Concomitant use of medicinal products or herbal remedies known to inhibit or induce CYP3A4 may affect the metabolism of tacrolimus and thereby increase or decrease tacrolimus blood levels. In healthy subjects, the average total body clearance (TBC) estimated from whole blood concentrations was 2.25 l/h. If abnormalities develop, dose reduction of Prograf therapy, or change of treatment to another immunosuppressive agent should be considered.

The capsules should be swallowed with fluid (preferably water). Due to the need of treatment, tacrolimus can be considered in pregnant women when there is no safer alternative and when the perceived benefit justifies the potential risk to the foetus. In rats, female reproductive function including birth was impaired at toxic dosages and the offspring showed reduced birth weights, viability and growth. If there is a … If patients taking tacrolimus present with symptoms indicating PRES such as headache, altered mental status, seizures, and visual disturbances, a radiological procedure (e.g. telaprevir, boceprevir, and the combination of ombitasvir and paritaprevir with ritonavir, when used with and without dasabuvir), or the CMV antiviral letermovir, the pharmacokinetic enhancer cobicistat, and the tyrosine kinase inhibitors nilotinib and imatinib. pronounced adverse reactions - see section 4.8) the dose of Prograf may need to be reduced.For conversion to Prograf, treatment should begin with the initial oral dose recommended for primary immunosuppression.For information on conversion from ciclosporin to Prograf, see below under “Dose adjustments in specific patient populations”.Prograf can be used with antibody induction (allowing for delayed start of Prograf therapy) or alternatively in clinically stable patients without antibody induction.Following antibody induction, oral Prograf therapy should commence at a dose of 0.075 mg/kg/day administered as two divided doses (e.g.

To date, no other relevant epidemiological data are available.

Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.Experience with overdosage is limited. During treatment, careful monitoring with EBV-PCR is recommended. ritonavir, nelfinavir, saquinavir), HCV protease inhibitors (e.g.

Tacrolimus was started as continuous intravenous infusion at a dose of 0.05 mg/kg/day and oral tacrolimus was administered at a dose of 0.1 to 0.3 mg/kg/day with subsequent dose adjustments to target trough levels of 12 to 15 ng/ml. Administration should commence within 5 days after the completion of surgery as soon as the patient's clinical condition is stabilised. Ten capsules per blister. Both tacrolimus and aceclofenac can increase the risk of hyperkalaemia (hyperkalaemia is particularly notable when ACE inhibitors or angiotensin-II receptor antagonists are given with spironolactone or eplerenone). In prospective published studies tacrolimus was investigated as primary immunosuppressant in approximately 175 patients following lung, 475 patients following pancreas and 630 patients following intestinal transplantation.

endobj Results continuously improved with increasing experience over the course of 11 years. Overall, the safety profile of tacrolimus in these published studies appeared to be similar to what was reported in the large studies, where tacrolimus was used as primary treatment in liver, kidney and heart transplantation.

There is also evidence of gastrointestinal metabolism by CYP3A4 in the intestinal wall. Only one of these has been shownThe kidneys and the pancreas were the primary organs affected in toxicity studies performed in rats and baboons. pronounced adverse reactions - see section 4.8) the dose of Prograf may need to be reduced.For conversion to Prograf, treatment should begin with the initial oral dose recommended for primary immunosuppression.For information on conversion from ciclosporin to Prograf, see below under “Dose adjustments in specific patient populations”.Oral Prograf therapy should commence at 0.20 - 0.30 mg/kg/day administered as two divided doses (e.g. <> The interim analysis of a recent multicentre study discussed 110 patients who underwent 1:1 randomisation to either tacrolimus or ciclosporin. Potassium-sparing medicines may exacerbate tacrolimus-induced hyperkalaemia and should only be initiated with regular monitoring of U&Es. Patients should be advised to report changes in visual acuity, changes in colour vision, blurred vision, or visual field defect, and in such cases, prompt evaluation is recommended with referral to an ophthalmologist as appropriate.Patients treated with immunosuppressants, including Prograf are at increased risk for infections including opportunistic infections (bacterial, fungal, viral and protozoal) such as BK virus associated nephropathy and JC virus associated progressive multifocal leukoencephalopathy (PML). Tacrolimus suppresses T-cell activation and T-helper-cell dependent B-cell proliferation, as well as the formation of lymphokines (such as interleukins-2, -3, and γ-interferon) and the expression of the interleukin-2 receptor.Prograf has evolved into an accepted treatment as primary immunosuppressive medicinal product following pancreas, lung and intestinal transplantation. In some cases, it was necessary to switch to alternative immunosuppression.Reporting suspected adverse reactions after authorisation of the medicinal product is important. The 1-year patient survival was 83% in the tacrolimus and 71% in the ciclosporin group, the 2-year survival rates were 76% and 66%, respectively.