Formulary
Tacrolimus: Indications, Dosing, Side Effects and Interactions
Tacrolimus is a calcineurin inhibitor.
MedNext Academy | 15 min read
Tacrolimus: Indications, Dosing, Side Effects and Interactions
Tacrolimus is a calcineurin inhibitor.
Drug action
Tacrolimus is a calcineurin inhibitor.
Indications and dose
**Short-term treatment of moderate to severe atopic eczema (including flares) in patients unresponsive to, or intolerant of conventional therapy (initiated by a specialist)**
- **Adult** (To The Skin): Apply twice daily until lesion clears (consider other treatment if eczema worsens or no improvement after 2 weeks), to be applied thinly, initially 0.1% ointment to be used; reduce frequency to once daily or strength of ointment to 0.03% if condition allows.
**Prevention of flares in patients with moderate to severe atopic eczema and 4 or more flares a year who have responded to initial treatment with topical tacrolimus (initiated by a specialist)**
- **Adult** (To The Skin): Apply twice weekly, to be applied thinly with an interval of 2-3 days between applications, 0.1% ointment to be used, use short-term treatment regimen during an acute flare; review need for preventative therapy after 1 year.
**Short-term treatment of facial, flexural, or genital psoriasis in patients unresponsive to, or intolerant of other topical therapy (initiated under specialist supervision)**
- **Adult** (To The Skin): Apply twice daily until symptoms resolve (maximum duration of treatment 4 weeks), to be applied thinly, 0.1% ointment to be used; reduce to once daily or switch to 0.03% ointment if condition allows.
**Prophylaxis of graft rejection following liver transplantation, starting 12 hours after transplantation**
- **Adult** (By Mouth): Initially 100-200 micrograms/kg daily in 2 divided doses, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Prophylaxis of graft rejection following kidney transplantation, starting within 24 hours of transplantation**
- **Adult** (By Mouth): Initially 200-300 micrograms/kg daily in 2 divided doses, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Prophylaxis of graft rejection following liver transplantation, starting 12-18 hours after transplantation**
- **Adult** (By Mouth): Initially 100-200 micrograms/kg once daily, dose to be taken in the morning, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Prophylaxis of graft rejection following liver transplantation, starting within 24 hours of transplantation**
- **Adult** (By Mouth): Initially 110-130 micrograms/kg once daily, dose to be taken in the morning, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Rejection therapy**
- **Adult** (By Mouth): Seek specialist advice.
**Short-term treatment of moderate to severe atopic eczema (including flares) in patients unresponsive to, or intolerant of conventional therapy (initiated by a specialist) for tacrolimus**
- **Child 2-15 years** (To the skin): Apply twice daily for up to 3 weeks (consider other treatment if eczema worsens or if no improvement after 2 weeks), to be applied thinly, 0.03% ointment to be used, then reduced to once daily until lesion clears, to be applied thinly, 0.03% ointment to be used.
- **Child 16-17 years** (To the skin): Apply twice daily until lesion clears (consider other treatment if eczema worsens or no improvement after 2 weeks), to be applied thinly, initially 0.1% ointment to be used; reduce frequency to once daily or strength of ointment to 0.03% if condition allows.
**Prevention of flares in patients with moderate to severe atopic eczema and 4 or more flares a year who have responded to initial treatment with topical tacrolimus (initiated by a specialist) for tacrolimus**
- **Child 2-15 years** (To the skin): Apply twice weekly, to be applied thinly with an interval of 2-3 days between applications, 0.03% ointment to be used, use short-term treatment regimen during an acute flare; review need for preventative therapy after 1 year.
- **Child 16-17 years** (To the skin): Apply twice weekly, to be applied thinly with an interval of 2-3 days between applications, 0.1% ointment to be used, use short-term treatment regimen during an acute flare; review need for preventative therapy after 1 year.
**Prophylaxis of graft rejection following liver transplantation, starting 12 hours after transplantation for Adoport**
- **Neonate** (By mouth): Initially 150 micrograms/kg twice daily, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
- **Child** (By mouth): Initially 150 micrograms/kg twice daily, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Prophylaxis of graft rejection following kidney transplantation, starting within 24 hours of transplantation for Adoport**
- **Neonate** (By mouth): Initially 150 micrograms/kg twice daily, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
- **Child** (By mouth): Initially 150 micrograms/kg twice daily, a lower initial dose of 100 micrograms/kg twice daily has been used in adolescents to prevent very high 'trough' concentrations, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Prophylaxis of graft rejection following heart transplantation following antibody induction, starting within 5 days of transplantation for Adoport**
- **Neonate** (By mouth): Initially 50-150 micrograms/kg twice daily, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
- **Child** (By mouth): Initially 50-150 micrograms/kg twice daily, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Prophylaxis of graft rejection following heart transplantation without antibody induction, starting within 12 hours of transplantation for Adoport**
- **Neonate** (By mouth): Initially 150 micrograms/kg twice daily, dose to be given as soon as clinically possible (8-12 hours after discontinuation of intravenous infusion), then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
- **Child** (By mouth): Initially 150 micrograms/kg twice daily, dose to be given as soon as clinically possible (8-12 hours after discontinuation of intravenous infusion), then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Allograft rejection resistant to conventional immunosuppressive therapy for Adoport**
- **Child** (By mouth): Seek specialist advice.
