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Zortress everolimus .5 mg Tablet, 60-count

by Novartis Pharmaceuticals Corporation · 60 BLISTER PACK in 1 BOX (0078-0414-20) / 1 TABLET in 1 BLISTER PACK (0078-0414-61)

NDC 00078-0414-20

🏷️ FDA NDC (as labeled) 0078-0414-20 billing pads the labeler segment with a zero

Rx only Brand On market Non-controlled

🗂️ Data synced Jul 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 Dr. Brian Staiger, PharmD

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

🆔 Identity & classification

FDA NDC (as labeled) 0078-0414-20

Product NDC 0078-0414

11-digit billing NDC 00078041420

NCPDP billing unit EA — each (per item)

RxCUI 977427, 977431, 977434, 977436, 977438, 977440, 2056895, 2056897

UNII 9HW64Q8G6G

Application # NDA021560

SPL Set ID e082a024-7850-400b-a5c2-2a140612562a

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 NDA

Marketing status On market

FDA listing status Listed (active directory)

Marketing start 2010-04-22

Route ORAL

Dosage form TABLET

Substance EVEROLIMUS

GPI-14 99404035000325

GPI class Zortress

GCN Seq No 059248

GCN 24826

HICL code 032975

Ingredient (HICL) Everolimus

HIC1 code Z

Therapeutic class — broad (HIC1) Body As A Whole

HIC2 code Z2

Therapeutic class — intermediate (HIC2) Antihistamines, Antiserotonins, Immunosuppressants

HIC3 code Z2E

Therapeutic class — specific (HIC3) Immunosuppressives

AHFS code 10:00.00.00

AHFS class Antineoplastic Agents

FDB label name ZORTRESS 0.5 MG TABLET

FDB brand name Zortress

Legend status F — Federal legend — prescription drug or device

TE code (Orange Book) AB · RLD · RS

Why two NDCs? The FDA registers this code as 0078-0414-20 — a 4-4-2 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 labeler segment → 00078-0414-20. 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.

🏭 Manufacturer & labeler

LabelerNovartis Pharmaceuticals Corporation

Application holderNOVARTIS PHARMACEUTICALS CORP

FDA applicationNDA021560 (NDA)

Labeler code00078

First marketedApr 2010

Product typeHuman Prescription Drug

Portfolio209 products on file

🔎 All NDCs from Novartis Pharmaceuticals Corporation

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.

🩺 Clinical

Label name ZORTRESS 0.5 MG TABLET Ingredient Everolimus

📖 What it is MedlinePlus · NLM

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 ↗

📗 Our plain-language guide HelloPharmacist

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?

📖 Read our full Everolimus guide →

Patient education

📘 MedlinePlus patient leaflet ↗

Supplement & herbal interactions

Some supplements/herbs that may interact with Everolimus — tap one for details:

Activated CharcoalMajor Coffee CharcoalModerate European MandrakeModerate GlucomannanModerate Guar GumModerate Gum ArabicModerate Slippery ElmModerate TragacanthModerate

🌿 Every supplement checked against Everolimus (156 interactions) — ranked by severity →

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.

💊 What it looks like

Color White

ShapeRound

ImprintCU;NVR

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 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.
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.

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.

💲 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 each	Per package
Retail pharmacies payNADAC · weekly	Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo	$19.65	$1,179.20 / 60 tablet
Medicare drug plans payPart D · Q2 2026	$21.78	$1,307.04 / 60 tablet
Medicare Part B allowsASP · J7527	$1.163 / J7527 unit	—

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.

🧾 Billing & reimbursement

FDA NDC (as labeled)0078-0414-20

11-digit billing NDC00078-0414-20

Format4-4-2 as registered → padded to 5-4-2 for billing (zero added to the labeler segment)

HCPCS J-codeJ7527

DescriptorEVEROLIMUS, ORAL, 0.25 MG

Billing units / pkg2 units

Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)

Where does this data come from?

