Solid Organ Transplantation CSP Exam Prep Course Study Guide

Vocabulary flashcards covering solid organ transplant immunosuppressive pharmacology, dosing, therapeutic drug monitoring, adverse effect profiles, drug interactions, and clinical guidelines.

Triple Therapy

The standard maintenance immunosuppression protocol in solid organ transplantation, consisting of a calcineurin inhibitor (CNI), an antiproliferative agent, and a corticosteroid.

Calcineurin Inhibitors (CNIs)

An immunosuppressive medication class that inhibits the transcription of cytokines (primarily interleukin-2 [IL-2]) that regulate the activity and proliferation of T-lymphocytes.

Prograf (Tacrolimus Immediate-Release Capsules)

An immediate-release calcineurin inhibitor dosed every 12 hours on an empty stomach; available in $0.5\,\text{mg}$, $1\,\text{mg}$, and $5\,\text{mg}$ capsules, and not interchangeable with extended-release tablets.

Astagraf XL (Tacrolimus Extended-Release Capsules)

A once-daily extended-release capsule formulation of tacrolimus taken on an empty stomach; dosed at a 1:1 equivalent to the total daily dose of immediate-release tacrolimus capsules.

Envarsus (Tacrolimus Extended-Release Tablets)

A once-daily morning tablet formulation of tacrolimus taken on an empty stomach; its higher bioavailability reduces total daily dose requirements by approximately $20\%$ compared to immediate-release tacrolimus, resulting in less nephrotoxic exposure.

Tacrolimus 12-Hour Trough Level Targets

Average blood target levels for tacrolimus: $8-10\,\text{ng/mL}$ for $< 6$ months post-transplant; $5-7\,\text{ng/mL}$ for $6-12$ months post-transplant; and $3-5\,\text{ng/mL}$ for $> 12$ months post-transplant with no recent acute rejection.

Sandimmune (Cyclosporine Non-Modified)

A non-modified calcineurin inhibitor taken every 12 hours consistently with regard to meals; exhibits bile-dependent absorption and variable bioavailability leading to unpredictable trough levels, and is not interchangeable with modified cyclosporine.

Neoral / Gengraf (Cyclosporine Modified)

A microemulsion/modified formulation of cyclosporine that provides increased, consistent absorption with up to twice the bioavailability of non-modified cyclosporine (Sandimmune); it is not interchangeable with non-modified formulations.

Cyclosporine 12-Hour Trough Level Targets

Target 12-hour trough concentration goals for cyclosporine: $200-300\,\text{ng/mL}$ during $< 3$ months post-transplant, and $50-150\,\text{ng/mL}$ for $> 3$ months post-transplant.

CYP3A4 Inhibitors (CNI Interactions)

Agents that increase calcineurin inhibitor blood concentrations by inhibiting CYP3A4 metabolism, including azole antifungals, calcium channel blockers, macrolide antibiotics, protease inhibitors, grapefruit, and Seville oranges.

CYP3A4 Inducers (CNI Interactions)

Agents that decrease calcineurin inhibitor blood concentrations through metabolic induction, specifically rifampin and antiepileptics such as carbamazepine, phenobarbital, and phenytoin.

Cyclosporine and Statin Interaction

Concomitant use of cyclosporine with select HMG-CoA reductase inhibitors (atorvastatin, lovastatin, simvastatin) significantly elevates statin concentrations, increasing the risk of severe adverse effects like liver toxicity or rhabdomyolysis.

Antiproliferatives

A maintenance immunosuppressant class commonly used with a calcineurin inhibitor and prednisone that reduces B- and T-lymphocyte proliferation without causing nephrotoxicity or metabolic lipid/glucose derangements.

CellCept (Mycophenolate Mofetil / MMF)

An ester prodrug of mycophenolic acid (MPA) rapidly hydrolyzed by ubiquitous esterases; dosed $500-1000\,\text{mg}$ twice daily on an empty stomach and available as $250\,\text{mg}$ capsules, $500\,\text{mg}$ tablets, and $200\,\text{mg/mL}$ oral suspension.

Myfortic (Mycophenolate Sodium / MPA)

An enteric-coated formulation of mycophenolate designed to release in the small intestine rather than the stomach to reduce nausea and gastrointestinal adverse effects; dosed $360-720\,\text{mg}$ twice daily.

Mycophenolate Mofetil to Mycophenolate Sodium Equivalence

A non-interchangeable dosing equivalence where $500\,\text{mg}$ of mycophenolate mofetil (MMF / CellCept) is equivalent to $360\,\text{mg}$ of mycophenolate sodium (MPA / Myfortic).

Mycophenolate Black Box Warning

A severe warning for embryofetal toxicity, including first-trimester pregnancy loss and congenital malformations; managed by an FDA REMS program requiring effective contraception and waiting at least 6 weeks post-discontinuation before attempting pregnancy.

Azathioprine (Imuran)

An antiproliferative agent introduced in the 1960s metabolized by xanthine oxidase and TPMT; serves as an alternative for solid organ transplant patients intolerant to mycophenolate or those planning pregnancy.

Mammalian Target of Rapamycin (mTOR) Inhibitors

An immunosuppressive class that binds regulatory kinase FKBP12 to inhibit mTORC1 and block downstream IL-2 signaling; used as alternatives to CNIs in patients experiencing severe toxicities or recurrent skin malignancies.

Zortress (Everolimus)

An oral mTOR inhibitor derivative of sirolimus with better absorption and a half-life of $\sim 30\,\text{hours}$; dosed twice daily, heavily metabolized by CYP3A4, and not interchangeable with high-dose oncology formulations (Afinitor).

Rapamune (Sirolimus)

A once-daily mTOR inhibitor with an elimination half-life of $\sim 62\,\text{hours}$; available in oral tablet and solution dosage forms that are not bioequivalent.

mTOR Inhibitor Class Adverse Effects

Characteristic side effects associated with sirolimus and everolimus, including delayed wound healing, mouth sores, hyperlipidemia, elevated triglycerides, leukopenia, and peripheral edema.

Corticosteroids (Prednisone / Methylprednisolone)

Anti-inflammatory and immunosuppressive agents that inhibit cytokine gene expression derived from T cells and antigen-presenting cells; given in higher doses during induction and tapered down to daily maintenance regimens.

Belatacept (Nulojix)

A co-stimulation blocker fusion inhibitor administered via 30-minute IV infusion (post-op days 1, 5, end of weeks 2, 4, 8, then every 4 weeks) that prevents T-cell activation and induces apoptosis in CNI-sparing regimens.

Belatacept Boxed Warning

A black box warning restricting use exclusively to Epstein-Barr virus (EBV)-seropositive recipients due to an increased risk of post-transplant lymphoproliferative disorder (PTLD) and progressive multifocal leukoencephalopathy (PML) in EBV-seronegative individuals.

Induction Immunosuppression

The initial phase of immunosuppressive therapy characterized by high intensity to prevent early allograft rejection and allow successful graft implantation.

Maintenance Immunosuppression

The chronic, lower-potency phase of immunosuppression designed to block T- and B-lymphocyte proliferation and prevent late rejection while minimizing long-term drug toxicity.

Acute Rejection Immunosuppression

High-intensity immunosuppressive rescue intervention deployed during an active episode of immune-mediated graft rejection to salvage organ function.

Solid Organ Transplant Vaccination Rules

Vaccine safety parameters stating that live vaccines are contraindicated during active immunosuppression (wait $\sim 2\,\text{months}$ if therapy is halted), while inactivated vaccines are preferentially initiated starting 6 months post-transplant.