|
Envarsus 0.75mg, 1mg & 4mg prolonged-release tablets(十一)
e increased
Injury, poisoning and procedural complications
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.
In clinical studies in kidney transplant patients receiving Envarsus, the most frequent adverse reactions (at least in 2% of patients) were tremor, diabetes mellitus, blood creatinine increased, urinary tract infection, hypertension, BK virus infection, renal impairment, diarrhoea, toxicity to various agents, and toxic nephropathy all of which are known to occur in the respective patient population under immunosuppressive treatment. In all, there appears to be no significant difference in the pattern of adverse events suspected to be causally related to study drug between once daily Envarsus and tacrolimus immediate-release capsules (Prograf).
Among the most frequent adverse reactions (at least in 2% of patients) in clinical studies in liver transplant patients receiving Envarsus were tremor, headache, fatigue, hyperkalaemia, hypertension, renal failure, blood creatinine increased, dizziness, hepatitis C, muscle spasms, tinea infection, leukopenia, sinusitis , and URTI, all of which are known to occur in the respective patient population under immunosuppressive treatment. As in kidney transplant recipients, there appears to be no meaningful difference in the pattern of suspected adverse drug reactions between once daily Envarsus and tacrolimus immediate-release capsules (Prograf).
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 in the UK, Website: www.mhra.gov.uk/yellowcard or in Ireland to HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517; Website: www.hpra.ie; e-mail: medsafety@hpra.ie.
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.
It should be noted however, that there has been no direct experience with Envarsus in overdose.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Immunosuppressants, calcineurin inhibitors, ATC code: L04AD02
Mechanism of action
At the molecular leve |
|
