Immunosuppression

Question 1

cyclosporine

What is the indication of Cyclosporine?

Answer 1

prevention of rejection in transplant in kidney, liver, heart, lung, bone marrow transplant, and other disorders such as aplastic anemia and ulcerative colitis

Question 2

cyclosporine

How is absorption altered for Sandimmune?

Answer 2

• food intake
• time of day
• GI transit time
• GI autonomic neuropathy
• time post transplant

Question 3

cyclosporine

How does grapefruit juice effect cyclosporine?

Answer 3

grapefriut juice increases plasma concentration of cyclosporin

Question 4

What are the drug interactions of cyclosporine that effect absorption?

Answer 4

• grapefruit juice
• aluminum/magnesium hydroxide antacids
• orlistat
• CYP3A4 and P-gp inhibitors
• St. johns wort

Question 5

Describe the distribution of cyclosporine:

Answer 5

lipophilic, high tissue affinity, 90% protein bound, bound to RBCs, Vd= total body water, crosses placenta and distributes in breast milk

Question 6

What is the clearance of cyclosporine?

Answer 6

0.4 L/h/kg

Question 7

How is cyclosporine excreted?

Answer 7

biliary excretion

Question 8

cyclosporine

What are the toxicities seen with cyclosporine?

Answer 8

• nephrotoxicity
• hypertension
• hirsutism
• neurotoxicity (headache, tremor, seizure, coma)

Question 9

What drugs decrease the clearance of cyclosporine?

Answer 9

• erythromycin
• antifungals (-conazoles)
• diltiazem, verapamil, nicardipine, nifedipine
• indinavir, ritonavir

Question 10

cyclosporine

What is the initial dosing equation for cyclosporines?

Answer 10

Dose= (Cl x Css (trough level) x tau)/ F

Question 11

cyclosporine

What is correlation between drug levels and therapeutic response of cyclosporine?

Answer 11

• low plasma drug levels= increased risk of rejection/graft loss
• decreased Cmax and AUC= acute rejection
  Co levels (trough) does not correlate with risk of rejection

Question 12

cyclosporine

What is the goal Co (trough) for cyclosporines?

Answer 12

75-300 ng/mL

Question 13

cyclosporine

When are drug levels drawn for cyclosporine monitoring?

Answer 13

steady state, 2-5 days after therapy initiation or dosage changes

Question 14

cyclosporine

What is the recommended dose changes of cyclosporine if a patient must also take fluconazole?

Answer 14

decrease cyclosporine 21-50%

Question 15

cyclosporine

What is the recommended dose changes of cyclosporine if a patient must also take itraconazole?

Answer 15

decrease cyclosporine 50-60%

Question 16

cyclosporine

What is the recommended dose changes of cyclosporine if a patient must also take voriconazole?

Answer 16

decrease cyclosporine 50%

Question 17

cyclosporine

What is the recommended dose changes of cyclosporine if a patient must also take posaconazole?

Answer 17

decrease cyclosporine 0-30%

Question 18

tacrolimus

What is the indication of tacrolimus?

Answer 18

alternative to cyclosporine, prevention of rejection in transplant

Question 19

tacrolimus

What factors can cause alterations in absorption?

Answer 19

• small bowel recipients with open stomas
• race differences
• diabetic patients
• cystic fibrosis
• diurnal variations
• diarrhea

Question 20

tacrolimus

What are the drug interactions of tacrolimus?

Answer 20

• CYP enzymes and P-gp
• grapefruit juice

Question 21

tacrolimus

Describe the distribution of tacrolimus:

Answer 21

distributes extensively into cells, 99% protein bound, binds to erythrocytes, crosses placenta and distributes into breast milk

Question 22

tacrolimus

How is tacrolimus excreted?

Answer 22

billiary excretion

Question 23

What factors can account for the variations in clearance of tacrolimus?

Answer 23

• renal transplant > liver transplant
• hep C
• time post transplant
• age (due to CYP enzymes)

Question 24

What genetic polymorphisms impact tacrolimus metabolism?

Answer 24

CYP3A5, increased activity= 2x tacrolimus clearance, lots of variability

Question 25

tacrolimus

What are the toxicities associated with tacrolimus?

Answer 25

• nephrotoxicity
• neurotoxicity
• diabetogenesis
• GI disturbances

Question 26

tacrolimus

What drugs can potentiate the nephrotoxicity of tacrolimus?

Answer 26

• ACE inhibitors
• aminoglycosides
• amphotericin
• NSAIDs
• cyclosporine

Question 27

tacrolimus

What is the correlation of tacrolimus and drug levels?

Answer 27

• increased early tacrolimus exposure = decreased risk of acute rejection
• AUC > 200 = decreased risk for rejection, AUC=200 correlates with Co (trough) of 10
  Cmax does not correlate with risk for rejection

Question 28

tacrolimus

What is the goal trough for tacrolimus?

Answer 28

5-20, but typically 5-15