{
 "query": "tacrolimus",
 "ingredient": "tacrolimus",
 "slug": "tacrolimus",
 "rxcui": "42316",
 "brands": [
  "Prograf",
  "Envarsus"
 ],
 "names": [
  "tacrolimus",
  "tacrolimus monohydrate"
 ],
 "classes": [
  {
   "id": "D11AH",
   "name": "Agents for dermatitis, excluding corticosteroids"
  },
  {
   "id": "L04AD",
   "name": "Calcineurin inhibitors"
  }
 ],
 "alternatives": [
  "abrocitinib",
  "alitretinoin",
  "crisaborole",
  "cromolyn",
  "cyclosporine",
  "delgocitinib",
  "dupilumab",
  "lebrikizumab",
  "nemolizumab",
  "pimecrolimus",
  "ruxolitinib",
  "tralokinumab",
  "voclosporin"
 ],
 "label": {
  "route_mode": "ORAL",
  "route_counts": {
   "ORAL": 37,
   "TOPICAL": 5,
   "INTRAVENOUS": 2
  },
  "boxed_warning": "WARNING: MALIGNANCIES AND SERIOUS INFECTIONS Increased risk for developing serious infections and malignancies with PROGRAF or other immunosuppressants that may lead to hospitalization or death. ( 5.1 , 5.2 ) WARNING: MALIGNANCIES AND SERIOUS INFECTIONS See full prescribing information for complete boxed warning. Increased risk for developing serious infections and malignancies with PROGRAF or other immunosuppressants that may lead to hospitalization or death. ( 5.1 , 5.2 )",
  "indications_and_usage": "is a calcineurin-inhibitor immunosuppressant indicated for the prophylaxis of organ rejection in adult and pediatric patients receiving allogeneic liver, kidney, heart, or lung transplants, in combination with other immunosuppressants. ( 1.1 ) 1.1 Prophylaxis of Organ Rejection in Kidney, Liver, Heart, or Lung Transplant PROGRAF \u00ae is indicated for the prophylaxis of organ rejection, in adult and pediatric patients receiving allogeneic kidney transplant [see Clinical Studies ( 14.1 )], liver transplant [see Clinical Studies ( 14.2 )], heart transplant [see Clinical Studies ( 14.3 )], or lung transplant [see Clinical Studies ( 14.4 )] in combination with other immunosuppressants.",
  "contraindications": "is contraindicated in patients with a hypersensitivity to tacrolimus. PROGRAF 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 )] . \u2022 Hypersensitivity to tacrolimus or HCO-60 (polyoxyl 60 hydrogenated castor oil). ( 4 )",
  "warnings_and_cautions": "\u2022 Not Interchangeable with Extended-Release Tacrolimus Products - Medication Errors: Instruct patients or caregivers to recognize the appearance of PROGRAF capsules. ( 5.3 ) \u2022 New Onset Diabetes After Transplant: Monitor blood glucose. ( 5.4 ) \u2022 Nephrotoxicity (acute and/or chronic): Reduce the dose; use caution with other nephrotoxic drugs. ( 5.5 ) \u2022 Neurotoxicity: Including risk of Posterior Reversible Encephalopathy Syndrome (PRES); monitor for neurologic abnormalities; reduce or discontinue PROGRAF. ( 5.6 ) \u2022 Hyperkalemia: Monitor serum potassium levels. Consider carefully before using with other agents also associated with hyperkalemia. ( 5.7 ) \u2022 Hypertension: May require antihypertensive therapy. Monitor relevant drug-drug interactions. ( 5.8 ) \u2022 Anaphylactic Reactions with IV formulation: Observe patients receiving PROGRAF injection for signs and symptoms of anaphylaxis. ( 5.9 ) \u2022 Not recommended for use with sirolimus: Not recommended in liver and heart transplant due to increased risk of serious adverse reactions. ( 5.10 ) \u2022 Myocardial Hypertrophy: Consider dose reduction/discontinuation. ( 5.13 ) \u2022 Immunizations: Avoid live vaccines. ( 5.14 ) \u2022 Pure Red Cell Aplasia: Cons...",
  "warnings": "",
  "adverse_reactions": "The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling: \u2022 Lymphoma and Other Malignancies [see Warnings and Precautions ( 5.1 )] \u2022 Serious Infections [see Warnings and Precautions ( 5.2 )] \u2022 New Onset Diabetes After Transplant [see Warnings and Precautions ( 5.4 )] \u2022 Nephrotoxicity [see Warnings and Precautions ( 5.5 )] \u2022 Neurotoxicity [see Warnings and Precautions ( 5.6 )] \u2022 Hyperkalemia [see Warnings and Precautions ( 5.7 )] \u2022 Hypertension [see Warnings and Precautions ( 5.8 )] \u2022 Anaphylactic Reactions with PROGRAF Injection [see Warnings and Precautions ( 5.9 )] \u2022 Myocardial Hypertrophy [see Warnings and Precautions ( 5.13 )] \u2022 Pure Red Cell Aplasia [see Warnings and Precautions ( 5.15 )] \u2022 Thrombotic Microangiopathy, Including Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura [see Warnings and Precautions ( 5.16 )] The most common adverse reactions (\u2265 15%) were abnormal renal function, hypertension, diabetes mellitus, fever, CMV infection, tremor, hyperglycemia, leukopenia, infection, anemia, bronchitis, pericardial effusion, urinary tract infection, constipation, diarrhea, headache, abd...",
