following oral administration, everolimus is the main circulating component in human blood. Six main metabolites of everolimus have been detected in human blood, including 3 monohydroxylated metabolites, 2 hydrolytic ring-opened products, and a phosphatidylcholine conjugate of everolimus. These metabolites were also identified in animal species used in toxicity studies and showed approximately 100 times less activity than everolimus itself.

Excretion After a single dose of radiolabeled everolimus was given to transplant patients receiving cyclosporine, the majority (80%) of radioactivity was recovered from the feces and only a minor amount (5%) was excreted in urine. Parent drug was not detected in urine and feces. Pharmacokinetics in Kidney Transplant Patients Steady-state is reached by Day 4 with an accumulation in blood concentrations of 2- to 3-fold compared with the exposure after the first dose.

Table 4 below provides a summary of the steady-state pharmacokinetic parameters. Table 4. Steady-State Pharmacokinetic Parameters (mean +/- SD) Following the Administration of 0.75 mg Twice Daily 1 Population pharmacokinetic analysis.

C max T max AUC CL/F 1 Vc/F 1 Half-life (T 1/2 ) 11.1 + 4.6 ng/mL 1-2 h 75 + 31 ng • h/mL

8.8L/h 110 L 30 ± 11 h The half-life estimates from 12 maintenance renal transplant patients who received single doses of everolimus capsules at 0.75 mg or 2.5 mg with their maintenance cyclosporine regimen indicate that the pharmacokinetics of everolimus are linear over the clinically-relevant dose range. Results indicate the half-life of everolimus in maintenance renal transplant patients receiving single doses of 0.75 mg or 2.5 mg everolimus tablets during steady-state cyclosporine treatment was 30 ± 11 hours (range: 19 to 53 hours).

12.5Drug-Drug Interactions Eve… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 118 words ▾

12.1Mechanism of Action Everolimus inhibits antigenic and interleukin (IL-2 and IL-15) stimulated activation and proliferation of T and B lymphocytes. In cells, everolimus binds to a cytoplasmic protein, the FK506 Binding Protein-12 (FKBP-12), to form an immunosuppressive complex (everolimus: FKBP-12) that binds to and inhibits the mammalian target of rapamycin (mTOR), a key regulatory kinase. In the presence of everolimus phosphorylation of p70 S6 ribosomal protein kinase (p70S6K), a substrate of mTOR, is inhibited.

Consequently, phosphorylation of the ribosomal S6 protein and subsequent protein synthesis and cell proliferation are inhibited. The everolimus: FKBP-12 complex has no effect on calcineurin activity. In rats and nonhuman primate models, everolimus effectively reduces kidney allograft rejection resulting in prolonged graft survival.

📦 How Supplied / Storage and Handling 152 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Everolimus tablets are packed in child-resistant blisters and bottles. Table 11. Description of Everolimus Tablets Dosage strength 0.25 mg 0.5 mg 0.75 mg 1 mg Appearance White to off-white, flat faced tablets with beveled edge Imprint “i3” on one side and “3” on the other side “i3” on one side and “15” on the other side “i3” on one side and “16” on the other side “i3” on one side and “17” on the other side NDC number (Carton) 72319-003-60 72319-015-60 72319-016-60 72319-017-60 NDC number (Blister Pack) 72319-003-10 72319-015-10 72319-016-10 72319-017-10 NDC number (Bottles) 72319-003-02 72319-015-02 72319-016-02 72319-017-02 Each strength is available in boxes of 60 tablets (6 blister strips of 10 tablets each) and bottles of 60 tablets.

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.

📋 Description 98 words ▾

11 DESCRIPTION Everolimus tablets is a macrolide immunosuppressant. The chemical name of everolimus 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 958.25 g/mol.

The structural formula is: Everolimus tablets is supplied as tablets for oral administration containing 0.25 mg, 0.5 mg, 0.75 mg, and 1 mg of everolimus together with butylated hydroxytoluene, crospovidone, hypromellose, anhydrous lactose, and magnesium stearate as inactive ingredients. chemical-structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Administration Inform patients that everolimus tablets should be taken orally twice a day approximately 12 hours apart consistently either with or without food. Inform patients to avoid grapefruit and grapefruit juice, which increase blood drug concentrations of everolimus tablets [see Warnings and Precautions (5.20)] .

