Drugs-Induction

Question 1

rATG: mechanisms of T cell depletion

Answer 1

1. Complement-dependent cytotoxicity

2. Opsonization / phagocytosis via macrophages

Question 2

rATG: secondary effects besides T cell depletion

Answer 2

1. Induction of B cell apoptosis
2. Induction of Treg cells
3. Modulation of adhesion molecules/cell trafficking
4. Antibody-dependent cellular cytotoxicity

Question 3

rATG is indicated for induction for which organs?

Answer 3

Kidney txp only

Question 4

rATG - PI recommended dosing for induction

Answer 4

1.5 mg/kg x4 - 7 days

FIRST DOSE PRIOR TO REPERFUSION (reduce DGF)

Question 5

rATG - PI recommended duration of infusion

Answer 5

1st dose: minimum of 6 hours

Subsequent doses: minimum 4 hours

Question 6

rATG - PI recommended pre-medication

Answer 6

Corticosteroids, APAP, and/or an antihistamine 1 hour prior to each infusion

Question 7

rATG - PI recommended dose modifications for WBC and platelet

Answer 7

WBC 2-3: 1/2 dose
WBC <2: Consider stopping
Plt 50-75: 1/2 dose
Plt <50: Consider stopping

Question 8

rATG contraindications

Answer 8

History of allergy or anaphylactic reaction to rabbit proteins or to any product excipients, or who have active acute or chronic infections that contraindicate any additional immunosuppression

Question 9

rATG - How supplied, reconstitution, BUD, Filter

Answer 9

Supplied: 10 mL vial with 25 mg lyophilized product
Reconstitute: 5mL SWFI
BUD: 24 hours @ RT
Filter: 0.22 micrometer

Question 10

eATG is indicated for induction for which organs?

Answer 10

Kidney txp only

Question 11

eATG - PI recommended dosing for induction

Answer 11

10-15 mg/kg daily x14d

Question 12

eATG - PI recommended duration of infusion

Answer 12

At least 4 hours

Question 13

eATG - How supplied, BUD, Filter

Answer 13

Supplied: 50 mg/mL concentrate
BUD: 24 hours @ RT
Filter: 0.2 to 1.0 micron

Question 14

Alemtuzumab: Mechanism of depletion

Answer 14

Anti-CD52 monoclonal antibody (CD52 is a membrane glycoprotein on T cells, B cells, and innate cells)

1. Complement-dependent cytotoxicity
2. Antibody-dependent cellular cytotoxicity
3. Induction of apoptosis

Question 15

Alemtuzumab: indications in SOT

Answer 15

None

Question 16

Alemtuzumab: IV infusion instructions

Answer 16

Vial = 30 mg/mL (1 mL vial)
2 hours
Mix in 100 mL bag of NS or D5W
BUD: 8 hours
Incompatible with PVC

Question 17

Alemtuzumab: Premedication

Answer 17

Benadryl, APAP 30 minutes prior to each infusion

Question 18

Basiliximab: MOA

Answer 18

IL-2R Antagonist; competitively inhibits IL-2 mediated activation of lymphocytes by binding with high affinity to IL-2Ra on activated lymphocytes

Question 19

Basiliximab: indications in SOT

Answer 19

Kidney txp recipients receiving cyclosporine and corticosteroids

Question 20

Basiliximab: Administration per PI

Answer 20

Central or peripheral
Infusion: 20 - 30 minutes (bolus may be associatd with n/v, local rxn)
Dilute to 50 mL with NS or D5W
BUD: 24 hr fridge; 4 hr RT

Question 21

Basiliximab: Dosing per PI

Answer 21

Adults: 20 mg 
 - Dose 1 within 2 hours prior to txp surgery
- Dose 2: 4 days after txp
Peds: (same schedule as adults)
 - <35 kg: 10 mg
 - >35 kg: 20 mg

Question 22

Basiliximab: Concentration for effect

Answer 22

Serum conc of 0.2 mcg/mL saturates IL-2R

Question 23

Antithymocyte globulin: central vs peripheral administraiton

Answer 23

PI: “high-flow vein”
IRL: peripheral (heparin + hydrocort + inc volume) or central

Question 24

Kidney txp: most common induction agent

Answer 24

T-cell depleting agent&raquo_space;> IL2RA > None

Question 25

Liver txp: most common induction agent

Answer 25

None >>> IL2RA > T-cell depleting

Question 26

Pancreas txp: most common induction agent

Answer 26

T-cell depleting

Question 27

Intestine txp: most common induction agent

Answer 27

T-cell depleting > None > IL2RA

Question 28

Heart txp: most common induction agent

Answer 28

None >> IL2RA > T-cell depleting

Question 29

Lung txp: most common induction agent

Answer 29

IL-2RA >> None > T cell depleting

Question 30

Kidney txp: eATG vs rATG Efficacy

Answer 30

rATG = lower rates of BPAR and improved graft & patient survival

Question 31

Kidney txp: efficacy data supports which agent for high risk candidate?

Answer 31

T cell depleting agent (rATG or alemtuzumab)

Question 32

Liver txp: data supports which agent for induction?

Answer 32

Data sucks. Induction may reduce rates of rejection without clear effect on long term patient or graft outcomes

Question 33

Heart txp: data supports which agent?

Answer 33

Data sucks. Benefit with induction is unclear - may reduce rejection rates but long-term effects inconsistent. IL2RA may provide similar long term benefits compared with rATG. Consider in sensitized patients.

Question 34

Lung txp: data supports which agent?

Answer 34

Data sucks. Depleting therapy appears to reduce rejection with trade off of infection. IL2RA may be preferred though effect not clear.

Question 35

Intestinal txp: data supports which agent?

Answer 35

Alemtuzumab = lowest risk of rejection | rATG + rituximab = next lowest risk of rejection BUT lower risk of infxn compared with alemtuzumab