Immunosuppressant Drug Interactions Flashcards
What are the 4 drugs that are CYP3A4 and P-gp inducers?
Phenytoin
Phenobarbital
Carbamazepine
Rifampin/Rifabutin
What are the 4 drugs that are CYP3A4 and P-gp inhibitors?
Macrolide antibiotics
Non-DHP CCBs (diltiazem and verapamil)
Azole antifungals
Protease inhibitors, cobicistat
(T/F) - Azithromycin is not considered a CYP3AR inhibitor
TRUE - only macrolide antibiotic that is not
Which 3 immunosuppressant drugs should not be used concomitantly with statins?
CSA, SRL, and TAC
(T/F) - Statins are inhibitors of CYP3A4
FALSE - they’re substrates
(T/F) - CSA is an inhibitors of CYP3A4
TRUE - they’re also substrates
(T/F) - SRL is an inducer of CYP3A4
FALSE - weak inhibitor (also substrates)
(T/F) - TAC is an inhibitor of CYP3A4
TRUE - weak inhibitor, however
Why are statins avoided with CSA, SRL, TAC?
Rhabdomyolysis can occur due to statins breaking down more muscle cells and releasing myoglobin, which causes renal injury or failure; this is because statins are substrates and CSA, SRL, and TAC are inhibitors (weak or strong) of CYP3A4
What two food and herbs interact with CSA, TAC, SRL, EVR
Grapefruit juice and St. John’s Wort
Does grapefruit juice induce or inhibit CYP3A4 and P-gp?
Inhibits CYP3A4 and P-gp
In which location (hepatic or gut) does grapefruit juice inhibit CYP3A4 and P-gp? It can be both locations or different locations for each, by the way.
The gut for both CYP3A4 and P-gp
What is the culprit in grapefruit juice?
Metabolite of naringin (naringenin-metabolite)
Does St. John’s Wort induce or inhibit CYP3A4 and P-gp?
Induces CYP3A4 and P-gp
In which location (hepatic or gut) does St. John’s wort affect CYP3A4 and P-gp? It can be both locations or different locations for each, by the way.
CYP3A4 is affected in the liver and gut
P-gp is affected in the gut
What is a severe side effect for CSA and TAC?
Nephrotoxicity
What 4 drugs can increase the risk of nephrotoxicity?
Aminoglycosides
Vancomycin
NSAIDs
Amphotericin B
What is the most common supratherapeutic consequence of all 4 immunosuppressants?
Over-immunosuppression; increasing the risk of infection
What is the most common subtherapeutic consequence of all 4 immunosuppressants?
Transplant rejection
What are the most common supratherapeutic consequence of CSA and TAC?
Nephrotoxic
Hypertension
Electrolyte abnormalities (increase K and Mg, decrease PO4)
Tremors - specifically TAC
What are the most common supratherapeutic consequences of SRL and EVR?
Oral ulcers
Anemia
Leukopenia
Thrombocytopenia
If CSA or TAC have been administered with enzyme inhibitors (vice versa), what approach should be taken for monitoring?
Monitor trough levels 2-3 days after drug initiation and manage dose adjustments appropriately
If SRL have been administered with enzyme inhibitors (vice versa), what approach should be taken for monitoring?
Monitor trough levels 1 week after drug initiation and mange dose adjustments appropriately
If EVR have been administered with enzyme inhibitors (vice versa), what approach should be taken for monitoring?
Monitor trough levels for 4-5 days after drug initiation and manage dose adjustments appropriately
What monitoring approach should be taken when an enzyme inducer has been given with EVR/CSA/TAC?
Monitor trough levels for 4-7 days after drug initiation; increase 25% of the dose QD as needed
Which immunosuppressant drug has a risk of obtaining progressive multifocal leukoencephalopathy (PML) as a supratherapeutic consequence?
Sirolimus