  "drug_abuse_and_dependence": "",
  "controlled_substance": "",
  "recent_major_changes": "Warnings and Precautions ( 5.5 , 5.10 , 5.16 ) 11/2022 Warnings and Precautions, Cannabidiol Drug Interactions ( 5.17 ) 08/2023",
  "information_for_patients": "Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). 17.1 Administration Advise the patient or caregiver to: \u2022 Inspect their PROGRAF medicine when they receive a new prescription and before taking it. If the appearance of the capsule is not the same as usual, or if dosage instructions have changed, advise patients to contact their healthcare provider as soon as possible to make sure that they have the right medicine. Other tacrolimus products cannot be substituted for PROGRAF. \u2022 Take PROGRAF at the same 12-hour intervals every day to achieve consistent blood concentrations. \u2022 Take PROGRAF consistently either with or without food because the presence and composition of food decreases the bioavailability of PROGRAF. \u2022 Not to eat grapefruit or drink grapefruit juice in combination with PROGRAF [see Drug Interactions ( 7.2 )]. \u2022 If the patient is receiving PROGRAF Granules, advise that the dose should be given immediately after preparation and not to save the dose for later. Advise the caregiver to carefully read the Instructions for Use. 17.2 Development of Lymphoma and Other Malignancies Inform patients they are at increased ris...",
  "spl_medguide": "",
  "clinical_studies": "14.1 Kidney Transplantation PROGRAF/Azathioprine (AZA) PROGRAF-based immunosuppression in conjunction with azathioprine and corticosteroids following kidney transplantation was assessed in a randomized, multicenter, non-blinded, prospective trial. There were 412 kidney transplant patients enrolled at 19 clinical sites in the United States. Study therapy was initiated when renal function was stable as indicated by a serum creatinine \u2264 4 mg/dL (median of 4 days after transplantation, range 1 to 14 days). Patients less than 6 years of age were excluded. There were 205 patients randomized to PROGRAF-based immunosuppression and 207 patients were randomized to cyclosporine-based immunosuppression. All patients received prophylactic induction therapy consisting of an antilymphocyte antibody preparation, corticosteroids, and azathioprine. Overall, 1-year patient and graft survivals were 96.1% and 89.6%, respectively. Data from this trial of PROGRAF in conjunction with azathioprine indicate that during the first 3 months of that trial, 80% of the patients maintained trough concentrations between 7-20 ng/mL, and then between 5-15 ng/mL, through 1 year. PROGRAF/Mycophenolate Mofetil (MMF) PRO...",
  "brand_name": "Prograf",
  "manufacturer": "Astellas Pharma US, Inc.",
  "application_number": "NDA050708",
  "pharm_class_epc": [],
  "route": [
   "ORAL",
   "INTRAVENOUS"
  ],
  "effective_time": "20230825",
  "set_id": "7f667de1-9dfa-4bd6-8ba0-15ee2d78873b",
  "has_boxed_warning": true,
  "controlled": false,
  "mentions_rems": false
 },
 "faers": {
  "total": 133774,
  "serious": 117414,
  "death": 19405,
  "hospitalization": 52833,
  "primary_suspect": 131849,
  "top_reactions": [
   [
    "Off Label Use",
    14306
   ],
   [
    "Drug Ineffective",
    9149
   ],
   [
    "Product Use In Unapproved Indication",
    6555
   ],
   [
    "Acute Kidney Injury",
    6127
   ],
   [
    "Drug Interaction",
    5721
   ],
   [
    "Diarrhoea",
    4812
   ],
   [
    "Transplant Rejection",
    4156
   ],
   [
    "Covid-19",
    4115
   ],
   [
    "Cytomegalovirus Infection",
    3930
   ],
   [
    "Death",
    3920
   ],
   [
    "Pneumonia",
    3809
   ],
   [
    "Pyrexia",
    3773
   ],
   [
    "Toxicity To Various Agents",
    3627
   ],
   [
    "Condition Aggravated",
    2998
