Drug Action
Tacrolimus is a calcineurin inhibitor.
Source page 908
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Individual generic drug information
Extracted information for Tacrolimus only.
Tacrolimus is a calcineurin inhibitor.
Source page 908
ADOPORT ® Prophylaxis of graft rejection following liver transplantation, starting 12 hours after transplantation ▶BY MOUTH ▶Adult: Initially 100–200 micrograms/kg daily in 2 divided doses Prophylaxis of graft rejection following kidney transplantation, starting within 24 hours of transplantation ▶BY MOUTH ▶Adult: Initially 200–300 micrograms/kg daily in 2 divided doses Prophylaxis of graft rejection following heart transplantation following antibody induction, starting within 5 days of transplantation ▶BY MOUTH ▶Adult: Initially 75 micrograms/kg daily in 2 divided doses Prophylaxis of graft rejection following heart transplantation without antibody induction, starting within 12 hours of transplantation ▶BY MOUTH ▶Adult: Initially 75 micrograms/kg daily in 2 divided doses Allograft rejection resistant to conventional immunosuppressive therapy ▶BY MOUTH ▶Adult: Seek specialist advice ADVAGRAF ® Prophylaxis of graft rejection following liver transplantation, starting 12–18 hours after transplantation ▶BY MOUTH ▶Adult: Initially 100–200 micrograms/kg once daily, to be taken in the morning Prophylaxis of graft rejection following kidney transplantation, starting within 24 hours of transplantation ▶BY MOUTH ▶Adult: Initially 200–300 micrograms/kg once daily, to be taken in the morning Allograft rejection resistant to conventional immunosuppressive therapy ▶BY MOUTH ▶Adult: Seek specialist advice ENVARSUS ® MODIFIED-RELEASE TABLETS Prophylaxis of graft rejection following liver transplantation, starting within 24 hours of transplantation ▶BY MOUTH ▶Adult: Initially 110–130 micrograms/kg once daily, to be taken in the morning Prophylaxis of graft rejection following renal transplantation, starting within 24 hours of transplantation ▶BY MOUTH ▶Adult: Initially 170 micrograms/kg once daily, to be taken in the morning Rejection therapy ▶BY MOUTH ▶Adult: Seek specialist advice MODIGRAF ® Prophylaxis of graft rejection following liver transplantation, starting 12 hours after transplantation ▶BY MOUTH ▶Adult: Initially 100–200 micrograms/kg daily in 2 divided doses Prophylaxis of graft rejection following kidney transplantation, starting within 24 hours of transplantation ▶BY MOUTH ▶Adult: Initially 200–300 micrograms/kg daily in 2 divided doses Prophylaxis of graft rejection following heart transplantation following antibody induction, starting within 5 days of transplantation ▶BY MOUTH ▶Adult: Initially 75 micrograms/kg daily in 2 divided doses Prophylaxis of graft rejection following heart transplantation without antibody induction, starting within 12 hours of transplantation ▶BY MOUTH ▶Adult: Initially 75 micrograms/kg daily in 2 divided doses Rejection therapy ▶BY MOUTH ▶Adult: Seek specialist advice PROGRAF ® CAPSULES Prophylaxis of graft rejection following liver transplantation, starting 12 hours after transplantation ▶BY MOUTH ▶Adult: Initially 100–200 micrograms/kg daily in 2 divided doses Prophylaxis of graft rejection following kidney transplantation, starting within 24 hours of transplantation ▶BY MOUTH ▶Adult: Initially 200–300 micrograms/kg daily in 2 divided doses Prophylaxis of graft rejection following heart transplantation following antibody induction, starting within 5 days of transplantation ▶BY MOUTH ▶Adult: Initially 75 micrograms/kg daily in 2 divided doses Prophylaxis of graft rejection following heart transplantation without antibody induction, starting within 12 hours of transplantation ▶BY MOUTH ▶Adult: Initially 75 micrograms/kg daily in 2 divided doses Allograft rejection resistant to conventional immunosuppressive therapy ▶BY MOUTH ▶Adult: Seek specialist advice PROGRAF ® INFUSION Prophylaxis of graft rejection following liver transplantation, starting 12 hours after transplantation when oral route not appropriate ▶BY INTRAVENOUS INFUSION ▶Adult: Initially 10–50 micrograms/kg daily for up to 7 days (then transfer to oral therapy), dose to be administered over 24 hours Prophylaxis of graft rejection following kidney transplantation, starting within 24 hours of transplantation when