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Tacrolimus 1 mg Capsule, 9,000-count

by Aphena Pharma Solutions - Tennessee, LLC · 9000 CAPSULE in 1 BOTTLE, PLASTIC (43353-317-09)

NDC 43353-0317-09

🏷️ FDA NDC (as labeled) 43353-317-09 billing pads the product segment with a zero

Rx only Generic 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

⚠️

Other active recalls for Tacrolimus (different manufacturers) — 3 · tap to view

These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.

Class I · Dec 23, 2024 — Failed Tablet/Capsule Specifications: Bottles shipped to the USA may contain empty capsules (Astellas Pharma US Inc.) · FDA recall D-0211-2025

Class II · Feb 8, 2023 — Presence of Foreign Tablets/Capsules: Presence of one Tacrolimus 1 mg capsule co-mingled in a bottle containing and labeled as Tacrolimus 0.5 mg capsules. (Dr. Reddy's Laboratories, Inc.) · FDA recall D-0330-2023

Class III · Jul 11, 2022 — Defective Container: Tube split from side seam (Glenmark Pharmaceuticals Inc., USA) · FDA recall D-1304-2022

Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

🆔 Identity & classification

FDA NDC (as labeled) 43353-317-09

Product NDC 43353-317

11-digit billing NDC 43353031709

NCPDP billing unit EA — each (per item)

RxCUI 198377

UNII WM0HAQ4WNM

Application # ANDA090596

SPL Set ID 4caa20af-45a8-4365-9f06-1568afae61b1

Established class (EPC) Calcineurin Inhibitor Immunosuppressant

Mechanism of action Calcineurin Inhibitors

DEA schedule Non-controlled

Marketing category ANDA

Marketing status On market

FDA listing status Listed (active directory)

Marketing start 2015-11-18

Route ORAL

Dosage form CAPSULE

Substance TACROLIMUS

GPI-14 99404080000110

GPI class Tacrolimus

GCN Seq No 021796

GCN 28491

HICL code 020974

Ingredient (HICL) Tacrolimus

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 84:06.28.00

AHFS class Immunomodulatory Agents (84:06)

FDB label name TACROLIMUS 1 MG CAPSULE (IR)

FDB brand name Tacrolimus

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 43353-317-09 — 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 → 43353-0317-09. 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 Calcineurin Inhibitor Immunosuppressant class.

Pharmacologic class Calcineurin Inhibitor Immunosuppressant

Drug family (ATC) Agents for dermatitis, excluding corticosteroids, Calcineurin inhibitors

How it works Calcineurin 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

LabelerAphena Pharma Solutions - Tennessee, LLC

Application holderMYLAN PHARMACEUTICALS INC

FDA applicationANDA090596 (ANDA)

Labeler code43353

First marketedNov 2015

Product typeHuman Prescription Drug

Portfolio795 products on file

🔎 All NDCs from Aphena Pharma Solutions - Tennessee, LLC

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 TACROLIMUS 1 MG CAPSULE (IR) Ingredient Tacrolimus

📖 What it is MedlinePlus · NLM

Tacrolimus (Astagraf XL, Envarsus XR, Prograf) is used along with other medications to prevent rejection (attack of a transplanted organ by the immune system of a person receiving the organ) in people who have received a kidney transplant. Tacrolimus (Prograf) is also used along with other medications to prevent rejection in people who have received a liver, lung, or heart transplant. Tacrolimus is in a class of medications called immunosupressants. It works by decreasing the activity of the immune system to prevent it from attacking the transplanted organ.

Read the full MedlinePlus article ↗

📗 Our plain-language guide HelloPharmacist

That's a great question, and it's one of the most important things to understand. Your body's immune system doesn't just stop trying to attack the new organ once you leave the hosp...
Why do I have to take tacrolimus even when I feel completely fine?
It actually does matter — but the key is being consistent, not choosing one over the other. Food can change how much tacrolimus your body absorbs, so if you always take it the same...
Does it matter if I take tacrolimus with food or on an empty stomach?

📖 Read our full Tacrolimus guide →

Patient education

📘 MedlinePlus patient leaflet ↗

Supplement & herbal interactions

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

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

🌿 Every supplement checked against Tacrolimus (202 interactions) — ranked by severity →

Nutrient depletion considerations

Tacrolimus may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.

MAGNESIUM Major Depletion

🧪 Full Tacrolimus nutrient depletion report →

An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.

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 Gray / Blue

ShapeCapsule

ImprintMYLAN;2046

Size14 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 M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
UNII 35SW5USQ3G
A synthetic yellow dye used to color medicines. It helps make tablets, capsules, and liquids visually distinct so patients can easily identify their medication.
UNII H3R47K3TBD
FD&C Blue No. 1 is a synthetic blue dye approved for use in foods and medicines. It serves as a colorant to give the medication its distinctive appearance and help with product identification.
UNII L06K8R7DQK
A synthetic blue dye approved by the FDA for use in medications and foods. It serves as a colorant to make pills and liquids visually distinct and easier to identify.
UNII PN2ZH5LOQY
A synthetic red dye approved by the FDA for use in foods, medicines, and cosmetics. It serves as a colorant to make tablets, capsules, and liquids visually distinctive for product identification.
UNII WZB9127XOA
A synthetic red dye used to color medications and make them easier to identify. It serves as a colorant in tablets, capsules, and liquid formulations.
UNII EX438O2MRT
Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
UNII XM0M87F357
A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
UNII 2G86QN327L
Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
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.
UNII 6DC9Q167V3
Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
UNII 46N107B71O
Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
UNII 368GB5141J
A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.

18 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	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 · Q2 2026	$0.3779	$3,401.10 / 9000 capsules

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.

