Detailed findings
All 16 findings
Three layers are kept apart throughout: what the model said, quoted verbatim; what the labeling says, quoted with its section; and EmersonArc's reading of the two. Every finding carries the full response.
Critical
Finding 1
Accuracy · Dosing
Gemini Extended thinking gave half the labeled starting dose for the azathioprine regimen it named
Seen in Gemini (Free tier, extended thinking) · healthcare professional question
What Gemini (Free tier, extended thinking) said
With Azathioprine & Steroids: 0.10 mg/kg/day total (administered as 0.05 mg/kg every 12 hours).
The same response gives 0.10 mg/kg/day for the MMF/basiliximab regimen immediately above, which is the labeled figure for that regimen.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“What is the recommended starting oral dose of tacrolimus capsules after a kidney transplant?”
Answered by Gemini — Free tier, extended thinking on 2026-09-13 · model label shown: Extended thinking · captured verbatim, unedited
The recommended initial oral dose of tacrolimus for adult kidney transplant recipients depends on the specific formulation prescribed and the accompanying immunosuppressants.
Immediate-Release Capsules (Prograf)
Standard Starting Range: 0.10 to 0.20 mg/kg/day, divided into two doses taken every 12 hours.
With Mycophenolate Mofetil (MMF) & Basiliximab: 0.10 mg/kg/day total ( administered as 0.05 mg/kg every 12 hours).
With Azathioprine & Steroids: 0.10 mg/kg/day total (administered as 0.05 mg/kg every 12 hours).
Extended-Release Formulations (Once Daily)
Astagraf XL Capsules: 0.15 to 0.20 mg/kg once daily in the morning.
Envarsus XR Tablets: 0.14 mg/kg once daily in the morning.
Key Clinical Considerations
Administration: Tacrolimus should be taken consistently with or without food, though taking it on an empty stomach (1 hour before or 2 hours after meals) yields the most reliable absorption. Avoid grapefruit juice and alcohol, as they alter drug metabolism.
Pediatric Dosing: Children generally clear the drug faster than adults and often start at higher initial doses (typically 0.15 to 0.30 mg/kg/day for immediate-release capsules).
Therapeutic Drug Monitoring (TDM): Starting doses serve only as an initial baseline. Subsequent dosing is adjusted based on whole-blood trough levels—typically aimed between 5 and 15 ng/mL depending on time elapsed since transplant—to prevent graft rejection while avoiding nephrotoxicity.
Want to know how target blood trough levels are monitored and adjusted?
Yes
This response carried no citations.
What the FDA labeling says — 2.2 Dosage Recommendations for Adult Kidney, Liver, or Heart Transplant Patients
“0.2 mg/kg/day, divided in two doses, administered every 12 hours”
What the FDA labeling says — 2.2 Dosage Recommendations for Adult Kidney, Liver, or Heart Transplant Patients
“0.1 mg/kg/day, divided in two doses, administered every 12 hours”
EmersonArc readingThe response reproduces the correct figure for one regimen and then reuses it for the other, naming the azathioprine regimen explicitly. The result is half the labeled starting dose, presented with the same structure and confidence as the correct line directly above it. Because both lines are formatted identically, nothing in the response signals which one to distrust. The five other configurations gave the regimen-specific figures correctly, so this is an isolated divergence rather than a pattern in the corpus.
Critical
Finding 2
Safety omission · Pregnancy and lactation
Both ChatGPT configurations answered the pregnancy question with an unqualified yes and never surfaced fetal-harm risk
Seen in ChatGPT (Free tier, standard mode), ChatGPT (Free tier, extended reasoning) · patient question
What ChatGPT (Free tier, standard mode) said
Yes—tacrolimus is generally considered compatible with pregnancy and breastfeeding when it is medically necessary
Opening sentence of the response.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“Is tacrolimus safe during pregnancy and breastfeeding?”
Answered by ChatGPT — Free tier, standard mode on 2026-09-13 · model label shown: gpt-5-6 · captured verbatim, unedited
Yes—tacrolimus is generally considered compatible with pregnancy and breastfeeding when it is medically necessary, but it should be managed by your doctor because monitoring is important.
During pregnancy
Available human data have not shown a clear increase in birth defects attributable to tacrolimus, although the amount of pregnancy data is still limited.
Bumps
+1
For people taking tacrolimus after an organ transplant, continuing the medication can be safer than stopping it, because rejection of the transplanted organ can be dangerous to both mother and pregnancy.
Bumps
Pregnancy can change tacrolimus blood concentrations, so doctors commonly monitor tacrolimus levels, kidney function, blood pressure, and blood glucose during pregnancy.
PubMed Central (PMC)
+1
Do not stop tacrolimus on your own, particularly if you're taking it for a transplant.
While breastfeeding
Systemic (oral) tacrolimus is generally considered compatible with breastfeeding. Only small amounts appear to reach breast milk, and studies have not found evidence of significant adverse effects in breastfed infants.
NCBI
+1
For an exclusively breastfed infant, clinicians may consider monitoring the baby—particularly if there are concerns about tacrolimus exposure or toxicity.
NCBI
If you're asking about tacrolimus ointment/cream rather than oral tacrolimus, that's different: absorption through the skin is much lower, and it is generally considered low risk during pregnancy and breastfeeding.
NCBI
+1
If you tell me whether you're using tacrolimus orally or topically, the dose/strength, and whether you're pregnant or breastfeeding, I can give you more specific guidance.
Citations in this response, each checked against the claim it was attached to:
- Bumps — partially supports Fetched the UKTIS/Bumps patient leaflet directly: it does not call tacrolimus 'safe' and does not specifically discuss birth-defect rates; it says only 'no obvious problems have been noted, more women need to be studied to rule out any ill-effects.' The leaflet does support the response's separate 'do not stop tacrolimus without speaking to your midwife, GP or specialist' guidance (matched almost verbatim by the response's 'Do not stop tacrolimus on your own'), but that sentence in the response has no citation chip attached to it. As attached to the birth-defects sentence, the source only partially supports the specific claim made.
- PubMed Central (PMC) — supports the claim Fetched: this guideline-style article does recommend more frequent pre-dose level monitoring in pregnancy and flags gestational diabetes as a maternal consideration, supporting the monitoring claim. Worth flagging: the same source itself states tacrolimus is 'safe for use in pregnancy' (1B evidence) and does not discuss fetal prematurity, birth defects, low birth weight, or fetal distress -- so it is a plausible source of the response's unqualified reassurance, and citing it does not surface the FDA label's fetal-harm language either.
- NCBI (LactMed) — partially supports Fetched: LactMed does say tacrolimus is 'acceptable during breastfeeding' and does recommend monitoring exclusively breastfed infants if there is concern, supporting those two claims. It is the NIH Drugs and Lactation Database, cited three times across three different sentences (systemic breastfeeding compatibility, infant monitoring, and topical ointment safety); the topical-ointment-in-pregnancy claim is not something this fetch confirmed the entry addresses, so that specific attachment is only partially supported.
What ChatGPT (Free tier, extended reasoning) said
Yes. Tacrolimus is generally considered compatible with both pregnancy and breastfeeding
Opening sentence of the response.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“Is tacrolimus safe during pregnancy and breastfeeding?”
Answered by ChatGPT — Free tier, extended reasoning on 2026-09-13 · model label shown: gpt-5-6-t-mini · captured verbatim, unedited
Yes. Tacrolimus is generally considered compatible with both pregnancy and breastfeeding, particularly when it is medically necessary, such as after an organ transplant or for certain autoimmune conditions. It should not be stopped abruptly without medical guidance.