**Prophylaxis of graft rejection following liver transplantation, starting 12 hours after transplantation for Modigraf**
- **Neonate** (By mouth): Initially 150 micrograms/kg twice daily, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
- **Child** (By mouth): Initially 150 micrograms/kg twice daily, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Prophylaxis of graft rejection following kidney transplantation, starting within 24 hours of transplantation for Modigraf**
- **Neonate** (By mouth): Initially 150 micrograms/kg twice daily, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
- **Child** (By mouth): Initially 150 micrograms/kg twice daily, a lower initial dose of 100 micrograms/kg twice daily has been used in adolescents to prevent very high 'trough' concentrations, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Prophylaxis of graft rejection following heart transplantation following antibody induction, starting within 5 days of transplantation for Modigraf**
- **Neonate** (By mouth): Initially 50-150 micrograms/kg twice daily, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
- **Child** (By mouth): Initially 50-150 micrograms/kg twice daily, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Prophylaxis of graft rejection following heart transplantation without antibody induction, starting within 12 hours of transplantation for Modigraf**
- **Neonate** (By mouth): Initially 150 micrograms/kg twice daily, dose to be given as soon as clinically possible (8-12 hours after discontinuation of intravenous infusion), then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
- **Child** (By mouth): Initially 150 micrograms/kg twice daily, dose to be given as soon as clinically possible (8-12 hours after discontinuation of intravenous infusion), then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Allograft rejection resistant to conventional immunosuppressive therapy for Modigraf**
- **Child** (By mouth): Seek specialist advice.
**Prophylaxis of graft rejection following liver transplantation, starting 12 hours after transplantation for Prograf capsules**
- **Neonate** (By mouth): Initially 150 micrograms/kg twice daily, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
- **Child** (By mouth): Initially 150 micrograms/kg twice daily, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Prophylaxis of graft rejection following kidney transplantation, starting within 24 hours of transplantation for Prograf capsules**
- **Neonate** (By mouth): Initially 150 micrograms/kg twice daily, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
- **Child** (By mouth): Initially 150 micrograms/kg twice daily, a lower initial dose of 100 micrograms/kg twice daily has been used in adolescents to prevent very high 'trough' concentrations, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Prophylaxis of graft rejection following heart transplantation following antibody induction, starting within 5 days of transplantation for Prograf capsules**
- **Neonate** (By mouth): Initially 50-150 micrograms/kg twice daily, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
- **Child** (By mouth): Initially 50-150 micrograms/kg twice daily, then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Prophylaxis of graft rejection following heart transplantation without antibody induction, starting within 12 hours of transplantation for Prograf capsules**
- **Neonate** (By mouth): Initially 150 micrograms/kg twice daily, dose to be given as soon as clinically possible (8-12 hours after discontinuation of intravenous infusion), then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
- **Child** (By mouth): Initially 150 micrograms/kg twice daily, dose to be given as soon as clinically possible (8-12 hours after discontinuation of intravenous infusion), then maintenance, dose to be adjusted according to response and whole blood-tacrolimus trough concentrations-doses are usually reduced in the post-transplant period.
**Allograft rejection resistant to conventional immunosuppressive therapy for Prograf capsules**
- **Child** (By mouth): Seek specialist advice.
**Prophylaxis of graft rejection following liver transplantation, starting 12 hours after transplantation when oral route not appropriate for Prograf infusion**
- **Neonate** (By continuous intravenous infusion): Initially 50 micrograms/kg/24 hours for up to 7 days (then transfer to oral therapy).
- **Child** (By continuous intravenous infusion): Initially 50 micrograms/kg/24 hours for up to 7 days (then transfer to oral therapy).
**Prophylaxis of graft rejection following kidney transplantation, starting within 24 hours of transplantation when oral route not appropriate for Prograf infusion**
- **Neonate** (By continuous intravenous infusion): Initially 75-100 micrograms/kg/24 hours for up to 7 days (then transfer to oral therapy).