Advise patients that everolimus tablets should be used concurrently with reduced doses of cyclosporine and that any change in doses of these medications should be made under physician supervision. A change in the cyclosporine dose may also require a change in the dosage of everolimus tablets. Inform patients of the necessity of repeated laboratory tests according to physician recommendations while they are taking everolimus tablets.

Development of Lymphomas and Other Malignancies Inform patients they are at risk of developing lymphomas and other malignancies, particularly of the skin, due to immunosuppression. Advise patients to limit exposure to sunlight and ultraviolet (UV) light by wearing protective clothing and using a sunscreen with a high protection factor [see Warnings and Precautions (5.2)] . Increased Risk of Infection Inform patients they are at increased risk of developing a variety of infections, including opportunistic infections, due to immunosuppression.

Advise patients to contact their physician if they develop any symptoms of infection [see Warnings and Precautions (5.3, 5.13)] . Kidney Graft Thrombosis Inform patients that everolimus tablets has been associated with an increased risk of kidney arterial and venous thrombosis, resulting in graft loss, usually within the first 30 days posttransplantation [see Warnings and Precautions (5.4)] . Everolimus Tablets and Calcineurin Inhibitor-Induced Nephrotoxicity Advise patients of the risks of impaired kidney function with the combination of everolimus tablets and cyclosporine as well as the need for routine blood concentration monitoring for both drugs.

Advise patients of the importance of serum creatinine monitoring [see Warnings and Precautions (5.6)] . Angioedema Inform patients of the risk of angioedema and that concomitant use of ACE inhibitors may increase this risk. Advise patients to seek prompt medical attention if symptoms occur [see Warnings and Precautions (5.8)] .

Wound Healing Complications and Fluid Accumulation Inform patients that the use of everolimus tablets has been associated with impaired or delayed wound healing, fluid accumulation and the need for careful observation of their incision site [see Warnings and Precautions (5.9)] . Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis Inform patients that the use of everolimus tablets may increase the risk of non-infectious pneumonitis. Advise patients to seek medical attention if they develop clinical symptoms consistent with pneumonia [see Warnings and Precautions (5.10)] .

Hyperlipidemia Inform patients that the use of everolimus tablets has been associated with increased serum cholesterol and triglycerides that may require treatment and the need for monitoring of blood lipid concentrations [see Warnings and Precautions (5.11)] . Proteinuria Inform patients that the use of everolimus tablets has been associated with an increased risk of proteinuria [see Warnings and Precautions (5.12)] . Pregnancy and Lactation Advise women of childbearing age to avoid becoming pregnant throughout treatment and for 8 weeks after everolimus tablets therapy has stopped.

Everolimus tablets can cause fetal harm if taken during pregnancy. Advise a pregnant woman of the potential risk to a fetus. Also advise not to breastfeed while taking everolimus tablets [see Use in Specific Populations (8.1, 8.2)].

Male and Female Fertility Inform male and female patients that everolimus tablets may impair fertility [see Warnings and Precautions (5.18), Use in Specific Populations (8.1, 8.3),… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

This Medication Guide has been approved by the U.S. Food and Drug Administration. MEDICATION GUIDE Everolimus [E-ver-OH-li-mus] Tablets, for oral use What is the most important information I should know about everolimus tablets?

Everolimus tablets can cause serious side effects, including: Increased risk of getting certain cancers. People who take everolimus tablets 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. Everolimus tablets weakens the body’s immune system and affects your ability to fight infections. Serious infections can happen with everolimus tablets that may lead to death.

People taking everolimus tablets 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 everolimus tablets.

Your doctor should do regular blood tests to check your levels of both everolimus tablets and cyclosporine. Increased risk of death that can be related to infection, in people who have had a heart transplant. You should not take everolimus tablets without talking to your doctor if you have had a heart transplant.

See the section “What are the possible side effects of everolimus tablets?” for information about other serious side effects. What is everolimus tablets? Everolimus tablets is a prescription medicine used to prevent transplant rejection (antirejection medicine) in people who have received a kidney transplant or liver transplant.

