A discussion about the nuances of tacrolimus medication therapy
Hello my name is isabelle and i’m a p4 student at drake university and today i will be talking about the medication tacrolimus specifically its use in kidney transplant so starting off i just wanted to review that sacralamus does have several uses and indications both on and off label organ transplant for liver heart lung and then today we’ll be talking about the
Kidney atopic dermatitis and then several off-label uses as well it comes in a capsule formulation granule formulations and then a topical ointment as well tacrolimus does also carry two black box warnings the first being for increased risk for developing serious infections and malignancies and the malignancies were specifically skin and lymphoma malignancies
Which were found to be more related to long-term immunosuppression rather than this medication in particular but they still still want you to be aware of that and also it has an increased risk of mortality in female transplant patients with specifically the brand astagraph and that brand is also not approved for use in liver transplantation so next looking
At the mechanism of action of tacrolimus it is a calcineurin inhibitor or a cni there are actually two tacrolimus which i have outlined in red and then also cyclosporin the cni’s work by complexing with cytoplasmic proteins tachrolimus in particular binds with fk binding protein 12 in these complexes inhibit calcineurin phosphatase which results in reduced
Il2 gene transcription and reduction in il2 synthesis and this in turn diminishes t cell activation in kidney transplant patients in particular tacrolimus has been associated with significantly lower risk of allograft loss at six months and lower rates of acute rejection at one year and tacrolimus is the primary cni in many transplant centers due to its more
Favorable adverse reaction profile and tyrolimus is used in combination with a purine analog we have two azathioprine and mycophenolate um and each of those medications acts to diminish purine synthesis and in turn decrease dna replication and the combination of these drugs um being used in kidney transplant is important because each drug acts on a different
Phase of the cell cycle uh tachrylamus inhibits activation and then mycophenolate and acelfioprine inhibit proliferation or dna replication so next looking at potential side effects and adverse reactions of tepralimus and i do just want to note that this is not a full list of all of the potential side effects of this medication these are just some of the notable
Ones that i wanted to go over today so tacrolimus can cause hypertension it does this by reducing the glomerular filtration rate and renal blood flow increasing systemic and intra-renal vascular resistance promoting sodium retention and increasing concentrations of thromboxanes but when compared to cyclosporine the other cni tacrolimus has been shown to display
Less hypertension in patients they do require fewer antihypertensives with tachycalamus as compared to cyclosporine after transplant can also cause hyperlipidemia and then looking at more serious adverse events specifically in renal transplant nephrotoxicity can occur induction therapy plays an important role in preventing the cni atacrolymus induced
Nephrotoxicity um and then the induction therapy treatments can cause the cni initiation to be delayed until the graft regains some degree of function and those treatments we have a couple monoclonal antibodies used for that can also cause diabetes in some patients there are several factors that play into that tacrolimus use is just one of them but looking
At other risk factors like bmi genetics steroid use this medication can also cause hyperkalemia and then with just about any other immunosuppressive agent i’m also being aware of increased risk for malignancy for pharmacokinetics of taprolimus first looking at the absorption i just want to note that this medication can be administered with or without food
But absorption is decreased by a high fat meal so making sure patients are aware of that distribution this medication does cross the placenta and it is 99 protein bound to albumin and alpha one acid glycoprotein for metabolism it’s primary primarily hepatic metabolism and is a sip 3a4 substrate with elimination the half-life is 23 to hours and it is 93 percent
Excreted in the feces with monitoring of typrolimus it is important to ensure that the patient has a therapeutic serum concentration as lower serum concentrations have been correlated to higher rates of transplant rejection so you want to make sure that they are in their therapeutic range monthly appointments are needed to check serum levels and often could
Be even more frequent than that when first starting with the immediate release medication if you’re using it in combination with azathioprine have the the serum concentrations listed there from months one to three and then months four to twelve and then if you’re using it in combination with mycophenolate they have a separate serum concentration levels there
The trough for oral therapy is drawn typically within 30 minutes prior to the next dose being given but frequency varies depending on transplant type time since transplantation in clinician clinical situation and finally just some things to keep in mind some special considerations for tacrolimus this is an immunoimmunosuppressive agent as we have said throughout
The presentation here so just making sure patients are aware of that and understand the risks and side effects involved with that reinforcing the importance of minimizing the risk of infection hand hygiene wearing a mask in public avoiding crowded and enclosed spaces and then also following up with patients monthly to monitor side effects labs and vitals blood
Pressure blood glucose renal and hepatic function tests like cbc or bmp blood pressure can also be monitored three times a week for the first few weeks as it can increase that monitoring qt interval as well as it can be prolonged with this medication also dosing is dependent on immediate or extended release of the formulation of tachylamus and that is
It thank you so much for listening
Transcribed from video
Tacrolimus Medication Review By IM_Pharm_APPE