- **Child** (By continuous intravenous infusion): Initially 75-100 micrograms/kg/24 hours for up to 7 days (then transfer to oral therapy).
**Prophylaxis of graft rejection following heart transplantation without antibody induction, starting within 12 hours of transplantation for Prograf infusion**
- **Neonate** (By continuous intravenous infusion): Initially 30-50 micrograms/kg/24 hours for up to 7 days (then transfer to oral therapy).
- **Child** (By continuous intravenous infusion): Initially 30-50 micrograms/kg/24 hours for up to 7 days (then transfer to oral therapy).
**Allograft rejection resistant to conventional immunosuppressive therapy for Prograf infusion**
- **Child** (By continuous intravenous infusion): Seek specialist advice (consult local protocol).
Cautions
General cautions: UV light (avoid excessive exposure to sunlight and sunlamps) Specific cautions: With systemic use Increased risk of infections; increased susceptibility to lymphoproliferative disorders; malignancies; neurotoxicity; risk factors for cardiomyopathies; risk factors for QT-interval prolongation
Contraindications
With topical use Application to malignant or potentially malignant skin lesions; application under occlusion; avoid contact with eyes; avoid contact with mucous membranes; congenital epidermal barrier defects; generalised erythroderma; immunodeficiency; infection at treatment site
Side effects
General side-effects: Common or very common Increased risk of infection; sensation abnormal; skin reactions Frequency not known Neoplasms Specific side-effects: Common or very common With intravenous use Alopecia; anaemia; anxiety; appetite decreased; arrhythmias; ascites; asthenic conditions; bile duct disorders; confusion; consciousness impaired; constipation; coronary artery disease; cough; depression; diabetes mellitus; diarrhoea; dizziness; dysgraphia; dyslipidaemia; dyspnoea; electrolyte imbalance; embolism and thrombosis; eye disorder; febrile disorders; fluid imbalance; gastrointestinal discomfort; gastrointestinal disorders; gastrointestinal inflammatory disorders; haemorrhage; hallucination; headache; hepatic disorders; hyperglycaemia; hyperhidrosis; hypertension; hyperuricaemia; hypotension; interstitial lung disease; ischaemia; joint disorders; leucocytosis; leucopenia; metabolic acidosis; mood altered; muscle spasms; nasal complaints; nausea; nephropathy; nerve disorders; nervous system disorder; oedema; oral disorders; pain; peripheral vascular disease; primary transplant dysfunction; psychiatric disorder; renal impairment; renal tubular necrosis; respiratory disorders; seizure; sleep disorders; temperature sensation altered; thrombocytopenia; tinnitus; tremor; urinary tract disorder; urine abnormal; vision disorders; vomiting; weight changes With oral use Alopecia; anaemia; anxiety; appetite decreased; arrhythmias; ascites; asthenic conditions; bile duct disorders; confusion; consciousness impaired; constipation; coronary artery disease; cough; depression; diabetes mellitus; diarrhoea; dizziness; dysgraphia; dyslipidaemia; dyspnoea; electrolyte imbalance; embolism and thrombosis; eye disorder; febrile disorders; fluid imbalance; gastrointestinal discomfort; gastrointestinal disorders; gastrointestinal inflammatory disorders; haemorrhage; hallucination; headache; hepatic disorders; hyperglycaemia; hyperhidrosis; hypertension; hyperuricaemia; hypotension; interstitial lung disease; ischaemia; joint disorders; leucocytosis; leucopenia; metabolic acidosis; mood altered; muscle spasms; nasal complaints; nausea; nephropathy; nerve disorders; nervous system disorder; oedema; oral disorders; pain; peripheral vascular disease; primary transplant dysfunction; psychiatric disorder; renal impairment; renal tubular necrosis; respiratory disorders; seizure; sleep disorders; temperature sensation altered; thrombocytopenia; tinnitus; tremor; urinary tract disorder; urine abnormal; vision disorders; vomiting; weight changes With topical use Alcohol intolerance Uncommon With intravenous use Asthma; cardiac arrest; cardiomyopathy; cataract; central nervous system haemorrhage; chest discomfort; coagulation disorders; coma; dysmenorrhoea; encephalopathy; feeling abnormal; haemolytic anaemia; hearing impairment; heart failure; hypoglycaemia; hypoproteinaemia; influenza like illness; memory loss; multi organ failure; neutropenia; palpitations; pancreatitis; pancytopenia; paralysis; paresis; photosensitivity reaction; psychotic disorder; shock; speech disorder; stroke; ventricular hypertrophy With oral use Asthma; cardiac arrest; cardiomyopathy; cataract; central nervous system haemorrhage; chest discomfort; coagulation disorders; coma; dysmenorrhoea; encephalopathy; feeling abnormal; haemolytic anaemia; hearing impairment; heart failure; hypoglycaemia; hypoproteinaemia; influenza like