The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

🔁 Therapeutic equivalents

Product	Labeler	Pack	NADAC/unit	TE	Status	Price vs. this
Everolimus .5 mg 00054-0471-21	Hikma	60 tablets	$3.756	AB	Availability likely	—
Everolimus .5 mg 49884-0159-02	Par	60 tablets	$3.756	AB	Availability likely	—
Everolimus .5 mg 51991-0380-60	Breckenridge	600 tablets	$3.756	AB	Availability likely	—
Everolimus .5 mg 67877-0719-31	Ascend	60 tablets	$3.756	AB	Availability likely	—
Everolimus .5 mg 70377-0070-11	Biocon	60 tablets	$3.756	AB	Availability likely	—
Zortress .5 mgthis 00078-0414-20	Novartis	60 tablets	—	AB	FDA listed	—
everolimus .5 mg 59651-0932-60	Aurobindo	60 tablets	—	AB	FDA listed	—
Everolimus .5 mg 63850-0063-02	Natco	60 tablets	—	AB	FDA listed	—
Everolimus .5 mg 72319-0015-02	i3	60 tablets	—	AB	FDA listed	—

About this product: this is the brand-name version. FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available.

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

🏛️

2010

On the market since

Apr 2010

📍

2026

Currently FDA-listed

16 years listed

🔓

Generic versions listed

see equivalents

✅Generic appears available

FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.

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.

🗺️ Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for 00078-0414-20, not the drug overall. Other pack sizes report separately.

💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.

📅 Q1 2025 – Q4 2025 · 4 quarters of data

ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.

Prescriptions last 4 qtrs

124

Units reimbursed last 4 qtrs

15.7K

Gross reimbursed last 4 qtrs

$308.2K

Avg / prescription

$2,485.21

Avg / unit

$19.6534

Latest quarter Q4 2025

19Rx

Fee-for-service vs managed care ⓘ

21% FFS 79% MCO

Fee-for-service · 26 Rx Managed care · 98 Rx

State Medicaid map

Units reimbursed · per 100k residents

6.596.0

gray = no data reported ⓘ

Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.

Tap or hover a state

…for its Medicaid breakdown

🏆 Top states by units · per 100k residents

1 Massachusetts 96.0 /100k

2 Ohio 45.1 /100k

3 Utah 32.5 /100k

4 Illinois 10.0 /100k

5 New York 6.5 /100k

National units — by quarter

💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

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

Medicare Part D (outpatient prescription) spending for Zortress — the program that covers self-administered drugs. 1 manufacturer.

⚠️ 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 Zortress. 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

$188.8K

Claims incl. refills

Beneficiaries

Spend / beneficiary

$7,261.68

Spend / claim

$3,933.41

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.

📦 Packaging — all sizes for this product

Package NDC	Description	Marketing start	Status
00078-0414-20 You're viewing this	60 BLISTER PACK in 1 BOX (0078-0414-20) / 1 TABLET in 1 BLISTER PACK (0078-0414-61)	2010-04-22	Active

🧭 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	✓ Available
Medicaid utilization (CMS SDUD)	✓ Available

“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 FDA registers it as 0078-0414-20, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 00078-0414-20, written without dashes as 00078041420. The Identity section at the top of this page lists every form of this code.

What do the three segments of this NDC mean?

In 00078-0414-20, the first segment (00078) is the labeler code FDA assigned to Novartis Pharmaceuticals Corporation; the middle segment (0414) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (20) identifies this exact package size and type. Together they name one specific package of one specific product.

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 Novartis Pharmaceuticals Corporation. Listing status can change — the directory data on this page refreshes weekly.

Who lists this product with the FDA?

Novartis Pharmaceuticals Corporation 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.

Does this product have a billing J-code?

Yes — this NDC cross-references HCPCS code J7527 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.

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.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. 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

🚨 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 Zortress. 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 Zortress.

