Tacrolimus

Question 1

Consult local guidelines for

Answer 1

Consult local guidelines for therapeutic dosing and monitoring. Whole blood-tacrolimus trough
concentration should be monitored especially during episodes of diarrhoea
Loading doses may be required

Question 2

Monitoring

Answer 2

Blood pressure, ECG (for cardiomyopathy), fasting blood glucose concentration, renal function,
liver function, serum electrolytes (particularly K+), haematological, neurological (including visual) and
coagulation parameters

Question 3

Warning signs

Answer 3

• Neurotoxicity e.g. tremor, headache
• Nephrotoxicity e.g. elevated serum creatinine concentrations
• Eye disorders e.g. blurred vision, photophobia
• Skin disorders e.g. rash, toxic epidermal necrolysis
• Blood disorders (signs of infection such as fever, sore throat, mouth ulcers, also unexplained
bruising or bleeding) e.g. leucopenia, thrombocytopenia
• Hyperglycaemia – diabetes mellitus e.g. increased thirst or excessive urination
• Cardiovascular disorders – cardiomyopathy, arrhythmias, hypertension e.g. irregular heartbeat,
heaviness in the centre of chest triggered by effort or emotion
• Liver toxicity e.g. jaundice, nausea, vomiting, abdominal discomfort, dark urine

Question 4

Actions required

Answer 4

• Advise patient to report immediately to a doctor if any warning signs occur

• Advise patient to avoid excessive exposure to UV light, including sunlight and to use a wide-
spectrum sunscreen (may reduce risk of secondary skin malignancies)

• Oral tacrolimus medicines should be prescribed and dispensed by brand name only, to
minimise switching between products to reduce risk of toxicity and graft rejection. Any
switching between brands requires careful supervision by an appropriate specialist
• Ensure patient understands the importance of taking immunosuppressants regularly
• Advise patient that tacrolimus may affect performance of skilled tasks (e.g. driving) and to
avoid undertaking risk activities if they feel unft to do them
• Warn patients receiving tacrolimus that they must not receive immunisation with live vaccines
• Advise patient to avoid a high potassium diet and grapefruit juice

Question 5

Interactions

Answer 5

• Increased plasma concentrations with clarithromycin, diltiazem, erythromycin, fuconazole,
grapefruit juice, itraconazole, nifedipine, omeprazole, ranolazine
• Reduced plasma concentration with phenobarbital, St. John’s Wort, rifampicin, phenytoin
• Increased risk of nephrotoxicity when given with aminoglycosides, amphotericin and NSAIDs
(especially ibuprofen), certain antivirals (e.g. aciclovir, ganciclovir)
• Tacrolimus increases plasma concentration of ciclosporin
• Increased risk of hyperkalaemia when given with potassium-sparing diuretics (e.g. amiloride,
spironolactone), potassium salts, angiotensin II receptor antagonist