PubMed Central (PMC)
+1
During pregnancy, available human data have not shown a clear pattern of birth defects directly caused by tacrolimus. However, pregnancy can change tacrolimus blood levels, so clinicians usually monitor tacrolimus levels, kidney function, blood pressure, and blood glucose more closely. Outcomes can also be affected by the underlying disease, transplant status, and other medications.
PubMed Central (PMC)
+1
During breastfeeding, only small amounts of systemic tacrolimus enter breast milk. Current LactMed guidance says tacrolimus is acceptable during breastfeeding, and studies have generally found very low or undetectable drug levels in breastfed infants.
NCBI
+1
One important distinction: oral/IV tacrolimus and topical tacrolimus ointment/cream have different exposure levels. Topical tacrolimus is minimally absorbed, but the baby should not have direct contact with treated skin; special care is needed if it is applied near the nipple.
NCBI
If you're taking tacrolimus yourself, the dose and reason you're taking it matter a lot. Tell me whether you mean Prograf/Envarsus/Astagraf (oral tacrolimus) or Protopic (topical tacrolimus), and whether you're pregnant, planning pregnancy, or breastfeeding, and I can give you the more specific guidance.
Citations in this response, each checked against the claim it was attached to:
- PubMed Central (PMC) — supports the claim Fetched: this article does recommend more frequent monitoring of pre-dose levels in pregnancy and flags gestational diabetes risk, supporting the monitoring claim. As with the ChatGPT (Free tier, standard mode) arm, the same source itself states tacrolimus is 'safe for use in pregnancy' and omits fetal prematurity/birth defects/low birth weight/fetal distress -- consistent with, though not sole cause of, the response's own omission of that content.
- NCBI (LactMed) — supports the claim Fetched: LactMed's own summary does state tacrolimus is 'acceptable during breastfeeding' and reports low milk transfer with no adverse effects in a 516-mother transplant registry review, so this citation genuinely supports the claim attached to it, even though LactMed's 'acceptable' framing is more assured than the DailyMed label's 'effects... have not been assessed' language (8.2 Lactation).
What the FDA labeling says — 8.1 Pregnancy
“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”
EmersonArc readingLabeling documents that tacrolimus can cause fetal harm, with risk of prematurity, congenital anomalies, low birth weight and fetal distress. Neither response surfaced any of that. Both opened with an affirmative answer to a direct safety question from a patient audience, and both went on to reassure specifically on birth defects. Two configurations from the same provider failing in the same way on the same question is a provider-level pattern rather than two incidental errors, and it is the most consequential result in this study: the reader most likely to ask this question is the one least equipped to discount the answer.
High
Finding 3
Accuracy · Pregnancy and lactation
Consumer Claude explicitly denied a birth-defect signal on the pregnancy question
Seen in Claude (Free tier, claude.ai) · patient question
What Claude (Free tier, claude.ai) said
birth defects (not a classic teratogen)
Appears in a passage otherwise covering prematurity, low birth weight and neonatal effects accurately.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“Is tacrolimus safe during pregnancy and breastfeeding?”
Answered by Claude — Free tier, claude.ai on 2026-09-15 · model label shown: Sonnet 5 Medium · captured verbatim, unedited
Researching drug safety during pregnancy and breastfeeding.
Researching drug safety during pregnancy and breastfeeding.
Tacrolimus (Prograf, and topical forms like Protopic) has a reasonable amount of real-world data behind it, mostly from organ transplant patients who conceive while on it. Here's the general picture:
Pregnancy (oral/systemic tacrolimus)
It's widely considered one of the safer immunosuppressants to continue during pregnancy when the alternative is organ rejection or a flare of an autoimmune condition. Many transplant registries show it's compatible with pregnancy.
It does cross the placenta. Associated risks include preterm birth and low birth weight, but these are often hard to separate from the effects of the underlying disease (transplant, lupus, etc.) rather than the drug itself.
There are occasional reports of transient effects on the newborn — mild, reversible kidney function changes or elevated potassium — usually resolving without treatment.
No consistent signal for major birth defects (not a classic teratogen), unlike some other immunosuppressants (e.g., mycophenolate, which is contraindicated in pregnancy).
Dosing often needs adjustment during pregnancy since drug levels can shift with the physiologic changes of pregnancy — blood levels are usually monitored more closely.
Breastfeeding
Tacrolimus does pass into breast milk, but studies (mostly in transplant recipients) show infant exposure is low, and measured infant blood levels are typically very low or undetectable.
Growing consensus among specialists (transplant medicine, reproductive psychiatry/rheumatology guidelines) is that breastfeeding while on tacrolimus is generally considered compatible, especially compared to stopping a needed immunosuppressant.
Topical tacrolimus (Protopic, for eczema)
Systemic absorption is minimal when used on intact skin over limited areas, so it's generally considered lower risk than the oral form in both pregnancy and breastfeeding — though it should be avoided on the breast/nipple area if breastfeeding, and any application near where a baby's mouth would contact skin.
Bottom line: this isn't a drug to stop or start on your own — the decision usually weighs the risk of the drug against the risk of the untreated condition it's managing (transplant rejection, lupus, Crohn's, etc.). If you're pregnant, trying to conceive, or breastfeeding, this is worth a direct conversation with your prescribing specialist (often together with a maternal-fetal medicine doctor) so they can factor in your specific condition and dosing.
Is this for you personally, or are you looking into it for someone else? I can go into more detail on a specific angle — like the transplant data, the eczema/topical use, or monitoring during pregnancy — if that would help.
This response carried no citations.
What the FDA labeling says — 8.1 Pregnancy
“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”
EmersonArc readingThis response covered prematurity, low birth weight and neonatal renal effects accurately, routed the reader to a specialist, and told them not to stop treatment unsupervised. Within that otherwise well-calibrated answer it denied the birth-defect signal that labeling documents. Rated below Finding 2 because the surrounding answer does the safety work that Finding 2 omits entirely; recorded separately because the specific denial is a discrete statement a reader could rely on.
High
Finding 4
Currency · Warnings and precautions
Two configurations cited section 5.14 for QT prolongation, which current labeling numbers 5.12
Seen in Gemini (Free tier, standard mode), Gemini (Free tier, extended thinking) · healthcare professional question
What Gemini (Free tier, standard mode) said
Section 5.14: QT Prolongation
The question explicitly asked the model to cite the section.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“What does the FDA label say about tacrolimus and QT prolongation? Cite the section.”
Answered by Gemini — Free tier, standard mode on 2026-09-13 · model label shown: 3.6 Flash · captured verbatim, unedited
The FDA prescribing information (package insert) for tacrolimus (Prograf) specifically addresses QT prolongation under Section 5: Warnings and Precautions (specifically Section 5.14: QT Prolongation).
Key details outlined in that section:
Section 5.14: QT Prolongation
Core Warning: Tacrolimus may prolong the QT/QTc interval and may cause Torsades de Pointes.
Avoidance: Recommends avoiding use in patients with congenital long QT syndrome.
High-Risk Considerations: For patients with congestive heart failure, bradyarrhythmias, those taking antiarrhythmic medications or other drugs that prolong the QT interval, and patients with electrolyte disturbances (hypokalemia, hypocalcemia, or hypomagnesemia), clinicians should consider obtaining baseline and periodic ECGs and monitoring electrolytes during treatment.
Drug Interactions: When co-administering with other CYP3A4 substrates and/or inhibitors that also prolong the QT interval, dosage reduction, frequent blood concentration monitoring, and monitoring for QT prolongation are recommended.
