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 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).

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.

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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.

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Mycophenolate mofetil (CellCept) is occasionally used in combination with tacrolimus and steroids and it has helped to reduce dose-related toxicity of tacrolimus.

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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.

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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).

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

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

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

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

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

A prophylactic is a medication or a treatment designed and used to prevent a disease from occurring.

You will take a variety of these medications after transplant to help prevent opportunistic infections you are now more susceptible to because of the immunosuppression medication you have to take.

Antiviral used to treat or prevent cytomegalovirus (CMV). It comes in tablet form and should be taken with food or on a full stomach for full absorption.

Common Side Effects:

• Headache

• Diarrhea

• Nausea

• Vomiting

• Upset stomach

• Low white blood cells

• Low platelets

Important Tips and Special Instructions:

• Store at room temperature, away from excess heat, moisture, and direct sunlight.

• Missed Dose: If missed take as soon as possible; if close to the next dose do not take a double dose.

Prophylactically used as an antiviral to prevent and treat infections caused by viruses, particularly herpes virus; also used to treat chicken pox and shingles. It comes in the form of tablets, capsules, or liquid suspension.

Common Side Effects:

• Tiredness

• Lightheadedness

• Headache

• Nausea or vomiting

• Abdominal pain

• Skin reactions

• Kidney problems

Important Tips and Special Instructions:

• Most effective when taken as soon as possible after you notice symptoms of herpes infection (i.e. pain, burning, blisters).

• Does not prevent the spread of herpes virus.

Prophylactic antibiotic used to prevent a type of pneumonia caused by Pneumocystis jiroveci and comes in the form of a tablet.

Common Side Effects:

• Anemia

• Sensitivity to sunlight

• Dizziness

• Diarrhea

• Headache

• Loss of appetite

• Nausea, vomiting

• Skin rash

Important Tips and Special Instructions:

• Take exactly as prescribed with a full glass of water.

• Drink enough fluids throughout the day.

• Missed Dose: If missed take as soon as possible; if close to the next dose do not take a double dose.

Antibiotic used to prevent a type of pneumonia caused by Pneumocystis jiroveci used for patients with a sulfa allergy or who cannot tolerate oral Bactrim. It is inhaled into the body via a breathing treatment.

Common Side Effects:

• Dizziness

• Metallic taste

• Fatigue

• Loss of appetite

• Diarrhea

• Cough

• Upset stomach

• Congestion

Important Tips and Special Instructions:

• Store in room temperature, away from excess heat, moisture, and direct sunlight.

• Missed Dose: If missed take as soon as possible; if close to the next dose do not take a double dose.