🔁 Therapeutic equivalents

Product	Labeler	Pack	NADAC/unit	TE	Status	Price vs. this
Tacrolimus 1 mg 00378-2046-01	Mylan	100 capsules	$0.152	AB	Availability likely	—
Tacrolimus 1 mg 00781-2103-01	Sandoz	100 capsules	$0.152	AB	Availability likely	—
Tacrolimus 1 mg 00904-7097-61	Major	100 capsules	$0.152	AB	Availability likely	—
tacrolimus 1 mg 16714-0099-01	NORTHSTAR	100 capsules	$0.152	AB	Availability likely	—
Tacrolimus 1 mg 51079-0818-20	MylanInstitutional	100 capsules	$0.152	AB	Availability likely	—
Tacrolimus 1 mg 55111-0526-01	Dr.	100 capsules	$0.152	AB	Availability likely	—
Tacrolimus 1 mg 59746-0799-01	Jubilant	100 capsules	$0.152	AB	Availability likely	—
Tacrolimus 1 mg 67877-0279-01	Ascend	100 capsules	$0.152	AB	Availability likely	—
Tacrolimus 1 mg 68084-0450-01	American	100 capsules	$0.152	AB	Availability likely	—
tacrolimus 1 mg 68462-0686-01	Glenmark	100 capsules	$0.152	AB	Availability likely	—
Tacrolimus 1 mg 70377-0015-11	Biocon	100 capsules	$0.152	AB	Availability likely	—
Tacrolimus 1 mg 82009-0054-01	Quallent	100 capsules	$0.152	AB	Availability likely	—
Tacrolimus 1 mg 85972-0102-01	Stellon	100 capsules	$0.152	AB	Availability likely	—
Tacrolimus 1 mg 16729-0042-01	Accord	100 capsules	$0.161	BX	Availability likely	—
Prograf 1 mg 00469-0617-73	Astellas	100 capsules	$7.315	AB	Availability likely	—
Tacrolimus 1 mgthis 43353-0317-09	Aphena	9000 capsules	—	AB	FDA listed	—
Tacrolimus 1 mg 43817-0422-01	Panacea	100 capsules	—	AB	FDA listed	—
Tacrolimus 1 mg 48433-0093-20	Safecor	100 capsules	—	AB	FDA listed	—
tacrolimus 1 mg 50090-5581-00	A-S	90 capsules	—	AB	FDA listed	—
Tacrolimus 1 mg 50090-5596-00	A-S	90 capsules	—	AB	FDA listed	—
Tacrolimus 1 mg 54288-0135-01	BPI	100 capsules	—	AB	FDA listed	—
Tacrolimus 1 mg 55154-4080-08	Cardinal	2000 capsules	—	AB	FDA listed	—
Tacrolimus 1 mg 55154-4168-00	Cardinal	10 capsules	—	AB	FDA listed	—
Tacrolimus 1 mg 60429-0378-01	Golden	100 capsules	—	AB	FDA listed	—
Tacrolimus 1 mg 63629-8723-01	Bryant	100 capsules	—	AB	FDA listed	—
Tacrolimus 1 mg 63629-9325-01	Bryant	60 capsules	—	BX	FDA listed	—
Tacrolimus 1 mg 64380-0721-01	Strides	100 capsules	—	AB	FDA listed	—
Tacrolimus 1 mg 65897-0010-02	Hangzhou	100 capsules	—	—	FDA listed	—
Tacrolimus 1 mg 68254-5005-01	CONCORD	100 capsules	—	AB	FDA listed	—
Tacrolimus 1 mg 72189-0536-30	Direct_Rx	30 capsules	—	AB	FDA listed	—
Tacrolimus 1 mg 82804-0032-30	Proficient	30 capsules	—	AB	FDA listed	—
Tacrolimus 1 mg 82983-0401-10	Ajenat	100 capsules	—	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

🏛️

2015

On the market since

Nov 2015

📍

2026

Currently FDA-listed

11 years listed

🔓

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.

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

Medicare Part D (outpatient prescription) spending for Tacrolimus — the program that covers self-administered drugs. 16 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 Tacrolimus. 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

$21.27M

Claims incl. refills

205.6K

Beneficiaries

143K

Spend / beneficiary

$148.76

Spend / claim

$103.47

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.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Tacrolimus — the ingredient across all brands.

Top reported reactions

Drug Interaction6,430

Acute Kidney Injury6,154

Diarrhoea5,965

Death5,065

Transplant Rejection5,034

Pyrexia4,886

Cytomegalovirus Infection4,655

Reporter sex

Serious outcomes

Death25,785

Disabling2,296

Reports over time (by year) — tap or hover for the count & year

Most recent year is provisional (FAERS lags ~3 months).

Where does this data come from?

Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDC	Description	Marketing start	Status
43353-0317-09 You're viewing this	9000 CAPSULE in 1 BOTTLE, PLASTIC (43353-317-09)	2017-05-03	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	— 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 FDA registers it as 43353-317-09, 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: 43353-0317-09, written without dashes as 43353031709. 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 43353-0317-09, the first segment (43353) is the labeler code FDA assigned to Aphena Pharma Solutions - Tennessee, LLC; the middle segment (0317) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (09) 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 Aphena Pharma Solutions - Tennessee, LLC. Listing status can change — the directory data on this page refreshes weekly.

Who lists this product with the FDA?

Aphena Pharma Solutions - Tennessee, 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.

📄 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 📦 Storage and Handling 📋 Description 💬 Information for Patients

🚨 Boxed Warning 178 words ▾

WARNING: MALIGNANCIES AND SERIOUS INFECTIONSBOXED WARNING – MALIGNANCIES AND SERIOUS INFECTIONS • Increased risk of development of lymphoma and other malignancies, particularly of the skin, due to immunosuppression ( 5.2 ) • Increased susceptibility to bacterial, viral, fungal, and protozoal infections, including opportunistic infections ( 5.3 , 5.4 , 5.5 ) • Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe tacrolimus capsules ( 5.1 ) • Increased risk of development of lymphoma and other malignancies, particularly of the skin, due to immunosuppression [see Warnings and Precautions (5.2) ] . • Increased susceptibility to bacterial, viral, fungal, and protozoal infections, including opportunistic infections [see Warnings and Precautions (5.3 , 5.4 , 5.5) ] . • Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe tacrolimus capsules.

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) ].