Therefore, reduced doses of cyclosporine should be used in combination with Zortress 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 Zortress ( 5.1 ) Increased susceptibility to infection and the possible development of malignancies may result from immunosuppression ( 5.2 , 5.3 ) Increased incidence of kidney graft thrombosis ( 5.4 ) Reduced doses of cyclosporine are required for use in combination with Zortress in order to reduce nephrotoxicity ( 2.4 , 2.5 , 5.6 , 12.7 , 12.8 ) Increased mortality in a heart transplant clinical trial.

Use in heart transplantation is not recommended ( 5.7 )

🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE Zortress is an mTOR inhibitor immunosuppressant indicated for the prophylaxis of organ rejection in adult patients: Kidney Transplant : at low-moderate immunologic risk. Use in combination with basiliximab, cyclosporine (reduced doses) and corticosteroids ( 1.1) Liver Transplant : Administer no earlier than 30 days posttransplant. Use in combination with tacrolimus (reduced doses) and corticosteroids ( 1.2 , 5.5 ) Limitations of Use : Safety and efficacy have not been established in the following: Kidney transplant patients at high immunologic risk ( 1.3 ) Recipients of transplanted organs other than kidney or liver ( 1.3 , 5.7 ) Pediatric patients (less than 18 years) ( 1.3 )

1.1Prophylaxis of Organ Rejection in Kidney Transplantation Zortress is indicated for the prophylaxis of organ rejection in adult patients at low to moderate immunologic risk receiving a kidney transplant [ see Clinical Studies (14.1)] . Zortress is to be administered in combination with basiliximab induction and concurrently with reduced doses of cyclosporine and with corticosteroids. Therapeutic drug monitoring (TDM) of everolimus and cyclosporine is recommended for all patients receiving these products [ see Dosage and Administration (2.2 , 2.3)] .

1.2Prophylaxis of Organ Rejection in Liver Transplantation Zortress is indicated for the prophylaxis of allograft rejection in adult patients receiving a liver transplant. Zortress is to be administered no earlier than 30 days posttransplant concurrently in combination with reduced doses of tacrolimus and with corticosteroids [ s ee Warnings and Precautions (5. 5 ) , Clinical Studies (14.2) ] .

TDM of everolimus and tacrolimus is recommended for all patients receiving these products [ s ee Dosage and Administration (2.3 , 2.5)] .

1.3Limitations of Use The safety and efficacy of Zortress has not been established in the following populations: Kidney transplant patients at high immunologic risk. Recipients of transplanted organs other than kidney and liver [see Warnings and Precautions (5.7)] . Pediatric patients (less than 18 years).

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Patients receiving Zortress 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 Zortress 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 Zortress 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 Zortress 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 Zortress 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 [ s ee 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 Zortress 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 [ s ee 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 concentration values from different assays may not be int…

💊 Dosage Forms and Strengths 101 words ▾

3 DOSAGE FORMS AND STRENGTHS Zortress is available as 0.25 mg, 0.5 mg, 0.75 mg, and 1 mg tablets. Table 1. Description of Zortress (everolimus) Tablets Dosage strength 0.25 mg 0.5 mg 0.75 mg 1 mg Appearance White to yellowish, marbled, round, flat tablets with beveled edge Imprint “C” on one side and “NVR” on the other “CH” on one side and “NVR” on the other “CL” on one side and “NVR” on the other “CU” on one side and “NVR” on the other Zortress is available as 0.25 mg, 0.5 mg, 0.75 mg, and 1 mg tablets ( 3 )

⛔ Contraindications 37 words ▾

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

4.1Hypersensitivity Reactions Zortress 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 Zortress 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 Zortress. 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 Zortress, 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 Zortress, are at increased risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections [ s ee Warnings and Precautions ( 5.1 3 ) , 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 [ s ee 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, Zortress should not be administered earlier than 30 days after liver transplant.