   ],
   [
    "Post Transplant Lymphoproliferative Disorder",
    2937
   ]
  ],
  "by_year": {
   "2019": 12194,
   "2020": 14373,
   "2021": 13058,
   "2022": 12400,
   "2023": 13762,
   "2024": 14871,
   "2025": 14737,
   "2026": 6775
  },
  "by_year_primary": {
   "2019": 12180,
   "2020": 14354,
   "2021": 12932,
   "2022": 12018,
   "2023": 13307,
   "2024": 14483,
   "2025": 14359,
   "2026": 6659
  }
 },
 "faers_base": {
  "total": 20692304,
  "serious_share": 0.5742697381596559,
  "death_share": 0.09102355155810585
 },
 "recalls": [
  {
   "class": "Class I",
   "date": "20241223",
   "reason": "Failed Tablet/Capsule Specifications: Bottles shipped to the USA may contain empty capsules",
   "firm": "Astellas Pharma US Inc.",
   "status": "Ongoing"
  },
  {
   "class": "Class II",
   "date": "20231215",
   "reason": "Presence of Foreign Tablets/Capsules: One 0.5 mg Tacrolimus capsule found in a bottle of 1 mg Tacrolimus capsules.",
   "firm": "Dr. Reddy's Laboratories, Inc.",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20230208",
   "reason": "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.",
   "firm": "Dr. Reddy's Laboratories, Inc.",
   "status": "Ongoing"
  },
  {
   "class": "Class III",
   "date": "20220711",
   "reason": "Defective Container: Tube split from side seam",
   "firm": "Glenmark Pharmaceuticals Inc., USA",
   "status": "Ongoing"
  },
  {
   "class": "Class III",
   "date": "20201222",
   "reason": "Failed Moisture Limits",
   "firm": "Strides Pharma Inc.",
   "status": "Terminated"
  },
  {
   "class": "Class III",
   "date": "20200323",
   "reason": "Presence of foreign tablet/capsule - Potential presence of commingled one Tacrolimus 1 mg capsule in 5 mg bottles.",
   "firm": "Mylan Pharmaceuticals Inc.",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20120629",
   "reason": "Failed USP Content Uniformity Requirements: OOS result reported on retained samples.",
   "firm": "Mylan LLC.",
   "status": "Terminated"
  }
 ],
 "recall_total": 7,
 "drugsfda": {
  "applications": 26,
  "nda": 6,
  "anda": 20,
  "first_approval": "19940408",
  "rems": false,
  "rems_last": "",
  "labeling_supplements": 58,
  "labeling_recent": 9,
  "sponsors": [
   "ACCORD HLTHCARE",
   "AJENAT PHARMS",
   "ALKEM LABS LTD",
   "ASTELLAS",
   "BIOCON PHARMA",
   "CHENGDU",
   "CONCORD BIOTECH LTD",
   "DR REDDYS LABS LTD"
  ],
  "unapproved": false,
  "first_approval_fmt": "04/08/1994"
 },
 "trials": {
  "total": 1624,
  "completed": 910,
  "terminated": 242,
  "with_results": 453,
  "industry": 598,
  "phase3": 237,
  "results_share": 0.4978021978021978,
  "terminated_share": 0.14901477832512317
 },
 "pubmed": {
  "rct": 866,
  "meta": 161,
  "recent_rct": 103,
  "cochrane": [
   {
    "pmid": "35388476",
    "title": "Tacrolimus (FK506) for induction of remission in corticosteroid-refractory ulcerative colitis",
    "year": "2022"
   },
   {
    "pmid": "26132597",
    "title": "Topical tacrolimus for atopic dermatitis",
    "year": "2015"
   },
   {
    "pmid": "23728681",
    "title": "Tacrolimus versus cyclosporin as primary immunosuppression for lung transplant recipients",
    "year": "2013"
   },
   {
    "pmid": "18646177",
    "title": "Tacrolimus (FK506) for induction of remission in refractory ulcerative colitis",
    "year": "2008"
   },
   {
    "pmid": "17054241",
    "title": "Cyclosporin versus tacrolimus for liver transplanted patients",
    "year": "2006"
   },
   {
    "pmid": "16235347",
    "title": "Tacrolimus versus cyclosporin as primary immunosuppression for kidney transplant recipients",
    "year": "2005"
   }
  ]
 },
 "payments": {
  "year": "2024",
  "usd": 80958.65,
  "records": 660,
  "by_name": [
   [
    "Envarsus",
    80958.65
   ]
  ],
  "names_checked": [
   "tacrolimus",
   "Prograf",
   "Envarsus"
  ],
  "source": "bulk-index"
 },
 "partd": {
  "year": "2024",
  "claims": 670966,
  "beneficiaries": 266721,
  "spend": 107378649.46000001,
  "by_brand": [
   {
    "brand": "Tacrolimus",
    "claims": 646614,
    "per_claim": 133.00996687,
    "is_generic": true
   },
   {
    "brand": "Envarsus XR",
    "claims": 19015,
    "per_claim": 887.40849014,
    "is_generic": false
   },
   {
    "brand": "Prograf",
    "claims": 4634,
