Tacrolimus 1 mg Capsule, 30-count
Other active recalls for Tacrolimus (different manufacturers) — 3 · tap to view
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Calcineurin Inhibitor Immunosuppressant class.
Where does this data come from?
🏭 Manufacturer & labeler
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🩺 Clinical
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 ↗- 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?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Tacrolimus — tap one for details:
Tacrolimus may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
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Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 5138Q19F1X
Ammonia is a colorless gas made from nitrogen and hydrogen. It's used in medicines as a pH buffer to maintain the correct acidity level and help keep the product stable.
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UNII 8PJ61P6TS3
Butyl alcohol is a clear liquid organic solvent derived from petroleum or natural sources. In medicines, it helps dissolve active ingredients and serves as a solvent in liquid formulations and some topical products.
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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.
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UNII 1K09F3G675
Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
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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.
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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.
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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.
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UNII B1QE5P712K
Hypromellose 2208 is a plant-derived thickening agent that dissolves in water. It's used as a binder to help hold tablet ingredients together and as a coating on pills to control how quickly the medicine releases in your body.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII WZH3C48M4T
Potassium hydroxide is a strong alkaline chemical used in medicines to adjust and maintain the pH level of liquid formulations, helping keep the product stable and the active ingredients effective.
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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.
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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.
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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.
14 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
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?
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per 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 | $11.34 / 30 capsules |
Where does this data come from?
🔁 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 mg 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 mgthis 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 | — |
Where does this data come from?
⏳ Availability & generic status
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?
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 72189-0536-30 You're viewing this | 30 CAPSULE in 1 BOTTLE (72189-536-30) | 2024-02-07 | Active |
🧭 About this NDC listing & data coverage
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. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: MALIGNANCIES AND SERIOUS INFECTIONS Increased risk for developing serious infections and malignancies with tacrolimus or other immunosuppressants that may lead to hospitalization or death. (5.1, 5.2)
🎯 Indications and Usage ▾
1.1Prophylaxis of Organ Rejection in Kidney, Liver, or Heart Transplant Tacrolimus capsules are indicated for the prophylaxis of organ rejection, in adult patients receiving allogeneic kidney transplant [see Clinical Studies (14.1)], liver transplant [see Clinical Studies (14.2)], and heart transplant [see Clinical Studies (14.3)], and pediatric patients receiving allogeneic liver transplants [see Clinical Studies (14.2)] in combination with other immunosuppressants. Additional pediatric use information is approved for Astellas Pharma US, Inc.’s Prograf (tacrolimus) products.
However, due to Astellas Pharma US, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.
⏱️ Dosage and Administration ▾
2.1Important Administration Instructions Tacrolimus capsules should not be used without supervision by a physician with experience in immunosuppressive therapy. Tacrolimus capsules are not interchangeable or substitutable for other tacrolimus extended-release products. This is because rate of absorption following the administration of an extended-release tacrolimus product is not equivalent to that of an immediate-release tacrolimus drug product.
Under- or overexposure to tacrolimus may result in graft rejection or other serious adverse reactions. Changes between tacrolimus immediate-release and extended-release dosage forms must occur under physician supervision [see Warnings and Precautions (5.3)]. Intravenous Formulation – Administration Precautions due to Risk of Anaphylaxis Intravenous use is recommended for patients who cannot tolerate oral formulations, and conversion from intravenous to oral tacrolimus is recommended as soon as oral therapy can be tolerated to minimize the risk of anaphylactic reactions that occurred with injectables containing castor oil derivatives [see Warnings and Precautions (5.9)].
Oral Formulation (Capsules) If patients are able to initiate oral therapy, the recommended starting doses should be initiated. Tacrolimus capsules may be taken with or without food. However, since the presence of food affects the bioavailability of tacrolimus, if taken with food, it should be taken consistently the same way each time [see Clinical Pharmacology (12.3)].
General Administration Instructions Patients should not eat grapefruit or drink grapefruit juice in combination with tacrolimus capsules [see Drug Interactions (7.2)]. Tacrolimus should not be used simultaneously with cyclosporine. Tacrolimus or cyclosporine should be discontinued at least 24 hours before initiating the other.
In the presence of elevated tacrolimus or cyclosporine concentrations, dosing with the other drug usually should be further delayed. Therapeutic drug monitoring (TDM) is recommended for all patients receiving tacrolimus capsules [see Dosage and Administration (2.6)].