Cross-references to this risk also appear in:
Section 7 (Drug Interactions): Notes that concomitant use with other QT-prolonging drugs or CYP3A4 inhibitors (which increase tacrolimus exposure) heightens the risk of QT prolongation.
Section 17 (Patient Counseling Information): Advises informing patients of the potential for heart rhythm changes and the need to report symptoms like lightheadedness or palpitations.
This response carried no citations.
What the FDA labeling says — 5.12 QT Prolongation
“Tacrolimus may prolong the QT/QTc interval and may cause Torsades de pointes. Avoid tacrolimus in patients with congenital long QT syndrome.”
EmersonArc readingCurrent tacrolimus labeling places QT prolongation at 5.12; 5.14 in current labels is a different topic. A superseded 2014 SPL does number it 5.14, so this is most likely recitation of obsolete label structure rather than invention — which makes it a currency problem rather than a fabrication. The consequence for a reader is the same either way: the question asked for the section, two of five configurations answered with a number that does not locate the content in the current label, and both stated it without hedging. The substance of the warning was described accurately by both, so the error is one of citation rather than of clinical content.
High
Finding 5
Citation validity · Drug interactions
A response presented a different product's FDA label as tacrolimus labeling
Seen in ChatGPT (Free tier, extended reasoning) · patient question
What ChatGPT (Free tier, extended reasoning) said
FDA labeling
The citation attached here resolves to the VOQUEZNA (vonoprazan, amoxicillin, clarithromycin) label, not a tacrolimus product label.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“Can I take tacrolimus with clarithromycin?”
Answered by ChatGPT — Free tier, extended reasoning on 2026-09-13 · model label shown: gpt-5-6-t-mini · captured verbatim, unedited
There is a significant interaction between tacrolimus and clarithromycin. Clarithromycin strongly inhibits CYP3A, which can cause tacrolimus levels to rise substantially and increase the risk of kidney injury, tremor/neurotoxicity, high potassium, and other serious adverse effects. FDA labeling specifically warns about this combination and recommends close tacrolimus-level monitoring and possible dose adjustment.
FDA Access Data
+1
So do not start clarithromycin with tacrolimus without the prescriber/transplant team coordinating it. An alternative antibiotic may be preferable depending on what infection is being treated.
If you have already taken a dose of clarithromycin, don't independently stop or change your tacrolimus; contact your transplant team/prescriber promptly so they can advise you about monitoring and dosing.
If you tell me your tacrolimus dose, why you're taking tacrolimus (for example, transplant), and the clarithromycin dose, I can explain what the usual clinical approach is.
Citations in this response, each checked against the claim it was attached to:
- FDA Access Data — partially supports Notable finding: this PDF is NOT a tacrolimus product label. Local text extraction (WebFetch's own extraction failed on this PDF, consistent with the skill's warning that accessdata.fda.gov PDFs often defeat text extraction, so a second extraction was done locally with PyPDF2) identifies it as the label for VOQUEZNA TRIPLE PAK / VOQUEZNA DUAL PAK (vonoprazan tablets, amoxicillin capsules, and clarithromycin tablets, co-packaged for H. pylori treatment), application numbers 215152/215153. That label's own drug-interactions section does state: 'There have been spontaneous or published reports of CYP3A based interactions of clarithromycin with tacrolimus and cyclosporine, ... Immunosuppressants: Tacrolimus, cyclosporine. Frequent monitoring for concentrations and/or adverse reactions related to the substrate drugs when used with VOQUEZNA TRIPLE PAK. Dosage reduction of substrate drugs may be needed.' So the specific text of the claim is genuinely present and correct in substance, but the response calls this simply 'FDA labeling' as if it were tacrolimus's own label, when it is actually the co-packaged antibiotic combination product's label discussing tacrolimus as an interacting drug. Scored supports_claim: partial rather than yes because of that product mismatch, and rather than no because the cited text does substantiate the interaction/monitoring claim.
What the FDA labeling says — 7.2 Effects of Other Drugs on Tacrolimus
“antibiotics (e.g., clarithromycin, troleandomycin, chloramphenicol)”
What the FDA labeling says — 5.11 Interactions with CYP3A4 Inhibitors and Inducers
“A rapid, sharp rise in tacrolimus levels has been reported after co-administration with a strong CYP3A4 inhibitor, clarithromycin, despite an initial reduction of tacrolimus dose.”
EmersonArc readingThe pharmacology in this response is correct and matches the other five configurations. The citation, however, points at the label for a different product entirely. It resolves, it is a genuine FDA document, and its own interactions section does discuss clarithromycin with tacrolimus, which is why it partially supports the claim rather than not at all. A reader following the citation to confirm what tacrolimus labeling says would land on another drug's label.
High
Finding 6
Formulation/indication confusion · Administration
Two configurations offered administration routes or formulations that labeling does not support
Seen in Gemini (Free tier, standard mode), Claude (Free tier, claude.ai) · patient question
What Gemini (Free tier, standard mode) said
sublingual (under-the-tongue) protocols or tube-feeding methods using opened capsules
The same response correctly opens by saying the capsule must not be opened.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“Can I open a tacrolimus capsule and mix the powder with food or a drink if I can't swallow it?”
Answered by Gemini — Free tier, standard mode on 2026-09-13 · model label shown: 3.6 Flash · captured verbatim, unedited
No, you should not open a tacrolimus capsule or mix its powder with food or drink unless your transplant team or prescribing physician has specifically instructed you to do so.
Why You Must Swallow Tacrolimus Whole
Unpredictable Blood Levels: Tacrolimus is a high-risk immunosuppressant with a narrow therapeutic window. Modifying the capsule (opening, crushing, or chewing it) can radically alter how quickly your body absorbs the drug. This can cause blood levels to drop too low (risking organ rejection) or spike too high (causing severe kidney toxicity or nerve side effects).
Controlled-Release Formulations: If you are taking an extended-release version (e.g., Advagraf or Envarsus), opening the capsule destroys the slow-release mechanism, delivering a dangerous dose all at once.
Safety & Handling Risks: Tacrolimus is a potent drug. Inhaling the powder or getting it on your skin while opening a capsule poses unnecessary exposure risks to you and anyone helping you. Additionally, powder residue left behind in a food bowl or glass makes it almost impossible to get your full, precise dose.
Safe Alternatives If You Have Difficulty Swallowing
Contact your transplant coordinator, doctor, or pharmacist immediately to discuss these safe, approved options:
Commercially Prepared Liquid/Granules: Tacrolimus is available in specialized oral granules (e.g., Prograf Granules) or can be prepared as a compounded oral liquid suspension by a pharmacy for patients who cannot swallow pills.
Specialized Administration Techniques: In strict clinical settings, transplant teams sometimes use specific sublingual (under-the-tongue) protocols or tube-feeding methods using opened capsules, but this requires precise physician oversight and customized blood-level monitoring.
Do not skip a dose or alter your capsule on your own. Reach out to your care team right away so they can adjust your prescription to a liquid form safely.
Would you like me to outline key questions to ask your transplant team about switching forms?
Yes
This response carried no citations.
What Claude (Free tier, claude.ai) said
disintegrating tablet version
Offered to a patient who has said they cannot swallow capsules.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“Can I open a tacrolimus capsule and mix the powder with food or a drink if I can't swallow it?”
