IBD II Flashcards
TDM of Biologics
potential for determining concentrations of ___ and ___
- most data with infliximab and adalimumab
- consider if ___ of treatment response (reactive TDM) - role of proactive TDM unclear
- check ___ concurrently
- assay methodology may be important
- economic value unclear
* may help justify dose increases to insurer
- drugs, ADAs
- lose
- ADA
TDM of Biologics
optimal trough concentrations not clear – ___ ___
moving target
know how to use this chart:
- sub- thera drug levels + ADAs = ____
- sub-thera drug levels, no ADAs = ___
- thera drug levels +ADAs = ___
- thera drug levels, no ADAs = ___
- change to alternate drug wthin the same calss
- dose escalate
- repeat TDM, switch to out of class biologic agent
- switch to out of class biologic agent
Clinical Controversy: “Biosimilars”
- biological product that is
approved based on a showing
that it is highly ___ to an
already-approved biological
product - must show it has no clinically
meaningful differences in terms
of ___ and ___ - do not switch to corresponding
biosimilar if loss of ___ to
the brand
- similar
- safety, effectiveness
- response
Tofacitinib (Xeljanz)
oral ___ inhibitor
- family of enzymes involved in immune signaling
- approved for ___ only for pts who have had an inadequate response or who are intolerant to ___ blockers
- 10 mg bid or 22 mg XR daily for 8 weeks (up to 16)
- then 5 or 10 mg bid or 11 or 23 mg XR daily
- D/C after ___ weeks of 10 mg bid or 22 mg XR daily if response not adequate
- use lowest effective dose to maintain response
- JAK
- UC
- TNF
- 16
Tofacitinib (Xeljanz)
- relatively ___ onset
- option for patients who fail ___
- should NOT be used with ___
(e.g., AZA, CYA, etc.) or ___ - relatively ___ half live (3 h)
- eliminated via ___ metabolism (~70%) (CYP3A and CYP2C19) and renal excretion (~30%)
moderate/severe renal impairment or moderate hepatic impairment:
- decrease daily dosage by 50%
- avoid in severe hepatic impairment
- rapid
- biologics
- immunosuppressants, biologics
- short
- hepatic
Tofacitinib (Xeljanz) - Drug Interactions
strong CYP3A ___ (e.g., ketoconazole) or moderate CYP3A inhibitor with a strong ___ inhibitor (e.g., fluconazole )
* decrease daily dosage by 50%
strong CYP3A ___ (e.g., rifampin)
* avoid use
- inhibitor
- CYP2C19
- inducer
Tofacitinib (Xeljanz) - ADRs
common:
- diarrhea, elevated ___ , headache, ___ , increased creatine phosphokinase,
nasopharyngitis, rash, URI
rare
* malignancy ( ___ and other)
* serious infection (including activation of latent ___ )
* neutropenia (see PI for recommendations)
* hypersensitivity
– angioedema and urticaria
- cholesterol
- shingles
- lymphoma
- TB
Tofacitinib (Xeljanz) - ADRs
black-box warning:
- increase ___ in RA patients 50 years and older with at least one CV risk factor
- ___ (PE, DVT, arterial) = increased risk in RA patients 50 years and older with at least one CV risk factor
FDA Drug Safety Communication (DSC) (02/2021)
- review of surveillance trial including 4,362 RA patients with at least 1 CV risk factor receiving either tofacitinib 5 mg
bid, 10 mg bid, or a TNF blocker
- increased risk of death, serious CV events, blood clots, and malignancies (lymphomas, lung cancer [esp. in
current/past smokers) with both doses of tofacitinib
- mortality
- thrombosis
Tofacitinib (Xeljanz) - ADRs
increased risk of serious infections (bacterial, viral, fungal)
- avoid if active infection
- tuberculin test ( ___ ), ___ , Hepatitis B/C prior to therapy
- ensure vaccinations up to date
- live vaccines contraindicated during tx and for __ mo after
- PPD, CXR
- 3
Tofacitinib (Xeljanz) - monitoring
- CXR, ___
- Hep B, C
- ___ - q 3 months
- ___ - q 1-2 months then q 3 months
- ___ - 1-2 months after start, then periodically
- ___ - 1-2 months after start, then periodically
- infection - monitor for s/s
- ___ exam - periodically
- PPD
- ANC
- CBC
- lipids
- LFTs
- skin
Upadacitinib (Rinvoq)
oral selective ___ inhibitor
- family of enzymes involved in immune signaling