2.2Dosage Recommendations for Adult Kidney, Liver, or Heart Transplant Patients – Capsules Capsules If patients are able to tolerate oral therapy, the recommended oral starting doses should be initiated. 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.
The initial oral tacrolimus capsule dosage recommendations for adult patients with kidney, liver, or heart transplants and whole blood trough concentration range are shown in Table 1. Perform therapeutic drug monitoring (TDM) to ensure that patients are within the ranges listed in Table 1. Table 1.
Summary of Initial Oral Tacrolimus Capsules Dosage Recommendations and Whole Blood Trough Concentration Range in Adults * African-American patients may require higher doses compared to Caucasians (see Table 2) † 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)]. Patient Population Tacrolimus Capsules Initial Oral Dosage* Whole Blood Trough Concentration Range Kidney Transplant With Azathioprine 0.2 mg/kg/day, divided in two doses, administered every 12 hours Month 1 to 3: 7 to 20 ng/mL Month 4 to 12: 5 to 15 ng/mL With MMF/IL-2 receptor antagonist† 0.1 mg/kg/day, divided in two doses, administered every 12 hours Month 1 to 12: 4 to 11 ng/mL Liver Transplant With corticosteroids only 0.10 to 0.15 mg/kg/day, divided in two doses, administered every 12 hours Month 1 to 12: 5 to 20 ng/mL Heart Transplant With azathioprine or MMF 0.075 mg/kg/day, divided in two doses, a…
💊 Dosage Forms and Strengths ▾
Tacrolimus capsules, USP are available in 0.5 mg, 1 mg, and 5 mg strengths. Tacrolimus capsules, USP containing white to off white powder equivalent to 0.5 mg of anhydrous tacrolimus, are hard gelatin capsules with white opaque body and ivory cap. The body is imprinted ‘643’ and cap is imprinted ‘ ['S'] ’ in black ink.
Tacrolimus capsules, USP containing white to off white powder equivalent to 1 mg of anhydrous tacrolimus, are hard gelatin capsules with white opaque body and brown cap. The body is imprinted ‘644’ and cap is imprinted ‘ ['S'] ’ in black ink. Tacrolimus capsules, USP containing white to off white powder equivalent to 5 mg of anhydrous tacrolimus, are hard gelatin capsules with white opaque body and orange cap.
The body is imprinted ‘645’ and cap is imprinted ‘ ['S'] ’ in black ink.
⛔ Contraindications ▾
Tacrolimus capsules are contraindicated in patients with a hypersensitivity to tacrolimus. Hypersensitivity symptoms reported include dyspnea, rash, pruritus, and acute respiratory distress syndrome [see Adverse Reactions (6)].
⚠️ Warnings and Cautions ▾
5.1Lymphoma and Other Malignancies Patients receiving immunosuppressants, including tacrolimus, 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, examine patients for skin changes;exposure to sunlight and UV light should be limited by wearing protective clothing and using a broad-spectrum 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.
Monitor EBV serology during treatment.
5.2Serious Infections Patients receiving immunosuppressants, including tacrolimus, are at increased risk of developing bacterial, viral, fungal, and protozoal infections, including opportunistic infections. These infections may lead to serious, including fatal, outcomes. Serious viral infections reported include: • Polyomavirus-associated nephropathy (PVAN), mostly due to BK virus infection • JC virus-associated progressive multifocal leukoencephalopathy (PML) • Cytomegalovirus infections: CMV seronegative transplant patients who receive an organ from a CMV seropositive donor disease are at higher risk of developing CMV viremia and CMV disease.
Monitor for the development of infection and adjust the immunosuppressive regimen to balance the risk of rejection with the risk of infection [see Adverse Reactions (6.1, 6.2)].
5.3Not Interchangeable with Extended-Release Tacrolimus Products – Medication Errors Medication errors, including substitution and dispensing errors, between tacrolimus immediate-release products and tacrolimus extended-release products were reported outside the U.S. This led to serious adverse reactions, including graft rejection, or other adverse reactions due to under- or overexposure to tacrolimus. Tacrolimus is not interchangeable or substitutable for tacrolimus extended-release products.
Changes between tacrolimus immediate-release and extended-release dosage forms must occur under physician supervision. Instruct patients and caregivers to recognize the appearance of tacrolimus dosage forms [see Dosage Forms and Strengths (3)] and to confirm with the healthcare provider if a different product is dispensed.