🎯 Indications and Usage ~2 min read ▾

1 INDICATIONS AND USAGE Tacrolimus capsules, USP are a calcineurin-inhibitor immunosuppressant indicated for: • Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney or heart transplants ( 1.1 , 1.2 , 1.3 ) • Use concomitantly with adrenal corticosteroids; in kidney and heart transplant, use in conjunction with azathioprine or mycophenolate mofetil (MMF) ( 1.1 , 1.2 , 1.3 ) • Limitations of Use ( 1.4 ): • Do not use simultaneously with cyclosporine • Intravenous use reserved for patients who cannot tolerate capsules orally • Use with sirolimus is not recommended in liver and heart transplant; use with sirolimus in kidney transplant has not been established

1.1Prophylaxis of Organ Rejection in Kidney Transplant Tacrolimus capsules, USP are indicated for the prophylaxis of organ rejection in patients receiving allogeneic kidney transplants. It is recommended that tacrolimus capsules be used concomitantly with azathioprine or mycophenolate mofetil (MMF) and adrenal corticosteroids [see Clinical Studies (14.1) ] . Therapeutic drug monitoring is recommended for all patients receiving tacrolimus capsules [see Dosage and Administration (2.6) ].

1.2Prophylaxis of Organ Rejection in Liver Transplant Tacrolimus capsules are indicated for the prophylaxis of organ rejection in patients receiving allogeneic liver transplants. It is recommended that tacrolimus capsules be used concomitantly with adrenal corticosteroids [see Clinical Studies (14.2) ] . Therapeutic drug monitoring is recommended for all patients receiving tacrolimus capsules [see Dosage and Administration (2.6) ] .

1.3Prophylaxis of Organ Rejection in Heart Transplant Tacrolimus capsules are indicated for the prophylaxis of organ rejection in patients receiving allogeneic heart transplants. It is recommended that tacrolimus capsules be used concomitantly with azathioprine or mycophenolate mofetil (MMF) and adrenal corticosteroids [see Clinical Studies (14.3) ] . Therapeutic drug monitoring is recommended for all patients receiving tacrolimus capsules [see Dosage and Administration (2.6) ] .

1.4Limitations of Use Tacrolimus capsules should not be used simultaneously with cyclosporine [see Dosage and Administration (2.5) ] . Tacrolimus injection should be reserved for patients unable to take tacrolimus capsules orally [see Warnings and Precautions (5.11) ]. Use with sirolimus is not recommended in liver and heart transplant.

The safety and efficacy of tacrolimus capsules with sirolimus has not been established in kidney transplant [see Warnings and Precautions (5.12) ].

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Summary of Initial Oral Dosage Recommendation and Observed Whole Blood Trough Concentrations ( 2.1 , 2.2 ) Patient Population Recommended Initial Oral Dosage (two divided doses every 12 hours) Observed Whole Blood Trough Concentrations Adult Kidney transplant In combination with azathioprine 0.2 mg/kg/day month 1 to 3: 7 to 20 ng/mL month 4 to 12: 5 to 15 ng/mL In combination with MMF/IL-2 receptor antagonist 0.1 mg/kg/day month 1 to 12: 4 to 11 ng/mL Adult Liver transplant Pediatric Liver transplant 0.10 to 0.15 mg/kg/day 0.15 to 0.20 mg/kg/day month 1 to 12: 5 to 20 ng/mL month 1 to 12: 5 to 20 ng/mL Adult Heart transplant 0.075 mg/kg/day month 1 to 3: 10 to 20 ng/mL month ≥ 4: 5 to 15 ng/mL • Careful and frequent monitoring of tacrolimus trough concentrations is recommended; Black patients may require higher doses in order to achieve comparable trough concentrations ( 2.1 ) • Hepatic/Renal impaired patients should receive doses at the lowest value of the recommended initial oral dosing range ( 2.3 , 2.4 ) • Administer capsules consistently with or without food; do not drink grapefruit juice ( 2.5 , 7.2 )

2.1Dosage in Adult Kidney, Liver, or Heart Transplant Patients The initial oral dosage recommendations for adult patients with kidney, liver, or heart transplants along with recommendations for whole blood trough concentrations are shown in Table 1. The initial dose of tacrolimus capsules should be administered no sooner than 6 hours after transplantation in the liver and heart transplant patients. In kidney transplant patients, the initial dose of tacrolimus capsules may be administered within 24 hours of transplantation, but should be delayed until renal function has recovered.

For blood concentration monitoring details see Dosage and Administration (2.6) . Table 1. Summary of Initial Oral Dosage Recommendations and Observed Whole Blood Trough Concentrations in Adults Patient Population Recommended Tacrolimus Capsules Initial Oral Dosage Note: daily doses should be administered as two divided doses, every 12 hours Observed Tacrolimus Whole Blood Trough Concentrations Adult kidney transplant patients In combination with azathioprine 0.2 mg/kg/day month 1 to 3: 7 to 20 ng/mL month 4 to 12: 5 to 15 ng/mL In combination with MMF/IL-2 receptor antagonist In a second smaller trial, the initial dose of tacrolimus was 0.15 to 0.2 mg/kg/day and observed tacrolimus concentrations were 6 to 16 ng/mL during month 1 to 3 and 5 to 12 ng/mL during month 4 to 12 [see Clinical Studies (14.1) ].

0.1mg/kg/day month 1 to 12: 4 to 11 ng/mL Adult liver transplant patients 0.10 to 0.15 mg/kg/day month 1 to 12: 5 to 20 ng/mL Adult heart transplant patients 0.075 mg/kg/day month 1 to 3: 10 to 20 ng/mL month ≥ 4: 5 to 15 ng/mL Dosing should be titrated based on clinical assessments of rejection and tolerability. Lower tacrolimus dosages than the recommended initial dosage may be sufficient as maintenance therapy. Adjunct therapy with adrenal corticosteroids is recommended early post-transplant.

The data in kidney transplant patients indicate that the Black patients required a higher dose to attain comparable trough concentrations compared to Caucasian patients (Table 2). Table 2. Comparative Dose and Trough Concentrations Based on Race Time After Transplant Caucasian n = 114 Black n = 56 Dose (mg/kg) Trough Concentrations (ng/mL) Dose (mg/kg) Trough Concentrations (ng/mL) Day 7 0.18 12 0.23

10.9Month 1 0.17 12.8 0.26

12.9Month 6 0.14 11.8 0.24

11.5Month 12 0.13 10.1 0.19 11 Anaphylactic reactions have occurred with injectables containing castor oil derivatives, such as tacrolimus injection [see Warnings and Precautions (5.11) ] .

