Calcineurin inhibitor (immunosuppressant)
ATC code: L04AD02 (Tacrolimus)
Brand names
Envarsus XR, Prograf, Astagraf XL
Binds to FKBP-12 (FK506-binding protein); the complex inhibits calcineurin, blocking NFAT dephosphorylation and IL-2 transcription. Used post-organ transplant and topically in atopic dermatitis.
First line
Tacrolimus is a first-line calcineurin inhibitor for rejection prophylaxis after kidney, liver, heart, lung and pancreas transplantation. Combined with mycophenolate mofetil and a glucocorticoid. KDIGO 2024 and AEMPS prefer tacrolimus over ciclosporin because of lower acute rejection rates. Dose is titrated by trough blood concentration (target 5–10 ng/mL first 3 months, 3–7 ng/mL thereafter).
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Tacrolimus is a calcineurin inhibitor immunosuppressant, more potent than cyclosporine. It is prescribed to prevent organ transplant rejection and for severe atopic dermatitis (topical forms) (AEMPS Ficha Técnica). In alt-anti-aging circles, tacrolimus is promoted as a potent immunosuppressant to slow immune system aging. In healthy adults, no clinical studies of such use exist. The drug has serious risks: nephrotoxicity (often irreversible), neurotoxicity (tremor, headache, confusion, seizures), increased malignancy risk (especially lymphomas and skin cancer, boxed warning), hypertension, hyperkalemia, hyperglycemia and new-onset diabetes, and severe opportunistic infections. If tacrolimus was recommended to a healthy person, seek a second opinion immediately.
35 pairs found. Sorted from critical to minor.
Mechanism
Tacrolimus (a post-transplant immunosuppressant) is cleared via hepatic CYP3A4. Clarithromycin strongly inhibits CYP3A4. Tacrolimus plasma levels rise 4- to 5-fold. The narrow therapeutic window makes any rise clinically dangerous.
Symptoms
Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients, accelerated graft function decline.
Management
If the combination is unavoidable, reduce the tacrolimus dose by 50–66% immediately and check daily trough (C0) levels for the first 5–7 days. Better: replace clarithromycin with azithromycin (minimal CYP3A4 interaction, comparable spectrum).
Mechanism
Tacrolimus is almost entirely cleared via hepatic CYP3A4. Ritonavir is the strongest CYP3A4 inhibitor available. Tacrolimus plasma levels can rise 50-fold or more. Acute nephrotoxicity and neurotoxicity with encephalopathy have been reported.
Symptoms
Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients, accelerated graft function decline.
Management
Reduce tacrolimus dose 10- to 20-fold from day 1 and check daily trough (C0) levels. Post-transplant patients require joint management by transplant and infectious diseases teams. Where possible, switch antiretroviral therapy to a ritonavir-free regimen (dolutegravir + bictegravir-based).
Mechanism
Amiodarone blocks CYP3A4 and P-glycoprotein – two key tacrolimus clearance routes. Tacrolimus plasma levels rise 2- to 3-fold. Additional risk of additive QT prolongation.
Symptoms
Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients: accelerated graft function decline.
Management
When combined, reduce tacrolimus by 30–50%; check trough (C0) at days 3 and 7. ECG before start and at 2 weeks; maintain potassium and magnesium. Alternative antiarrhythmic in transplant patients: a beta-blocker for rate control or catheter ablation.
Mechanism
Carbamazepine strongly induces CYP3A4 and P-glycoprotein. Tacrolimus plasma levels fall 2- to 3-fold; immunosuppression is lost, raising rejection risk.
Symptoms
Rejection symptoms depend on the organ: fever, graft tenderness, rising creatinine (kidney); jaundice and rising liver enzymes (liver). Symptoms appear 1–3 weeks after starting carbamazepine.
Management
Avoid the combination. Alternative anticonvulsants without induction: levetiracetam, lamotrigine, gabapentin. If carbamazepine is unavoidable, raise tacrolimus 2- to 3-fold with trough (C0) twice weekly.