5.4New Onset Diabetes After Transplant Tacrolimus was shown to cause new onset diabetes mellitus in clinical trials of kidney, liver, or heart transplantation. New onset diabetes after transplantation may be reversible in some patients. African-American and Hispanic kidney transplant patients are at an increased risk. Blood glucose concentrations should be monitored closely in patients using tacrolimus [see Adverse Reactions (6.1)].
5.5Nephrotoxicity due to Tacrolimus and Drug Interactions Tacrolimus, like other calcineurin inhibitors, can cause acute or chronic nephrotoxicity in transplant patients due to its vasoconstrictive effect on renal vasculature, toxic tubulopathy and tubular-interstitial effects. Nephrotoxicity was reported in clinical trials [see Adverse Reactions (6.1)]. Acute renal impairment associated with tacrolimus toxicity can result in high serum creatinine, hyperkalemia, decreased secretion of urea and hyperuricemia, and is usually reversible.
In patients with elevated serum creatinine and tacrolimus whole blood trough concentrations greater than the recommended range, consider dosage reduction or temporary interruption of tacrolimus administration. The risk for nephrotoxicity may increase when tacrolimus is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminogly…
🤒 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 Warnings and Precautions (5.1)] • Serious Infections [see Warnings and Precautions (5.2)] • New Onset Diabetes After Transplant [see Warnings and Precautions (5.4)] • Nephrotoxicity [see Warnings and Precautions (5.5)] • Neurotoxicity [see Warnings and Precautions (5.6)] • Hyperkalemia [see Warnings and Precautions (5.7)] • Hypertension [see Warnings and Precautions (5.8)] • Anaphylactic Reactions with Tacrolimus Injection [see Warnings and Precautions (5.9)] • Myocardial Hypertrophy [see Warnings and Precautions (5.13)] • Pure Red Cell Aplasia [see Warnings and Precautions (5.15)] • Thrombotic Microangiopathy, Including Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura [see Warnings and Precautions (5.16)]
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 Transplantation 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 a 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%), African-American (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. Based on reported adverse reaction terms related to decreased renal function, nephrotoxicity was reported in approximately 52% of kidney transplantation patients.
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 ≥15% of Patients Treated with Tacrolimus in Conjunction with Azathioprine (AZA) Tacrolimus /AZA (N=205) Cyclosporine/AZA (N=207) Nervous System Tremor 54% 34% Headache 44% 38% Insomnia 32% 30% Paresthesia 23% 16% Dizziness 19% 16% Gastrointestinal Diarrhea 44% 41% Nausea 38% 36% Constipation 35% 43% Vomiting 29% 23% Dyspepsia 28% 20% Cardiovascular Hypertension 50% 52% Chest Pain 19% 13% Urogenital Creatinine Increased 45% 42% Urinary Tract Infection 34% 35% Metabolic and Nutritional Hypophosphatemia 49% 53% Hypomagnesemia 34% 17% Hyperlipemia 31% 38% Hyperkalemia 31% 32% Diabetes Mellitus 24% 9% Hypokalemia 22% 25% Hyperglycemia 22% 16% Edema 18% 19% Hemic and Lymphatic Anemia 30% 24% Leukopenia 15% 17% Miscellaneous Infection 45% 49% Peripheral Edema 36% 48% Asthenia 34% 30% Abdominal Pain 33% 31% Pain 32% 30% Fever 29% 29% Back Pain 24% 20% Respiratory System Dyspnea 22% 18% Cough Increased 18% 15% Musculoskeletal Arthralgia 25% 24% Skin Rash 17% 12% Pruritus 15% 7% Two trials…
🔄 Drug Interactions ▾
7.1Mycophenolic Acid When tacrolimus is prescribed with a given dose of a mycophenolic acid (MPA) product, exposure to MPA is higher with tacrolimus co-administration than with cyclosporine co-administration with MPA, because cyclosporine interrupts the enterohepatic recirculation of MPA while tacrolimus does not. Monitor for MPA-associated adverse reactions and reduce the dose of concomitantly administered mycophenolic acid products as needed.
