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Post-Transplant

Medications

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Section 1: Immunosuppression

Tacrolimus (Prograf)


Calcineurin Inhibitor

Pharmacology: Suppresses the immune system by inhibiting calcineurin which blocks the synthesis of interleukin-2, the cytokine that is needed for the development and proliferation of T cells.

Major adverse effects:

  • Nephrotoxic: causes vasoconstriction of the afferent and efferent glomerular arterioles and reduction in renal blood flow and glomerular filtration rate. This renal effect often results in the development of hypertension.
  • Hyperkalemia
  • Hyperglycemia
  • Hypomagnesemia
  • Tremors




Sirolimus (Rapamune)


mTOR Inhibitor

Pharmacology: Suppresses the immune system by inhibiting activation of T cells and B cells by reducing their sensitivity to interleukin-2 through mTOR inhibition and inhibiting the ability for cell proliferation.

Note: mTOR inhibitors block the response to IL-2 by blocking cell cycle progression which blocks the IL-2 mediated activation of T cells and B cells, while calcineurin inhibitors, such as tacrolimus, inhibit the secretion of IL-2.

Major adverse effects:

  • Hypertriglyceridemia
  • Hypercholesteremia
  • Opportunistic infections
  • Thrombocytopenia
  • Leukopenia
  • Myalgia




Antithymocyte Globulins (Thymoglobulin)


Pharmacology: When administered, the antibodies bind to the surface of circulating T lymphocytes in the blood and undergo various reactions include complement mediated destruction, antibody-dependent cytotoxicity, apoptosis, and opsonization; making it an efficacious immunosuppressive agent.

Major adverse effects:

  • Hyperkalemia
  • Hypertension
  • Leukopenia
  • Headache




Alemtuzumab (Campath-1H)


Pharmacology: This is a humanized monoclonal antibody against CD52 on T and B lymphocytes. By binding to the receptors on these cells it triggers antibody-dependent cytolysis or complement mediated cytolysis, depleting the cells in peripheral circulation.

Major adverse effects:

  • Myalgia
  • Cytopenia
  • Infusion reactions
  • Shortness of breath




Mycophenolate Mofetil (CellCept)


Pharmacology: It is a prodrug with its active form being mycophenolic acid. The antimetabolite inhibits the de novo synthesis of purine by inhibiting iosine monophosphate dehydrogenase (IMPDH) which deprives the rapidly dividing T cell and B cells of a key component of nucleic acids needed for DNA formation and replication.

Major adverse effects:

  • Leukopenia
  • Nausea
  • Diarrhea
  • Tumors




Basic Premise of Intestinal Transplant Immunosuppression


The intestine is a highly immunogenic organ, containing a large portion of the body’s immune cells. Due to this, intestinal transplant has posed a large challenge compared to other solid organ transplants. The therapeutic protocols for immunosuppression that have been established focus on recipient preconditioning with lymphocyte depleting agents and minimization of post-transplant immunosuppression. For more information refer to (1,2,3).




Induction Therapy


Induction therapy is used to describe the administration of mono- or polyclonal antilymphocyte antibody therapy for a short course, immediately pre- or post-transplant. The purpose for the potent immunosuppressive antibody therapy is to diminish the host immune response to the graft. For more information, refer to (1,2,3).




General Protocol for Intestinal Transplant Immunosuppression


Currently, most centers follow the following general protocol for immunosuppression:

  • Induction regimen of rabbit anti-thymocyte-globulin (rATG, Thymoglobulin) or alemtuzumab (Campath) used for recipient lymphoid depletion.
  • rATG or alemtuzumab are infused over in a single dose before allograft reperfusion.
  • Intravenous steroids are given before and after the infusion.
Post-transplant immunosuppression consists of a regimen of tacrolimus with or without corticosteroids.
  • ​Initially tacrolimus is given intravenously and is switched to oral once the intestine begins to function.
  • Target trough levels for tacrolimus in the first 90 days is 10-15 ng/mL; after which the target trough level is 5-10 ng/mL.
  • Corticosteroids are indicated in the case of adrenal insufficiency or patients who develop significant rejection.
Mycophenolate mofetil (CellCept) is occasionally used in combination with tacrolimus and steroids and it has helped to reduce dose-related toxicity of tacrolimus. Sirolimus (Rapamune, Rapamycin) may be used as a primary or secondary agent and is a valuable agent in intestinal transplantation as it is not nephrotoxic. If a patient enters into acute rejection, or encounters other complications such as PTLD or GVHD, then immunosuppression therapies must be modified accordingly. For more information refer to (1,2,3).





Section 2: Prophylaxis

Valganciclovir


  • CMV infection is one of the most common infections after intestinal transplant, particularly in CMV sero-negative recipients who are grafted a sero-positive donor.
  • Preemptive therapy or prophylaxis with intravenous ganciclovir or oral valganciclovir can be used to help prevent CMV infection.
  • Monitoring for CMV with PCR in weekly bloodwork is usually standard for most transplant centers, so therapy can be initiated if CMV infection is detected to avoid significant morbidity and mortality.

For more information refer to (4).




Acylovir (Zovirax)


Utilized by some transplant centers to prevent reactivation of herpes simplex infections in post-transplant patients.




Sulfamethoxazole/ Trimethoprim (Bactrim)


  • Intestinal transplant recipients are at increased risk for infection with Pneumocystis jirovecii pneumonia.
  • Sulfamethoxazole/ Trimethoprim (Bactrim) is the prophylactic drug of choice to use to prevent this infection.
  • If this medication is not tolerated or absorbed, a once a month Pentamidine breathing treatment is the alternative.




Nystatin


  • Nystatin is a polyene antifungal medication that is active against molds and yeast infections, particularly Candida.
  • Candida is particularly dangerous to intestinal transplant patients because it can infect the entire GI tract.
  • The swish and swallow nystatin is recommended as a lifelong prophylaxis to transplant patients to prevent this opportunistic infection.
  • An alternative to Nystatin is Clotrimazole troche, however, this can interact with tacrolimus levels, so it should be used with caution.

For more information refer to (7).





Section 3: Other Common Medications

Pantoprazole (Protonix)


It is not uncommon for intestinal transplant patients to experience acid reflux. Many patients will be on a proton pump inhibitor or another form of acid reducer.




Metoclopramide (Reglan)


It is not uncommon for intestinal transplant patients to still experience dysmotility and nausea following transplant. The prescribing of motility medications may be necessary to help promote oral feeding and symptom relief.




Loperamide (Lomotil)


Many patients will experience high output ostomies or diarrhea once they have stoma closure. The prescribing of multiple bowel stoppers is common. It is important to help your patients retain as much fluid as possible and decrease the amount of stool output in order to avoid dehydration and be able to wean them off any intravenous fluids they may require.




Warfarin (Coumadin) or Enoxaparin (Lovenox)


Many intestinal transplant patients will experience some form of thrombosis before or after transplant. Blood thinning medications are common to find on an intestinal transplant patient medication list.





Section 4: Additional Resources

Patient and Clinician Resource: Medication Assistance Websites.


Medication Assistance: Listing of websites you can provide patients to help pay for medications. Many sites have both patient and clinician sections for educational materials as well.




Page References


References here.