5.6Zortress and Calcineurin Inhibitor-Induced Nephrotoxicity In kidney transplant recipients, Zortress with standard dose cyclosporine increases the risk of nephrotoxicity resulting in a lower glomerular filtration rate. Reduced doses of cyclosporine are required for use in combination wit…

🤒 Adverse Reactions ~3 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 Novartis Pharmaceuticals Corporation at 1-888-669-6682 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 an d Precautions ( 5.4 ) ] Hepatic Artery Thrombosis [ see Warnings and Precautions (5. 5 ) ] Zortress 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 ( 5.1 2 ) ] Polyoma Virus Infections [ see Warnings and Precautions ( 5.1 3 ) ] Thrombotic Microangiopathy/Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome (TMA/TTP/HUS) [ see Warnings and Precautions ( 5.1 5 ) ] New Onset Diabetes After Transplant [ see Warnings and Precautions ( 5.1 6 ) ] Male Infertility [ see Warnings and Precautions ( 5.1 8 ) ]

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 Zortress in an open-label, randomized trial of de novo kidney transplant patients of concentration-controlled everolimus at an initial Zortress 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 Zortress group, 47 years control group); a majority of recipients were male (64% in the Zortress group, 69% control group); and a majority of patients were Caucasian (70% in the Zortress 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 Zortress 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 Zortress 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 Zortress at a higher dose (3 mg per day) was 95/279, 34%, including 20% due to adverse react…

🔄 Drug Interactions ~3 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 Zortress dose adjustment ( 5.14 ) Therapeutic drug monitoring and dose reduction for Zortress should be considered when Zortress 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 Zortress with CYP3A4 and CYP2D6 substrates with a narrow therapeutic index [ s ee Dosage and Administration ( 2.

3 ) ] . All in vivo interaction studies were conducted without concomitant cyclosporine. Pharmacokinetic interactions between Zortress 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 [ s ee Clinical Pharmaco logy (12. 5 )] . Dose adjustment of Zortress might be needed if the cyclosporine dose is altered [ s ee Dosage and Administration ( 2.

3)] . Zortress 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 Zortress [ s ee Warnings and Precautions ( 5. 1 4 ), Clinical Pharmaco logy (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 [ s ee Clinical Pharmaco logy (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 [ s ee Clinical Pharmaco logy (12. 5 ) ] .

7.6Atorvastatin (CYP3A4 Substrate) and Pravastatin (P-gp Substrate) Single-dose administration of Zortress 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 extrapolated to other HMG-CoA reductase inhibitors. Patients shou…

👥 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)] , Zortress can cause fetal harm when administered to a pregnant woman. There are limited case reports of Zortress use in pregnant women; however, these reports are insufficient to inform a drug-associated risk of adverse developmental outcomes. Reproductive studies in animals have demonstrated that everolimus was maternally toxic in rabbits and caused embryo-fetal toxicities in rats and rabbits, at exposures near or below those achieved in human transplant patients.

Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data Everolimus crossed the placenta and was toxic to the conceptus.

Everolimus administered daily to pregnant rats by oral gavage at 0.1 mg/kg (approximately one tenth the exposure in humans administered the lowest starting dose of 0.75 mg twice daily), from before mating through organogenesis, resulted in increased preimplantation loss and embryonic resorptions. These effects occurred in the absence of maternal toxicities. Everolimus administered daily by oral gavage to pregnant rabbits during organogenesis resulted in abortions, maternal toxicity and lethality, and increased fetal resorptions.

At these doses, exposure to everolimus (AUC) was approximately one-tenth-, one-half-, and one- and one-half-fold the exposures in humans administered the starting clinical dose, respectively. In a pre- and post-natal development study in rats, animals were dosed from implantation through lactation. At a dose of 0.1 mg/kg (0.6 mg/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 Zortress in human milk, the effects on breastfed infants, or the effects on milk production. Everolimus and/or its metabolites are readily transferred into milk of lactating rats at a concentration 3.5 times higher than in maternal rat serum. In pre-post-natal and juvenile studies in rats, exposure to everolimus during the postnatal period caused developmental toxicity [see Use in Specific Populations (8.1), Nonclinical Toxicology (13.2)] .