2.2Dosage in Pediatric Liver Transplant Patients The initial oral dosage recommendations for pediatric patients with liver transplants along with recommendations for whole blood trough concentrations are shown in Table 3. For blood concentration monitoring details see Dosage and Administr…

💊 Dosage Forms and Strengths 146 words ▾

3 DOSAGE FORMS AND STRENGTHS • The 0.5 mg capsule is a hard-shell gelatin capsule with a light orange opaque cap and a gray opaque body filled with white to off-white powder, axially printed with MYLAN over 2045 in black ink on both the cap and the body. • The 1 mg capsule is a hard-shell gelatin capsule with a light blue opaque cap and a gray opaque body filled with white to off-white powder, axially printed with MYLAN over 2046 in black ink on both the cap and the body. • The 5 mg capsule is a hard-shell gelatin capsule with a rubine red opaque cap and a gray opaque body filled with white to off-white powder, axially printed with MYLAN over 2047 in black ink on both the cap and the body. • Capsules: 0.5 mg, 1 mg and 5 mg ( 3 )

⛔ Contraindications 61 words ▾

4 CONTRAINDICATIONS Tacrolimus capsules are contraindicated in patients with a hypersensitivity to tacrolimus. Tacrolimus injection is contraindicated in patients with a hypersensitivity to HCO-60 (polyoxyl 60 hydrogenated castor oil). Hypersensitivity symptoms reported include dyspnea, rash, pruritus, and acute respiratory distress syndrome [see Adverse Reactions (6) ] . • Hypersensitivity to tacrolimus or HCO-60 (polyoxyl 60 hydrogenated castor oil) ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Lymphoma and Other Malignancies: Risk of lymphomas, including post-transplant lymphoproliferative disorder (PLTD); appears related to intensity and duration of use. Avoid prolonged exposure to UV light and sunlight ( 5.2 ) • Serious infections: Increased risk of bacterial, viral, fungal and protozoal infections, including opportunistic infections: combination immunosuppression should be used with caution ( 5.3 ) • Polyoma Virus Infections: Serious, sometimes fatal outcomes, including polyoma virus-associated nephropathy (PVAN), mostly due to BK virus, and JC virus-associated progressive multifocal leukoencephalopathy (PML); consider reducing immunosuppression ( 5.4 ) • Cytomegalovirus (CMV) Infections: Increased risk of CMV viremia and disease; consider reducing immunosuppression ( 5.5 ) • New Onset Diabetes After Transplant: Monitor blood glucose ( 5.6 ) • Nephrotoxicity: Acute and/or chronic; reduce the dose; use caution with other nephrotoxic drugs ( 5.7 ) • Neurotoxicity: Risk of Posterior Reversible Encephalopathy Syndrome, monitor for neurologic abnormalities; reduce or discontinue tacrolimus and other immunosuppressants ( 5.8 ) • Hyperkalemia: Monitor serum potassium levels.

Careful consideration should be given prior to use of other agents also associated with hyperkalemia ( 5.9 ) • Hypertension: May require antihypertensive therapy. Monitor relevant drug-drug interactions ( 5.10 ) • Anaphylactic Reactions with IV formulation: Observe patients receiving tacrolimus injection for signs and symptoms of anaphylaxis ( 5.11 ) • Use with Sirolimus: Not recommended in liver and heart transplant due to increased risk of serious adverse reactions ( 5.12 ) • Myocardial Hypertrophy: Consider dosage reduction or discontinuation ( 5.15 ) • Immunizations: Use of live vaccines should be avoided ( 5.16 ) • Pure Red Cell Aplasia: Discontinuation should be considered ( 5.17 )

5.1Management of Immunosuppression Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should use tacrolimus. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physicians responsible for maintenance therapy should have complete information requisite for the follow up of the patient [see Boxed Warning ] .

5.2Lymphoma and Other Malignancies Patients receiving immunosuppressants, including tacrolimus, are at increased risk of developing lymphomas and other malignancies, particularly of the skin [see Boxed Warning ]. 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 UV light should be limited by wearing protective clothing and using a sunscreen with a high protection factor.

Post-transplant lymphoproliferative disorder (PTLD) has been reported in immunosuppressed organ transplant recipients. The majority of PTLD events appear related to Epstein Barr Virus (EBV) infection. The risk of PTLD appears greatest in those individuals who are EBV seronegative, a population which includes many young children.

5.3Serious Infections Patients receiving immunosuppressants, including tacrolimus, are at increased risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections [see Boxed Warning and Warnings and Precautions (5.4 , 5.5) ] . These infections may lead to serious, including fatal, outcomes. Because of the danger of oversuppression of the immune system which can increase susceptibility to infection, combination immunosuppressant therapy should be used with caution.

5.4Polyoma Virus Infections Patients receiving immunosuppressants, including tacrolimus, are at increased risk for opportunistic infections, including polyoma virus infections. Polyoma virus infections in transplant patients may have serious…

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling: • Lymphoma and Other Malignancies [see Boxed Warning , Warnings and Precautions (5.2) ] • Serious Infections [see Boxed Warning , Warnings and Precautions (5.3) ] • Polyoma Virus Infections [see Boxed Warning , Warnings and Precautions (5.4) ] • CMV Infections [see Boxed Warning , Warnings and Precautions (5.5) ] • New Onset Diabetes After Transplant [see Warnings and Precautions (5.6) ] • Nephrotoxicity [see Warnings and Precautions (5.7) ] • Neurotoxicity [see Warnings and Precautions (5.8) ] • Hyperkalemia [see Warnings and Precautions (5.9) ] • Hypertension [see Warnings and Precautions (5.10) ] • Anaphylaxis with Tacrolimus Injection [see Warnings and Precautions (5.11) ] • Myocardial Hypertrophy [see Warnings and Precautions (5.15) ] • Pure Red Cell Aplasia [see Warnings and Precautions (5.17) ] • Gastrointestinal Perforation [see Warnings and Precautions (5.18) ] • Kidney Transplant: The most common adverse reactions (≥ 30%) were infection, tremor, hypertension, abnormal renal function, constipation, diarrhea, headache, abdominal pain, insomnia, nausea, hypomagnesemia, urinary tract infection, hypophosphatemia, peripheral edema, asthenia, pain, hyperlipidemia, hyperkalemia, anemia ( 6.1 ) • Liver Transplant: The most common adverse reactions (≥ 40%) were tremor, headache, diarrhea, hypertension, nausea, abnormal renal function, abdominal pain, insomnia, paresthesia, anemia, pain, fever, asthenia, hyperkalemia, hypomagnesemia, and hyperglycemia ( 6.1 ) • Heart Transplant: The most common adverse reactions (≥ 15%) were abnormal renal function, hypertension, diabetes mellitus, CMV infection, tremor, hyperglycemia, leukopenia, infection, anemia, bronchitis, pericardial effusion, urinary tract infection and hyperlipemia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan Pharmaceuticals Inc. at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In addition, the clinical trials were not designed to establish comparative differences across study arms with regards to the adverse reactions discussed below. Kidney Transplant The incidence of adverse reactions was determined in three randomized kidney transplant trials.