Transplant rejection happens when the body’s immune system perceives the new transplanted kidney or liver as “foreign” and attacks it. Everolimus tablets is used with other medicines called cyclosporine, corticosteroids and certain other transplant medicines to prevent rejection of your transplanted kidney. Everolimus tablets is used with other medicines called tacrolimus and corticosteroids to prevent rejection of your transplanted liver.

It is not known if everolimus tablets is safe and effective in transplanted organs other than the kidney and liver. It is not known if everolimus tablets is safe and effective in children under 18 years of age. Do not take everolimus tablets if you are allergic to: everolimus (everolimus tablets/Afinitor ® ) or any of the ingredients in everolimus tablets.

See the end of this Medication Guide for a complete list of ingredients in everolimus tablets. sirolimus (Rapamune®) Before taking everolimus tablets, tell your doctor about all of your medical conditions, including if you: have liver problems have skin cancer or it runs in your family have high cholesterol or triglycerides (fat in your blood) have Lapp lactase deficiency or glucose-galactose malabsorption. You should not take everolimus tablets if you have this disorder. are pregnant or could become pregnant. Everolimus tablets may harm your unborn baby.

If you are able to become pregnant, you should use effective birth control during treatment and for 8 weeks after your last dose of everolimus tablets. Talk to your doctor about birth control methods that may be right for you during this time. If you become pregnant or think you are pregnant, tell your healthcare provider right away.

You should not become pregnant during treatment with everolimus tablets. are breastfeeding or plan to breastfeed. It is not known if everolimus tablets passes into your breast milk. T… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~2 min read ▾

12.3Pharmacokinetics Everolimus pharmacokinetics have been characterized after oral administration of single and multiple doses to adult kidney transplant patients, hepatically-impaired patients, and healthy subjects. Absorption After oral dosing, peak everolimus concentrations occur 1 to 2 hours post dose. Over the dose range of 0.5 mg to 2 mg twice daily, everolimus C max and AUC are dose proportional in transplant patients at steady-state.

Food Effect In 24 healthy subjects, a high-fat breakfast (44.5 g fat) reduced everolimus C max by 60%, delayed T max by a median 1.3 hours, and reduced AUC by 16% compared with a fasting administration. To minimize variability, everolimus should be taken consistently with or without food [see Dosage and Administration (2.6)] . Distribution The blood-to-plasma ratio of everolimus is concentration dependent ranging from 17% to 73% over the range of 5 ng/mL to 5000 ng/mL.

Plasma protein binding is approximately 74% in healthy subjects and in patients with moderate hepatic impairment. The apparent distribution volume associated with the terminal phase (Vz/F) from a single-dose pharmacokinetic study in maintenance kidney transplant patients is 342 to 107 L (range: 128 to 589 L). Elimination Metabolism Everolimus is a substrate of CYP3A4 and P-gp.

Following oral administration, everolimus is the main circulating component in human blood. Six main metabolites of everolimus have been detected in human blood, including 3 monohydroxylated metabolites, 2 hydrolytic ring-opened products, and a phosphatidylcholine conjugate of everolimus. These metabolites were also identified in animal species used in toxicity studies and showed approximately 100 times less activity than everolimus itself.

Excretion After a single dose of radiolabeled everolimus was given to transplant patients receiving cyclosporine, the majority (80%) of radioactivity was recovered from the feces and only a minor amount (5%) was excreted in urine. Parent drug was not detected in urine and feces. Pharmacokinetics in Kidney Transplant Patients Steady-state is reached by Day 4 with an accumulation in blood concentrations of 2- to 3-fold compared with the exposure after the first dose.

Table 4 below provides a summary of the steady-state pharmacokinetic parameters. Table 4. Steady-State Pharmacokinetic Parameters (mean +/- SD) Following the Administration of 0.75 mg Twice Daily 1 Population pharmacokinetic analysis.

C max T max AUC CL/F 1 Vc/F 1 Half-life (T 1/2 ) 11.1 + 4.6 ng/mL 1-2 h 75 + 31 ng • h/mL

8.8L/h 110 L 30 ± 11 h The half-life estimates from 12 maintenance renal transplant patients who received single doses of everolimus capsules at 0.75 mg or 2.5 mg with their maintenance cyclosporine regimen indicate that the pharmacokinetics of everolimus are linear over the clinically-relevant dose range. Results indicate the half-life of everolimus in maintenance renal transplant patients receiving single doses of 0.75 mg or 2.5 mg everolimus tablets during steady-state cyclosporine treatment was 30 ± 11 hours (range: 19 to 53 hours).