Mechanism
Celecoxib (a selective COX-2 inhibitor) reduces renal blood flow via prostaglandin suppression. Tacrolimus is nephrotoxic in its own right. Additive acute kidney injury risk, especially with borderline renal function.
Symptoms
Reduced urine output, rising creatinine, potassium accumulation. In kidney transplant patients: accelerated graft function decline.
Management
Avoid chronic celecoxib on tacrolimus. For analgesia post-transplant, use paracetamol (up to 2 g/day) or a short opioid course. For neuropathic pain, gabapentin or pregabalin. Check creatinine monthly.
Mechanism
Tacrolimus prolongs the QT interval, especially with hypomagnesaemia (common on calcineurin inhibitors). Citalopram also prolongs QT dose-dependently ( caps at 40 mg/day). Effects add up.
Symptoms
QT prolongation on ECG, dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk rises with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination. Alternative antidepressants with minimal QT effect post-transplant: mirtazapine, agomelatine, sertraline (up to 100 mg/day). ECG before start and at 2 weeks; maintain potassium and magnesium.
Mechanism
Tacrolimus and colchicine are both P-glycoprotein substrates. Competition at this transporter raises colchicine levels, especially in transplant patients with borderline renal function.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain. With prolonged combination: muscle weakness, peripheral neuropathy, falling leukocytes and platelets. In transplant patients: accelerated graft decline.
Management
For acute gout in transplant patients, a short colchicine course (3–5 days) at 0.3 mg every other day with muscle symptom and blood count monitoring. For chronic gout, allopurinol. For acute attacks, intra-articular glucocorticoid.
Mechanism
Diclofenac (NSAID) suppresses renal prostaglandin synthesis maintaining glomerular perfusion. Tacrolimus is nephrotoxic in its own right. Additive acute kidney injury risk in transplant patients.
Symptoms
Reduced urine output, rising creatinine, potassium accumulation. In kidney transplant patients: accelerated graft function decline.
Management
Avoid chronic diclofenac on tacrolimus. For analgesia post-transplant, use paracetamol (up to 2 g/day) or a short opioid course. For neuropathic pain, gabapentin or pregabalin.
Mechanism
Dronedarone blocks the P-glycoprotein transporter – the main tacrolimus clearance route. Tacrolimus plasma levels rise. Additional risk of additive QT prolongation.
Symptoms
Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients: accelerated graft function decline.
Management
Avoid the combination. Alternative antiarrhythmics in transplant patients: a beta-blocker for rate control or catheter ablation. If unavoidable, reduce tacrolimus by 30% and check level at days 3 and 7.
Mechanism
Erythromycin inhibits CYP3A4. Tacrolimus rises 2-3 fold – nephrotoxicity, neurotoxicity.
Symptoms
Rising creatinine, tremor, headache.
Management
Reduce tacrolimus by 50%, check blood level on day 3. Alternative – azithromycin.
Mechanism
Tacrolimus prolongs the QT interval, especially with hypomagnesaemia (typical on calcineurin inhibitors). Escitalopram also prolongs QT dose-dependently ( caps at 20 mg/day). Effects add up.
Symptoms
QT prolongation on ECG, dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Limit the combination: cap escitalopram at 10 mg/day. ECG before start and at 2 weeks; maintain potassium and magnesium. Alternative antidepressant with minimal QT effect: mirtazapine or agomelatine.
Mechanism
Esomeprazole inhibits CYP2C19. Tacrolimus is minimally metabolised by CYP2C19, but in patients with slow metabolism (CYP2C19 genetic polymorphism) this route becomes the main one. In such patients tacrolimus plasma levels rise.
Symptoms
Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients: accelerated graft function decline.
Management
In most patients, no clinically significant effect. In East Asian patients (high frequency of CYP2C19 slow metabolisers), alternative PPIs: pantoprazole or rabeprazole (weaker CYP2C19 effect). Check tacrolimus trough (C0) 1 week after starting esomeprazole.
Mechanism
Fluconazole at 200 mg/day or above blocks CYP3A4 – the main tacrolimus metabolic route. Tacrolimus plasma levels rise 2- to 3-fold, with nephrotoxicity and neurotoxicity risks.
