Drugs Flashcards
Eltrombopag
For ITP: 50mg PO daily and titrate to plt>50
For severe AA in triple IST
150mg daily
Avatrombopag
20mg PO daily, titrate to plt >50
If liver disease for pre-op, 40-60mg PO daily x5 days, finish ~8d prior to the surgery or procedure
Romiplostim
1mcg/kg SC/IV weekly, titrate to plt>50
Max 10mcg/kg/week
Rituximab for ITP, WAIHA [off label], TTP [with plex]
375mg/m2 weekly x4
*1g q14d x2 doses more for autoimmune [can be later lines of rx or off label though]
- RA, myasthenia, MS, pemphigus, mixed cryoglobulinemia, neuromyelitis optica, IgG4 disease, dermatomyositis/polymyositis
Either dosing in some renal: minimal change disease, membranous nephropathy, lupus nephritis, GPA, MPA, EGPA
Gemtuzumab target
CD-33
Inotuzumab target
CD-22
Rituximab target
CD-20
Blinatumumab drug target
Bispecific antibody
Anti-CD19 and anti-CD3
Alemtuzumab
CD52
Rituximab Risks
Infusion reactions
serum sickness
Hypogammaglobulinemia
Infection risk
Hep B reactivation, strongyloides
Cardiac arrhythmia
Progressive Multifocal Leukoencephalopathy [PML] from JC virus reactivation
Steroid Side effects
Insomnia
Mood issues
HTN
hyperglycemia
Osteoporosis
Infection risk
PJP
Weight gain, fluid retention
Fostamatinib
Syk inhibitor [spleen tyrosine kinase]
100mg PO BID -> 150mg BID
S/E: HTN, diarrhea
Anticoag in HIT
Argatroban: for HIT, HITT, HIT with PCI
- hepatic clearance, adjust if liver issues to 0.5-1.2 mcg/kg/min
- no adjustment for renal (ARgat, Alright for Renal)
Dose: 1-2mcg/kg/min drip, adjust to PTT
Bivalirudin: for HIT needing PCI
Dose: 0.15 mg/kg/h drip, adjust to PTT.
Lower if renal/liver issues
Danaparoid: for pregnant
IV or subcut. Renal clearance, longer half-life
Dose: 2250 units IV bolus, then 400/300/200 units per hour
Use danaparoid anti-Xa level to monitor
If subcut, dont need to monitor
Fondaparinux: easy
- long half life, not in renal disease [renally cleared], ok in pregnancy
- 5-10mg subcut daily [weight based]
DOACs: not approved for acute HIT [lack of controlled trial data, but clinical experience present] but can be used with pt discussion
- Dose: same as treatment of VTE
- Issue: Has peaks and troughs… Apix BID maybe more stable levels, but Riva has been used more. Dabig not without parenteral first.
- if life threatening thrombosis prob not
- no PTT confounding
Tranexamic acid risks
Contraindication: hematuria. Risk ureteral clots and obstructive uropathy
Caution in recent/active VTE or atherosclerotic disease
Headache
Abdominal discomfort
TXA MOA
Lysine analog, prevents plasminogen from binding lysine residue on fibrin strands -> prevents fibrinolysis
UFH heparin issues
IV, mostly inpatient
unpredictable, AT level, heparin resistance
Bleeding
Osteoporosis with prolonged use
LMWH pros/cons
Osteoporosis in long use
renal clearance, careful if CrCl<30
Still small risk of HIT
Can try Protamine if bleed
Fondaparinux pros/cons
Long half life, renally cleared
CI if CrCl<30
Caution if CrCl<50
No reversal
OK in HIT
Direct Thrombin inhibitors
Argatroban, Bivalirudin
Short half lives = drip. Monitor with PTT
Bival off label for HIT
Dabigatran is oral, not for HIT.