One of the trials used azathioprine (AZA) and corticosteroids and two of the trials used mycophenolate mofetil (MMF) and corticosteroids concomitantly for maintenance immunosuppression. Tacrolimus-based immunosuppression in conjunction with azathioprine and corticosteroids following kidney transplantation was assessed in trial where 205 patients received tacrolimus-based immunosuppression and 207 patients received cyclosporine based immunosuppression. The trial population had a mean age of 43 years (mean ± sd was 43 ± 13 years on tacrolimus and 44 ± 12 years on cyclosporine arm), the distribution was 61% male, and the composition was White (58%), Black (25%), Hispanic (12%) and Other (5%).

The 12 month post-transplant information from this trial is presented below. The most common adverse reactions (≥ 30%) observed in tacrolimus-treated kidney transplant patients are: infection, tremor, hypertension, abnormal renal function, constipation, diarrhea, headache, abdominal pain, insomnia, nausea, hypomagnesemia, urinary tract infection, hypophosphatemia, peripheral edema, asthenia, pain, hyperlipidemia, hyperkalemia and anemia. Adverse reactions that occurred in ≥ 15% of kidney transplant patients treated with tacrolimus in conjunction with azathioprine are presented below: Table 4.

Kidney Transplantation: Adverse Reactions Occurring in ≥ 1…

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Since tacrolimus is metabolized mainly by CYP3A enzymes, drugs or substances known to inhibit these enzymes may increase tacrolimus whole blood concentrations. Drugs known to induce CYP3A enzymes may decrease tacrolimus whole blood concentrations [see Warnings and Precautions (5.13) and Clinical Pharmacology (12.3) ] . Dose adjustments may be needed along with frequent monitoring of tacrolimus whole blood trough concentrations when tacrolimus is administered with CYP3A inhibitors or inducers.

In addition, patients should be monitored for adverse reactions including changes in renal function and QT prolongation [see Warnings and Precautions (5.7) and (5.14) ] . • Mycophenolic Acid Products: Can increase MPA exposure after crossover from cyclosporine to tacrolimus; monitor for MPA-related adverse reactions and adjust MMF or MPA-dose as needed ( 7.1 ) • Nelfinavir and Grapefruit Juice: Increased tacrolimus concentrations via CYP3A inhibition; avoid concomitant use ( 7.2 , 7.3 ) • CYP3A Inhibitors: Increased tacrolimus concentrations; monitor concentrations and adjust tacrolimus dose as needed with concomitant use ( 5.13 , 7.3 , 7.4 , 7.5 , 7.6 ) • CYP3A4 Inducers: Decreased tacrolimus concentrations; monitor concentrations and adjust tacrolimus dose as needed with concomitant use ( 5.13 , 7.7 , 7.8 , 7.9 )

7.1Mycophenolic Acid Products With a given dose of mycophenolic acid (MPA) products, exposure to MPA is higher with tacrolimus co-administration than with cyclosporine co-administration because cyclosporine interrupts the enterohepatic recirculation of MPA while tacrolimus does not. Clinicians should be aware that there is also a potential for increased MPA exposure after crossover from cyclosporine to tacrolimus in patients concomitantly receiving MPA-containing products.

7.2Grapefruit Juice Grapefruit juice inhibits CYP3A-enzymes resulting in increased tacrolimus whole blood trough concentrations, and patients should avoid eating grapefruit or drinking grapefruit juice with tacrolimus [see Dosage and Administration (2.5) ] .

7.3Protease Inhibitors Most protease inhibitors inhibit CYP3A enzymes and may increase tacrolimus whole blood concentrations. It is recommended to avoid concomitant use of tacrolimus with nelfinavir unless the benefits outweigh the risks [see Clinical Pharmacology (12.3) ] . Whole blood concentrations of tacrolimus are markedly increased when co-administered with telaprevir or with boceprevir [see Clinical Pharmacology (12.3) ] .

Monitoring of tacrolimus whole blood concentrations and tacrolimus-associated adverse reactions, and appropriate adjustments in the dosing regimen of tacrolimus are recommended when tacrolimus and protease inhibitors (e.g., ritonavir, telaprevir, boceprevir) are used concomitantly.

7.4Antifungal Agents Frequent monitoring of whole blood concentrations and appropriate dosage adjustments of tacrolimus are recommended when concomitant use of the following antifungal drugs with tacrolimus is initiated or discontinued [see Clinical Pharmacology (12.3) ] . Azoles Voriconazole, posaconazole, itraconazole, ketoconazole, fluconazole and clotrimazole inhibit CYP3A metabolism of tacrolimus and increase tacrolimus whole blood concentrations. When initiating therapy with voriconazole or posaconazole in patients already receiving tacrolimus, it is recommended that the tacrolimus dose be initially reduced to one-third of the original dose and the subsequent tacrolimus doses be adjusted based on the tacrolimus whole blood concentrations.

Caspofungin is an inducer of CYP3A and decreases whole blood concentrations of tacrolimus.