- approved for ___ and ___
- who have had an inadequate response to or who are intolerant to ___ blockers
- JAK
- UC, CD
- TNF
Upadacitinib (Rinvoq)
UC
- 45 mg daily for __ weeks then 15 mg daily
- can use 30 mg daily for refractory, severe, extensive disease
- D/C if response not adequate with ___ mg daily
- use lowest effective dose to maintain response
CD
- 45 mg daily for __ weeks then 15 mg daily
- can use 30 mg daily for refractory, severe, extensive disease
- D/C if response not adequate with ___ mg daily
- use lowest effective dose to maintain response
- 8, 30
- 16, 30
Upadacitinib (Rinvoq)
- relatively ___ onset
- option for patients who fail ___
- should NOT be used with ___
(e.g., AZA, CYA, etc.) or ___ - relatively ___ half live (4 h)
- eliminated via ___ metabolism (~35% esp.CYP3A), renal excretion (~25%), unchanged in feces (~38%)
- dose adjustments required in renal impairment and mild-moderate hepatic impairment
- not recommended in end stage renal disease or severe hepatic impairment
- rapid
- biologics
- immunosuppressants, biologics
- short
- hepatic
Upadacitinib (Rinvoq) - Drug interactions
strong CYP3A ___
- 30 mg daily for ___, 15 mg daily for ___
strong CYP3A ___
- avoid use
- inhibitor
- induction, maintenance
- inducer
Upadacitinib (Rinvoq) - ADRs
black-box warnings similar to ___
- unclear if same safety concerns extend to upadacitinib
risk of serious ___ (bacterial, viral, fungal)
- avoid if active infection
- tuberculin test ( ___ ), CXR, Hepatitis B/C prior to therapy
- ensure vaccinations up to date
- live vaccines contraindicated immediately ___ to and during therapy
- tofacitinib
- infections
- PPD
- prior
Upadacitinib (Rinvoq) - ADRs
common:
- upper respiratory tract infection, ___ , increased creatine phosphokinase, elevated ___ , headache, ___
- acne
- lipids
- shingles
Upadacitinib (Rinvoq) - ADRs
rare:
- malignancy ( ___ and other)
- serious infection (including activation of latent ___ )
- increases in ___
- anemia
- neutropenia (see PI)
- lymphopenia (see PI)
- lymphoma
- TB
- LFTs
Upadacitinib (Rinvoq) - ADRs
rare
- hypersensitivity - angioedema and urticaria
potentially ___ , excreted in breast milk
- avoid in ___ and ___
- teratogenic
- pregnancy, lactation
Upadacitinib (Rinvoq) - monitoring
- ___ , ___
- Hep B, C
- ___ / ___ - q 3 months
- ___ - q 1-2 months then q 3 months
- ___ - 12 weeks after start, then periodically
- ___ - 1-2 months after start, then periodically
- ___ - monitor for s/s
- ___ - exam periodically
- CXR, PPD
- ANC/ALC
- CBC
- lipids
- LFTs
- infection
- skin
Ozanimod (Zeposia)
oral selective ___ receptor modulator
- prevents ___ mobilization to inflammatory sites
approved for ___ only
- moderate – severe active UC
- 7 day dose titration: 0.23 mg daily days 1-4, 0.46 mg daily days 5-7, 0.92 mg daily day 8 and after
- if a dose is missed in the first __ weeks of treatment, ___ titration regimen
should not be used with non-corticosteroid ___ or immune-modulating drugs
- S1P
- lymphocyte
- UC
- 2, reinitiate
- immunosuppressive
Ozanimod (Zeposia)
contraindicated in patients who in last 6 months experienced:
- ___ , unstable angina, ___, TIA, decompensated heart failure
requiring hospitalization, Class III or IV heart failure
- with Mobitz type II 2 nd or 3rd degree AV block, sick sinus syndrome, or SA block unless patient has functioning
pacemaker
- with severe untreated ___ ___
- taking a ___ inhibito r- active metabolite of ozanimod is an ___ inhibitor
- half life ~ __ hours
metabolized by ALDH/ADH and CYP3A4
- active metabolites metabolized by CYP2C8
- not recommended for use in ___ impairment
- MI, stroke
- sleep apnea
- MAO, MAO-B
- 21
Ozanimod (Zeposia) - ADRs
potential increased risk of infections
* potential risk of ___ (reported in patients treated with
S1P receptor modulators)
* recommended to vaccinate against ___ prior to
treatment if unvaccinated/not previously infected
* live-attenuated vaccines contraindicated (within __
month of start, during, or __ months after stopping)
