Cyclosporine

Question 1

indications to cyclosporine - Wolverton (ie non-canadian)

Answer 1

absolute: decreased renal fxn, uncontrolled HTN, hypersensitivity (bold in CAN)

personal hx or current malignancy

CTCL

relative: HTN - controlled

live vaccine

active infection

pregnancy, lactation (Cat C)

unreliable patient

meds that interfere

immunodeficiencies

phototherapy, MTX or other immunosupressants

<18 or >64

Question 2

cyclosporine t1/2 ? optional: peak serum

Answer 2

5-18 hrs 2-4 hrs

Question 3

List 7 off-label uses for cyclosporine?

Answer 3

• PRP
• AD
• LP
• LPP
• BP
• PV
• PF
• scleromyxedema
• morphea
• GA

Question 4

Indications for Cyclosporine (Health Canada)? List 3

Answer 4

severe PsO, resistant to other tx

RA

organ transplant - solid

organ transplant - marrow

nephrotic syndrome (remember, not renally excreted)

Question 5

2 trade names of cyclosporine? most bioavailable option?

Answer 5

Sandimmune and Neoral, neural more bioavailable

Question 6

creatinine increased by 55% while on cyclosporine - > your actions

Answer 6

d/c until level normal

Question 7

c/i to cyclosporine - Health Canada?

Answer 7

absolute: hypersensitivity to cyclosporine or any of its ingredients
relative: active uncontrolled infection

1’ or 2’ immunodeficiency

active malignancy outside of skin malignancies (NMSCa ok)

abn renal function

uncontrolled HTN

Question 8

how is cyclosporine exreted?

Answer 8

>90% excreted via liver/bile

only minimal renal excretion (but renal failure is c/i due to potential for damage)

Question 9

lyte abn in cyclosporine

Answer 9

OMG - > hyPO Mg

hypER K

uricemia (gout)

Question 10

cyclosporine - list 5 common adverse effects

Answer 10

per canadian drug monograph:

#1 hypertrichosis (15%)

paresthesias (12%)

h/a

nausea (5%)

gingival hyperplasia (5%)

GI issues, fatigue, flu-like symptoms and URTIs also listed

Question 11

what is the best PsO drug to combine with cyclosporine?

Answer 11

acitretin - slow onset, but safe LT, excellent “partner” for cyclosporine

side effects of acitretin and cyclosporine are almost mutually exclusive apart from hyperlipidemia - excellent combo for weaning off cyclo

Question 12

List 5 serious adverse effects of cyclosporine?

Answer 12

• renal dysfunction
• HTN
• malignancy
• immunosupression -> infection incl PML
• hepatic dysfunction

see next card for others

Question 13

What can decrease the risk of lymphoma on cyclosporine?

Answer 13

• < 2 years of use
• <5 mg/kg
• do not use with other immunosupressants
• no issues with lymphoma in PsO pts who are healthy and follow above

Question 14

How would you treat HTN from cyclo?

Answer 14

nifedipine (but also increases gingival hyperplasia)

isradipine no gingival hyperplasia, available in canada

Question 15

what does cyclosporine have to complex with to block calcineurin?

Answer 15

CYCLOphilin

Question 16

max dose and duration of cyclosporine for PsO by world consensus?

Answer 16

max 5 mg/kg/d x 2 yrs

FDA 4 mg/kg/day x 1 yr

severe: 5 mg/kg/day if severe, then decrease by 1 mg/kg/week until minimal stable dose achieved

Question 17

cyclosporine dose in kids? age limits

Answer 17

up to 5 mg/kg/day x 6 weeks safe in kids 2-16 (not in monograph)

Question 18

How do you treat hyperlipidemia 2’ cyclosporine? Why?

Answer 18

conservative measures first

if not successful rosuvastatin (receive a statin)

NO ATORVA, LOVA or SIMVA - increased chance of rhabdo due to CYP3A4 interaction

Question 19

Cyclosporine - list 3 cutaneous adverse effects?

Answer 19

• gingival hyperplasia
• hypertrichosis (15% of all pts)
• NM skin cancers
• acneform eruptions
• sebaceous hyperplasia
• epidermal inclusion cysts
• warts (immunosupressant!)