Advise lactating women not to breastfeed because of the potential for serious adverse reactions in infants exposed to everolimus.

8.3Females and Males of Reproductive Potential Contraception Females should not be pregnant or become pregnant while receiving Zortress. Advise females of reproductive potential that animal studies have been performed showing Zortress to be harmful to the mother and developing fetus [see Use in Specific Populations (8.1)] . Females of reproductive potential are recommended to use highly effective contraception methods while receiving Zortress and up to 8 weeks after treatment has been stopped.

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

Males Zortress treatment may impair fertility in males based on human [see Warnings and Precautions (5.…

🤰 Pregnancy ~1 min read ▾

There were no drug-related effects on the developmental parameters (morphological development, motor activity, learning, or fertility assessment) in the offspring.

🧒 Pediatric Use 26 words ▾

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

🧓 Geriatric Use 52 words ▾

8.5Geriatric Use There is limited clinical experience on the use of Zortress in patients of age 65 years or older. There is no evidence to suggest that elderly patients will require a different dosage recommendation from younger adult patients [ s ee C linical Pharmacology ( 12. 5 ) ] .

🆘 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 [ s ee 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 Zortress during steady-state cyclosporine treatment was 30 ± 11 hours (range: 19 to 53 hours).

12.5 Drug-Drug Interactions Everolimus…

🧬 Mechanism of Action 118 words ▾

📦 How Supplied / Storage and Handling 128 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Zortress (everolimus) tablets are packed in child-resistant blisters. Table 11. Description of Zortress (everolimus) Tablets Dosage strength 0.25 mg 0.5 mg 0.75 mg 1 mg Appearance White to yellowish, marbled, round, flat tablets with beveled edge Imprint “C” on one side and “NVR” on the other “CH” on one side and “NVR” on the other “CL” on one side and “NVR” on the other “CU” on one side and “NVR” on the other NDC number 0078-0417-20 0078-0414-20 0078-0415-20 0078-0422-20 Each strength is available in boxes of 60 tablets (6 blister strips of 10 tablets each).

Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Protect from light and moisture.

📋 Description 129 words ▾

11 DESCRIPTION Zortress (everolimus) 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: Zortress 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, lactose anhydrous, lactose monohydrate, and magnesium stearate as inactive ingredients. Zortress structural formula 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[30.3.1.04,9] hexatriaconta-16,24,26,28-tetraene-2, 3,10,14,20-pentaone.

💬 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 Zortress 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 Zortress [see Warnings and Precautions (5.20)] .

Advise patients that Zortress 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 Zortress. Inform patients of the necessity of repeated laboratory tests according to physician recommendations while they are taking Zortress.

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 [ s ee 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 [ s ee Warnings and Precautions (5.3, 5.1 3 ) ] . Kidney Graft Thrombosis Inform patients that Zortress has been associated with an increased risk of kidney arterial and venous thrombosis, resulting in graft loss, usually within the first 30 days posttransplantation [ s ee Warnings and Precautions ( 5.4 ) ] . Zortress and Calcineurin Inhibitor-Induced Nephrotoxicity Advise patients of the risks of impaired kidney function with the combination of Zortress and cyclosporine as well as the need for routine blood concentration monitoring for both drugs.

Advise patients of the importance of serum creatinine monitoring [ s ee Warning s 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 [ s ee Warnings and Precautions ( 5. 8 ) ] . Wound Healing Complications and Fluid Accumulation Inform patients that the use of Zortress has been associated with impaired or delayed wound healing, fluid accumulation and the need for careful observation of their incision site [ s ee Warnings and Precautions ( 5.