Danaparoid
Indirect Xa inhibitor, IV or subcut
Adjust for renal dysfunction, renally cleared
VTE proph, off label for HIT
Risks of Splenectomy
Surgical and anesthetic risks
Infection with encapsulated organisms: strep pneumonia, meningococcal, HIB
Post splenectomy sepsis: 3.2%, 1.4% mortality
Need vaccinations. If can’t vaccinate in time, give PCN proph
Thrombosis
Small risk of pulmonary HTN
ATG side effects
What proph?
Infusion reactions: fever, rigours, rash, hypotension, hypertension, third spacing
Serum sickness = fever, rash, joint pain, malaise, B symptoms
Pre-meds: Benadryl, tylenol
Prednisone 1mg/kg x10d then taper rapidly [for serum sickness proph]
Triple IST for severe AA or very severe AA
horse ATG [ATGAM] 40mg/kg IV daily x4days [inpatient]
CsA 10 mg/kg/d split BID,. target trough 200-350, 6-12 months then slow taper
Eltrombopag, 150mg daily [75mg daily if east asian or liver disease]. 6 months then taper or stop.
Response 10-12 weeks
CsA side effects
Hair growth, gingival hyperplasia, renal insufficiency, HTN, neurotoxicity [PRES, sz, PML], magnesium wasting
IFN side effects
fatigue, myalgias, influenza like symptoms, mood change, suicidality, optic changes, autoimmunity, neuropathy
Less with pegylated IFN
Not teratogenic, ok in pregnancy`
IFN= influenza-like, fatigue, Neuro (eyes, neuropathy, mood)
Ruxolitinib Side effects
Myelosuppression [esp MF], weight gain, high cholesterol, increased skin cancers, increased infections like Zoster
In ALL: want proph, but what type cannot be used concurrently with Vincristine?
Potent Azoles: Posa and Vori
Increase neurotoxicity with Vincristine
Often use Micafungin, then fluconazole later in therapy
Drug induced ITP
drug-Ab complex = heparin
Hapten = penicillin, cephalosporin
Ab binds drug adsorbed on platelet = quinine
BM suppression = valproate
Abx: B lactam, TMPSMX, vanco
anti-epileptic or antipsychotic: valproate, carbamazepine
GP2b3a - platelet clumping and thrombocytopenia within hours
Caplacizumab dose/duration
11mg subcut x30d
Eculizumab dosing/frequency
aHUS
900mg weekly x4, then 1.2g q2weeks
PNH
600mg qweekly x4, then 900mg q2 weeks
Ravulizumab dosing/loading/frequency
aHUS or PNH [treatment by weight]
60-100kg: 2700mg load, then 3300mg 2 weeks later and then every 8 weeks
Drug induced neutropenia
anti-thyroids
antibiotics
anti convulsants
other: Clozapine, Ritux, Sulfasalazine, Deferiprone, Levimasole in drugs
What is 7+3?
7 days of Cytarabine 200mg/m2/d over 24h infusion for 7 days
3 days of anthracycline:
- Daunorubicin 60-90mg/m2 daily
- Idarubicin 12mg/m2 daily
What is FLAG-Ida?