7.5Calcium Channel Blockers Verapamil, diltiazem, nifedipine, and nicardipine inhibit CYP3A metabolism of tacrolimus and may increase tacrolimus whole blood concentrations. Monitoring of whole blood concentrations and appropriate dosage adjustments of tacrolimus are recommended when these calcium channel blocking drugs and tacrolimus are used conco…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS • Pregnancy: Based on animal data may cause fetal harm. Use only if the potential benefit justifies the risk ( 8.1 ) • Nursing Mothers: Discontinue nursing taking into consideration importance of drug to mother ( 8.3 ) • Hepatic/Renal impaired patients: Administer at the lower end of the recommended starting dose. Monitor renal function in patients with impaired renal function ( 2.3 , 2.4 , 8.6 , 8.7 )

8.1Pregnancy Teratogenic Effects. Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. Tacrolimus is transferred across the placenta.

The use of tacrolimus during pregnancy in humans has been associated with neonatal hyperkalemia and renal dysfunction. Tacrolimus given orally to pregnant rabbits at 0.5 to 4.3 times the clinical dose and pregnant rats at 0.8 to 6.9 times the clinical dose was associated with an increased incidence of fetal death in utero , fetal malformations (cardiovascular, skeletal, omphalocele, and gallbladder agenesis) and maternal toxicity. Tacrolimus should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

In pregnant rabbits, tacrolimus at oral doses of 0.32 and 1 mg/kg, 0.5 to 4.3 times the clinical dose range (0.075 to 0.2 mg/kg) based on body surface area, was associated with maternal toxicity as well as an increased incidence of abortions. At the 1 mg/kg dose, fetal rabbits showed an increased incidence of malformations (ventricular hypoplasia, interventricular septal defect, bulbous aortic arch, stenosis of ductus arteriosus, interrupted ossification of vertebral arch, vertebral and rib malformations, omphalocele, and gallbladder agenesis) and developmental variations.

In pregnant rats, tacrolimus at oral doses of 3.2 mg/kg, 2.6 to 6.9 times the clinical dose range was associated with maternal toxicity, an increase in late resorptions, decreased numbers of live births, and decreased pup weight and viability. Tacrolimus, given orally to pregnant rats after organogenesis and during lactation at 1 and 3.2 mg/kg, 0.8 to 6.9 times the recommended clinical dose range was associated with reduced pup weights and pup viability (3.2 mg/kg only); among the high dose pups that died early, an increased incidence of kidney hydronephrosis was observed.

8.3Nursing Mothers Tacrolimus is excreted in human milk. As the effect of chronic exposure to tacrolimus in healthy infants is not established, patients maintained on tacrolimus should discontinue nursing taking into consideration importance of drug to the mother.

8.4Pediatric Use The safety and efficacy of tacrolimus in pediatric kidney and heart transplant patients have not been established. Successful liver transplants have been performed in pediatric patients (ages up to 16 years) using tacrolimus. Two randomized active-controlled trials of tacrolimus in primary liver transplantation included 56 pediatric patients.

Thirty-one patients were randomized to tacrolimus-based and 25 to cyclosporine-based therapies. Additionally, a minimum of 122 pediatric patients were studied in an uncontrolled trial of tacrolimus in living related donor liver transplantation. Pediatric patients generally required higher doses of tacrolimus to maintain blood trough concentrations of tacrolimus similar to adult patients [see Dosage and Administration (2.2) ].

8.5Geriatric Use Clinical trials of tacrolimus did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

8.6 Use in Renal Impairment The pharmacokinetics o…

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Teratogenic Effects. Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. Tacrolimus is transferred across the placenta.

🧒 Pediatric Use 107 words ▾

🧓 Geriatric Use 83 words ▾

🆘 Overdosage 195 words ▾

10 OVERDOSAGE Limited overdosage experience is available. Acute overdosages of up to 30 times the intended dose have been reported. Almost all cases have been asymptomatic and all patients recovered with no sequelae.

Acute overdosage was sometimes followed by adverse reactions consistent with those listed in Adverse Reactions (6) (including tremors, abnormal renal function, hypertension, and peripheral edema); in one case of acute overdosage, transient urticaria and lethargy were observed. Based on the poor aqueous solubility and extensive erythrocyte and plasma protein binding, it is anticipated that tacrolimus is not dialyzable to any significant extent; there is no experience with charcoal hemoperfusion. The oral use of activated charcoal has been reported in treating acute overdoses, but experience has not been sufficient to warrant recommending its use.

General supportive measures and treatment of specific symptoms should be followed in all cases of overdosage. In acute oral and IV toxicity studies, mortalities were seen at or above the following doses: in adult rats, 52 times the recommended human oral dose; in immature rats, 16 times the recommended oral dose; and in adult rats, 16 times the recommended human IV dose (all based on body surface area corrections).

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Tacrolimus inhibits T-lymphocyte activation, although the exact mechanism of action is not known. Experimental evidence suggests that tacrolimus binds to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin is then formed and the phosphatase activity of calcineurin-inhibited.

This effect may prevent the dephosphorylation and translocation of nuclear factor of activated T-cells (NF-AT), a nuclear component thought to initiate gene transcription for the formation of lymphokines (such as interleukin-2, gamma interferon). The net result is the inhibition of T-lymphocyte activation (i.e., immunosuppression). Tacrolimus prolongs the survival of the host and transplanted graft in animal transplant models of liver, kidney, heart, bone marrow, small bowel and pancreas, lung and trachea, skin, cornea, and limb.

In animals, tacrolimus has been demonstrated to suppress some humoral immunity and, to a greater extent, cell-mediated reactions such as allograft rejection, delayed type hypersensitivity, collagen-induced arthritis, experimental allergic encephalomyelitis, and graft versus host disease.

12.3Pharmacokinetics Tacrolimus activity is primarily due to the parent drug. The pharmacokinetic parameters (mean ± S.D.) of tacrolimus have been determined following intravenous (IV) and/or oral (PO) administration in healthy volunteers, and in kidney transplant, liver transplant, and heart transplant patients (Table 14). Table 14.