oral route not appropriate ▶BY INTRAVENOUS INFUSION ▶Adult: Initially 50–100 micrograms/kg daily for up to 7 days (then transfer to oral therapy), dose to be administered over 24 hours Prophylaxis of graft rejection following heart transplantation following antibody induction, starting within 5 days of transplantation ▶BY INTRAVENOUS INFUSION ▶Adult: Initially 10–20 micrograms/kg daily for up to 7 days (then transfer to oral therapy), dose to be administered over 24 hours Prophylaxis of graft rejection following heart transplantation without antibody induction, starting within 12 hours of transplantation ▶BY INTRAVENOUS INFUSION ▶Adult: Initially 10–20 micrograms/kg daily for up to 7 days (then transfer to oral therapy), dose to be administered over 24 hours Allograft rejection resistant to conventional immunosuppressive therapy ▶BY CONTINUOUS INTRAVENOUS INFUSION ▶Adult: Seek specialist advice (consult local protocol) DOSE EQUIVALENCE AND CONVERSION ▶For Prograf ®: Intravenous and oral doses are not interchangeable due to differences in bioavailability. Follow correct dosing recommendations for the dosage form when switching formulations. TACNI ® Prophylaxis of graft rejection following liver transplantation, starting 12 hours after transplantation ▶BY MOUTH ▶Adult: Initially 100–200 micrograms/kg daily in 2 divided doses Prophylaxis of graft rejection following kidney transplantation, starting within 24 hours of transplantation ▶BY MOUTH ▶Adult: Initially 200–300 micrograms/kg daily in 2 divided doses Prophylaxis of graft rejection following heart transplantation following antibody induction, starting within 5 days of transplantation ▶BY MOUTH ▶Adult: Initially 75 micrograms/kg daily in 2 divided doses Prophylaxis of graft rejection following heart transplantation without antibody induction, starting within 12 hours of transplantation ▶BY MOUTH ▶Adult: Initially 75 micrograms/kg daily in 2 divided doses Allograft rejection resistant to conventional immunosuppressive therapy ▶BY MOUTH ▶Adult: Seek specialist advice
Source pages 908, 909
Increased risk of infections. lymphoproliferative disorders. malignancies. neurotoxicity. QT-interval prolongation. UV light (avoid excessive exposure to sunlight and sunlamps)
Source page 909
Contra-indicated if history of hypersensitivity to macrolides.
Source page 910
NICE decisions ▶Immunosuppressive therapy for kidney transplant in adults (October 2017) NICE TA481 Immediate-release tacrolimus, when used as part of an immunosuppressive regimen, is recommended as an initial option to prevent organ rejection in adults having a kidney transplant. Treatment should be started with the least expensive product, but if this is not suitable, an alternative dosage form may be given. Tacrolimus granules for oral suspension (Modigraf ®) should be used only if the manufacturer provides it at the same price or lower than that agreed with the Commercial Medicines Unit. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/TA481 ▶Immunosuppressive therapy for kidney transplant in adults (October 2017) NICE TA481 Prolonged-release tacrolimus is not recommended as an initial treatment to prevent organ rejection in adults having a kidney transplant. Patients whose treatment was started within the NHS before this guidance was published should have the option to continue treatment, without change to their funding arrangements, until they and their NHS clinician consider it appropriate to stop. www.nice.org.uk/guidance/TA481 Scottish Medicines Consortium (SMC) decisions The Scottish Medicines Consortium has advised (December 2010) that tacrolimus granules for suspension (Modigraf ®) are accepted for restricted use within NHS Scotland in patients for whom tacrolimus is an appropriate choice of immunosuppressive therapy and where small changes (less than 500 micrograms) in dosing increments are required (such as, in paediatric patients) or in seriously ill patients who are unable to swallow tacrolimus capsules. The Scottish Medicines Consortium has advised (April 2015) that tacrolimus (Envarsus ®) is accepted for use in NHS Scotland for prophylaxis of graft rejection and treatment of rejection resistant to treatment with other immunosuppressive medicinal products in adults.
Source page 910
Extracted information for Tacrolimus only.
