calcineurin inhibitors (Cs, Tacrolimus)

Question 1

MOA

Answer 1

inhibitors production and release of lymphokines, thereby suppressing cell-mediated immune response

Question 2

important safety info re prescribing and dispensing

Answer 2

must be prescribed and dispensed by brand name
pt need to be stabilised on one brand because switching between formulations without close monitoring may lead to clinically important changes in blood-ciclosporin conc

Question 3

Why do pt need to be maintained on a particular brand

Answer 3

switching between formulations without close monitoring may lead to clinically important changes in blood-ciclosporin concentration

Question 4

is it used for malignancy

Answer 4

no, contraindicated in malignancy with systemic use (in non transplant indications)

Question 5

3 CI

Answer 5

Malignancy (in non-transplant indications); uncontrolled hypertension (in non-transplant indications); uncontrolled infections (in non-transplant indications)

Question 6

Can patient who has uncontrolled hypertension be put on ciclosporin

Answer 6

No, contraindicated in non transplant indications

Question 7

Food & drink interactions - 2x juices

CICLOSPORIN

Answer 7

POMELO juice predicted to INCREASE exposure to ciclosporin

PURPLE GRAPE juice predicted to DECREASE ciclosporin exposure

Question 8

Effect of pomelo juice

Answer 8

predicted to increase ciclosporin exposure

Question 9

Effect of purple grape juice

Answer 9

predicted to decrease ciclosporin exposure

Question 10

name a common SE (to do with eye) of Cs

Answer 10

eye inflammation

Question 11

trough level is dependent on…

Answer 11

indication.

monitor whole blood ciclosproinc conc

Question 12

tacrolimus - what has been reported to occur primarily in children with tacrolimus blood trough conc much higher than recommended max levels?

Answer 12

Cardiomyopathy
Patients should be monitored by echocardiography for hypertrophic changes—consider dose reduction or discontinuation if these occur.

Question 13

tacrolimus is contraindicated if Hx hypersensitivity to this abx drug class!

Answer 13

macrolides

Question 14

monitoring tacrolimus

Answer 14

after initial dosing and for maintenance, tacrolimus doses should be adjusted according to whole blood tacrolimus trough conc, esp during diarrhoea

Question 15

pt from this ethnic background may require higher doses of tacrolimus

Answer 15

black African or afto Caribbean

Question 16

monitoring patient parameters

Answer 16

Monitor blood pressure, ECG (for hypertrophic changes—risk of cardiomyopathy), fasting blood-glucose concentration, haematological and coagulation parameters, plasma protein, electrolytes, neurological (including visual) status, hepatic and renal function.

Monitor for posterior reversible encephalopathy syndrome (PRES).

Question 17

advice to give to pt about what to avoid

Answer 17

Advise patients to avoid excessive exposure to UV light including sunlight and to report symptoms of eye disorders for prompt evaluation by an ophthalmologist.

Question 18

do they cause bone marrow suppression?

Answer 18

no

Question 19

incidence of neurotoxicity is greater with

Answer 19

tacrolimus

Question 20

interactions

• drugs plus drinks

Answer 20

hyperkalaemia drugs increased hyperkalaemia

increased levels if inhibitors given

grapefruit juice and pomelo juice increases

reduced levels with inducers

increased nephrotixicty with nephrotoxic drugs