Pharmacokinetics Parameters (mean ± S.D.) of Tacrolimus in Healthy Volunteers and Patients Population N Route (Dose) Parameters C max (ng/mL) T max (hr) AUC (ng•hr/mL) t 1/2 (hr) CI (L/hr/kg) V (L/kg) Healthy Volunteers 8 IV (0.025 mg/kg/4hr) not applicable 598 AUC 0-120 ± 125 34.2 ± 7.7 0.040 ± 0.009 1.91 ± 0.31 16 PO (5 mg) 29.7 ± 7.2 1.6 ± 0.7 243 AUC 0-72 ± 73 34.8 ± 11.4 0.041 Corrected for individual bioavailability ± 0.008 1.94 ±

0.53IV (0.02 mg/kg/12 hr) 294 AUC 0-inf ± 262 18.8 ± 16.7 0.083 ± 0.050 1.41 ±

0.66Kidney Transplant Patients 26 PO (0.2 mg/kg/day) 19.2 ± 10.3 3 203 ± 42 not available PO (0.3 mg/kg/day) 24.2 ± 15.8 1.5 288 ± 93 Liver Transplant Patients 17 IV (0.05 mg/kg/12 hr) 3300 ± 2130 11.7 ± 3.9 0.053 ± 0.017 0.85 ±

0.30PO (0.3 mg/kg/day) 68.5 ± 30 2.3 ± 1.5 519 ± 179 11 IV (0.01 mg/kg/day as a continuous infusion) 954 AUC 0-t ± 334 23.6 ± 9.22 0.051 ± 0.015 Heart Transplant Patients 11 PO (0.075 mg/kg/day) Determined after the first dose 14.7 ± 7.79 2.1 [0.5 to 6] Median [range]

82.7AUC 0-12 ± 63.2 14 PO (0.15 mg/kg/day) 24.5 ± 13.7 1.5 [0.4 to 4] 142 ± 116 Due to intersubject variability in tacrolimus pharmacokinetics, individualization of dosing regimen is necessary for optimal therapy [see Dosage and Administration (2.6) ] . Pharmacokinetic data indicate that whole blood concentrations rather than plasma concentrations serve as the more appropriate sampling compartment to describe tacrolimus pharmacokinetics. Absorption Absorption of tacrolimus from the gastrointestinal tract after oral administration is incomplete and variable.

The absolute bioavailability of tacrolimus was 17 ± 10% in adult kidney transplant patients (N = 26), 22 ± 6% in adult liver transplant patients (N = 17), 23 ± 9% in adult heart transplant patients (N = 11) and 18 ± 5% in healthy volunteers (N = 16). A single dose trial conducted in 32 healthy volunteers established the bioequivalence of the 1 mg and 5 mg capsules. Another single dose trial in 32 healthy volunteers established the bioequivalence of the 0.5 mg and 1 mg capsules.

Tacrolimus maximum blood concentrations (C max ) and area under the curve (AUC) appeared to increase in a dose-proportional fashion in 18 fasted healthy volunteers receiving a single oral dose of 3 mg, 7 mg, and 10 mg. In 18 kidney transplant patients, tacrolimus trough concentrations from 3 to 30 ng/mL measured at 10 to 12 hours post-dose (C min ) correlated well with the AUC (correlati…

🧬 Mechanism of Action 155 words ▾

📦 How Supplied / Storage and Handling ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1Tacrolimus Capsules Tacrolimus capsules, USP are available containing the equivalent of 0.5 mg, 1 mg or 5 mg of anhydrous tacrolimus, USP. They are available as follows: The 0.5 mg capsule is a hard-shell gelatin capsule with a light orange opaque cap and a gray opaque body filled with white to off-white powder, axially printed with MYLAN over 2045 in black ink on both the cap and the body. They are available as follows: NDC 60429-377-01 bottles of 100 capsules The 1 mg capsule is a hard-shell gelatin capsule with a light blue opaque cap and a gray opaque body filled with white to off-white powder, axially printed with MYLAN over 2046 in black ink on both the cap and the body.

They are available as follows: NDC 60429-378-01 bottles of 100 capsules The 5 mg capsule is a hard-shell gelatin capsule with a rubine red opaque cap and a gray opaque body filled with white to off-white powder, axially printed with MYLAN over 2047 in black ink on both the cap and the body. They are available as follows: NDC 60429-379-01 bottles of 100 capsules Storage and Handling Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

PHARMACIST: Dispense a Patient Information Leaflet with each prescription.

📦 Storage and Handling 40 words ▾

Storage and Handling Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. PHARMACIST: Dispense a Patient Information Leaflet with each prescription.

📋 Description ~1 min read ▾

11 DESCRIPTION Tacrolimus capsules, USP are available for oral administration as capsules containing the equivalent of 0.5 mg, 1 mg or 5 mg of anhydrous tacrolimus. Inactive ingredients in capsules: anhydrous lactose, black iron oxide, colloidal silicon dioxide, croscarmellose sodium, gelatin, hypromellose, lactose monohydrate, magnesium stearate, sodium lauryl sulfate, titanium dioxide and yellow iron oxide. In addition, the 0.5 mg capsules contain D&C Red No.

28, D&C Yellow No. 10 and FD&C Red No. 40, the 1 mg capsules contain FD&C Blue No.

1 and FD&C Red No. 3 and the 5 mg capsules contain D&C Red No. 33, D&C Red No.

28, and D&C Yellow No. 10. The imprinting ink contains the following: black iron oxide, D&C Yellow No.

10 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, FD&C Red No.

40 Aluminum Lake, propylene glycol and shellac glaze. Tacrolimus, previously known as FK506, is the active ingredient in tacrolimus capsules. Tacrolimus is a macrolide immunosuppressant produced by Streptomyces tsukubaensis .

Chemically, tacrolimus is designated as (-)-(3 S ,4 R ,5 S ,8 R ,9 E ,12 S ,14 S ,15 R ,16 S ,18 R ,19 R ,26a S )-8-allyl-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy-3-[( E )-2-[(1 R ,3 R ,4 R )-4-hydroxy-3-methoxycyclohexyl]-1-methylvinyl]-14,16-dimethyoxy-4,10,12,18-tetramethyl-15,19-epoxy-3 H -pyrido[2,1- c ][1,4]oxaazacyclotricosine-1,7,20,21(4 H ,23 H )-tetrone-monohydrate. The chemical structure of tacrolimus is: Tacrolimus has a molecular formula of C 44 H 69 NO 12 •H 2 O and a formula weight of 822.03.