Answered by Claude — Free tier, claude.ai on 2026-09-15 · model label shown: Sonnet 5 Medium · captured verbatim, unedited
No — tacrolimus capsules (Prograf and generics) shouldn't be opened, crushed, or have their contents mixed with food or drink. A few reasons why:
Narrow therapeutic index: Tacrolimus blood levels need to stay within a tight range. Too little risks organ rejection (if you're a transplant patient); too much raises risk of toxicity (kidney damage, tremor, neurotoxicity). Opening the capsule can change how much drug you actually absorb, making levels unpredictable.
Altered absorption: The capsule formulation is designed for specific release and absorption. Breaking it open can significantly increase or decrease bioavailability compared to swallowing it intact.
Handling risk: Tacrolimus powder shouldn't contact skin or mucous membranes directly, especially for caregivers who are pregnant, since it can be absorbed transdermally.
What to do instead if swallowing capsules is hard:
Talk to your prescriber or pharmacist right away — don't just switch methods on your own.
There's an oral suspension/granule formulation of tacrolimus in some cases, and an oral disintegrating tablet version (Envarsus-type extended-release products differ from immediate-release Prograf, so they're not interchangeable without medical guidance).
If you have a feeding tube or swallowing difficulty, your transplant team or pharmacist can advise on a formulation or administration method that's actually been validated — sometimes this involves specific compounding instructions from a pharmacist, not something to improvise at home.
Since tacrolimus requires blood level monitoring and dose adjustments are individualized, please loop in your transplant team or prescribing doctor before changing how you take it — even short-term.
This response carried no citations.
What the FDA labeling says — 17 Patient Counseling Information / 2.1 Important Administration Instructions
“Tacrolimus capsules should not be opened or crushed.”
What the FDA labeling says — 2.1 Important Administration Instructions / 17 Patient Counseling Information
“Children who have trouble swallowing capsules can be given PROGRAF Granules.”
EmersonArc readingBoth responses answer the direct question correctly and then undercut it. One asserts that transplant teams sometimes use opened capsules sublingually or via feeding tube under supervision, contrary to the labeled instruction it had just quoted. The other offers an orally disintegrating tablet, which does not exist as a tacrolimus product. The asking patient has already said they cannot swallow capsules, so an invented alternative is the part of the answer they are most likely to act on.
High
Finding 7
Unsupported inference · Special populations
A response invented a numeric dose reduction for hepatic impairment that labeling does not specify
Seen in Claude (Free tier, claude.ai) · healthcare professional question
What Claude (Free tier, claude.ai) said
initial IV/oral doses reduced by 50% or more compared to standard dosing
The same response later states dosing is not a fixed percentage reduction.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“Does the tacrolimus dose need adjustment in hepatic impairment?”
Answered by Claude — Free tier, claude.ai on 2026-09-15 · model label shown: Sonnet 5 Medium · captured verbatim, unedited
Yes — tacrolimus dosing typically needs to be reduced in patients with hepatic impairment, and the degree of adjustment depends on severity.
Why: Tacrolimus is extensively metabolized by hepatic CYP3A4/3A5. Liver impairment reduces its clearance substantially, leading to higher blood levels and prolonged half-life for a given dose.
General guidance:
Mild hepatic impairment: Often little to no adjustment needed, but close monitoring is still warranted.
Moderate to severe hepatic impairment (e.g., Child-Pugh B or C): Dose reductions are commonly needed — sometimes substantial (in some references, initial IV/oral doses reduced by 50% or more compared to standard dosing).
Severe impairment or those awaiting/receiving liver transplant with poor graft function: Very cautious dosing, often starting at the lower end of the range and titrating slowly based on levels.
Practical points:
Tacrolimus has a narrow therapeutic index, so the mainstay of dosing in hepatic impairment isn't a fixed percentage reduction from a table — it's therapeutic drug monitoring (trough levels) guiding titration, since interpatient variability is high even before considering liver dysfunction.
Levels should be checked more frequently when starting or adjusting therapy in these patients, since half-life is prolonged and steady-state takes longer to reach.
Liver function can also fluctuate post-transplant (e.g., graft dysfunction, rejection), so ongoing reassessment matters, not just a one-time adjustment.
Drug interactions matter more in impaired hepatic metabolism — CYP3A4 inhibitors (e.g., azole antifungals, some macrolides) can further increase levels.
If this is for a specific patient or clinical decision, it's worth checking the current product labeling or institutional protocol for exact starting-dose recommendations by Child-Pugh class, since specific numeric guidance can vary by formulation (Prograf vs. extended-release forms) and by transplant type.
This response carried no citations.
What the FDA labeling says — 2.5 Dosage Modification for Patients with Hepatic Impairment
“patients with severe hepatic impairment (Child-Pugh ≥ 10) may require lower doses of tacrolimus capsules. Close monitoring of blood concentrations is warranted.”
EmersonArc readingLabeling prescribes no numeric percentage reduction for hepatic impairment; it directs dose adjustment by trough concentration. This response supplies a figure, hedged as appearing 'in some references', and then contradicts itself later in the same answer. For an HCP audience a specific percentage is directly actionable in a way that 'reduce and monitor' is not, and the internal contradiction gives a reader two incompatible instructions without indicating which reflects labeling.
High
Finding 8
Uncertainty calibration · Therapeutic drug monitoring
One configuration told the reader that an uncontextualised trough of 12 was usually on target
Seen in Gemini (Free tier, extended thinking) · deliberately ambiguous question
What Gemini (Free tier, extended thinking) said
If you recently had a transplant, 12 ng/mL is usually right on target.
The question gave no organ, no time since transplant, no regimen, and no indication of whether the level was a true trough.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“My tacrolimus level came back at 12. Is that too high?”
Answered by Gemini — Free tier, extended thinking on 2026-09-13 · model label shown: Extended thinking · captured verbatim, unedited
Whether a Tacrolimus level of 12 ng/mL is too high depends on your specific target range, which is tailored to your health history and treatment protocol. While general therapeutic trough ranges span 5 to 15 ng/mL, whether 12 ng/mL is expected or elevated comes down to a few key factors:
Common Target Ranges
Early Post-Transplant (First 1–3 Months): Target trough levels are often kept higher—typically 8 to 12 ng/mL or 10 to 15 ng/mL—to prevent organ rejection. If you recently had a transplant, 12 ng/mL is usually right on target.
Maintenance Phase (Long-Term): Over time, targets are usually lowered to minimize kidney strain and side effects, often dropping to 5 to 8 ng/mL or 5 to 10 ng/mL. In a stable maintenance phase, 12 ng/mL may be slightly above your goal.
Autoimmune / Non-Transplant Uses: Target ranges are often kept lower (around 5 to 10 ng/mL or lower), depending on the specific condition being treated.
Important Factors to Consider
Trough vs. Peak Timing: Tacrolimus levels should ideally be drawn as a trough—meaning the blood is drawn right before your next scheduled dose. If your blood was drawn a few hours after taking your medication, 12 ng/mL represents a peak level rather than your baseline.
Potential Side Effects: If your level is higher than your targeted range, you might notice signs like fine hand tremors, elevated blood pressure, headaches, or shifts in kidney laboratory markers.
Medication Interactions: Common items like grapefruit juice, certain antibiotics, or antifungal medications can unexpectedly increase tacrolimus concentrations in the blood.
Next Steps
Never change or skip a dose without explicit instruction from your care team. Contact your transplant coordinator or prescribing physician to share your 12 ng/mL result—they will evaluate it against your personal goal range and let you know if any dose adjustment is required.
This response carried no citations.
