PharmTher - IBD - Exam 5

IBD - Tx Goals

-alleviation of signs and symptoms

-suppression of inflammation during acute episodes

-maintenance of remission

IBD - remission maintenance

-prevention of disease relapse

-improvement in patient's QOL

-prevention of surgical intervention or hospitalization

-management of extraintestinal manifestations

-prevention of malnutrition

-prevention of tx-associated adverse effects

Vitamin D and Ca2+

_________ and _________ supplementation should be used in ALL IBD patients receiving long-term CCS

no

is there a specific dietary restriction recommendation for IBD?

IBD - Surgical intervention

-considered in pts with complications (fistulae/abscess) or refractory disease

-total colectomy is curative in UC

-resection of affected areas of intestine possible in CD, however CD may still recur

IBD - Major drug classes

-Aminosalicylates

-CCS

-Immunosuppressants

-Biologic Agents

-Other Agents

Aminosalicylates

-MOA: anti-inflammatory

-5-Aminosalicylic Acid derivative

-Sulfasalazine

-Mesalamine

-Olsalazine

-balsalazide

Pentasa - Site of Action

rectum, distal colon, proximal colon, terminal ileum, ileum, jejunum

Sulfasalazine - AE and DI

-more AE than mesalamine due to sulfapyridine component

-common dose-related adverse effects: HA, dyspepsia, N/V, fatigue

-severe AE: bone marrow suppression, reduction in sperm counts, hepatitis, pulmonitis

sulfa allergies

patients with what allergy should avoid sulfasalazine d/t risk of hypersensitivity rxn?

salicylate

patients with what allergy should avoid all aminosalicylates d/t risk of hypersensitivity reaction?

nonsulfapyridine-based aminosalicylates

what is an alternative aminosalicylate used in pts with a sulfa allergy?

Osalazine

associated with secretOry diarrhea more than other aminosalicylates

Corticosteroids

-anti-inflammatory, used in IBD to suppress inflammation rapidly

-may be admin systemically or locally to site of action

-should be restricted to short-term management of active dz

-long-term use associated with significant ADE

budesonide

what is a common CCS used in IBD tx?

CCS - Long-term ADE

-cataracts

-skin atrophy

-hypertension

-hyperglycemia

-adrenal suppression

-osteoporosis

-increased risk of infection

-delayed growth (children)

CCS - Short term ADE

-hyperglycemia

-insomnia

-GI upset

-increased appetite

immunosuppressants

-target the excessive immune response or cytokines involved in IBD

-Used for IBD unresponsive to other tx

-more useful for CD than UC

Azathioprine and 6-MP

-inhibit purine biosynthesis and decrease GI inflammation

-useful for maintaining remission of IBD and decreasing need for long-term CCS use

-ADE: hypersensitivity rxn --> pancreatitis, fever, rash, hepatitis, leukopenia

-should be tested for activity of thiopurine methyltransferase

Methotrexate

-folate antagonist

-in IBD, used primarily for maintaining remission of CD

-may be admin orally, subq, or IV

-long-term use may result in serious adverse effects including hepatotoxicity, pulmonary fibrosis, and bone marrow suppression

Cyclosporine

-immunosuppressant, usually used to prevent organ rejection in transplant patients

-used in IBD restricted to those with fulminant or refractory symptoms in patients with active dz

-significant toxicities include: nephrotoxicity, risk of infxn, seizures, hypertension, and LFT abnormalities

folic acid

what should be admin with MTX?

Biologic Agents

-MOA: anti-TNF-a, anti-integrin antibodies, anti-IL-12/23 antibodies

-Disadvantages: cost, require parenteral admin, serious adverse reactions

Biologic Agents - Adverse Rxns

-reactivation of serious infections (TB, hep B)

-exacerbations of HF

-Infusion-related rxns (fever, chest pain, hypotension, dyspnea)

-Risk of lymphoma (higher risk in young males using concomitant azathioprine or 6-MP)

Anti-TNF-a

-reduction in TNF-a activity associated with improper inflammatory process

-Infliximab --> prototypical agent

-adalimumab

-certolizumab

-Golimumab

Anti-Integrin

-blocks integrin molecules associating with vascular receptors, thus limiting leukocyte adhesion and migration across the endothelium

-Natalizumab and Vedolizumab

Natalizumab

-has been associated with progressive multifocal leukoencephalopathy (PML)

-use is restricted to pts with CD who have failed other therapies, including TNF-a inhibitors

-1 dose of 300 mg: $7200.00

Vendolizumab

-theoretical risk of PML, but none reported to date

-1 dose of 300 mg: $6504.86

Anti-IL-12/23

-targets regulatory cytokines IL-12 and IL-23, thus disrupting the resulting inflammatory cascade

-Ustekinumab --> can be used for psoriasis

-Solution Prefilled syringe (stelara subq)