Symptoms
Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients: accelerated graft function decline.
Management
For short fluconazole courses (up to 7 days), reduce tacrolimus by 30% and check trough (C0) daily. For prolonged systemic therapy, alternative antifungals (echinocandins) or titrate tacrolimus to level.
Mechanism
Additive nephrotoxicity via two distinct mechanisms. Gentamicin (an aminoglycoside) directly injures proximal renal tubules. Tacrolimus (calcineurin inhibitor) causes afferent arteriolar vasoconstriction. Co-administration sharply raises acute kidney injury risk, especially in transplant patients.
Symptoms
Reduced urine output, rising creatinine and urea. In kidney transplant patients: accelerated graft decline. Gentamicin ototoxicity too: tinnitus, hearing loss.
Management
Avoid the combination. Alternative antibiotics: a cephalosporin, carbapenem, or vancomycin (with its own renal monitoring). If gentamicin is irreplaceable: minimum effective dose, daily creatinine checks, and gentamicin level monitoring per protocol.
Mechanism
Additive QT prolongation. Haloperidol strongly prolongs QT, especially parenterally (IV). Tacrolimus prolongs QT with hypomagnesaemia. Combined action raises torsades de pointes risk.
Symptoms
QT prolongation on ECG, dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination, especially IV haloperidol. Alternative antipsychotics with minimal QT effect post-transplant: olanzapine or aripiprazole. For acute delirium: dexmedetomidine (no QT effect).
Mechanism
Ibuprofen reduces renal blood flow via PGE2 inhibition. Tacrolimus is nephrotoxic in its own right. Additive acute kidney injury risk in transplant patients.
Symptoms
Reduced urine output, rising creatinine and potassium, oedema. Symptoms appear earlier in older patients and in chronic kidney disease.
Management
Avoid prolonged combination. For analgesia post-transplant, use paracetamol (up to 2 g/day) or a short opioid course. For neuropathic pain: gabapentin or pregabalin.
Mechanism
Contrast (iopromide) and nephrotoxic immunosuppressant (tacrolimus) – high contrast-induced nephropathy risk. The effect is stronger in transplant patients due to already reduced renal function.
Symptoms
Reduced urine output, rising creatinine and potassium, oedema. Symptoms appear earlier in older patients and chronic kidney disease.
Management
For planned contrast studies, provide adequate hydration with saline (1 mL/kg/h for 12 hours before and after). Check tacrolimus trough (C0) 1–3 days after contrast. Alternative imaging: non-gadolinium MRI.
Mechanism
Itraconazole is a strong CYP3A4 inhibitor. Tacrolimus rises 5+ fold – severe nephrotoxicity.
Symptoms
Rising creatinine, hypertension, tremor within 3-7 days.
Management
Reduce tacrolimus by 75% with frequent blood level monitoring. If possible, switch itraconazole to an echinocandin.
Mechanism
Strong CYP3A4 inhibitor – tacrolimus rises 4-5 fold.
Symptoms
Nephrotoxicity.
Management
Reduce tacrolimus by 75%.
Sources
Mechanism
Ketorolac is the most nephrotoxic NSAID, limited to 5 days of use. Tacrolimus is nephrotoxic in its own right. Additive acute kidney injury risk multiplies in transplant patients.
Symptoms
Reduced urine output, rising creatinine and potassium, oedema. Symptoms appear earlier in older patients and chronic kidney disease.
Management
The combination is not prescribed. For post-transplant analgesia: paracetamol (up to 2 g/day), metamizole, or a short opioid course. For neuropathic pain: gabapentin or pregabalin.
Mechanism
NSAID (meloxicam) + nephrotoxic calcineurin inhibitor (tacrolimus) – additive acute kidney injury risk in transplant patients.
Symptoms
Reduced urine output, rising creatinine and potassium, oedema. Symptoms appear earlier in older patients and chronic kidney disease.
Management
Avoid prolonged combination. For post-transplant analgesia: paracetamol (up to 2 g/day) or a short opioid course. For neuropathic pain: gabapentin or pregabalin.
