ty of water and the rinsings consumed by the patient. The suspension should be administered immediately after preparation.
4.3 Contraindications
Hypersensitivity to tacrolimus or to any of the excipients listed in section 6.1.
Hypersensitivity to other macrolides.
4.4 Special warnings and precautions for use
There are no safety data available on the use of Modigraf granules following a temporary switch from Prograf or Advagraf in critically ill patients.
Modigraf should not be switched with Advagraf as a clinically relevant difference in bioavailability between the two formulations cannot be excluded. Medication errors, including inadvertent, unintentional or unsupervised substitution of immediate- or prolonged-release tacrolimus formulations, have been observed. This has led to serious adverse reactions, including graft rejection, or other adverse reactions which could be a consequence of either under- or over-exposure to tacrolimus. Patients should be maintained on a single formulation of tacrolimus with the corresponding daily dosing regimen; alterations in formulations or regimen should only take place under the close supervision of a transplant specialist (see sections 4.2 and 4.8).
During the initial post-transplant period, monitoring of the following parameters should be undertaken on a routine basis: blood pressure, ECG, neurological and visual status, fasting blood glucose levels, electrolytes (particularly potassium), liver and renal function tests, haematology parameters, coagulation values, and plasma protein determinations. If clinically relevant changes are seen, adjustments of the immunosuppressive regimen should be considered.
When substances with a potential for interaction (see section 4.5) – particularly strong inhibitors of CYP3A4 (such as telaprevir, boceprevir, ritonavir, ketoconazole, voriconazole, itraconazole, telithromycin or clarithromycin) or inducers of CYP3A4 (such as rifampicin, rifabutin) – are being combined with tacrolimus, tacrolimus blood levels should be monitored to adjust the tacrolimus dose as appropriate in order to maintain similar tacrolimus exposure.
Herbal preparations containing St. John's Wort (Hypericum perforatum) or other herbal preparations should be avoided when taking Modigraf due to the risk of interactions that lead to either a decrease in blood concentrations of tacrolimus and reduced clinical effect of tacrolimus, or an increase in blood concentrations of tacrolimus and risk of tacrolimus toxicity (see section 4.5).
The combined administration of ciclosporin and tacrolimus should be avoided and care should be taken when administering tacrolimus to patients who have previously received ciclosporin (see sections 4.2 and 4.5).
High potassium intake or potassium-sparing diuretics should be avoided (see section 4.5).
Certain cmbinations of tacrolimus with drugs known to have nephrotoxic or neurotoxic effects may increase the risks of these effects (see section 4.5).
Immunosuppressants may affect the response to vaccination and vaccination during treatment with tacrolimus may be less effective. The use of live attenuated vaccines should be avoided.
Gastrointestinal disorders
Gastrointestinal perforation has been reported in patients treated with tacrolimus. As gastrointestinal perforation is a medically important event that may lead to a life-threatening or serious condition, adequate treatment |