Tofacitinib

-oral biologic

-indications: ankylosing spondylitis, psoriasis, psoriatic arthritis, rheumatoid arthritis, UC, COVID-19 hospitalized patients

-inhibits JAK enzymes

-associated with severe toxicities (thrombosis, bone marrow suppression)

-Drug interactions

-use only if failure or intolerance of any TNF agent

Antibiotics

-may interrupt the inflammatory response directed against endogenous bacterial flora

-Metronidazole and ciprofloxacin

-Both can cause diarrhea

Metronidazole

may benefit some pts with pouchitis (inflammation of surgically created intestinal pouches) and pts with CD who have had ileal resection or have perianal fistulas

Ciprofloxacin

shown some efficacy in refractory active CD

Nicotine

-smoking is associated with reduced symptoms of UC

-mixed results with studies regarding benefit of treatment using nicotine

-transdermal nicotine may result in some improvement in mild-mod UC symptoms

Transdermal nicotine

-may result in some improvement in mild-mod UC symptoms

-may be more effective in ex-smokers

-daily doses between 15-25 mg appear to be the most effective

Probiotics

-Lactobacillus acidophilus or Bifidobacterium

-Rationale: modification of the host flora may alter the inflammatory response

-minimal data to support use in CD

-UC: probiotic preparation VSL#3 demonstrated efficacy in reduction of recurrence of pouchitis and may prevent relapse in mild-mod disease

Mild Distal UC

-oral sulfasalazine or mesalamine or mesalazine enema or suppository

-remission: oral mesalamine or sulfasalazine or mesalamine enema or suppository

Mild-Mod Extensive UC

-oral mesalamine 2-3 g/day or controlled release budesonide 9 mg/day

-remission: reduce mesalamine dose to 2-3 g/day or continue budesonide for up to 8 wks

Mod-Severe UC

-budesonide MMX 9 mg/day or prednisone 40-60 mg/day

-remission: taper prednisone after 1-2 mo or continue budesonide for 8 wks

-Inadequate or no response: infliximab plus azathioprine

Fulminant UC

-methylprednisolone 40-60 mg or hydrocortisone IV 100 mg every 6-8 hr

Basic UC Tx

-start here: 5ASA

-bump up: Steroids

-bump up higher: Immunosuppressants

Maintenance - CD Tx

-maintenance of remission is often more difficult than with UC

-sulfasalazine and oral mesalamine

-Corticosteroids

-Azathioprine and 6-MP

-Biologic Agents

Sulfasalazine and Oral Mesalamine - Remission

-marginally effective in preventing CD relapse

-however these are often used to attempt remission due to their favorable SE profile and lower cost compared with the immunosuppressive and biologic agents

Corticosteroids - Remission

-no place in the prevention of recurrence

-budesonide may be considered for up to 1 yr in pts who have become CCS dependent

Azathioprine and 6-MP - Remission

-effective in maintaining remission in CD in up to 70% of patients, especially in infliximab or steroid-induced remission

-considered 1st line

15-25 mg IM

for CD patients who initially respond to MTX, for remission tx, lowering weekly dosing at _____________ is also effective in up to 66% of patients

Symptomatic Interventions - IBD

-avoid antidiarrheal meds that reduce GI motility due to risk of precipitating acute colonic dilation (toxic megacolon)

-Anticholinergics used for intestinal spasm and pain should also be avoided because they also reduce GI motility

-Avoid NSAIDs for pain management

-Use caution with opioid analgesics

Cholestyramine (Questran)

-may decrease diarrheal symptoms in patients with CD who have had multiple intestinal resections

-multiple intestinal resections may lead to diarrhea related to the inability to reabsorb bile salts

Elderly - IBD

-elderly have more comorbid diseases

-elderly use more meds

-Treatment is similar, but considerations present

-CCS may worsen DM, HTN, HF, Osteoporosis

-TNF-a inhibitors should be used cautiously in HF

-Those requiring surgery are at higher risk for comp

Children and Adolescents - IBD

-CD occurs twice as frequently as UC in children

-Major issue: risk of growth failure secondary to inadequate nutritional intake and CCS therapy

-Aminosalicylates, azathioprine, 6-MP, and infliximab are options for treatment and maintenance of IBD in peds pts

Pregnant Women - IBD

-active IBD may result in prematurity and low birth weight

-Azathioprine and 6-MP have been used successfully in pregnant patients and appear to have minimal risk

-Infliximab, adalimumab, and certolizumab appear to carry minimal risk

-Metronidazole has risk of mutagenicity, however short courses are safe during pregnancy

-Ciprofloxacin should be avoided during pregnancy

diphenoxylate

avoid ___________ during 1st trimester d/t risk of fetal malformations

Sulfasalazine

Aminosalicylates are considered safe to use in pregnancy, however ____________ is associated with folate malabsorption

folic acid - pregnancy

what should you supplement sulfasalazine with?

Methotrexate

_____________ is a known abortifacient and is CI during pregnancy