9 ) ] . Interstitial Lung Disease (ILD)/Non-Infectious Pneumonitis Inform patients that the use of Zortress may increase the risk of non-infectious pneumonitis. Advise patients to seek medical attention if they develop clinical symptoms consistent with pneumonia [ s ee Warnings and Precautions (5.

10 )] . Hyperlipidemia Inform patients that the use of Zortress has been associated with increased serum cholesterol and triglycerides that may require treatment and the need for monitoring of blood lipid concentrations [ s ee Warnings and Precautions ( 5. 11 ) ] .

Proteinuria Inform patients that the use of Zortress has been associated with an increased risk of proteinuria [ s ee Warnings and Precautions ( 5.1 2 ) ] . Pregnancy and Lactation Advise women of childbearing age to avoid becoming pregnant throughout treatment and for 8 weeks after Zortress therapy has stopped. Zortress 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 Zortress [see Use in Specific Populations (8.1, 8.2)] . Male and Female Fertility Inform male and female patients that Zortress may impair fertility [see Warnings and Precautions (5.18), Use in Specific Populations (8.1, 8.3), Nonclinical Toxicology (13.1)] .

Medications That Interfere With Zortress Some medications can increase or dec…

💬 Medication Guide ~3 min read ▾

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: February 2024 MEDICATION GUIDE ZORTRESS [ZOR-tres] (everolimus) tablets, for oral use What is the most important information I should know about ZORTRESS?

ZORTRESS can cause serious side effects, including: Increased risk of getting certain cancers. People who take ZORTRESS have a higher chance of getting lymphoma and other cancers, especially skin cancer. Talk to your doctor about your risk for cancer.

Increased risk of serious infections. ZORTRESS weakens the body’s immune system and affects your ability to fight infections. Serious infections can happen with ZORTRESS that may lead to death.

People taking ZORTRESS have a higher chance of getting infections caused by viruses, bacteria, and fungi (yeast). Call your doctor if you have symptoms of infection, including fever or chills. Blood clot in the blood vessels of your transplanted kidney.

If this happens, it usually occurs within the first 30 days after your kidney transplant. Tell your doctor right away if you: have pain in your groin, lower back, side or stomach (abdomen) make less urine or you do not pass any urine have blood in your urine or dark colored urine (tea-colored) have fever, nausea, or vomiting Serious problems with your transplanted kidney (nephrotoxicity) . You will need to start with a lower dose of cyclosporine when you take it with ZORTRESS.

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

See the section “What are the possible side effects of ZORTRESS?” for information about other serious side effects. What is ZORTRESS? ZORTRESS is a prescription medicine used to prevent transplant rejection (antirejection medicine) 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. ZORTRESS is used with other medicines called cyclosporine, corticosteroids and certain other transplant medicines to prevent rejection of your transplanted kidney. ZORTRESS is used with other medicines called tacrolimus and corticosteroids to prevent rejection of your transplanted liver.

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

See the end of this Medication Guide for a complete list of ingredients in ZORTRESS. sirolimus (Rapamune ® ) Before taking ZORTRESS, 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 ZORTRESS if you have this disorder. are pregnant or could become pregnant. ZORTRESS 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 ZORTRESS. 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 ZORTRESS. are breastfeeding or plan to breastfeed. It is not known if ZORTRESS passes into your breast milk. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Especially tell your doctor if you take: antifungal medicine antibiotic medicine heart med…

Glossary — plain-language definitions of medical terms used in this label:

contraindicated: Should not be used in that situation, because the risk is considered too high.

immunosuppressant: A medicine that lowers the activity of the immune system.

immunosuppressive: Describes something that lowers the activity of the immune system.

in vitro: In a laboratory dish or test tube rather than in a living person or animal; results may not carry over to people.

in vivo: In a living person or animal rather than in a laboratory dish.

abdominal pain: Pain, cramping, or discomfort felt anywhere in the belly area.