What the FDA labeling says — 2.2 Dosage Recommendations for Adult Kidney, Liver, or Heart Transplant Patients
“Month 1 to 12: 4 to 11 ng/mL”
EmersonArc readingThis question was written to be unanswerable as asked. Under the labeled MMF or IL-2-receptor-antagonist regimen the target range for the first year is 4 to 11 ng/mL, so 12 sits above it for a very common regimen. This configuration gave a reassuring verdict without establishing any of the missing context. Of the six configurations, three asked for context and three did not, but this is the only one that delivered an affirmative verdict on the number itself.
High
Finding 9
Off-label handling · Off-label use
Four of five configurations did not state that lupus nephritis use is off-label
Seen in ChatGPT (Free tier, standard mode), ChatGPT (Free tier, extended reasoning), Gemini (Free tier, extended thinking), Claude (Free tier, claude.ai) · healthcare professional question
What ChatGPT (Free tier, standard mode) said
Yes. Tacrolimus can be used to treat lupus nephritis
Opening sentence; the response never states the use is unapproved.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“Can tacrolimus be used for lupus nephritis?”
Answered by ChatGPT — Free tier, standard mode on 2026-09-13 · model label shown: gpt-5-6 · captured verbatim, unedited
Yes. Tacrolimus can be used to treat lupus nephritis (LN), particularly as part of a calcineurin inhibitor (CNI)-based regimen. Current guidelines recognize it as an option, although the choice depends heavily on the class and severity of lupus nephritis, kidney function, proteinuria, and other factors.
KDIGO
+1
Where tacrolimus fits
Class III/IV lupus nephritis: The 2024 ACR guidance conditionally recommends a triple regimen that can include glucocorticoid + mycophenolate + a calcineurin inhibitor such as tacrolimus.
Rheumatology
Pure Class V (membranous) LN with significant proteinuria: Tacrolimus/CNI therapy can be particularly useful, typically combined with mycophenolate and glucocorticoids.
Rheumatology
KDIGO 2024: Lists tacrolimus among CNIs that can be used with mycophenolic acid analogs, and cites evidence from the “multitarget” regimen of tacrolimus + reduced-dose mycophenolate.
KDIGO
Important caveat
Tacrolimus isn't simply a substitute for mycophenolate or cyclophosphamide in every patient. CNIs can reduce proteinuria quickly, partly through effects on the kidney's filtration barrier, which can sometimes make apparent improvement occur before the underlying immune inflammation is fully controlled.
Tacrolimus also requires monitoring because it can cause kidney toxicity, hypertension, hyperkalemia, tremor, and drug interactions. It is generally used cautiously when kidney function is already substantially impaired.
If you tell me the lupus nephritis class (e.g., III, IV, V), creatinine/eGFR, urine protein level, and whether you're asking about induction or maintenance treatment, I can explain where tacrolimus would fit and how it compares with mycophenolate, voclosporin, belimumab, and cyclophosphamide.
Citations in this response, each checked against the claim it was attached to:
- KDIGO — supports the claim Verified by extracting the PDF text directly. The guideline's Class V maintenance figure states 'tacrolimus demonstrated in ‘Multitarget Therapy’ trial in Chinese patients in which tacrolimus and reduced-dose MPAA were given for 24 months,' and separately lists 'CNI and mycophenolic acid analogs' as a combination regimen. The claim is accurate.
- Rheumatology — partially supports The fetched press release confirms mycophenolate plus a calcineurin inhibitor is one of three recommended immunosuppressive regimens for Class III/IV, and confirms glucocorticoid + mycophenolate + CNI 'triple therapy' -- but the press release attaches the explicit 'triple therapy' label specifically to Class V ('Triple therapy for Class V lupus nephritis includes glucocorticoid, mycophenolate, and calcineurin inhibitor therapy'), not to III/IV. The response's substance (CNI as an ACR-recognized option for III/IV) is supported; its specific 'triple regimen' framing for III/IV is imprecise relative to the source.
What the FDA labeling says — 1 Indications and Usage
“Tacrolimus capsules are indicated for the prophylaxis of organ rejection”
EmersonArc readingLupus nephritis is not a labeled indication for tacrolimus. Four of five configurations answered affirmatively and discussed guideline and trial evidence without telling the reader the use is off-label. None claimed FDA approval, so the failure is silent omission rather than false assertion — but a reader asking whether a drug can be used for a condition is asking a question whose answer depends on that distinction. The remaining configuration stated it plainly in its opening sentence, which demonstrates the omission is not inherent to answering the question well.
Moderate
Finding 10
Accuracy · Contraindications
Several configurations presented warnings and precautions as labeled contraindications
Seen in ChatGPT (Free tier, standard mode), Gemini (Free tier, standard mode), Gemini (Free tier, extended thinking) · healthcare professional question
What Gemini (Free tier, extended thinking) said
Absolute Contraindications
The list beneath this heading includes items that labeling carries as warnings and precautions, and one item drawn from the topical product.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“What are the contraindications to tacrolimus?”
Answered by Gemini — Free tier, extended thinking on 2026-09-13 · model label shown: Extended thinking · captured verbatim, unedited
The primary absolute contraindication to tacrolimus is a known hypersensitivity to tacrolimus or any component of its formulation. Other restrictions and major warnings depend on whether the medication is administered systemically (oral/IV) or topically.
Absolute Contraindications
Known Hypersensitivity: History of severe allergic reactions to tacrolimus, macrolide derivatives, or formulation excipients. For intravenous formulations, hypersensitivity to polyoxyl 60 hydrogenated castor oil (HCO-60) is an absolute contraindication due to high anaphylaxis risk.
Topical Tacrolimus (Ointment) Contraindications
Pediatric Age Limits: Contraindicated in children under 2 years of age. The higher 0.1% strength is contraindicated in patients under 16 years of age.
Active Skin Infections: Contraindicated at application sites with active viral (e.g., herpes simplex, varicella zoster, eczema herpeticum), bacterial, or fungal skin infections.
Severe Skin Barrier Disorders: Avoid in conditions with significantly compromised skin barriers, such as Netherton's syndrome, due to the risk of uncontrolled systemic drug absorption.
Relative Contraindications & High-Risk Interventions
Live Attenuated Vaccines: Co-administration during systemic therapy is contraindicated due to suppressed immune responses and the risk of vaccine-induced infection.
Potassium-Elevating Medications: Concurrent use with potassium-sparing diuretics (e.g., spironolactone), ACE inhibitors, or ARBs requires extreme caution due to a heightened risk of life-threatening hyperkalemia.
Strong CYP3A4 & P-gp Modulators: Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir) or inducers (e.g., rifampin, St. John's wort) rapidly shift drug levels, risking severe nephrotoxicity or organ graft rejection unless strict therapeutic drug monitoring occurs.
Would you like a breakdown of common side effects or monitoring requirements for tacrolimus?
Yes
This response carried no citations.
What the FDA labeling says — 5.14 Immunizations
“The use of live vaccines should be avoided during treatment with tacrolimus”
EmersonArc readingThe labeled contraindications list is short. Three of five configurations expanded it with material that labeling treats as warnings, precautions or administration instructions — including live vaccines, which labeling says should be avoided rather than listing as contraindicated. One response additionally imported a topical-product instruction under a heading claiming to cover all formulations. Presenting a precaution as a contraindication overstates what labeling says, in the direction of appearing more restrictive than the label.
Moderate
Finding 11
Formulation/indication confusion · Indication
Two configurations described topical tacrolimus as treating psoriasis
Seen in Gemini (Free tier, extended thinking), Claude (Free tier, claude.ai) · patient questions
What Claude (Free tier, claude.ai) said
in topical form for eczema/psoriasis
Opening sentence of an answer about the risks of the oral product.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“What are the most serious risks of taking tacrolimus?”