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Prevention of Organ Rejection After Kidney Transplantation A 24-month, multi-national, open-label, randomized (1:1:1) trial was conducted comparing two concentration-controlled everolimus tablets regimens of 1.5 mg per day starting dose (targeting 3 to 8 ng/mL using an LC/MS/MS assay method and 3 mg per day starting dose (targeting 6 to 12 ng/mL using an LC/MS/MS assay method) with reduced exposure cyclosporine and corticosteroids, to 1.44 g per day of mycophenolic acid with standard exposure cyclosporine and corticosteroids.

The mean cyclosporine starting dose was 5.2, 5 and 5.7 mg/kg body weight/day in the everolimus tablets 1.5 mg, 3 mg and in mycophenolic acid groups, respectively. The cyclosporine dose in the everolimus tablets group was then adjusted to the blood trough concentration ranges indicated in Table 5, whereas in the mycophenolic acid group the target ranges were 200 to 300 ng/mL starting Day 5: 200 to 300 ng/mL, and 100 to 250 ng/mL from Month 2 to Month 12. All patients received basiliximab induction therapy.

The study population consisted of 18- to 70-year-old male and female low-to-moderate risk renal transplant recipients undergoing their first transplant. Low to moderate immunologic risk was defined in the study as an ABO blood type compatible first organ or tissue transplant recipient with anti-human leukocyte antigen (HLA) Class I panel reactive antibody (PRA) less than 20% by a complement dependent cytotoxicity-based assay, or less than 50% by a flow cytometry or ELISA-based assay, and with a negative T-cell cross match.

Eight hundred thirty- three (833) patients were randomized after transplantation; 277 randomized to the everolimus tablets 1.5 mg per day group, 279 to the everolimus tablets 3 mg per day group and 277 to the mycophenolic acid 1.44 g per day group. The study was conducted at 79 renal transplant centers across Europe, South Africa, North and South America, and Asia-Pacific. There were no major baseline differences between treatment groups with regard to recipient or donor disease characteristics.

The majority of transplant recipients in all groups (70% to 76%) had three or more HLA mismatches; mean percentage of panel reactive antibodies ranged from 1% to 2%. The rate of premature treatment discontinuation at 12 months was 30% and 22% in the everolimus tablets 1.5 mg and control groups, respectively, (p = 0.03, Fisher’s exact test) and was more prominent between groups among female patients. Results at 12 months indicated that everolimus tablets 1.5 mg per day is comparable to control with respect to efficacy failure, defined as treated biopsy-proven acute rejection*, graft loss, death, or loss to follow-up.

The percentage of patients experiencing this endpoint and each individual variable in the everolimus tablets and control groups is shown in Table 7. Table 7. Efficacy Failure by Treatment Group (ITT Population) at 12 Months After Kidney Transplantation Abbreviation: CsA, cyclosporine. * Treated biopsy-proven acute rejection (tBPAR) was defined as a histologically confirmed acute rejection with a biopsy graded as IA, IB, IIA, IIB, or III according to 1997 Banff criteria that were treated with anti-rejection medication.

1 The difference in rates (everolimus tablets–mycophenolic acid) with 95% confidence interval (CI) for primary efficacy failure endpoint is 1.1% (-6.1%, 8.3%); and for the graft loss, death or loss to follow-up endpoint is 2.2% (-2.9%, 7.3%). 2 Includes treated BPAR, graft loss, death or loss to follow-up by Month 12 where loss to follow-up represents patient who did not experience treated BPAR, graft loss or death and whose last contact date is prior to 12-month visit. 3 Loss to follow-up (for Graft Loss, Death, or Loss to Follow-up) represents patient who did not experience death or graft loss and whose last contact date is prior to 12-month visit.