Absorption: How a medicine moves from where it is taken, such as the stomach or gut, into the bloodstream.

accumulation: A buildup of a medicine in the body when new doses are taken before earlier ones are fully removed.

adverse reaction: An unwanted or harmful effect that a medicine causes in the body.

Adverse Reactions: Unwanted or harmful effects that people experienced while taking a medicine, listed on its official label.

amenorrhea: The absence of monthly menstrual periods.

anemia: A low level of red blood cells or the oxygen-carrying protein inside them, which can cause tiredness, weakness, and paleness.

angioedema: Rapid swelling deep under the skin, often around the eyes, lips, tongue, or throat.

AUC: A measure of total drug exposure over time, showing how much medicine the blood is exposed to overall.

Boxed Warning: The strongest safety warning the FDA can require, set inside a bold black border because the risk it describes can be very serious.

Clinical Pharmacology: The label section explaining how a medicine works in the body and how the body processes it.

Clinical Studies: The label section summarizing the research trials used to show that a medicine works and is acceptably safe.

constipation: Having bowel movements less often than usual, or passing stools that are hard, dry, and difficult to move.

contraception: Methods used to prevent pregnancy, such as birth control pills, condoms, or an intrauterine device.

Contraindications: A list of situations or health conditions in which a medicine should not be used because the chance of harm is too high.

CYP2D6: A liver enzyme that breaks down many medicines; people inherit different versions, so it works faster in some and slower in others.

CYP3A4: One of the most important liver and gut enzymes, responsible for breaking down a large share of all medicines.

diarrhea: Loose, watery bowel movements that happen more often than normal.

Distribution: How a medicine spreads from the blood into the body's tissues and organs after it is absorbed.

Dosage and Administration: The label section explaining how much of a medicine to use and how to take or give it.

dose reduction: Lowering the amount of a medicine, often to ease side effects or fit a person's needs.

Drug Interactions: The label section listing other medicines, foods, or substances that can change how a medicine works or raise the chance of side effects.

edema: Swelling caused by extra fluid trapped in the body's tissues.

efficacy: How well a treatment works under the controlled conditions of a clinical study.

Elimination: The overall removal of a medicine from the body by breaking it down and passing it out.

embryo-fetal toxicity: Harm to a developing baby in the womb, such as birth defects, slowed growth, or loss of the pregnancy.

estimated background risk: The normal chance that any pregnancy will have a birth defect or problem, even without taking any medicine.

Excretion: How the body removes a medicine or its leftover pieces, mainly through the urine or stool.

fertility: The natural ability to become pregnant or to father a child.

fetal harm: Injury or damage to a developing baby while it is growing inside the womb.

food effect: A change in how much or how fast a medicine is absorbed when it is taken with food.

Full Prescribing Information: The complete, detailed label for a prescription medicine that follows the summary highlights.

Half-life: The time it takes for the amount of medicine in the blood to drop by half.

hemodialysis: A treatment that uses a machine to filter waste and extra fluid from the blood when the kidneys cannot.

hepatic impairment: Reduced liver function, meaning the liver does not work as well as normal at processing substances, including medicines.

How Supplied/Storage and Handling: The label section describing the forms and strengths a medicine comes in and how to store it properly.

hypercholesterolemia: A higher-than-normal level of cholesterol, a type of fat, in the blood.

hypersensitivity: An overreaction of the body's defense system to a substance, causing symptoms such as rash, swelling, or trouble breathing.

hypertension: Blood pressure that stays higher than normal, commonly called high blood pressure.

immunosuppression: A weakening of the body's defense system, which makes it harder to fight off infections.

incidence: How often a new event, such as a side effect, happens in a group of people over a set period of time.