7.2Effects of Other Drugs on Tacrolimus Table 15 displays the effects of other drugs on tacrolimus. * Tacrolimus dosage adjustment recommendation based on observed effect of co-administered drug on tacrolimus exposures [see Clinical Pharmacology (12.3)], literature reports of altered tacrolimus exposures, or the other drug’s known CYP3A inhibitor/inducer status. † High dose or double strength grapefruit juice is a strong CYP3A inhibitor; low dose or single strength grapefruit juice is a moderate CYP3A inhibitor. Table 15.
Effects of Other Drugs/Substances on Tacrolimus* Drug/Substance Class or Name Drug Interaction Effect Recommendations Grapefruit or grapefruit juice† May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions (5.6, 5.11, 5.12)]. Avoid grapefruit or grapefruit juice. Strong CYP3A Inducers:Antimycobacterials (e.g., rifampin, rifabutin), anticonvulsants (e.g., phenytoin, carbamazepine and phenobarbital), St John’s wort May decrease tacrolimus whole blood trough concentrations and increase the risk of rejection [see Warnings and Precautions (5.11)].
Increase tacrolimus dose and monitor tacrolimus whole blood trough concentrations [see Dosage and Administration (2.2, 2.6) and Clinical Pharmacology (12.3)]. Strong CYP3A Inhibitor: Protease inhibitors (e.g., nelfinavir, telaprevir, boceprevir, ritonavir), azole antifungals (e.g., voriconazole, posaconazole, itraconazole, ketoconazole), antibiotics (e.g., clarithromycin, troleandomycin, chloramphenicol), nefazodone, letermovir, Schisandra sphenanthera extracts May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation).
A rapid, sharp rise in tacrolimus levels may occur early, despite an immediate reduction of tacrolimus dose [see Warnings and Precautions (5.6, 5.11, 5.12)]. Reduce tacrolimus dose (for voriconazole and posaconazole, give one-third of the original dose) and adjust dose based on tacrolimus whole blood trough concentrations [see Dosage and Administration (2.2, 2.6) and Clinical Pharmacology (12.3)]. Early and frequent monitoring of tacrolimus whole blood trough levels should start within 1-3 days and continue monitoring as necessary [see Warnings and Precautions (5.11)].
Mild or Moderate CYP3A Inhibitors: Clotrimazole, antibiotics (e.g., erythromycin, fluconazole), calcium channel blockers (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions (5.6, 5.11, 5.12)]. Monitor tacrolimus whole blood trough concentrations and reduce tacrolimus dose if needed [see Dosage and Administration (2.2, 2.6) and Clinical Pharmacology (12.3)].
Other drugs, such as: Magnesium and aluminum hydroxide antacids Metoclopramide May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions (5.6, 5.11, 5.12)]. Monitor tacrolimus whole blood trough concentrations and reduce tacrolimus dose if needed [see Dosage and Administration (2.2, 2.6) and Clinical Pharmacology (12.3)]. Mild or Moderate CYP3A Inducers Methylprednisolone, prednisone May decrease tacrolimus whole b…
👥 Use in Specific Populations ▾
8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy registry that monitors pregnancy outcomes in women exposed to tacrolimus during pregnancy. The Transplantation Pregnancy Registry International (TPRI) is a voluntary pregnancy exposure registry that monitors outcomes of pregnancy in female transplant recipients and those fathered by male transplant recipients exposed to immunosuppressants including tacrolimus. Healthcare providers are encouraged to advise their patients to register by contacting the Transplantation Pregnancy Registry International at 1-877-955-6877 or HTTPS://WWW.TRANSPLANTPREGNANCYREGISTRY.ORG/.
Risk Summary Tacrolimus can cause fetal harm when administered to a pregnant woman. Data from postmarketing surveillance and TPRI suggest that infants exposed to tacrolimus in utero are at a risk of prematurity, birth defects/congenital anomalies, low birth weight, and fetal distress [see Human Data]. Advise pregnant women of the potential risk to the fetus.
Administration of oral tacrolimus to pregnant rabbits and rats throughout the period of organogenesis was associated with maternal toxicity/lethality, and an increased incidence of abortion, malformation and embryofetal death at clinically relevant doses (0.5 to 6.9 times the recommended clinical dose range [0.2 to 0.075 mg/kg/day], on a mg/m2 basis). Administration of oral tacrolimus to pregnant rats after organogenesis and throughout lactation produced maternal toxicity, effects on parturition, reduced pup viability and reduced pup weight at clinically relevant doses (0.8 to 6.9 times the recommended clinical dose range, on a mg/m2 basis).