MHRA/CHM ADVICE: ORAL TACROLIMUS PRODUCTS: PRESCRIBE AND DISPENSE BY BRAND NAME ONLY, TO MINIMISE THE RISK OF INADVERTENT SWITCHING BETWEEN PRODUCTS, WHICH HAS BEEN ASSOCIATED WITH REPORTS OF TOXICITY AND GRAFT REJECTION (JUNE 2012) Inadvertent switching between oral tacrolimus products Immune system and malignant disease has been associated with reports of toxicity and graft rejection. To ensure maintenance of therapeutic response when a patient is stabilised on a particular brand, oral tacrolimus products should be prescribed and dispensed by brand name only. . Adoport ®, Prograf ®, Capexion ® and Tacni ® are immediate-release capsules that are taken twice daily, once in the morning and once in the evening; . Modigraf ® granules are used to prepare an immediate- release oral suspension which is taken twice daily, once in the morning and once in the evening; . Advagraf ® is a prolonged-release capsule that is taken once daily in the morning. Switching between tacrolimus brands requires careful supervision and therapeutic monitoring by an appropriate specialist. Important: Envarsus ® is not interchangeable with other oral tacrolimus containing products; the MHRA has advised (June 2012) that oral tacrolimus products should be prescribed and dispensed by brand only.
Source page 909
→Appendix 1: tacrolimus
Source page 909
GENERAL SIDE-EFFECTS ▶Common or very common 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. increased risk of infection. ischaemia. joint disorders. leucocytosis. leucopenia. metabolic acidosis. mood altered. muscle spasms. nasal complaints. nausea. nephropathy. nervous system disorder. oedema. oral disorders. pain. peripheral neuropathy. peripheral vascular disease. primary transplant dysfunction. psychiatric disorder. renal impairment. renal tubular necrosis. respiratory disorders. seizure. sensation abnormal. skin reactions. sleep disorders. temperature sensation altered. thrombocytopenia. tinnitus. tremor. urinary tract disorder. urine abnormal. vision disorders. vomiting. weight changes ▶Uncommon 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 ▶Rare or very rare 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 Agranulocytosis. neoplasm malignant. neoplasms. polyomavirus-associated nephropathy. progressive multifocal leukoencephalopathy (PML). pure red cell aplasia Immune system and malignant disease SPECIFIC SIDE-EFFECTS ▶With intravenous use Anaphylactoid reaction (due to excipient). hypersensitivity 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.
Source pages 909, 910
Exclude pregnancy before treatment.
Source page 910
Avoid unless potential benefit outweighs risk—crosses the placenta and risk of premature delivery, intra-uterine growth restriction, and hyperkalaemia.
Source page 910
Avoid—present in breast milk (following systemic administration).
Source page 910
Manufacturer advises caution in severe impairment. Dose adjustments Manufacturer advises consider dose reduction in severe impairment.
Source page 910
▶After initial dosing, and for maintenance treatment, tacrolimus doses should be adjusted according to whole- blood concentration. Monitor whole blood-tacrolimus trough concentration (especially during episodes of diarrhoea)—consult local treatment protocol for details. ▶Monitor blood pressure, ECG (for hypertrophic changes— risk of cardiomyopathy), fasting blood-glucose concentration, haematological and neurological (including visual) and coagulation parameters, electrolytes, hepatic and renal function.
Source page 910
Extracted information for Tacrolimus only.
▶With intravenous use For intravenous infusion (Prograf ®); give continuously in Glucose 5% or Sodium Chloride 0.9%. Dilute concentrate in infusion fluid to a final concentration of 4–100 micrograms/mL; give over 24 hours. Tacrolimus is incompatible with PVC.
