Cyclosporine Flashcards by Tet Kim

indications to cyclosporine - Wolverton (ie non-canadian)

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

How well did you know this?

Not at all

Perfectly

cyclosporine t1/2 ? optional: peak serum

5-18 hrs 2-4 hrs

How well did you know this?

Not at all

Perfectly

List 7 off-label uses for cyclosporine?

PRP
AD
LP
LPP
BP
PV
PF
scleromyxedema
morphea
GA

How well did you know this?

Not at all

Perfectly

Indications for Cyclosporine (Health Canada)? List 3

severe PsO, resistant to other tx

organ transplant - solid

organ transplant - marrow

nephrotic syndrome (remember, not renally excreted)

How well did you know this?

Not at all

Perfectly

2 trade names of cyclosporine? most bioavailable option?

Sandimmune and Neoral, neural more bioavailable

How well did you know this?

Not at all

Perfectly

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

d/c until level normal

How well did you know this?

Not at all

Perfectly

c/i to cyclosporine - Health Canada?

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

How well did you know this?

Not at all

Perfectly

how is cyclosporine exreted?

>90% excreted via liver/bile

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

How well did you know this?

Not at all

Perfectly

lyte abn in cyclosporine

OMG - > hyPO Mg

hypER K

uricemia (gout)

How well did you know this?

Not at all

Perfectly

cyclosporine - list 5 common adverse effects

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

How well did you know this?

Not at all

Perfectly

what is the best PsO drug to combine with cyclosporine?

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

How well did you know this?

Not at all

Perfectly

List 5 serious adverse effects of cyclosporine?

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

see next card for others

How well did you know this?

Not at all

Perfectly

What can decrease the risk of lymphoma on cyclosporine?

< 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

How well did you know this?

Not at all

Perfectly

How would you treat HTN from cyclo?

nifedipine (but also increases gingival hyperplasia)

isradipine no gingival hyperplasia, available in canada

How well did you know this?

Not at all

Perfectly

what does cyclosporine have to complex with to block calcineurin?

CYCLOphilin

How well did you know this?

Not at all

Perfectly

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

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

cyclosporine dose in kids? age limits

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

How do you treat hyperlipidemia 2’ cyclosporine? Why?

conservative measures first

if not successful rosuvastatin (receive a statin)

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

Cyclosporine - list 3 cutaneous adverse effects?

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

what nuclear transcription factor cells does cyclosporine block?

NFAT 1= nucear factor activated T cells

MOA for cyclosporine? (class only)

calcineurin inhibitor

MOA of cyclosporine - details?

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

cyclosporine dosing in adults?

PsO

CIU

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

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

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

Required baseline monitoring for cyclosporine start? and follow-up

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...**

cyclosporine dosing: current or ideal body weight?

ideal body weight if obese

how do you taper cyclosporine

taper slowly while another immunosupressive is added to avoid rebound

cyclosporine - list 10 s/e

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

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

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"

when should you d/c (per Can monograph)

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

What is cyclosporine's relationship to Botox?

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

relationship of cyclosporine to SCCs?

increases chance of SCCs along with Azathioprine