Administration of oral tacrolimus to rats prior to mating, and throughout gestation and lactation produced maternal toxicity/lethality, marked effects on parturition, embryofetal loss, malformations, and reduced pup viability at clinically relevant doses (0.8 to 6.9 times the recommended clinical dose range, on a mg/m2 basis). Interventricular septal defects, hydronephrosis, craniofacial malformations and skeletal effects were observed in offspring that died [see Animal Data]. The background risk of major birth defects and miscarriage in the indicated population is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo-Fetal Risk Risks during pregnancy are increased in organ transplant recipients. The risk of premature delivery following transplantation is increased.
Pre-existing hypertension and diabetes confer additional risk to the pregnancy of an organ transplant recipient. Pre-gestational and gestational diabetes are associated with birth defects/congenital anomalies, hypertension, low birth weight and fetal death. Cholestasis of pregnancy (COP) was reported in 7% of liver or liver-kidney (LK) transplant recipients, compared with approximately 1% of pregnancies in the general population.
However, COP symptoms resolved postpartum and no long‑term effects on the offspring were reported. Maternal Adverse Reactions Tacrolimus may increase hyperglycemia in pregnant women with diabetes (including gestational diabetes). Monitor maternal blood glucose levels regularly [see Warnings and Precautions (5.4)].
Tacrolimus may exacerbate hypertension in pregnant women and increase pre-eclampsia. Monitor and control blood pressure [see Warnings and Precautions (5.7, 5.8)]. Fetal/Neonatal Adverse Reactions Renal dysfunction, transient neonatal hyperkalemia and low birth weight have been reported at the time of delivery in infants of mothers taking tacrolimus.
Labor or Delivery There is an increased risk for premature delivery (<37 weeks) following transplantation and maternal exposure to tacrolimus. Data Human Data There are no adequate and well controlled studies on the effects of tacrolimus in human pregnancy. Safety data from the…
🆘 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 reported with the use of tacrolimus [see Adverse Reactions (6.1, 6.2)], 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.
🧬 Clinical Pharmacology ▾
12.1Mechanism of Action Tacrolimus binds to an intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium, calmodulin, and calcineurin (a ubiquitous mammalian intracellular enzyme) is then formed, after which the phosphatase activity of calcineurin is inhibited. Such inhibition prevents the dephosphorylation and translocation of various factors such as the nuclear factor of activated T-cells (NF-AT), and nuclear factor kappa-light-chain enhancer of activated B-cells (NF-κB).
Tacrolimus inhibits the expression and/or production of several cytokines that include interleukin (IL)-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, gamma interferon, tumor necrosis factor-alpha, and granulocyte macrophage colony-stimulating factor. Tacrolimus also inhibits IL-2 receptor expression and nitric oxide release, induces apoptosis and production of transforming growth factor beta that can lead to immunosuppressive activity. The net result is the inhibition of T-lymphocyte activation and proliferation, as well as T-helper-cell-dependent B-cell response (i.e., immunosuppression).
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 17). Table 17.
Pharmacokinetics Parameters (mean±S.D.) of Tacrolimus in Healthy Volunteers and Patients * Not applicable † AUC0-inf ‡ Not available § AUC0-t ¶ Determined after the first dose # Median [range] Þ AUC0-12 Population N Route (Dose) Parameters Cmax (ng/mL) Tmax (hr) AUC (ng•hr/mL) t1/2 (hr) CL (L/hr/kg) V (L/kg) Healthy Volunteers 8 IV (0.025 mg/kg/4 hr) * * 652†± 156 34.2 ± 7.7 0.040 ± 0.009 1.91 ± 0.31 16 PO (5 mg) (capsules) 28.8 ± 8.9 1.5 ± 0.7 266†± 95 32.3 ± 8.8 ‡ ‡ Kidney Transplant Patients 26 IV (0.02 mg/kg/12 hr) * * 294†± 262 18.8 ± 16.7 0.083 ± 0.050 1.41 ±
0.66PO (0.2 mg/kg/day) 19.2 ± 10.3 3 203†± 42 ‡ ‡ ‡ 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 ‡ ‡ ‡ Heart Transplant Patients 11 IV (0.01 mg/kg/day as a continuous infusion) * * 954§ ± 334 23.6 ± 9.22 0.051 ± 0.015 ‡ 11 PO (0.075 mg/kg/day)¶ 14.7 ± 7.79 2.1 [0.5-6]# 82.7Þ ± 63.2 * ‡ ‡ 14 PO (0.15 mg/kg/day)¶ 24.5 ± 13.7 1.5 [0.4-4]# 142Þ ± 116 * ‡ ‡ Due to intersubject variability in tacrolimus pharmacokinetics, individualization of the 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 (Cmax) 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, 7, 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 (Cmin) correlated well with the AUC (correlation coefficient 0.93).