Source page 910
There can be variation in the licensing of different medicines containing the same drug. Modified-release tablet ▶Envarsus (Chiesi Ltd) Tacrolimus (as Tacrolimus monohydrate) 750 microgram Envarsus 750microgram modified-release tablets | 30 tablet P £44.33 DT = £44.33 Tacrolimus (as Tacrolimus monohydrate) 1 mg Envarsus 1mg modified-release tablets | 30 tablet P £59.10 DT = £59.10 Tacrolimus (as Tacrolimus monohydrate) 4 mg Envarsus 4mg modified-release tablets | 30 tablet P £236.40 DT = £236.40 Granules CAUTIONARY AND ADVISORY LABELS 13, 23 ▶Modigraf (Astellas Pharma Ltd) Tacrolimus (as Tacrolimus monohydrate) 200 microgram Modigraf 0.2mg granules sachets sugar-free | 50 sachet P £71.30 DT = £71.30 Tacrolimus (as Tacrolimus monohydrate) 1 mg Modigraf 1mg granules sachets sugar-free | 50 sachet P £356.65 DT = £356.65 Modified-release capsule CAUTIONARY AND ADVISORY LABELS 23, 25 ▶Advagraf (Astellas Pharma Ltd) Tacrolimus (as Tacrolimus monohydrate) 500 microgram Advagraf 0.5mg modified-release capsules | 50 capsule P £35.79 DT = £35.79 Tacrolimus (as Tacrolimus monohydrate) 1 mg Advagraf 1mg modified-release capsules | 50 capsule P £71.59 DT = £71.59 | 100 capsule P £143.17 DT = £143.17 Tacrolimus (as Tacrolimus monohydrate) 3 mg Advagraf 3mg modified-release capsules | 50 capsule P £214.76 DT = £214.76 Tacrolimus (as Tacrolimus monohydrate) 5 mg Advagraf 5mg modified-release capsules | 50 capsule P £266.92 DT = £266.92 Solution for infusion EXCIPIENTS: May contain Polyoxyl castor oils ▶Prograf (Astellas Pharma Ltd) Tacrolimus 5 mg per 1 ml Prograf 5mg/1ml solution for infusion ampoules | 10 ampoule P £584.51 Capsule CAUTIONARY AND ADVISORY LABELS 23 ▶Adoport (Sandoz Ltd) Tacrolimus 500 microgram Adoport 0.5mg capsules | 50 capsule P £42.92 DT = £61.88 Tacrolimus 1 mg Adoport 1mg capsules | 50 capsule P £55.69 DT = £80.28 | 100 capsule P £111.36 Tacrolimus 5 mg Adoport 5mg capsules | 50 capsule P £205.74 DT = £296.58 ▶Prograf (Astellas Pharma Ltd) Tacrolimus 500 microgram Prograf 500microgram capsules | 50 capsule P £61.88 DT = £61.88 Tacrolimus 1 mg Prograf 1mg capsules | 50 capsule P £80.28 DT = £80.28 | 100 capsule P £160.54 Tacrolimus 5 mg Prograf 5mg capsules | 50 capsule P £296.58 DT = £296.58 IMMUNOSUPPRESSANTS › MONOCLONAL ANTIBODIES
Source pages 910, 911
Extracted information for Tacrolimus only.
Avoid excessive exposure to UV light including sunlight. Driving and skilled tasks May affect performance of skilled tasks (e.g. driving).
Source page 910
Filter the extracted dose blocks for this individual drug.
First line only; read the complete Indications and dose section above.
Initially 100–200 micrograms/kg daily in
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Initially 200–300 micrograms/kg daily in
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Initially 75 micrograms/kg daily in 2 divided
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Initially 75 micrograms/kg daily in 2 divided
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Seek specialist advice
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Initially 100–200 micrograms/kg once daily, to
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Initially 200–300 micrograms/kg once daily, to
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Seek specialist advice
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Initially 110–130 micrograms/kg once daily, to
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Initially 170 micrograms/kg once daily, to be
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Seek specialist advice
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Initially 100–200 micrograms/kg daily in
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Initially 200–300 micrograms/kg daily in
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Initially 75 micrograms/kg daily in 2 divided
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Initially 75 micrograms/kg daily in 2 divided
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Seek specialist advice
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Initially 100–200 micrograms/kg daily in
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Initially 200–300 micrograms/kg daily in
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Initially 75 micrograms/kg daily in 2 divided
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Initially 75 micrograms/kg daily in 2 divided
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 908
First line only; read the complete Indications and dose section above.
Seek specialist advice
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 909
First line only; read the complete Indications and dose section above.
Initially 10–50 micrograms/kg daily for up to
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 909
First line only; read the complete Indications and dose section above.
Initially 50–100 micrograms/kg daily for up to
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 909
First line only; read the complete Indications and dose section above.
Initially 10–20 micrograms/kg daily for up to
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 909
First line only; read the complete Indications and dose section above.
Initially 10–20 micrograms/kg daily for up to
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 909
First line only; read the complete Indications and dose section above.
Seek specialist advice (consult local protocol)
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 909
First line only; read the complete Indications and dose section above.
Initially 100–200 micrograms/kg daily in
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 909
First line only; read the complete Indications and dose section above.
Initially 200–300 micrograms/kg daily in
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 909
First line only; read the complete Indications and dose section above.
Initially 75 micrograms/kg daily in 2 divided
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 909
First line only; read the complete Indications and dose section above.
Initially 75 micrograms/kg daily in 2 divided
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 909
First line only; read the complete Indications and dose section above.
Seek specialist advice
This is a first-line fragment. Read the full Indications and Dose section above.
Candidate age grouping · source page 909