Mechanism
Dual immunosuppression plus additive nephrotoxicity. The combination is used in rheumatoid arthritis patients on methotrexate when tacrolimus is added (e.g., in ANCA vasculitis), requiring careful monitoring.
Symptoms
Stomatitis, diarrhoea, falling leukocyte, platelet, and erythrocyte counts. Severe cases: fatal pancytopenia, nephrotoxicity.
Management
The combination is possible in rheumatic disease with careful monitoring. Check full blood count, creatinine, and liver enzymes every 2 weeks for the first 3 months, then monthly. Keep tacrolimus trough (C0) at the lower end of target range.
Mechanism
NSAID (naproxen) + nephrotoxic calcineurin inhibitor (tacrolimus) – additive acute kidney injury risk in transplant patients.
Symptoms
Reduced urine output, rising creatinine and potassium, oedema. Symptoms appear earlier in older patients and chronic kidney disease.
Management
Avoid prolonged combination. For post-transplant analgesia: paracetamol (up to 2 g/day) or a short opioid course. For neuropathic pain: gabapentin or pregabalin.
Mechanism
Omeprazole blocks CYP2C19. In CYP2C19 slow metabolisers (genetic polymorphism), tacrolimus is predominantly metabolised by CYP2C19, and plasma levels may double.
Symptoms
Acute nephrotoxicity: rising creatinine, hypertension, tremor, headache. In transplant patients: accelerated graft function decline.
Management
In most patients, no clinically significant effect. In East Asian patients (high frequency of CYP2C19 slow metabolisers), alternative PPIs: pantoprazole or rabeprazole (weaker CYP2C19 effect). Check tacrolimus trough (C0) 1 week after starting omeprazole.
Mechanism
Phenytoin induces CYP3A4. Tacrolimus level falls 2–3 fold with transplant rejection risk.
Symptoms
Tacrolimus trough below target, laboratory signs of rejection.
Management
For post-transplant epilepsy: levetiracetam or lacosamide as alternative. If phenytoin is needed, increase tacrolimus 2–3 fold with frequent monitoring.
Mechanism
Posaconazole is a strong CYP3A4 inhibitor. Tacrolimus rises 4-5 fold.
Symptoms
Nephrotoxicity, tremor.
Management
Reduce tacrolimus by 67%, check blood level on days 3-5.
Mechanism
Strong CYP3A4 inducer. Tacrolimus falls 3-fold – transplant rejection risk.
Symptoms
Rejection signs, rising creatinine.
Management
For TB in transplant patient – increase tacrolimus 3-5 fold with blood level monitoring. Alternative – rifabutin (weaker).
Sources
Mechanism
Spironolactone retains potassium via aldosterone receptor blockade. Tacrolimus reduces renal potassium secretion via a distal tubular inhibitory effect. Additive hyperkalaemia.
Symptoms
Muscle weakness, paraesthesia, slowed pulse, arrhythmias. ECG: peaked T waves, widened QRS. Severe cases progress to cardiac arrest.
Management
Avoid the combination in transplant patients. Alternative diuretics: furosemide (loop, removes potassium) or hydrochlorothiazide. If spironolactone is needed, check potassium and creatinine every 1–2 weeks.
Mechanism
Voriconazole inhibits CYP3A4. Tacrolimus concentration rises 3-fold with risk of nephrotoxicity and neurotoxicity (tremor, headache, paresthesia). requires reducing tacrolimus to one third of baseline and frequent blood-level monitoring.
Symptoms
Rising creatinine, tremor, headache, paresthesia, hypertension within 7 days. Tacrolimus trough above target range.
Management
Reduce tacrolimus to one third of baseline. Check trough after 2 days, then weekly. Up-titrate after voriconazole withdrawal.
Sources
Mechanism
Tacrolimus is a weak CYP3A4 inhibitor; alprazolam is a CYP3A4 substrate. Alprazolam levels may rise moderately. Additive sedative effect.
Symptoms
Sedation, fatigue, slowed reactions, impaired coordination. In older patients: fall and fracture risk. Driving and operating machinery: accident risk.
