IBD Therapies Flashcards
5-aminosalicylates MoA
Act topically to decrease GI tract inflammation
Frequency of 5-ASA dosing
Most require multiple daily dosages
5-ASA drugs
Sulfasalazine, mesalamine, olsalazine, balsalazide
Sulfasalazine is cleaved by gut bacteria into what molecules?
5-ASA and sulfapyridine
What is the carrier and what is the active component in sulfasalazine
Carrier: sulfapyridine
Active component: 5-ASA
What is responsible for the ADEs in sulfasalazine?
Sulfa moiety
ADEs of sulfasalazine
GI symptoms, rash, photosensitivity, blood dyscrasias
Sulfasalazine dosing
500-1500mg PO q6h
Where are 5-ASAs used in IBD treatment?
UC!
Mesalamine routes of administration
PO and PR
Mesalamine PR products
Rowasa is an enema
Canasa is a suppository
Where does Rowasa deliver drug to?
Rectum and distal colon
Where does Canasa deliver drug to?
Rectum only
PO formulation of mesalamine comes in what kind of duration?
Delayed/controlled release
Olsalazine (Dipentum) is cleaved by gut bacteria into what?
2 5-ASA molecules
2=Di, brand name is Dipentum!
Olsalazine/Dipentum dosing
500-1000mg PO BID
Olsalazine/Dipentum ADE
Diarrhea
Feature of balsalazide (Colazal)
It’s basically sulfasalazine without the sulfa
What is balsalazide cleaved into?
5-ASA and 4-aminobenzyol-beta-alanine
What are the active and carrier components of balsalazide?
Active: 5-ASA
Carrier: 4-aminobenzoyl-beta-alanine
Balsalazide (Colazal) dosing
3, 750mg capsules PO TID
What are immunomodulators used to do in IBD treatment?
Maintain treatment remission
Immunomodulators used in IBD treatment
Azathioprine, 6-MP, methotrexate, cyclosporine and tacrolimus have also been used
Azathioprine is a prodrug for what drug?
6-MP
Azathioprine dosing
2-2.5mg/kg/day
What can you use AZA in combo with?
Biologics (but can also use alone)
What disease states can you use AZA in?
Both Crohn’s and UC
6-MP dosing
1-1.5mg/kg/day
Methotrexate dosing
15-25mg/week IM or SQ, but can switch to PO after being on IM or SQ treatment for a long time
What disease state can you use methotrexate in?
Crohn’s
Immunomodulator monitoring
CBC at least q3 months
Check LFTs and pancreatic enzymes
Watch out for lymphomas
ABX are used in what disease state?
Best for perianal Crohn’s
ABX used in IBD
Metronidazole and ciprofloxacin
Metronidazole dosing
500mg TID or 20mg/kg/day
Ciprofloxacin dosing
400mg IV or 500mg PO BID
What do corticosteroids do in IBD therapy?
Work quickly to reduce inflammation
Corticosteroids used in IBD
Prednisone, methylprednisolone, hydrocortisone, budesonide
Prednisone dosing
20-60mg PO QD
Methylprednisolone formulation/route of administration
IV
Hydrocortisone topical formulations
10mg enema, 25mg suppository, 10% foam
Hydrocortisone also comes in what formulation?
IV
Budesonide formulation
EC capsule
Budesonide dosing to induce remission
9mg PO QD up to 8 weeks; recurring episodes can be treated with repeated courses
Budesonide dosing to maintain remission in Crohn’s
After 8 weeks, can continue at 6mg PO QD with a down taper if needed
Budesonide brand for Crohn’s
Entocort
Where does Entocort release?
Terminal ileum
Budesonide brand for UC
Uceris
Where does Uceris release?
Throughout the colon
Role of biologics in IBD
Induce and maintain remission
Anti-TNFs for IBD
Infliximab (Remicade)
Adalimumab (Humira)
Certolizumab (Cimzia)
Golimumab (Simponi)
Selective adhesion molecules inhibitors for IBD
Natalizumab (Tysabri)
Vedolizumab (Entyvia)
IL-12, IL-23 inhibitor for IBD
Ustekinumab (Stelara)
JAK inhibitors for IBD
Tofacitinib (Xeljanz)
Upadacitinib (Rinvoq)
Biologics used in BOTH Crohn’s and UC
Infliximab (Remicade)
Adalimumab (Humira)
Vedolizumab (Entyvia)
Ustekinumab (Stelara)
Biologics used in Crohn’s only
Natalizumab (Tysabri)
Certolizumab (Cimzia)
Biologics used in UC only
Golimumab (Simponi)
Tofacitinib (Xeljanz)
Upadacitinib (Rinvoq)
Biologics with IV route of administration
Infliximab (Remicade)
Natalizumab (Tysabri)
Vedolizumab (Entyvia)
Ustekinumab (Stelara) when used as induction Tx
Biologics with SQ route of administration
Adalimumab (Humira)
Certolizumab (Cimzia)
Golimumab (Simponi)
Ustekinumab (Stelara) when used as maintenance Tx
Biologics with PO route of administration
Tofacitinib (Xeljanz)
Upadacitinib (Rinvoq)
ADRs of biologics: acute infusion-related reactions
Headache, dizziness, nausea, flushing, fever, chest pain, cough, dyspnea, pruritus
How to control acute infusion-related reactions
Decrease infusion rate, pre-medicate with 1000mg APAP, 50mg IV/PO diphenhydramine +/- 50mg IV hydrocortisone
ADRs of biologics: delayed infusion-related reactions
Myalgias, arthralgias, fever, rash, pruritis, urticaria, headaches
How long does it take for delayed infusion-related reactions to take place?
3-14 days
How to manage delayed infusion-related reactions
Can go away on its own or require a short course of steroids
ADRs of biologics: injection site reactions
Pain and redness at the site of injection
BBWs on TNFis and JAKis
Infections, malignancy
Kinds of infections that are possible while on TNFis and JAKis
Active TB, invasive fungal infections, bacterial, viral, or other opportunistic infections
How to monitor for infections while on TNFis and JAKis
Monitor for signs/symptoms of infection
D/C when there’s a serious infection or sepsis
What should patients be tested for before starting TNFis or JAKis therapy?
TB skin test, chest x-ray, must be vaccinated or treated for HBV
What vaccines can you not get while on a TNFi or JAKi?
Live attenuated vaccines
ADE of natalizumab
Progressive multifocal leukoencephalopathy
BBW on natalizumab, cautionary for vedolizumab
What causes progressive multifocal leukoencephalopathy?
Reactivation of the JC polyomavirus which can lead to CNS infection and death
Due to its ADE/BBW, how must natalizumab be administered?
As monotherapy
How do you get natalizumab?
Patients and prescribers must enroll in the TOUCH program
The safety review for JAKis found that there was an increased risk of what?
Cancer, CV-related events, thrombosis, and death
The increased risks of cancer, CV-related events, thrombosis, and death while taking JAKis are more likely to happen to what kinds of patients?
> 50 years old with at least 1 CV risk factor (smoking, HTN, HLD, etc.)
The FDA has limited the use of JAKis to what?
Patients who haven’t responded or can’t tolerate 1 or more TNFIs