Calcineurin Inhibitors PK/DDIs

Question 1

Factors affecting CNI PK

Answer 1

Fat content from meals
Time post-transplant
Type of transplanted organ
Compromised GI function
Overall bioavailability
Drug interactions

Question 2

Drugs that cause inhibition of 3A4 and pGp

Answer 2

CCBs, antifungals, ABX, protease inhibitors, gastric acid inhibitors, grapefruit juice

Question 3

Inhibition of 3A4 and pGp on the trough and AUC

Answer 3

Higher trough and AUC

Question 4

CCB affected by inhibition

Answer 4

Nicardipine

Question 5

Antifungals affected by inhibition

Answer 5

Itraconazole, posaconazole, ketoconazole, fluconazole

Question 6

ABX affected by inhibition

Answer 6

Clarithromycin

Question 7

Protease inhibitors affected by inhibition

Answer 7

Indinavir, boceprevir

Question 8

Gastric acid suppressors affected by inhibition

Answer 8

Lansoprazole, omeprazole, cimetidine, magnesium and aluminum hydroxide antacids

Question 9

Grapefruit juice effect on inhibition

Answer 9

Naringin in large amounts

Question 10

Cyclosporine and tacrolimus both exhibit what kind of kinetics?

Answer 10

Linear

Question 11

What concentration is used for CNI monitoring?

Answer 11

Trough concentration

Question 12

Monitoring of CNI troughs and renal function in early post-transplant period

Answer 12

Check SCr, BUN, eGFR weekly in the first 3 months post-transplant

Question 13

Monitoring of CNI troughs and renal function in stable patients

Answer 13

Check monthly unless an acute clinical change occurs

Question 14

Things to check for when doing CNI TDM

Answer 14

Verify the time of the last dose, drug formulation, and dosing regimen, and monitor ADEs concurrent to trough

Question 15

Nephrotoxicity of CNIs is due to…

Answer 15

…vasoconstriction of the afferent arteriolar constriction, which results in a higher SCr

Question 16

CNI nephrotoxicity is related to…

Answer 16

…the amount of CNI exposure (higher dose, higher SCr)

Question 17

What to do when an elevated SCr occurs

Answer 17

Repeat all labs and trough should be repeated

Question 18

What happens when the labs and trough are repeated and the SCr is the same?

Answer 18

Patient should be counseled to stay hydrated, evaluate their renal function and do any pertinent diagnostic tests for evaluation of the allograft

Question 19

What happens when the SCr is elevated?

Answer 19

Reduce the CNI dose by 30-35% after holding one dose of the drug and re-evaluate the renal function and CNI trough within 24-36 hours

(Also adjust any other meds that have renal dosing until renal function improves)