    "per_claim": 863.36294346,
    "is_generic": false
   },
   {
    "brand": "Astagraf XL",
    "claims": 703,
    "per_claim": 707.88964438,
    "is_generic": false
   }
  ],
  "per_claim": 160.03590265378574
 },
 "mdl": [],
 "dsc": [],
 "settlements": [],
 "prescrire": {
  "section": "Allergy",
  "names": [
   "pimecrolimus",
   "tacrolimus"
  ],
  "reason": "Topical pimecrolimus and topical tacrolimus, two immunosuppressants used in atopic eczema, can cause skin cancer and lymphoma. These adverse effects are disproportionate, as the drugs\u2019 efficacy is barely different from that of high-potency topical corticosteroids (Prescrire Int n\u00b0 71, 101, 110, 118, 131, 224; Rev Prescrire n\u00b0 311, 331, 343, 367 , 428) ( c). Judicious use of a topical corticosteroid to treat flare-ups is a better option in this situation. There are almost no comparative evaluation data available on pimecrolimus or tacrolimus in patients in whom a topical corticosteroid has fail...",
  "edition": "2026",
  "qualifier": "topical tacrolimus",
  "qualified": true,
  "matched": "tacrolimus"
 },
 "eml": {
  "listed": true,
  "status": "AddedToEml",
  "name": "tacrolimus",
  "matched": "tacrolimus",
  "stewardship": []
 },
 "exposure": {
  "years": [
   "2024",
   "2025",
   "2026"
  ],
  "reports_recent": 35501,
  "fills": 670966,
  "per_million": 52910.28159400029,
  "ratio": 19.108429656974064,
  "median": 2768.949753790441
 },
 "scores": {
  "safety": {
   "score": 40,
   "letter": "F",
   "why": [
    "Carries an FDA boxed warning, the strongest warning the FDA issues (-30)",
    "Prescrire lists one form only (topical tacrolimus) as a drug to avoid; shown for context, no score effect",
    "52,910 FDA reports naming it as the suspect drug per million Medicare fills, 19.1x the median drug on this site (-15)",
    "Death appears in 1.6x the FAERS average share of reports (within the margin this measure deserves)",
    "Off-label use is among the five most-reported items: widely used beyond its approved evidence (-5)",
    "1 Class I recall(s): reasonable probability of serious harm (-10)"
   ],
   "weight": 0.35
  },
  "evidence": {
   "score": 86,
   "letter": "B",
   "why": [
    "866 randomized trials and 161 systematic reviews/meta-analyses indexed in PubMed",
    "On the WHO Model List of Essential Medicines (shown for context; no score effect)",
    "6 independent Cochrane review(s) exist",
    "Only 50% of completed registered trials posted results (-8)"
   ],
   "weight": 0.25
  },
  "regulatory": {
   "score": 63,
   "letter": "C",
   "why": [
    "Recalls since 2016: 1 Class I, 2 Class II, 3 Class III across 20 generic makers (-24)",
    "9 label changes approved since 2021: the safety story is still moving (-8)",
    "Label lists recent major changes to warnings or indications (-5)"
   ],
   "weight": 0.15
  },
  "conflict": {
   "score": 100,
   "letter": "A",
   "why": [
    "Pharma paid doctors $80,959 tied to this drug last year: negligible",
    "Not named in any pending federal MDL"
   ],
   "weight": 0.15
  },
  "options": {
   "score": 100,
   "letter": "A",
   "why": [
    "Generic versions approved (20 applications)",
    "13 same-class alternatives exist"
   ],
   "weight": 0.1
  }
 },
 "total": 70,
 "grade": "C",
 "questions": [
  "An independent reviewer (Prescrire) lists this as a drug to avoid because the harms outweigh the benefits versus alternatives. What is your view on that?",
  "This drug carries a boxed warning. Which specific risk does it cover, and does it apply to me?",
  "The most-reported problems in FDA's adverse event data are product use in unapproved indication, acute kidney injury. How would we recognize and handle those?",
  "Off-label use is among the most-reported items for this drug. Is my use on-label, and if not, what evidence supports it?",
  "Why this one over abrocitinib, alitretinoin, crisaborole? What would make you pick one of those instead?",
  "What result are we expecting, by when, and what is the plan if it does not happen?",
  "If 100 people like me took this drug, how many would actually get better because of it, and how many would be harmed by it? (Doctors call these the number needed to treat and the number needed to harm.)"
 ]
}