Everolimus tablets 1.5 mg per day with reduced exposure CsA N = 277 n (%) Mycophenolic acid 1.4… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~1 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Everolimus was not carcinogenic in mice or rats when administered daily by oral gavage for 2 years at doses up to 0.9 mg/kg, the highest dose tested. In these studies, AUCs in mice were higher (at least 20 times) than those in humans receiving 0.75 mg twice daily, and AUCs in rats were in the same range as those in humans receiving 0.75 mg twice daily. Everolimus was not mutagenic in the bacterial reverse mutation, the mouse lymphoma thymidine kinase assay, or the chromosome aberration assay using V79 Chinese hamster cells, or in vivo following two daily doses of 500 mg/kg in the mouse micronucleus assay.

In a 13-week male fertility oral gavage study in rats, testicular morphology was affected at 0.5 mg/kg and above, and sperm motility, sperm head count and plasma testosterone concentrations were diminished at 5 mg/kg which caused a decrease in male fertility. There was evidence of reversibility of these findings in animals examined after 13 weeks post- dosing. The 0.5 mg/kg dose in male rats resulted in AUCs in the range of clinical exposures, and the 5 mg/kg dose resulted in AUCs approximately 5 times the AUCs in humans receiving 0.75 mg twice daily.

Oral doses of everolimus in female rats greater or equal to 0.1 mg/kg (approximately 0.13-fold the estimated AUC 0-24h in patients receiving the starting dose 0.75 mg twice daily) resulted in increased incidence of pre-implantation loss.

13.2Animal Toxicology and/or Pharmacology In an oral neonatal and juvenile development study in rats, oral administration of everolimus from postnatal Day 7 to 70 produced dose-related delayed attainment of developmental landmarks, including delayed eye-opening, delayed reproductive development in males and females, and increased latency time during the learning and memory phases were observed at doses as low as 0.15 mg/kg/day. Exposures in the rat at these doses were equal to or less than those obtained in adult human transplant patients.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~1 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Everolimus was not carcinogenic in mice or rats when administered daily by oral gavage for 2 years at doses up to 0.9 mg/kg, the highest dose tested. In these studies, AUCs in mice were higher (at least 20 times) than those in humans receiving 0.75 mg twice daily, and AUCs in rats were in the same range as those in humans receiving 0.75 mg twice daily. Everolimus was not mutagenic in the bacterial reverse mutation, the mouse lymphoma thymidine kinase assay, or the chromosome aberration assay using V79 Chinese hamster cells, or in vivo following two daily doses of 500 mg/kg in the mouse micronucleus assay.

In a 13-week male fertility oral gavage study in rats, testicular morphology was affected at 0.5 mg/kg and above, and sperm motility, sperm head count and plasma testosterone concentrations were diminished at 5 mg/kg which caused a decrease in male fertility. There was evidence of reversibility of these findings in animals examined after 13 weeks post- dosing. The 0.5 mg/kg dose in male rats resulted in AUCs in the range of clinical exposures, and the 5 mg/kg dose resulted in AUCs approximately 5 times the AUCs in humans receiving 0.75 mg twice daily.

Oral doses of everolimus in female rats greater or equal to 0.1 mg/kg (approximately 0.13-fold the estimated AUC 0-24h in patients receiving the starting dose 0.75 mg twice daily) resulted in increased incidence of pre-implantation loss.

📄 Recent Major Changes 10 words ▾

Warnings and Precautions, Cannabidiol Drug Interactions ( 5.22 ) 9/2023

📄 Package Label / Principal Display Panel ~2 min read ▾

PRINCIPAL DISPLAY PANEL - 0.25 mg Tablet Carton Label NDC 72319- 003 -60 Rx only Everolimus Tablets 0.25 mg per tablet Contents: 60 Tablets (6 blister cards of 10 tablets each) PHARMACIST: DISPENSE WITH MEDICATION GUIDE ENCLOSED OR PROVIDED SEPARATELY. i3 Pharmaceuticals, LLC everolimus-carton-0-25-mg

PRINCIPAL DISPLAY PANEL - 0.25 mg Tablet Blister Pack NDC 72319- 003 -10 Rx only Everolimus Tablets 0.25 mg per tablet Contents: 10 Tablets i3 Pharmaceuticals, LLC everolimus-blister-pack-0-25-mg