Indications and Usage: The label section stating which medical conditions the FDA has officially approved the medicine to treat, prevent, or manage.

inhibitor: A substance that blocks an enzyme or transporter, which can raise the levels of drugs it normally handles.

interstitial lung disease: A group of conditions in which the tissue around the lungs' air sacs becomes scarred or inflamed, making breathing harder.

lactation: The making and release of milk from a mother's breasts after giving birth.

leukopenia: A low level of white blood cells, the cells that help the body fight off infections.

maintenance dose: The regular ongoing dose taken to keep a steady, effective amount of medicine in the body over time.

Mechanism of Action: How a medicine produces its effect in the body, described at the level of cells or body chemistry.

Medication Guide: An FDA-approved handout written for patients that explains important safety information about certain medicines in plain language.

Metabolism: How the body chemically changes a medicine, usually in the liver, into other substances.

narrow therapeutic index: Describes a medicine where the helpful dose and the harmful dose are very close, so small changes in the amount matter a lot.

NDC: A unique number that identifies a specific medicine, its maker, strength, and package size.

nephrotoxicity: Damage to the kidneys caused by a medicine or other substance.

Nonclinical Toxicology: The label section summarizing safety findings from laboratory and animal studies, rather than from studies in people.

open-label: A study in which both the patients and their doctors know which treatment each person is receiving.

organogenesis: The early stage of pregnancy when the developing baby's organs are first forming.

Overdosage: The label section describing what can happen if too much of a medicine is taken and how it may be treated.

P-glycoprotein: A tiny pump in cells that pushes certain medicines back out, affecting how much of a medicine is absorbed or stays in the body.

P-gp: A protein pump in cells that pushes certain drugs back out, limiting how much is absorbed or reaches tissues.

p-value: A number showing how likely a result could have happened by chance; smaller numbers make the result more convincing.

Patient Counseling Information: The label section telling health professionals what to explain to patients about using a medicine safely.

peripheral edema: Swelling, usually in the feet, ankles, or legs, caused by extra fluid building up in the tissues.

pharmacokinetic interaction: When one medicine changes how the body absorbs, spreads, breaks down, or removes another, altering its level in the blood.

Pharmacokinetics: The study of how the body takes in a medicine, spreads it around, breaks it down, and removes it over time.

pneumonitis: Inflammation of the lung tissue that is not caused by an infection and can lead to cough and breathlessness.

Prescribing Information: The official, detailed document approved by the FDA that tells health professionals how to use a prescription medicine.

prophylaxis: Treatment given to prevent an infection or illness before it starts, rather than to treat one that is already present.

protein binding: How much of a medicine sticks to proteins in the blood instead of moving freely through the body.

proteinuria: Protein leaking into the urine, which can be a sign that the kidneys' filters are damaged.

purpura: Purple spots or patches on the skin caused by bleeding just under the surface.

pyrexia: A raised body temperature; a fever.

randomized: Assigned to a treatment group purely by chance, like a coin flip, so the groups being compared start out fair and similar.

reproductive potential: The ability to have children, meaning a person who could become pregnant or could father a child.

serum creatinine: A waste product measured in a blood test; higher levels can mean the kidneys are not filtering as well as normal.

substrate: A drug or other substance that a particular enzyme or transporter acts on.

therapeutic drug monitoring: Measuring the amount of a medicine in the blood to keep it in a safe and effective range.

therapeutic index: A measure of how much room there is between a helpful dose of a medicine and a dose that could be harmful.

thrombosis: The forming of a blood clot inside a blood vessel, which can block normal blood flow.

trough: The lowest level a medicine reaches in the blood, just before the next dose is due.

Use in Specific Populations: The label section describing how a medicine affects particular groups, such as pregnant people, children, or older adults.

Warnings and Precautions: The label section describing serious risks to know about and safety steps to follow while using a medicine.

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

← 00078-0406-05 · Novartis 00078-0415-20 · Novartis →

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.

Zortress everolimus .5 mg Tablet, 60-count

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