very common:
renal impairment
common:
renal failure, renal failure acute, nephropathy toxic, renal tubular necrosis, urinary abnormalities, oliguria, bladder and urethral symptoms
uncommon:
haemolytic uraemic syndrome, anuria
very rare:
nephropathy, cystitis haemorrhagic
Reproductive system and breast disorders
uncommon:
dysmenorrhoea and uterine bleeding
General disorders and administration site conditions
common:
febrile disorders, pain and discomfort, asthenic conditions, oedema, body temperature perception disturbed
uncommon:
influenza like illness, feeling jittery, feeling abnormal, multi-organ failure, chest pressure sensation, temperature intolerance
rare:
fall, ulcer, chest tightness, thirst
very rare:
fat tissue increased
Investigations
very common:
liver function tests abnormal
common:
blood alkaline phosphatase increased, weight increased
uncommon:
amylase increased, ECG investigations abnormal, heart rate and pulse investigations abnormal, weight decreased, blood lactate dehydrogenase increased
very rare:
echocardiogram abnormal, electrocardiogram QT prolonged
Injury, poisoning and procedural complications
common:
primary graft dysfunction
Medication errors, including inadvertent, unintentional or unsupervised substitution of immediate- or prolonged-release tacrolimus formulations, have been observed. A number of associated cases of transplant rejection have been reported (frequency cannot be estimated from available data).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
4.9 Overdose
Experience with overdose is limited. Several cases of accidental overdose have been reported with tacrolimus; symptoms have included tremor, headache, nausea and vomiting, infections, urticaria, lethargy and increases in blood urea nitrogen, serum creatinine and alanine aminotransferase levels.
No specific antidote to tacrolimus therapy is available. If overdose occurs, general supportive measures and symptomatic treatment should be conducted.
Based on its high molecular weight, poor aqueous solubility, and extensive erythrocyte and plasma protein binding, it is anticipated that tacrolimus will not be dialysable. In isolated patients with very high plasma levels, haemofiltration or -diafiltration have been effective in reducing toxic concentrations. In cases of oral intoxication, gastric lavage and/or the use of adsorbents (such as activated charcoal) may be helpful, if used shortly after intake.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Immunosuppressants, calcineurin inhibitors, ATC code: L04AD02
Mechanism of action
At the molecular level, the effects of tacrolimus ap
