Drugs-Induction Flashcards
rATG: mechanisms of T cell depletion
- Complement-dependent cytotoxicity
2. Opsonization / phagocytosis via macrophages
rATG: secondary effects besides T cell depletion
- Induction of B cell apoptosis
- Induction of Treg cells
- Modulation of adhesion molecules/cell trafficking
- Antibody-dependent cellular cytotoxicity
rATG is indicated for induction for which organs?
Kidney txp only
rATG - PI recommended dosing for induction
1.5 mg/kg x4 - 7 days
FIRST DOSE PRIOR TO REPERFUSION (reduce DGF)
rATG - PI recommended duration of infusion
1st dose: minimum of 6 hours
Subsequent doses: minimum 4 hours
rATG - PI recommended pre-medication
Corticosteroids, APAP, and/or an antihistamine 1 hour prior to each infusion
rATG - PI recommended dose modifications for WBC and platelet
WBC 2-3: 1/2 dose
WBC <2: Consider stopping
Plt 50-75: 1/2 dose
Plt <50: Consider stopping
rATG contraindications
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
rATG - How supplied, reconstitution, BUD, Filter
Supplied: 10 mL vial with 25 mg lyophilized product
Reconstitute: 5mL SWFI
BUD: 24 hours @ RT
Filter: 0.22 micrometer
eATG is indicated for induction for which organs?
Kidney txp only
eATG - PI recommended dosing for induction
10-15 mg/kg daily x14d
eATG - PI recommended duration of infusion
At least 4 hours
eATG - How supplied, BUD, Filter
Supplied: 50 mg/mL concentrate
BUD: 24 hours @ RT
Filter: 0.2 to 1.0 micron
Alemtuzumab: Mechanism of depletion
Anti-CD52 monoclonal antibody (CD52 is a membrane glycoprotein on T cells, B cells, and innate cells)
- Complement-dependent cytotoxicity
- Antibody-dependent cellular cytotoxicity
- Induction of apoptosis
Alemtuzumab: indications in SOT
None
Alemtuzumab: IV infusion instructions
Vial = 30 mg/mL (1 mL vial) 2 hours Mix in 100 mL bag of NS or D5W BUD: 8 hours Incompatible with PVC
Alemtuzumab: Premedication
Benadryl, APAP 30 minutes prior to each infusion
Basiliximab: MOA
IL-2R Antagonist; competitively inhibits IL-2 mediated activation of lymphocytes by binding with high affinity to IL-2Ra on activated lymphocytes
Basiliximab: indications in SOT
Kidney txp recipients receiving cyclosporine and corticosteroids
Basiliximab: Administration per PI
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
Basiliximab: Dosing per PI
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
Basiliximab: Concentration for effect
Serum conc of 0.2 mcg/mL saturates IL-2R
Antithymocyte globulin: central vs peripheral administraiton
PI: “high-flow vein”
IRL: peripheral (heparin + hydrocort + inc volume) or central
Kidney txp: most common induction agent
T-cell depleting agent»_space;> IL2RA > None
Liver txp: most common induction agent
None»_space;> IL2RA > T-cell depleting
Pancreas txp: most common induction agent
T-cell depleting
Intestine txp: most common induction agent
T-cell depleting > None > IL2RA
Heart txp: most common induction agent
None»_space; IL2RA > T-cell depleting
Lung txp: most common induction agent
IL-2RA»_space; None > T cell depleting
Kidney txp: eATG vs rATG Efficacy
rATG = lower rates of BPAR and improved graft & patient survival
Kidney txp: efficacy data supports which agent for high risk candidate?
T cell depleting agent (rATG or alemtuzumab)
Liver txp: data supports which agent for induction?
Data sucks. Induction may reduce rates of rejection without clear effect on long term patient or graft outcomes
Heart txp: data supports which agent?
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.
Lung txp: data supports which agent?
Data sucks. Depleting therapy appears to reduce rejection with trade off of infection. IL2RA may be preferred though effect not clear.
Intestinal txp: data supports which agent?
Alemtuzumab = lowest risk of rejection
rATG + rituximab = next lowest risk of rejection BUT lower risk of infxn compared with alemtuzumab