Question 20

what nuclear transcription factor cells does cyclosporine block?

Answer 20

NFAT 1= nucear factor activated T cells

Question 21

MOA for cyclosporine? (class only)

Answer 21

calcineurin inhibitor

Question 22

MOA of cyclosporine - details?

Answer 22

peptide - MHC II complex on APC -> T cell Receptor with CD3 complex -> T cell activation ->

normally: calcineurin interacts with calcium and calmodullin (Calcium + modullator) -> NFAT1 activated (nuclear factor activated T cells) -> IL 2 and IL 2 Receptor -> more T cell activation

cyclosporine with cyclophilin form a complex that inhibits calcineurin from activating NFAT1 ->

• decreased IL 2 -> decreased T cell activation
• decreased IL 2 receptor activation - > decreased T cell activation
• decreased ICAM1
• decreased interferon gamma

Question 23

cyclosporine dosing in adults?

PsO

PG

CIU

Answer 23

2.5 - 5 mg/kg/day in adults

severe -> 5 mg/kg/day -> decrease by 1 mg /kg/week until stable minimal dose found

moderate -> 2.5 - d mg/kg/day, can increase by 0.5-1 mg/kg/day if needed every 2 weeks

5-7 mg/kg/day for PG (off label)

urticaria: 2-3 mg/kg x 12 weeks, then 1 mg/kg

Question 24

creatinine increased by 30% while on cyclosporine -> what are your next steps?

Answer 24

if Cr increased by 25-50% on cyclosporine, continue the drug, repeat Cr in 2 weeks, if continues to increase, decrease cyclosporine dose by 1 mg/kg/day for 2-4 weeks and recheck levels

if normalizes -> continue

if continues to increase -> decrease dose more or d/c

Question 25

Required baseline monitoring for cyclosporine start? and follow-up

Answer 25

1. BP x 2 at least 12-24 hrs apart
2. Cr, LFTs, CBC, lipid panel (fasting), Mg, K, uric acid

Check Q2 weeks x 3 months (Canada), then Q monthly

BP on every visit

in Canadian monograph, 3x 12 hr fasting serum Cr within 2 weeks

BP Q2W x 3 months on start…

Question 26

cyclosporine dosing: current or ideal body weight?

Answer 26

ideal body weight if obese

Question 27

how do you taper cyclosporine

Answer 27

taper slowly while another immunosupressive is added to avoid rebound

Question 28

cyclosporine - list 10 s/e

Answer 28

cutaneous: hypertrihcosis (+++), gingival hyperplasia (+), skin Ca
metabolic: HTN, hyperlipidemia
labs: OMG => hypO Mg, hyperK, urecemia, lipidemia above

CNS: paresthesias (+++), h/a (++), tremours (+)

GI: N/V/ abdo pain, hepatic dysfunction, renal dysfunction

MSK: myalgias, arthralgias, lethargy

Infections: generalized/localized infections incl PML(progressive multifocal leukoencephalopathy) +++ URTIs

Heme: anemia, thrombocytopenia

renal: renal dysfunction and failure, lytes above

Cyclo = > cyclist

hairy biker (hypertrichosis) with gout (uricemia) blowing bubbles (gingival hyperplasia) and getting skin cancers from biking in the sun w/o SPF screaming OMG (hyPOMg) b/c he won the rase, but N/V/abdo pain from overexertion, HTN, myalgias, arthralgias, lethargy

and on top tremours, paresthesias, headache

Question 29

3 requirements for measure/testing before cyclosporine start in Canada?

Answer 29

1) BP measures x 2 prior to start
2) Cr assessment:

“prior to tx, 12 hr fasting serum Cr should be measured on at least 3 occasions w/i 2 weeks for accurate baseline”

3) “careful examination of tumours of the skin. if lesion not typical of PsO bx to r/o MF”

Question 30

when should you d/c (per Can monograph)

Answer 30

if 5 mg/kg /day x 6 weeks does not reach desired effect or lower if max dose not compatible with health indications

Question 31

What is cyclosporine’s relationship to Botox?

Answer 31

per ASDS, can potentiate action of botox, along with CCBs and aminoglycosides

Question 32

relationship of cyclosporine to SCCs?

Answer 32

increases chance of SCCs along with Azathioprine