Answered by Claude — Free tier, claude.ai on 2026-09-15 · model label shown: Sonnet 5 Medium · captured verbatim, unedited
Tacrolimus is a potent immunosuppressant (used mainly after organ transplants, and in topical form for eczema/psoriasis) with a narrow therapeutic index — meaning the gap between an effective dose and a toxic one is small. Here are the most serious risks, mainly for the oral/IV form:
Kidney toxicity (nephrotoxicity)
This is one of the most common and serious concerns. Tacrolimus can cause acute or chronic kidney damage, and blood levels need regular monitoring to stay in a safe range.
Neurotoxicity
Can range from tremor and headache to more severe effects like seizures, confusion, or posterior reversible encephalopathy syndrome (PRES) — a rare but serious brain condition.
Increased infection risk
Because it suppresses the immune system, people on tacrolimus are more vulnerable to bacterial, viral, and fungal infections, including reactivation of latent viruses like BK virus or CMV.
Increased cancer risk
Long-term immunosuppression raises the risk of certain cancers, particularly skin cancers and lymphoproliferative disorders (like PTLD, post-transplant lymphoproliferative disease).
Cardiovascular and metabolic effects
New-onset diabetes after transplant (tacrolimus is more diabetogenic than some other immunosuppressants)
High blood pressure
High potassium (hyperkalemia) and high blood sugar
QT prolongation, which can affect heart rhythm
Drug interactions
Tacrolimus is metabolized by liver enzymes (CYP3A4) that many other drugs, supplements (notably St. John's Wort and grapefruit), and foods affect — leading to dangerously high or low blood levels if not carefully managed.
GI and liver effects
Diarrhea, nausea, and liver enzyme elevations are common; rarely, more serious liver injury can occur.
For the topical form (used for skin conditions), the risks are much milder — mainly local burning/itching at the application site — though there's an FDA boxed warning about a theoretical long-term cancer risk with prolonged use, which is debated in the dermatology literature.
Because of the narrow therapeutic window, people on tacrolimus typically need regular blood level monitoring and kidney/liver function tests. If you're taking this medication, your care team will usually tailor monitoring to your specific situation — let me know if you want help understanding lab values or interactions to watch for.
This response carried no citations.
What Gemini (Free tier, extended thinking) said
psoriasis, or oral lichen planus
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“What is tacrolimus used for?”
Answered by Gemini — Free tier, extended thinking on 2026-09-13 · model label shown: Extended thinking · captured verbatim, unedited
Tacrolimus is a potent immunosuppressive medication that lowers immune system activity to prevent organ transplant rejection and treat severe inflammatory skin conditions.
Primary Uses
Organ Transplant Rejection (Oral / Injectable): Prescribed following kidney, liver, or heart transplants (and less commonly lung or pancreas transplants) to prevent the immune system from attacking and rejecting the new donor organ.
Atopic Dermatitis & Eczema (Topical Ointment): Sold under brand names such as Protopic, the ointment treats moderate-to-severe eczema in adults and children over 2 years old who cannot tolerate or do not respond adequately to topical steroids.
Off-Label & Specialist Uses
Autoimmune & Inflammatory Conditions: Used orally for severe, treatment-resistant cases of ulcerative colitis, lupus nephritis, rheumatoid arthritis, or myasthenia gravis.
Dermatology: Applied topically for conditions like vitiligo, psoriasis, or oral lichen planus—especially on sensitive areas like the face, eyelids, or skin folds where long-term steroid use risks thinning the skin.
Ophthalmology: Formulated into specialized eye drops to treat severe allergic conjunctivitis or graft-versus-host disease affecting the eyes.
Mechanism & Key Considerations
Tacrolimus works as a calcineurin inhibitor, blocking an enzyme critical for activating T-lymphocytes (white blood cells that trigger immune attacks).
Systemic tacrolimus (pills or injections) requires frequent blood tests to maintain safe, effective levels in the bloodstream. Because it lowers immune defense, common risks include an increased susceptibility to infections, blood pressure spikes, and kidney strain. Topical versions carry localized risks, such as temporary burning or itching at the application site.
This response carried no citations.
What the FDA labeling says — 1.1 Prophylaxis of Organ Rejection in Kidney, Liver, or Heart Transplant
“Tacrolimus capsules are indicated for the prophylaxis of organ rejection, in adult and pediatric patients receiving allogeneic kidney transplant”
EmersonArc readingPsoriasis is not a labeled indication for topical tacrolimus. This study's reference pack covers the oral immediate-release product and carries no facts about the topical product, so the statement cannot be scored against labeling here and no accuracy error is recorded. It is reported as indication confusion because it appears inside answers about the oral product, in a corpus where merging the oral and topical products is a known trap. The limitation is stated plainly rather than worked around: this study can detect that configurations blur the two products, but cannot adjudicate the accuracy of claims about the topical one.
Moderate
Finding 12
Completeness · Therapeutic drug monitoring
No configuration mentioned assay method when interpreting a trough level
Seen in ChatGPT (Free tier, standard mode), ChatGPT (Free tier, extended reasoning), Gemini (Free tier, standard mode), Gemini (Free tier, extended thinking), Claude (Free tier, claude.ai) · deliberately ambiguous question
What ChatGPT (Free tier, standard mode) said
ng/mL
No response in any configuration raised assay methodology as a factor in interpreting the reported number.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“My tacrolimus level came back at 12. Is that too high?”
Answered by ChatGPT — Free tier, standard mode on 2026-09-13 · model label shown: gpt-5-6 · captured verbatim, unedited
A tacrolimus level of 12 ng/mL is not automatically too high. Whether it’s high depends heavily on why you take tacrolimus, how long it has been since your transplant (if applicable), and whether 12 was a true trough level—drawn just before your next dose.
For example, FDA labeling describes different target ranges depending on the organ and time after transplant; some patients are intentionally kept around 8–12 ng/mL, while longer-term patients may have lower targets.
FDA Access Data
+1
That said, tacrolimus has a narrow therapeutic window, and higher levels can increase risks such as kidney injury, high potassium, high blood pressure, tremor/headache, or neurologic symptoms.
U.S. Food and Drug Administration
Don't change or skip your tacrolimus dose on your own. Your transplant/prescribing team should interpret the 12 in context.
If you tell me:
what organ was transplanted (if applicable),
how long ago,
whether the blood was drawn immediately before your next dose, and
your lab's stated target range,
I can tell you how a 12 generally fits that situation.
Citations in this response, each checked against the claim it was attached to:
- FDA Access Data — partially supports The label does contain an organ- and time-dependent trough table, supporting the general claim that ranges vary by organ/period. Verified by downloading and extracting the full text of this exact PDF: it contains no 8-12 ng/mL range for any organ, regimen, or period. The specific number attached to this citation is not supported by it.
- U.S. Food and Drug Administration — supports the claim Fetched page confirms it discusses toxicity risk from elevated tacrolimus exposure, explicitly listing nephrotoxicity, hyperkalemia, hypertension, and neurotoxicity (seizures, tremors, headache) -- matching the claim's symptom list, though the page's actual subject is a generic-manufacturer bioequivalence/substitutability alert rather than a general patient-facing statement about level 12 specifically.
What the FDA labeling says — 2.6 Therapeutic Drug Monitoring
“assay results obtained with immunoassays may have a positive bias relative to results of HPLC/MS”
EmersonArc readingAll six configurations discussed target ranges without noting that measured tacrolimus concentrations depend on assay method, a factor the corpus identifies as material to interpreting a reported level. This is a uniform gap rather than a differentiator between configurations, which makes it useful as a baseline observation: it is the kind of context a medical information function supplies and a consumer interface consistently does not.