___ /AV conduction delays
* consult with cardiologist if any underlying ___ ,
CV disease
- infections
- PML
- varicella
- 1, 3
- bradycardia, arrhythmias
Ozanimod (Zeposia) - ADRs
___ injury/elevated transaminases
* ~1-1.6% of patients with elevations of ALT to 5-fold
upper limit of normal, ~2.6-5.5% with elevations up to 3-fold upper limit of normal
* not recommended in patients with LFTs > __ -fold upper
limit of normal
moderate increase in ___ (~5 mm Hg)
* ___ crisis has been reported
- ___ effects are dose dependent reductions in FEV1
- ___ edema
- reversible posterior leukeoencephalopathy syndrome
( ___ )/posterior reversible encephalopathy syndrome ( ___ )) (case report)
- liver
- 5
- SBP
- hypertensive
- respiratory
- macular
- RPLS, PRES
Ozanimod (Zeposia) - Drug interactions
___ and ___ drugs
* potential ___ crisis (active metabolite inhibits ___ )
combination ___ and ___
* potential additive effects on heart rate (not studied)
foods high in ___
- ___ inhibitors = contraindication (active metabolite inhibits ___ )
strong CYP2C8 inhibitors = ___ exposure of active metabolites, co-administration not recommended
strong CYP2C8 inducers = ___ exposure of active metabolites (possible reduced efficacy), co-administration should be avoided
- adrenergic, serotonergic
- hypertensive, MAO-B
- BB, CCB
- tyramine
- MAO, MAO-B
- increases
- decreases
Ozanimod (Zeposia) - monitoring
**“treat it like a ___ ”
- ___ , ___
- Hep B, C
- CBC - periodically
- ___ - periodically
- infection - monitor for s/s (for 3 months after d/c)
- ___ - each visit
- spirometry - if clinically indicated
- ___
- ___ - regular exams
biologic
- CXR, PPD
- LFTs
- BP
- ECG
- optho
Estrasimod (Velsipity)
oral selective ___ receptor modulator - interacts with S1P receptors on ___
- prevents lymphocyte ___ to inflammatory sites
approved for ___ only
- moderate – severe active UC
- 2 mg daily
should not be used with non-corticosteroid ___ or immune-modulating drugs
- S1P, lymphocytes
- mobilization
- UC
- immunosuppressive
Estrasimod (Velsipity)
contraindicated in patients who in last 6 months experienced:
- ___ , unstable angina, ___ , TIA, decompensated ___ requiring hospitalization, Class III or IV heart failure
- various cardiac ___ abnormalities
- half life ~ __ hours
metabolized by CYP2C8, CYP2C9, CYP3A4
- interactions possible (see PI)
- does not have same warnings regarding ___ inhibitors
as oxanimod
- MI, stroke, HF
- conduction
- 30
- MAO
Estrasimod (Velsipity) - ADR
potential increased risk of infections
* potential risk of ___ due to __ virus infection
* recommended to vaccinate against ___ prior to treatment if unvaccinated/not previously infected
* live-attenuated vaccines contraindicated (within __
month of start, during, or __ months after stopping)
- ___ / AV conduction delays
* consult with cardiologist if any underlying ___ , CV disease
- PML, JC
- varicella
- 1, 3
- bradycardia
- arrhythmias
Estrasimod (Velsipity) - ADRs
___ injury/elevated transaminases
* not recommended in patients with severe ___ impairment
- moderate increase in ___
- ___ edema
- reversible posterior leukeoencephalopathy syndrome
( ___ )/posterior reversible encephalopathy syndrome ( ___ )) (case report) - ___ effects (recall oxanimod is c/o with ___ ___)
- liver
- hepatic
- SBP
- macular
- RPLS, PRES
- respiratory, sleep apnea
Estrasimod (Velsipity)
“treat it like a ___ ”
- ___ , ___
- Hep B, C*
- CBC - periodically*
- ___ - periodically*
- ___ - monitor for s/s (for 3 months after d/c)
- ___ - each visit*
- spirometry if clinically indicated
- ___
- ___ regular exams*
biologic
- CXR, PPD
- LFTs
- infection
- BP
- ECG
- optho
Antimicrobials
ciprofloxacin, metronidazole, rifamycin antibiotics
- can be used as ___ therapy for treatment of complications
* may be used in ___ associated with fistulas/abscesses, perianal
involvement, post resection
little efficacy in treating luminal disease, generally not recommended
ADRs
* agent specific ADRs
* resistance
* Clostridium difficile
- adjunctive
- CD