Management
On starting the combination, begin alprazolam at 0.25 mg at bedtime. In transplant patients, prefer buspirone or CBT for anxiety over benzodiazepines. If unavoidable, tacrolimus monitoring is unchanged, but check sedation at 1 and 2 weeks after starting alprazolam.
Mechanism
Tacrolimus prolongs QT; the TCA does the same independently via a quinidine-like effect on cardiomyocyte Na/K channels. Additive ventricular arrhythmia risk.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Maximum risk in older transplant patients with electrolyte disturbances.
Management
Avoid in prior QT prolongation or electrolyte disturbance. For neuropathic pain, alternatives: gabapentin or pregabalin (minimal QT effect). For depression: sertraline (minimal QT effect). If unavoidable: ECG before starting amitriptyline and at 1 and 4 weeks. Keep potassium and magnesium in the upper half of normal range.
Mechanism
Tacrolimus and amlodipine are both CYP3A4 substrates competing for the enzyme. Tacrolimus plasma levels may rise.
Symptoms
Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients: accelerated graft decline.
Management
The combination is acceptable in post-transplant patients with hypertension. Check tacrolimus trough (C0) 1 week after starting or changing amlodipine. Alternative: an ARB or α-blocker (no CYP3A4 dependence).
Mechanism
Tacrolimus is a weak CYP3A4 inhibitor and P-glycoprotein substrate. P-glycoprotein competition may slightly raise apixaban levels; clinical effect is minimal.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, black or tarry stools, haematuria. Higher risk in older patients, prior peptic ulcer disease, and chronic kidney disease.
Management
No dose adjustment needed. In post-transplant patients with chronic kidney disease, watch for any bleeding signs and check creatinine clearance every 4 weeks — if it falls below 50 mL/min, reduce apixaban to 2.5 mg twice daily.
Mechanism
Tacrolimus is a weak CYP3A4 inhibitor; atorvastatin is a substrate. Atorvastatin plasma levels rise by 30–50%, raising myalgia risk. Tacrolimus itself can cause myopathy.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Symptoms usually appear 2–6 weeks after starting the combination.
Management
For transplant patients needing a statin, use pravastatin up to 20 mg/day or fluvastatin (minimal tacrolimus interaction). Atorvastatin is acceptable when no alternative exists, capped at 10 mg/day with creatine kinase every 4 weeks.
Mechanism
Additive QT prolongation (tacrolimus prolongs QT in hypomagnesaemia, common on calcineurin inhibitors).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
For short azithromycin courses post-transplant: check magnesium and replete if needed. ECG before start if other QT-prolonging drugs are on board. Alternative antibiotics: a cephalosporin or doxycycline.
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FDA Category C. Tacrolimus is among the immunosuppressants acceptable in pregnant transplant recipients. Registries show increased risk of preterm birth, low birthweight and gestational diabetes without a clear excess of major malformations. SEC and the transplant team maintain dose by plasma trough levels.
Compatible with caution. Hale L3. Transfers into milk in small amounts (RID about 0.1%) due to low oral bioavailability. Infant renal function and immune status are monitored.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
tacrolimus is evaluated for the following indications with varying evidence strength: Transplant rejection prophylaxis (evidence tier A), Anti-aging and longevity (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of tacrolimus (≥ 1 in 100): Tremor, Headache and insomnia, Hypertension, Hyperglycaemia, Hyperkalaemia, Nephrotoxicity. See the Safety section for uncommon and serious reactions.
FDA category C. FDA Category C. Tacrolimus is among the immunosuppressants acceptable in pregnant transplant recipients. Registries show increased risk of preterm birth, low birthweight and gestational diabetes without a clear excess of major malformations. SEC and the transplant team maintain dose by plasma trough levels.
Compatible with caution. Hale L3. Transfers into milk in small amounts (RID about 0.1%) due to low oral bioavailability. Infant renal function and immune status are monitored.
tacrolimus is contraindicated in: Hypersensitivity to tacrolimus or other macrolides; Severe hepatic impairment (topical forms); Active malignancy with topical use. Full list in the Safety section.