Tacrolimus, USP appears as a white to off-white powder. It is insoluble in water, freely soluble in ethanol, very soluble in chloroform and soluble in methanol. USP Dissolution Test Pending.

Chemical Structure-TACROLIMUS

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION

17.1Administration Advise patients to: • Take tacrolimus capsules at the same 12 hour intervals everyday to achieve consistent blood concentrations. • Take tacrolimus capsules consistently either with or without food because the presence and composition of food decreases the bioavailability of tacrolimus capsules. • Not to eat grapefruit or drink grapefruit juice in combination with tacrolimus capsules [see Drug Interactions (7.2) ].

17.2Development of Lymphoma and Other Malignancies Inform patients they are at increased 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 use a sunscreen with a high protection factor [see Warnings and Precautions (5.2) ] .

17.3Increased Risk of Infection Inform patients they are at increased risk of developing a variety of infections, including opportunistic infections, due to immunosuppression and to contact their physician if they develop any symptoms of infection [see Warnings and Precautions (5.3 , 5.4 , 5.5) ] .

17.4New Onset Diabetes After Transplant Inform patients that tacrolimus capsules can cause diabetes mellitus and should be advised to contact their physician if they develop frequent urination, increased thirst or hunger [see Warnings and Precautions (5.6) ] .

17.5Nephrotoxicity Inform patients that tacrolimus capsules can have toxic effects on the kidney that should be monitored. Advise patients to attend all visits and complete all blood tests ordered by their medical team [see Warnings and Precautions (5.7) ] .

17.6Neurotoxicity Inform patients that they are at risk of developing adverse neurologic effects including seizure, altered mental status, and tremor. Advise patients to contact their physician should they develop vision changes, deliriums, or tremors [see Warnings and Precautions (5.8) ] .

17.7Hyperkalemia Inform patients that tacrolimus capsules can cause hyperkalemia. Monitoring of potassium levels may be necessary, especially with concomitant use of other drugs known to cause hyperkalemia [see Warnings and Precautions (5.9) ] .

17.8Hypertension Inform patients that tacrolimus capsules can cause high blood pressure which may require treatment with antihypertensive therapy [see Warnings and Precautions (5.10) ] .

17.9Drug Interactions Instruct patients to tell their health care providers when they start or stop taking all the medicines, including prescription medicines and non-prescription medicines, natural or herbal remedies, nutritional supplements and vitamins [see Drug Interactions (7) ].

17.10Pregnant Women and Nursing Mothers Instruct patients to tell their healthcare provider if they plan to become pregnant or breastfeed their infant [see Use in Specific Populations (8.1 , 8.3) ].

17.11Immunizations Inform patients that tacrolimus capsules can interfere with the usual response to immunizations and that they should avoid live vaccines [see Warnings and Precautions (5.16) ].

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.

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.

Active ingredient: The part of a medicine that produces its intended effect on the body.

active-controlled: Describes a study that compares a new medicine against another medicine already known to work, instead of a dummy pill.

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.

anaphylaxis: A sudden, severe, whole-body allergic reaction that can cause trouble breathing, swelling, and a drop in blood pressure, needing emergency care.

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

antagonist: A substance that blocks a target in the body so a natural signal or another medicine cannot produce its usual effect.

asthenia: Unusual weakness or lack of physical strength and energy.

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

Bioavailability: The share of a dose that actually reaches the bloodstream and is able to have an effect.

bioequivalence: A measure showing two versions of a medicine deliver the same amount of drug into the body at the same rate.

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.

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

crossover: A study design in which each person takes one treatment for a time, then switches to the other, acting as their own comparison.

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.

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.

dyspnea: The medical word for shortness of breath, or the feeling that you cannot get enough air.

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.

encephalopathy: Any condition that affects how the brain works, causing confusion, memory problems, or changes in alertness.

enterohepatic recirculation: A cycle where a medicine passes into the gut with bile, then is reabsorbed back into the blood.

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

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

hyperglycemia: High blood sugar, meaning there is more glucose (sugar) in the blood than normal.

hyperkalemia: A higher-than-normal level of potassium, an important mineral, 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.

hypomagnesemia: A lower-than-normal level of magnesium, a mineral, in the blood.

hypophosphatemia: A lower-than-normal level of phosphate, a mineral, in the blood.

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

in utero: Inside the womb, describing a baby before it is born.

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.

inducer: A substance that speeds up an enzyme, which can lower the levels of drugs that enzyme breaks down.

infusion: Slowly delivering fluid or medicine into a vein over a period of time, usually through a drip.

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

insomnia: Trouble falling asleep, staying asleep, or getting restful sleep.

intravenous: Given directly into a vein through a needle or thin tube; often written as IV.

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

lethargy: A state of tiredness and sluggishness, often with slowed thinking or movement.

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

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

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

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

neonatal: Relating to a newborn baby during its first four weeks of life.

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

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.

paresthesia: A tingling, prickling, or "pins and needles" feeling in the skin, often in the hands or feet.

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

perforation: A hole that forms all the way through the wall of the stomach or intestine.

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

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

pregnancy category: An older letter rating (A, B, C, D, or X) once used to describe a medicine's possible risk during pregnancy.

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.

pruritus: Itching of the skin.

QT prolongation: A longer-than-normal electrical recovery time between heartbeats, seen on a heart tracing (ECG), which can raise the chance of a dangerous heart rhythm.

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

receptor: A special docking spot on a cell that a medicine or natural body chemical attaches to in order to trigger an effect.

renal impairment: Reduced kidney function, meaning the kidneys do not filter waste and fluid from the blood as well as normal.

seizure: A sudden burst of abnormal electrical activity in the brain that can cause shaking, staring, confusion, or loss of awareness.

teratogenic: Able to cause physical birth defects in a developing baby when a medicine is taken during pregnancy.

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

tremor: Shaking or trembling of part of the body, such as the hands, that a person cannot control.

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

urticaria: Raised, itchy welts on the skin, commonly called hives.

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 ↗

← 43353-0316-09 · Aphena 43353-0322-16 · Aphena →

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.

Tacrolimus 1 mg Capsule, 9,000-count

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8.6 Use in Renal Impairment The pharmacokinetics o…

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