In 24 liver transplant patients over a concentration range of 10 to 60 ng/mL, the correlation coefficient was 0.94. In 25…
📦 How Supplied / Storage and Handling ▾
16.1Tacrolimus Capsules, USP Tacrolimus capsules, USP containing white to off-white powder equivalent to 0.5 mg of anhydrous tacrolimus, are hard gelatin capsules with white opaque body and ivory cap. The body is imprinted ‘643’ and cap is imprinted ‘ ['S'] ’ in black ink. They are supplied as follows: NDC 72189-0536-30, bottle of 100 capsules with child-resistant closure Tacrolimus capsules, USP containing white to off-white powder equivalent to 1 mg of anhydrous tacrolimus, are hard gelatin capsules with white opaque body and brown cap.
The body is imprinted ‘644’ and cap is imprinted ‘ ['S'] ’ in black ink. They are supplied as follows: NDC 72189-0536-30, bottle of 30 capsules with child-resistant closure Tacrolimus capsules, USP containing white to off-white powder equivalent to 5 mg of anhydrous tacrolimus, are hard gelatin capsules with white opaque body and orange cap. The body is imprinted ‘645’ and cap is imprinted ‘ ['S'] ’ in black ink.
They are supplied as follows: NDC 0781-2104-01, bottle of 100 capsules with child-resistant closure
📦 Storage and Handling ▾
Store and Dispense Tacrolimus capsules, USP should be stored at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
16.4Handling and Disposal Tacrolimus can cause fetal harm. Tacrolimus capsules should not be opened or crushed. Avoid inhalation or direct contact with skin or mucous membranes of the powder contained in tacrolimus capsules.
If such contact occurs, wash the skin thoroughly with soap and water; if ocular contact occurs, rinse eyes with water. In case a spill occurs, wipe the surface with a wet paper towel. Follow applicable special handling and disposal procedures1.
📋 Description ▾
Tacrolimus, previously known as FK506, is the active ingredient in tacrolimus capsules. Tacrolimus is a calcineurin-inhibitor immunosuppressant produced by Streptomyces tsukubaensis. Chemically, tacrolimus is designated as [3S-[3R*[E(1S*,3S*,4S*)],4S*,5R*,8S*,9E,12R* ,14R*, 15S*,16R*,18S*,19S*,26aR*]]-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy-3-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl]-14,16-dimethoxy-4,10,12,18-tetramethyl-8-(2-propenyl)-15,19-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclotricosine-1,7,20,21(4H,23H)-tetrone, monohydrate.
The chemical structure of tacrolimus is: [chemical structure] Tacrolimus has a molecular formula of C44H69NO12•H2O and a formula weight of 822.03. Tacrolimus appears as white crystals or crystalline powder. It is practically insoluble in water, freely soluble in ethanol, and very soluble in methanol and chloroform.
Tacrolimus capsules, USP are available for oral administration containing the equivalent of 0.5 mg, 1 mg or 5 mg of anhydrous tacrolimus. In addition, each capsule contains the following inactive ingredients: croscarmellose sodium, hypromellose, lactose monohydrate, and magnesium stearate. The tacrolimus capsule shell for 0.5 mg strength consists of gelatin, titanium dioxide and yellow iron oxide.
The tacrolimus capsule shell for 1 mg strength consists of black iron oxide, gelatin, red iron oxide, titanium dioxide, and yellow iron oxide. The tacrolimus capsule shell for 5 mg strength consists of red iron oxide, gelatin, and titanium dioxide. Tacrolimus capsules, USP 0.5 mg, 1 mg and 5 mg are printed with edible black ink.
The black ink is comprised of ammonia, black iron oxide, butyl alcohol, potassium hydroxide, propylene glycol, and shellac. USP Dissolution test 2 and Organic Impurities procedure 2 used.