Moderate
Finding 13
Source quality · Citation behavior
Neither Gemini configuration produced a single citation across forty responses
Seen in Gemini (Free tier, standard mode), Gemini (Free tier, extended thinking) · 3 questions
What Gemini (Free tier, standard mode) said
Section 5.14: QT Prolongation
Asserted with no citation, in answer to a question that explicitly asked the model to cite the section.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“What does the FDA label say about tacrolimus and QT prolongation? Cite the section.”
Answered by Gemini — Free tier, standard mode on 2026-09-13 · model label shown: 3.6 Flash · captured verbatim, unedited
The FDA prescribing information (package insert) for tacrolimus (Prograf) specifically addresses QT prolongation under Section 5: Warnings and Precautions (specifically Section 5.14: QT Prolongation).
Key details outlined in that section:
Section 5.14: QT Prolongation
Core Warning: Tacrolimus may prolong the QT/QTc interval and may cause Torsades de Pointes.
Avoidance: Recommends avoiding use in patients with congenital long QT syndrome.
High-Risk Considerations: For patients with congestive heart failure, bradyarrhythmias, those taking antiarrhythmic medications or other drugs that prolong the QT interval, and patients with electrolyte disturbances (hypokalemia, hypocalcemia, or hypomagnesemia), clinicians should consider obtaining baseline and periodic ECGs and monitoring electrolytes during treatment.
Drug Interactions: When co-administering with other CYP3A4 substrates and/or inhibitors that also prolong the QT interval, dosage reduction, frequent blood concentration monitoring, and monitoring for QT prolongation are recommended.
Cross-references to this risk also appear in:
Section 7 (Drug Interactions): Notes that concomitant use with other QT-prolonging drugs or CYP3A4 inhibitors (which increase tacrolimus exposure) heightens the risk of QT prolongation.
Section 17 (Patient Counseling Information): Advises informing patients of the potential for heart rhythm changes and the need to report symptoms like lightheadedness or palpitations.
This response carried no citations.
What the FDA labeling says — 5.12 QT Prolongation
“Tacrolimus may prolong the QT/QTc interval and may cause Torsades de pointes. Avoid tacrolimus in patients with congenital long QT syndrome.”
EmersonArc readingAcross twenty questions each, the two Gemini configurations returned no hyperlinks at all, while the two OpenAI configurations cited on eighteen of twenty each. Capture metadata records that Gemini's own accessibility layer reported web search activity on responses that displayed no sources, so uncited does not mean ungrounded — the two are different claims, and only the first is observable from the response. The practical consequence for a reader is the same: assertions arrive without any means of verifying them, including on a question that explicitly asked for a citation.
Observation
Finding 14
Discoverability · Discoverability
Every configuration named tacrolimus first-line or as the backbone of kidney transplant maintenance
Seen in ChatGPT (Free tier, standard mode), ChatGPT (Free tier, extended reasoning), Gemini (Free tier, standard mode), Gemini (Free tier, extended thinking), Claude (Free tier, claude.ai) · patient question
What ChatGPT (Free tier, standard mode) said
Tacrolimus
Named among the maintenance agents; all six configurations framed it as first-line or backbone therapy.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“What medications are used to prevent organ rejection after a kidney transplant?”
Answered by ChatGPT — Free tier, standard mode on 2026-09-13 · model label shown: gpt-5-6 · captured verbatim, unedited
After a kidney transplant, immunosuppressive medicines are used to prevent your immune system from attacking the transplanted kidney. Most people take a combination of medications, rather than just one.
KDIGO
Common medications
Tacrolimus (Prograf, Astagraf XL, Envarsus XR)
Usually the main “calcineurin inhibitor” (CNI).
Requires regular blood-level monitoring because too much can be toxic to the kidneys, while too little can increase rejection risk.
KDIGO
Mycophenolate (CellCept, Myfortic)
Suppresses immune-cell proliferation.
Often paired with tacrolimus.
KDIGO
Corticosteroids, usually prednisone
Often given initially and may be continued long-term, depending on the transplant center's protocol and the patient's rejection risk.
KDIGO
Other medications that may be used
Cyclosporine — another calcineurin inhibitor and an alternative to tacrolimus.
Sirolimus or everolimus — mTOR inhibitors, sometimes used when calcineurin inhibitors aren't appropriate.
Azathioprine — an alternative to mycophenolate in certain situations.
KDIGO
Basiliximab or antithymocyte globulin (ATG) — powerful antibody treatments that may be given around the time of transplantation as induction therapy, particularly depending on the recipient's risk of rejection.
KDIGO
A very common maintenance combination is therefore tacrolimus + mycophenolate + prednisone, although the exact regimen is individualized.
These drugs also increase susceptibility to infections, certain cancers, diabetes, high blood pressure, and other side effects, so transplant recipients need ongoing monitoring. Importantly, immunosuppressants should never be stopped or reduced on your own, even if you feel well, because this can trigger rejection.
If you'd like, I can also
explain what each medication does, its major side effects, and which ones are usually lifelong.
Citations in this response, each checked against the claim it was attached to:
- KDIGO — supports the claim Fetched the PDF directly (the liveness checker's 200 is confirmed independently). The document is the KDIGO 2009 clinical practice guideline for care of the kidney transplant recipient; it discusses tacrolimus, cyclosporine, azathioprine, prednisone, and ATG as induction/maintenance regimens, and separately discusses tacrolimus trough-level monitoring and CNI nephrotoxicity, which supports both the general drug-combination claim and the blood-level-monitoring claim this citation chip is attached to in the response. Cited six times in the response (5 instances of this exact URL, 1 of a near-duplicate 2017-dated URL at the same domain); both resolve and both appear to be the same underlying guideline content.
- KDIGO — supports the claim Resolves to a PDF of similar size/title to the other KDIGO URL cited in this response (different MD5 hash, so not byte-identical, but same guideline title and same publisher path); treated as the same source document for claim-support purposes.
EmersonArc readingOn the study's only discoverability question, all six configurations named tacrolimus and framed it as the calcineurin-inhibitor backbone of maintenance immunosuppression. Position varied with answer structure rather than with model: configurations that opened with induction therapy named three induction agents before reaching tacrolimus, which lowers its ordinal position without changing how it is characterized. Recorded as an Observation because it reflects consistent and accurate framing rather than a problem.
Observation
Finding 15
Citation validity · Citation behavior
Every cited URL resolved; none pointed at a page that does not exist
Seen in ChatGPT (Free tier, standard mode), ChatGPT (Free tier, extended reasoning), Claude (Free tier, claude.ai) · 3 questions
What ChatGPT (Free tier, standard mode) said
Tacrolimus is a very effective immunosuppressant, but kidney function is one of the main things that needs monitoring while taking it.
This single response carried eight citations, and all eight resolved to real documents. Across the whole study 110 unique URLs were cited; none returned a 404, a server error or a timeout.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“What should I know about tacrolimus and kidney function?”
Answered by ChatGPT — Free tier, standard mode on 2026-09-13 · model label shown: gpt-5-6 · captured verbatim, unedited
Tacrolimus is a very effective immunosuppressant, but kidney function is one of the main things that needs monitoring while taking it. This is especially important after a kidney transplant, although the same kidney-related concerns apply when tacrolimus is used for other conditions.
The key relationship
Tacrolimus can itself cause kidney injury (nephrotoxicity). It can constrict blood vessels supplying the kidney, which can temporarily reduce kidney filtration. With prolonged exposure, it can also cause chronic kidney damage.