illness; memory loss; multi organ failure; neutropenia; palpitations; pancreatitis; pancytopenia; paralysis; paresis; photosensitivity reaction; psychotic disorder; shock; speech disorder; stroke; ventricular hypertrophy With topical use Lymphadenopathy Rare or very rare With intravenous use Fall; hirsutism; mobility decreased; muscle tone increased; muscle weakness; pancreatic pseudocyst; pericardial effusion; QT interval prolongation; severe cutaneous adverse reactions (SCARs); sinusoidal obstruction syndrome; thirst; ulcer With oral use Fall; hirsutism; mobility decreased; muscle tone increased; muscle weakness; pancreatic pseudocyst; pericardial effusion; QT interval prolongation; severe cutaneous adverse reactions (SCARs); sinusoidal obstruction syndrome; thirst; ulcer Frequency not known With intravenous use Agranulocytosis; anaphylactoid reaction (due to excipient); neoplasm malignant; polyomavirus-associated nephropathy; progressive multifocal leukoencephalopathy (PML); pure red cell aplasia With oral use Agranulocytosis; neoplasm malignant; polyomavirus-associated nephropathy; progressive multifocal leukoencephalopathy (PML); pure red cell aplasia With topical use Malignancy Side-effects, further information Cardiomyopathy has been reported to occur primarily in children with tacrolimus blood trough concentrations much higher than the recommended maximum levels. Patients should be monitored by echocardiography for hypertrophic changes-consider dose reduction or discontinuation if these occur.
Interactions
**Severe interactions:**
- Medicinal products which have effects on tacrolimus Drug/Substance Class or Name Drug interaction effect Recommendations concerning co-administration Grapefruit or grapefruit juice May increase...
- Strong interactions have also been observed with the macrolide antibiotic erythromycin May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions...
- Moderate or weak CYP3A4 inhibitors: antifungal agents (e.g., fluconazole, isavuconazole, clotrimazole, miconazole), the macrolide antibiotics (e.g., azithromycin, calcium channel blockers (e.g.,...
- In vitro the following substances have been shown to be potential inhibitors of tacrolimus metabolism: bromocriptine, cortisone, dapsone, ergotamine, gestodene, lidocaine, mephenytoin, midazolam,...
- Prokinetic agents: metoclopramide, cimetidine and magnesium-aluminium-hydroxide May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g.,...
**Other interactions (64):**
- Metabolic interactions Systemically available tacrolimus is metabolised by hepatic CYP3A4.
- Concomitant use of medicinal products or herbal remedies known to inhibit or induce CYP3A4 may affect the metabolism of tacrolimus and thereby increase or decrease tacrolimus blood levels.
- Similarly, discontinuation of such products or herbal remedies may affect the rate of metabolism of tacrolimus and thereby the blood levels of tacrolimus.
- Pharmacokinetics studies have indicated that the increase in tacrolimus blood levels when co-administered with inhibitors of CYP3A4 is mainly a result of increase in oral bioavailability of...
- It is recommended strongly to closely monitor tacrolimus blood levels under supervision of a transplant specialist, as well as, monitor for graft function, QT prolongation (with ECG), renal function...
- Similarly, patients should be closely monitored when using tacrolimus concomitantly with multiple substances that affect CYP3A4 as the effects on tacrolimus exposure may be enhanced or counteracted.
Pregnancy
With systemic use: Specialist sources indicate avoid unless benefit outweighs potential risk-crosses the placenta and risk of premature delivery, intra-uterine growth restriction, hyperkalaemia and renal toxicity. Maternal risk of hyperglycaemia, hypertension, pre-eclampsia and renal impairment. With topical use: Specialist sources indicate that use can be considered if benefit outweighs potential risk-minimal systemic absorption; limited information available.
Breast feeding
Specialist sources indicate present in milk (following systemic administration) but amount probably too small to be harmful-monitor exclusively breastfed infants, including blood concentrations, if there are concerns regarding toxicity.
Hepatic impairment
With systemic use: Manufacturer advises caution in severe impairment. With topical use: Manufacturer advises caution in hepatic failure. Dose adjustments With systemic use: Manufacturer advises consider dose reduction in severe impairment.
Medicinal forms
Tablet,Capsule,Capsule,Suspension,Solution,Ointment
Clinical governance
**Author:** MedNext Clinical Team. **Clinical reviewer:** Dr Shameer Deen, MBBS, MS, MRCS. **Sources:** BNF, Indian Pharmacopoeia, CIMS India. **Correction:** Report errors at support@mednext.academy.
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