Fludarabine 30mg/m2 D1-5
Cytarabine 2g/m2 over 4h D1-5 [high dose]
G-CSF 300mcg daily D1-5
Idarubicin 10mg/m2 D1-3
GO dosing
AML
APL
in AML: ALFA 0701 trial, add GO to 7+3 in low/int risk
GO 3mg/m2 days 1/3/7. Other option is higher dose on D1
Low risk: 5y OS 77% vs 55%
Int risk: 5y OS 40% vs 35%
in APL: add in higher risk to ATRA/ATO
9mg/m2 on day 1
Midostaurin dosing
RATIFY trial, ITD or TKD [ITD is the inferior/worse one, in 2/3 of FLT3]
Dose: 50mg PO BID days 8-21 of 28d cycle
Watch for QTC
Gilteritinib dose
120mg PO daily
Approved for R/R FLT3 positive
Is type 1 inhibitor like midostaurin, so works on ITD and TKD
Newer trial [MORPHO], in FLT3+ with MRD+ before transplant, benefit of post-transplant Gilteritinib maintenance
Special drugs:
Oral or IV/subcut:
Aza
Ven
IDH1
IDH2
Glasdegib
Midostaurin
Gilteritib
GO
Menin inhibitors
Aza: Subcut or PO [Onureg]
Venetoclax: PO
IDH1: PO
IDH2: PO
Glasdegib: PO
Midostaurin: PO
Gilteritib: PO
Quizartinib: type 2 inh of FLT3-ITD only
Gemtuzumab Ozogamicin: IV
Menin inhibitors: Revumenib PO, Zeftomenib PO
Lococo protocol
Induction:
Consolidation:
For low risk APL [WBC<10]
INDUCTION:
ATRA: 45mg/m2/d PO split BID
ATO: 0.15mg/kg/d IV
–Continue until CR with hematologic recovery
– if WBC goes >10 give HU
– maybe DS proph prednisone 0.5mg/kg/d
Consolidation [7 cycles of 28d]
ATRA: 45mg/m2/d for 15/28d cycle
ATO: 0.15mg/kg/d for Mon-Fri (5 doses/wk), 4 weeks on/4 weeks off
APML4
Induction
Consolidation
ATRA: 45mg/m2/d split BID, D1-36
ATO: 0.15mg/kg/d D9-36
Idarubicin: 12mg/m2 D2/4/6/8
DS proph: Pred 1mg/kg daily D1-10
Alternative: GO + ATRA/ATO
Consolidation varies
Treatment of HLH
Dex
Etoposide
Dex 10mg BID
Etoposide 150mg/m2 IV
- 2x/wk for 2 weeks
- 1x/wk for 6 weeks
- every 2 weeks after if needed
*if not cancer HLH, there is max cumulative dose of etoposide, 2-3g/m2 [~13-20 doses]
Is a topoisomerase II inhibitor
t-AML latencies for:
1. Alkylators or RT?
2. Topoisomerase inh?
How many TP53 mutated?
- Alkylators: 5-10 years, monsoonal karyotypes [5,7,27], TP53
- TopoII: 1-5 years, MLL/KMT2A or RUNX1
TP53 mutations in 30-40%
CHIP predisposes to therapy associated myeloid neoplasm if have CHIP and get Chemotherapy
Blina Dosing? Drug class?
Trials/Indications
Side effects?
9mcg over 24h D1-7, then 28mcg over 24h D8-28
BiTE for CD19/CD3. Not good for bulky, but gets MRD negative well
- BLAST: Ph- B-ALL if MRD+ after initial therapy [not overt relapse]
- TOWER: in R/R Ph- B-ALL, better than standard chemo
- In Ph+ B-ALL: in older for decreased intensity regimens, for MRD+ after therapy, for R/R
Side effects: Neurotoxicity, CRS
Meds in ABVD
Who can drop the Bleo?
Which trial?
Neutropenia -> do they get feb neut? G-csf proph?
Adriamycin=doxo
Bleo
Vinblastine
Dacarbazine
Drop bleo if PET2 is negative, per RATHL
Omit bleo if BLI, underlying lung or renal disease, drop in DLCO or pulm symptoms from treatment, age >70
What was the ESCHELON 1 trial?
Phase 3
Advanced stage cHL
Brentuximab-AVD vs ABVD
5y mPFS 82 vs 75%
Side effects of Brentuximab?
MOA of Brentuximab?
What proph do they need?
Peripheral neuropathy 30% >gr2
Most over 60 got neutropenia gr3+
Feb neut 20%
More infection/hospitalization
Anti-cd30 drug antibody conjugate, with MMAE
Use G-CSF proph!
What is escBEACOPP
Outcomes and risks
Bleo
Etop
Doxo
Cyclo
Vincristine
Procarbazine-> dacarbazine
Pred
With escalating doses based on tolerance
For young and high risk patients
HD15: Better control than ABVD but more early and late toxicities, more infertility, more secondary malignancies
HD18: neg PET2 -> 4 cycles ok
What is BrECADD?