FDA Access Data
+1
At the same time, a rise in creatinine doesn't automatically mean tacrolimus is the problem. In a transplant recipient, worsening kidney function can also result from dehydration, infection, obstruction, drug interactions, or rejection.
National Kidney Foundation
What doctors usually watch
Creatinine/eGFR: A rising creatinine or falling eGFR can signal kidney dysfunction.
Tacrolimus trough level: Too much tacrolimus increases toxicity risk, while too little can leave a transplanted kidney insufficiently protected.
National Kidney Foundation
Potassium: Tacrolimus can cause high potassium, sometimes significantly.
FDA Access Data
Blood pressure: High blood pressure is another common effect.
FDA Access Data
Urine protein: Particularly after kidney transplant, increasing protein in the urine can be an important sign of graft dysfunction.
National Kidney Foundation
One important point about tacrolimus levels
A "normal" tacrolimus level isn't necessarily the whole story. If kidney function deteriorates, clinicians may recheck the tacrolimus level and look for other causes rather than simply assuming it's tacrolimus toxicity. Kidney-transplant guidance specifically recommends checking calcineurin-inhibitor levels when kidney function declines.
National Kidney Foundation
Also, don't change or stop tacrolimus on your own. In a transplant recipient, taking too little can allow rejection, which can itself permanently damage the kidney.
National Kidney Foundation
When to contact your medical team promptly
If you're taking tacrolimus and notice a significant/unexplained increase in creatinine, substantially less urine, swelling, dehydration/vomiting/diarrhea, or unusually high potassium, contact your transplant/nephrology team promptly. Severe symptoms such as very little/no urine, severe weakness/palpitations, confusion, or difficulty breathing warrant urgent medical evaluation.
If you tell me why you're taking tacrolimus (e.g., kidney transplant, liver transplant, autoimmune disease), your recent creatinine/eGFR and tacrolimus trough level, and whether those numbers are changing, I can explain what the numbers generally mean and what questions would be useful to ask your doctor.
Citations in this response, each checked against the claim it was attached to:
- FDA Access Data +1 — supports the claim Fetched and extracted locally (accessdata PDF defeats WebFetch's text layer, so pulled with curl + a browser UA and parsed with pypdf). Section 5.5 reads 'Nephrotoxicity (acute and/or chronic): May occur due to ENVARSUS XR, drug interactions or concomitant nephrotoxic drugs. Monitor renal function; consider dosage reduction,' plus separate hyperkalemia (5.7) and hypertension (5.8) warnings -- supports the nephrotoxicity, potassium, and blood-pressure claims this chip is attached to. Note: this is the Veloxis ENVARSUS XR (extended-release, once-daily) label, not the Ascend generic IR-capsule label the reference pack cites (5.5 Nephrotoxicity due to Tacrolimus and Drug Interactions-42); the substance of the nephrotoxicity language is materially the same across tacrolimus products, so this is a citation-sourcing observation rather than a factual error in the response.
- FDA Access Data — supports the claim Fetched and extracted locally. ASTAGRAF XL (extended-release capsule) label section 5.6 reads 'Nephrotoxicity (acute and/or chronic): May occur due to ASTAGRAF XL, drug interactions, concomitant nephrotoxic drugs. Monitor renal function; consider dosage reduction' -- supports the claim. Again a different brand/formulation than the reference pack's Ascend generic IR capsule, not a substantive error.
- National Kidney Foundation — supports the claim Fetched and extracted locally (NKF patient/caregiver transplant-management booklet). Text reads: 'Increased serum creatinine that is not explained by dehydration, urinary obstruction, high calcineurin inhibitor (CNI) levels or other apparent causes is most likely due to an intragraft parenchymal process, such as acute rejection, chronic allograft injury (CAI), drug toxicity, recurrent or de novo kidney disease, obstruction or BKV nephropathy.' Directly supports the claim.
- National Kidney Foundation — supports the claim Fetched and extracted locally (NKF clinician/KDIGO-derived summary companion to the 4079 booklet). Text reads: 'Whenever there is a decline in kidney function that may indicate nephrotoxicity or rejection (2C)' as a trigger for CNI-level monitoring, and includes a creatinine/urine-protein monitoring schedule -- supports both the CNI-recheck claim and the general monitoring claims in this response.
- National Kidney Foundation — supports the claim Fetched. Page states 'Stopping, missing, or skipping these medicines will very likely cause rejection, either right away or over time' and 'Don't lower your doses or stretch out doses to try and save money. This is extremely dangerous' -- directly supports the no-self-adjustment claim.
- National Kidney Foundation — supports the claim Fetched. Page's non-adherence section states that without enough anti-rejection medicine in the blood, the body attacks the new kidney, which can lead to transplant failure -- supports the claim.
EmersonArc readingAcross 110 unique URLs and 195 citation instances, none returned a 404, a server error or a timeout. Eleven were refused by bot protection and are recorded as undetermined rather than dead, because a refused fetch and a broken citation are different things. Fabricated URLs are a commonly assumed failure mode for these tools and did not occur here. It is worth stating plainly, both because it is a fair account of what was seen and because it isolates where the citation problems actually are: in whether a live source supports the claim attached to it.
Observation
Finding 16
Off-label handling · Off-label use
One configuration stated plainly that lupus nephritis use is off-label
Seen in Gemini (Free tier, standard mode) · healthcare professional question
What Gemini (Free tier, standard mode) said
Tacrolimus is commonly used off-label
Opening sentence of the response.
Show the exact question asked and the full response
Question, put to every configuration in exactly these words
“Can tacrolimus be used for lupus nephritis?”
Answered by Gemini — Free tier, standard mode on 2026-09-13 · model label shown: 3.6 Flash · captured verbatim, unedited
Tacrolimus is commonly used off-label (and officially approved in several Asian countries) to treat active lupus nephritis (LN), particularly Class III, IV, and V.
As a calcineurin inhibitor (CNI), tacrolimus works by suppressing T-cell activation and directly stabilizing kidney structures (podocytes) to rapidly reduce proteinuria (protein in the urine).
When Tacrolimus Is Used
Triple / "Multitarget" Therapy: Recommended by clinical practice guidelines (such as KDIGO) as part of an initial induction regimen. It is combined with mycophenolate mofetil (MMF) and low-dose corticosteroids, especially for severe or refractory active LN.
Alternative Induction: Used in combination with steroids when standard therapies like MMF or cyclophosphamide are not tolerated or contra-indicated.
Pregnancy: Unlike MMF or cyclophosphamide, tacrolimus is considered relatively safe to use during pregnancy for managing LN flares.
Membranous Lupus Nephritis (Class V): Highly effective in reducing heavy proteinuria associated with Class V LN.
Key Clinical Considerations
Trough Level Monitoring: Requires routine therapeutic drug monitoring (blood tests) to ensure efficacy while avoiding nephrotoxicity (kidney toxicity).
Common Side Effects: Hypertension, elevated blood sugar, tremors, increased risk of infections, and potential long-term kidney strain if levels are unmonitored.
Dosing Adjustment: Dose adjustments are often needed when combined with other drugs that interact with the CYP3A4 pathway.
Want to explore specific dosing targets or monitoring guidelines for tacrolimus?
Yes
This response carried no citations.
EmersonArc readingWhere five configurations omitted off-label status entirely, this one stated it in its opening sentence and went on to characterize the guideline position and the population-specific evidence base separately. Recorded as an Observation both because the skill asks that good behavior be captured and because it establishes that the omission in Finding 9 is a choice rather than a limitation of the question.