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The conversion ratio of PO:IV for cyclosporine
3:1 PO:IV
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Are generic cyclosporine formulations such as Gengraf interchangeable with Neoral?
Yes
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What is the standard of care at most insitutions for monitoring CSA?
Pre-dose trough whole blood concentration
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Single point sampling 2 hours after CSA administration
- Provide a simplified and acurate marker of immunosuppressive efficacy and toxicity
- Correlates better with AUC
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What is the initial dose of CSA?
2.5 mg/kg PO q 12
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What it the target therapeutic range of CSA during the first 6 months post-txp kidney and liver?
200-300 ng/mL
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What is the target therapeutic range for CSA during the first 6 months post-txp heart/lung?
300-400 ng/mL
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How often do you monitor the steady state levels of CSA?
- 3 times/week x 1 month
- 2 times/week x 2 months
- 1 time/week x 3 months
- Monthly thereafter or after any dose changes
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By what amount should CSA doses be adjusted?
25-50 mg PO a 12 hour to achieve therapeutic levels
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Does Neoral have a large or small Vd?
Large 3-7 L/kg
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Does Neoral have a high or low F?
Low-- 30%
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Is Neoral heavily renally eliminated?
No
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What is the half life of Neoral?
12-16 hours
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What is the PO:IV ratio for tacrolimus?
3:1
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Does oral tacrolimus have good or poor absorption?
Poor
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What is the standard of care for monitoring TAC?
Pre-dose trough whole blood concentration
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What is the Tacrolimus dose?
0.075 mg/kg PO Q 12 hours
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What is the therapeutic range for tacrolimus?
5-15 ng/mL
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When should you monitor steady state of tacrolimus?
- 3 times/week x 1 month
- 2 times/week x 2 months
- 1 time/week x 3 months
- Monthly thereafter or after any dose changes
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By what amount should tacrolimus doses be changed?
1-2 mg PO q 12
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Which drug should be separated from cyclosporine by at least 4 hours?
Sirolimus
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What is the 1/2 life of siroliumus?
57-63 hours
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Sirolimus dose for low-moderate immunologic risk patients (kidney, liver)
6 mg LD followed by 2 mg QD
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Siroliumus dose for high immunologic risk patients (intestines, heart, lungs)
15 mg LD followed by 5 mg QD
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What is the therapeutic range of sirolimus?
5-15 ng/mL
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When should steady state concentrations of sirolimus be obtained?
- Weekly x 1 month
- Monthly- every 3 months thereafter or after any dose change
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By what increment should the sirolimus maintenance dose be adjusted?
1-2 mg/day
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What is the most abundant and active CYP 450 enzyme in the liver and small intestine?
3A4
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Where are P-glycoprotein's found?
apical side of the brush border in enterocytes
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Do P-glycoproteins pump lipophilic or lipophobic substrates into the intestinal lumen?
Lipophilic
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List the drugs/drug classes that are 3A4/P-gp inhibitors
- Macrolides (except azithromycin)
- Non-DHP CCB
- Azole antifungals ( ketoconazole, voriconazole, itraconzole are the worst)
- Protease inhibitors
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List the drugs/drug classes that are 3A4/P-gp inducers
- Phenobarbital
- Phenytoin
- Rifampin/Rifabutin
- Carbamazepine
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What is the maximum dose of a statin in a transplant patient?
1/2 the max dose for a healthy patient
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Are CSA, TAC/SRL inhibitors or inducers of 3A4? Are they substrates?
Inhibitors and substrates
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What are 3 complications of myoglobin release?
- Renal vasoconstriction
- Tubular toxicity
- Intraluminal cast formation
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Is grapefruit juice an inhibitor or inducer?
Inhibitor of CYP 3A4 in the gut
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Describe the effects of grapefruit jucie on the Cmax, AUC, Cl, and t1/2 for CSA/TAC/SRL
- Increase Cmax and AUC
- No change on Cl and t 1/2
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What part of grapefruit is responsible for the inhibition?
- Naringin
- Naringenin-metabolite
- 6'7' dihydroxybergamottin
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Is St John's wort an inducer or inhibitor?
Inducer
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Does St. John's Wort increase or decrease the bioavailability of CSA/TAC/SRL?
Decrease
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What are some risks of supratherapeutic levels of SRL?
- Anemia
- Leukopenia
- Thrombocytopenia
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Which drug is related to tremors if level is supratherapeutic?
Tacrolimus
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When should you monitor CSA/TAC levels after starting an enzyme inhibitor?
Monitor trough level 2-3 days after drug initiation and monitor dosage appropriately
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When should you monitor SRL levels after starting an enzyme inhibitor?
1 week after drug initiation
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Which drugs should prophylactically be adjusted when combined with an enzyme inducer?
- CSA/TAC
- Increase by 25%
- Monitor 4-7 days after drug initiation
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