Immunosuppression Flashcards
cyclosporine
What is the indication of Cyclosporine?
prevention of rejection in transplant in kidney, liver, heart, lung, bone marrow transplant, and other disorders such as aplastic anemia and ulcerative colitis
cyclosporine
How is absorption altered for Sandimmune?
- food intake
- time of day
- GI transit time
- GI autonomic neuropathy
- time post transplant
cyclosporine
How does grapefruit juice effect cyclosporine?
grapefriut juice increases plasma concentration of cyclosporin
What are the drug interactions of cyclosporine that effect absorption?
- grapefruit juice
- aluminum/magnesium hydroxide antacids
- orlistat
- CYP3A4 and P-gp inhibitors
- St. johns wort
Describe the distribution of cyclosporine:
lipophilic, high tissue affinity, 90% protein bound, bound to RBCs, Vd= total body water, crosses placenta and distributes in breast milk
What is the clearance of cyclosporine?
0.4 L/h/kg
How is cyclosporine excreted?
biliary excretion
cyclosporine
What are the toxicities seen with cyclosporine?
- nephrotoxicity
- hypertension
- hirsutism
- neurotoxicity (headache, tremor, seizure, coma)
What drugs decrease the clearance of cyclosporine?
- erythromycin
- antifungals (-conazoles)
- diltiazem, verapamil, nicardipine, nifedipine
- indinavir, ritonavir
cyclosporine
What is the initial dosing equation for cyclosporines?
Dose= (Cl x Css (trough level) x tau)/ F
cyclosporine
What is correlation between drug levels and therapeutic response of cyclosporine?
- 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
cyclosporine
What is the goal Co (trough) for cyclosporines?
75-300 ng/mL
cyclosporine
When are drug levels drawn for cyclosporine monitoring?
steady state, 2-5 days after therapy initiation or dosage changes
cyclosporine
What is the recommended dose changes of cyclosporine if a patient must also take fluconazole?
decrease cyclosporine 21-50%
cyclosporine
What is the recommended dose changes of cyclosporine if a patient must also take itraconazole?
decrease cyclosporine 50-60%
cyclosporine
What is the recommended dose changes of cyclosporine if a patient must also take voriconazole?
decrease cyclosporine 50%
cyclosporine
What is the recommended dose changes of cyclosporine if a patient must also take posaconazole?
decrease cyclosporine 0-30%
tacrolimus
What is the indication of tacrolimus?
alternative to cyclosporine, prevention of rejection in transplant
tacrolimus
What factors can cause alterations in absorption?
- small bowel recipients with open stomas
- race differences
- diabetic patients
- cystic fibrosis
- diurnal variations
- diarrhea
tacrolimus
What are the drug interactions of tacrolimus?
- CYP enzymes and P-gp
- grapefruit juice
tacrolimus
Describe the distribution of tacrolimus:
distributes extensively into cells, 99% protein bound, binds to erythrocytes, crosses placenta and distributes into breast milk
tacrolimus
How is tacrolimus excreted?
billiary excretion
What factors can account for the variations in clearance of tacrolimus?
- renal transplant > liver transplant
- hep C
- time post transplant
- age (due to CYP enzymes)
What genetic polymorphisms impact tacrolimus metabolism?
CYP3A5, increased activity= 2x tacrolimus clearance, lots of variability