PRINCIPAL DISPLAY PANEL - 0.25 mg Tablet Container Label NDC 72319- 003 -02 Rx only Everolimus Tablets 0.25 mg per tablet Contents: 60 Tablets PHARMACIST: DISPENSE WITH MEDICATION GUIDE ENCLOSED OR PROVIDED SEPARATELY. i3 Pharmaceuticals, LLC everolimus-container-0-25-mg

PRINCIPAL DISPLAY PANEL - 0.5 mg Tablet Carton Label NDC 72319- 015 -60 Rx only Everolimus Tablets 0.5 mg per tablet Contents: 60 Tablets (6 blister cards of 10 tablets each) PHARMACIST: DISPENSE WITH MEDICATION GUIDE ENCLOSED OR PROVIDED SEPARATELY. i3 Pharmaceuticals, LLC everolimus-carton-0-5-mg

PRINCIPAL DISPLAY PANEL - 0.5 mg Tablet Blister Pack NDC 72319- 015 -10 Rx only Everolimus Tablets 0.5 mg per tablet Contents: 10 Tablets i3 Pharmaceuticals, LLC everolimus-blister-pack-0-5-mg

PRINCIPAL DISPLAY PANEL - 0.5 mg Tablet Container Label NDC 72319- 015 -02 Rx only Everolimus Tablets 0.5 mg per tablet Contents: 60 Tablets PHARMACIST: DISPENSE WITH MEDICATION GUIDE ENCLOSED OR PROVIDED SEPARATELY. i3 Pharmaceuticals, LLC everolimus-container-0-5-mg

PRINCIPAL DISPLAY PANEL - 0.75 mg Tablet Carton Label NDC 72319- 016 -60 Rx only Everolimus Tablets 0.75 mg per tablet Contents: 60 Tablets (6 blister cards of 10 tablets each) PHARMACIST: DISPENSE WITH MEDICATION GUIDE ENCLOSED OR PROVIDED SEPARATELY. i3 Pharmaceuticals, LLC everolimus-carton-0-75-mg

PRINCIPAL DISPLAY PANEL - 0.75 mg Tablet Blister Pack NDC 72319- 016 -10 Rx only Everolimus Tablets 0.75 mg per tablet Contents: 10 Tablets i3 Pharmaceuticals, LLC everolimus-blister-pack-0-75-mg

PRINCIPAL DISPLAY PANEL - 0.75 mg Tablet Container Label NDC 72319- 016 -02 Rx only Everolimus Tablets 0.75 mg per tablet Contents: 60 Tablets PHARMACIST: DISPENSE WITH MEDICATION GUIDE ENCLOSED OR PROVIDED SEPARATELY. i3 Pharmaceuticals, LLC everolimus-container-0-75-mg

PRINCIPAL DISPLAY PANEL - 1 mg Tablet Carton Label NDC 72319- 017 -60 Rx only Everolimus Tablets 1 mg per tablet Contents: 60 Tablets (6 blister cards of 10 tablets each) PHARMACIST: DISPENSE WITH MEDICATION GUIDE ENCLOSED OR PROVIDED SEPARATELY. i3 Pharmaceuticals, LLC everolimus-carton-1-mg

PRINCIPAL DISPLAY PANEL - 1 mg Tablet Blister Pack NDC 72319- 017 -10 Rx only Everolimus Tablets 1 mg per tablet Contents: 10 Tablets i3 Pharmaceuticals, LLC everolimus-blister-pack-1-mg

PRINCIPAL DISPLAY PANEL - 1 mg Tablet Container Label NDC 72319- 017 -02 Rx only Everolimus Tablets 1 mg per tablet Contents: 60 Tablets PHARMACIST: DISPENSE WITH MEDICATION GUIDE ENCLOSED OR PROVIDED SEPARATELY. i3 Pharmaceuticals, LLC everolimus-container-1-mg

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Everolimus — the program that covers self-administered drugs. 8 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Everolimus. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$35.76M
Claims incl. refills
12.2K
Beneficiaries
5.2K
Spend / beneficiary
$6,882.81
Spend / claim
$2,940.07
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by i3 Pharmaceuticals, LLC. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 600 tablets (72319-0015-60). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
i3 Pharmaceuticals, LLC is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 72319-0012-03 · i3 72319-0016-02 · i3 →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.