HD21 trial
Brentuximab
Etop
Cyclo
Doxo
Dacarbazine
Dex
Vs esc beacopp
Advanced stage cHL
better 3y PFS 94.9 vs 92.4
Benefit across all subgroups, especially benefit in low IPI
Less AE, less TRMB, less TRM
PET2 guided 4 vs 6 cycles
Better tolerability, less fertility issues
Nivo-AVD: who to use it in?
SWOG S1826
Nivo-AVD vs BV-AVD in advanced stage cHL
2y PFS 92 vs 83%
Less TRM, better tolerability, much less neuropathy. Less feb neut in older but still present in both
More hyper/hypo thyroid. Risk other immune related adverse effects
Bleomycin lung toxicity:
Risk factors?
Mortality?
Treatment?
10% get it, 1% die
RFs: age >70, higher cumulative dose, renal disease, underlying lung disease
Dry cough, SOB
CT changes: fibrosis, diffuse alveolar danc damage, NSIP, BOOP, organizing pneumonia
PFT: DLCO decreases first
RX:
Stop Bleo
Steroids: pred 1mg/kg or pulse
Oxygen to 89-92% (NOT high fiO2 doses)
CT to monitor
Potentially Abx if infection
2nd line: NAC, imatinib, anti-TNF infliximab
What is AETHERA trial
BV maintenance after auto in high risk pts
High risk:
Primary Refractory
Early relapse <1y
Extranodal disease at relapse
What long term monitoring after HL therapy?
RT related? In general?
Relapse
Secondary malignancy
Cardiac toxicity: cardiomyopathy or CVD
Neuropathy (BV)
Pulmonary (Bleo)
H&P, labs, CXR
RT: breast cancer screen (8-10y after chest RT or age 40), lung cancer, TSH if neck RT, CRC screen early if abdo/pelvic RT
Bone density
Dental
Cataract
Psychosocial
Examples of, Side effects, proph:
PIs
IMIDs
anti-CD38 ab
PIs:
Bortezomib, Carfilz, Ixazomib
s/e: neuropathy, VZV, low plt, N/V/D, rash, fatigue
proph: valtrex
IMIDs:
Len, Thal, Pomalidomide
s/e: thromboemb, cytopenias, rash, fatigue, diarrhea, 2nd malignancies
proph: ASA or LMWH or ?DOAC. depends on other RFs for thrombosis
Anti-CD38 Ab:
Dara, Isatuximab, Elotuzumab
s/e: infusion/injection site reaction, hypogammaglobulinemia, infections, shingles
proph: Valtrex, +/- IVIG
Types of myeloma CAR-Ts
Idecel [KARMMA]
Ciltacel [CARtitude] prob better
S/e: CRS, ICANs, hypogammaglobulinemia, infection
Less grade 3+ CRS than B-ALL or NHL CAR-T though. Grade 1/2 still ~60-75%
Valtrex, PJP proph
Revaccinate after
Myeloma bispecifics, targets, and side effects?
anti-BCMA
Teclistimab [majesTIC]
Elrenatamab (magnetisMM-3)
anti-GPRC5D
Talquetamab [monumenTAL]
s/e: CRS, hypogammaglobulinemia is common, often need IVIG, infections.
Valtrex proph, maybe PJP proph
Revaccinate after
Maybe CMV monitoring
Aza dosing
Mono therapy
With Ven
75mg/m2 subcutaneous x7d
Cycle 3+ can increase to 100mg/m2 if no response so far and tolerating well without cytopenias
With Ven
75mg/m2 dose
Ven 100->200->400mg day 1/2/3
Ven 20->50->70mg if on Posa
Polatuzumab MOA
Use?
ADC CD79a and MMAE
neuropathy, cytopenias
DLBCL
Pola-R-CHP (1L DLBCL or HGBL)
- POLARIX trial vs RCHOP, better PFS
- IPI2+
Pola-BR (RR DLBCL
