Transplant Drugs Flashcards by Kathryn Krchniak

Pre-Transplant

Induction Agent
IV Bolus MEPN
MPA Dose

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Post-Transplant (1-7)

Few doses of Induction Agent then D/C
IV MEPN converted to PO PRED w/ taper
MPA
Low Dose CNI

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Maintenance Therapy

MPA
CNI titrated through TDM
PRED taper
Monitor Allograft function

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Cyclosporine Therapeutic Trough

50-400 ng/ml

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Tacrolimus Therapeutic Trough

3-20 ng/ml

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Factors that affect CNI PK

Fat Content in Meals/Bile
Time post-transplant
Type of Organ Transplanted
Compromised GI Function
Overall Bioavailability
Drug Interactions

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Prograf (Astellas)

Tacrolimus IR (Prototype)
Capsules

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Astagraf XL (Astellas)

Tacrolimus ER
Polymer
1 mg ER: 1 mg IR
Troughs may be lower than IR

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Envarsus

Tacrolimus ER
Molecular particles w/ meltdose technology (cont. drug release)
70% of IR daily dose

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IV Prograf (Astellas)

Tacrolimus ER
Poloxy 60 hydrogenated castor oil with TAC
cont. infusion over 24 hrs
Anaphylaxis may occur; short term use
Glass/Polyethylene Containers

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Neoral (Novartis)

Modified CYA
Microemulsion capsules and modified emulsion solution
BID (q12h)
May dilute the solution in apple/orange juice only

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Gengraf (Abbvie/Abbott)

Modified CYA
Emulsion Capsules and modified emulsion solution
Bioequivalent to Neoral

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Sandimmune (Novartis/Sandoz)

Non-modified CYA
Castor Oil Capsules and solution
Can flocculate/gel below 20C, use glass to admin
Not bioequivalent to modified CYA
Dosing qd
Erratic Bioavail
May dilute with milk/OJ

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IV Sandimmune

Non-modified CYA
Cremophor EL (Castor Oil Complex in CYA)
Anaphylaxis may occur; short term use
Reserved for those who can't do PO
Discard after 24 hrs

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Cyclosporine AE

Hyperlipidemia, Nephrotoxicity, Tremor, HA, HTN

Hyperglycemia, Gingival Hyperplasia, Hirsutism, Diarrhea, Vomiting

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Tacrolimus

Diarrhea, Nausea, Nephrotoxicity, Tremor, HA, insomnia

Hyperglycemia, Hyperlipidemia, HTN

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Common DDI (Inhibition) w/ CNI

CCB, Antifungals, Antibiotics, Protease Inhibitors, Gastric Acid Suppressors, Grapefruit Juice

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Common DDI (Induction) w/ CNI

Antibiotics, Antifungals, Anticonvulsants, Herbals, Others

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Mycophenolic Acid (MPA)

Inhibits IMPDH, interfering w/ purine metab needed for lymphocyte development (prevents proliferation of committed T cells)

Mycophenolate Mofetil (MMF) - CellCept

MPA
Ester pro-drug
Regular Release
1000 mg

Mycophenolic Acid Sodium (MPS) - Myfortic

MPA
Sodium Salt
Delayed Release (enteric coating)
720 mg

Better Biavailability – CYA or MPA?

MPA

Factors affecting MPA PK

Time After Transplantation
DI
Enterohepatic Circulation
Concurrent Disease States
Food
Ethnicity
Gender
Genetic Polymorphorphisms

MPA DI (EHC)

CYA, Tacrolimus, Cholestyramine and Bile Acid Resins, Antibiotics

MPA DI (Renal Elim)

Acyclovir/Ganicyclovir, Co-trimoxazole

MPA DI (COC)

Use barrier method

MPA DI (Protein Binding)

Alters binding of Phenytoin and ASA

MPA DI (Inc Metab)

Glucocorticoids

MPA AE

GI (N/V, Diarrhea, dyspepsia), Hematologic (Leuko/Neutro/Thrombocytopenia, Anemia), Opportunistic Infections, CNS (dizziness, insomnia, HA), Cardiovascular

MPA Dosing w/ declining renal function

Use lower dose w/ a longer interval based upon the patient's ADE response

Equivalents to Cortisone Dosage (25 mg)

Prednisone (5 mg) | Methylprednisolone (4 mg)

Glucocorticoid Usage

Lowest Dose for Shortest Duration

Metabolic Inhibition of Glucocorticoids

Oral Contraceptives, Conjugated Estrogens, Macrolide Antibiotics, Ketoconazole, Isoniazid, Naproxen, Cyclosporine

Metabolic Induction of Glucocorticoids

Phenytoin, Phenobarbital, Rifampin, Carbamazepine, Ephedrine (dexameth)

Metabolic Induction BY Glucocorticoids

Tacrolimus, CYA (high dose MePn), MPA

Decrease Steroid Absorption

Cholestyramine and Antacids

Maintenance Glucocorticoid AE

Adrenal Atrophy, Cushing's Syndrome, Dyslipidemia, HTN, thrombosis, Vasculitis, Changes in Behavior/Cognition/Memory/Mood, Cerebral Atrophy, GI bleeding, Pancreatitis, Peptic Ulcer, Broad Immunosuppression, Activation of Latent Viruses, Delayed Wound Healing, Dermatitis, Bone Necrosis, Muscle Atrophy, Osteoporosis, Cataracts, Glaucoma

Post Transplant Complications

HTN, Opportunistic Infections, Diabetes, Hyperlipidemia, Osteoporosis, Lymphoproliferative Disorder

We use multiple drugs with different MOA to

use lower doses and minimize AE

Induction Immunosuppression

More intense immunosuppression initiated just prior and during the acute post-transplant phase

Role of Induction Therapy

Avoid Full Dose CYA/TAC (result in renal vasconstriction/slower function of renal graft), block Tcell/immunologic activation at time of graft placement

Disadvantage of Induction Therapy

Increased Costs, Increased risk of Cytomegalovirus (CMV) infection and post-transplantation lymphoproliferative disease (PTLD)

Induction Therapy Drug Plan

ONE Induction Agent, Mycophenolate mofetil (MMF), Glucocorticoids (at high doses with rapid dose tapering)

ATG (Anti-thymocyte Globulin)

Depleting Induction Polyclonal Antibodies 4-6 hours IV for 2-4 doses Coat T cells, opsonization of donor tissue AE: flu-like symptoms (fever, chills, N/V) on 1st dose; leukopenia, lymphopenia, thrombocytopenia, pruritis, erythema, serum sickness Premedicate w/ Diphenhydramine and APAP

Alemtuzumab (Campath)

Depleting Induction Monoclonal Antibody against CD52 surface antibody 2 doses OR 1 Dose IV Precede each dose by IV MePn, use anti-infective agent for at least 2 mo after d/c Causes prolonged lymphocyte depletion (up to 3 years) AE: HAMA, GI (N/V, diarrhea), lymphopenia, neutropenia, thrombocytopenia

Basiliximab (Simulect) | Daclizumab (Zenapax)

Non-Depleting Monoclonal Antibodies Against CD25 portion of the IL-2 receptor which prevents T cell proliferation ADE: GI (N/V, diarrhea - minimal)

possible drug use to decrease CNI dosage

Verapamil