IBD Treatment - PDF

*Drug selection and route of administration are based on the clinical status of the patient (e... severity of illness, location of disease), past treatments (successful and failed therapies), inpatient versus outpatient status and more. MAINTENANCE OF REMISSION: COMPARISON OF COMMON CD AND UC TREATM...

*Drug selection and route of administration are based on the clinical status of the patient (e... severity of illness, location of disease), past treatments (successful and failed therapies), inpatient versus outpatient status and more. MAINTENANCE OF REMISSION: COMPARISON OF COMMON CD AND UC TREATMENTS CROHN'S DISEASE ULCERATIVE COLITIS Mild disease of the ileum and/or right colon Mild disease • Oral budesonide for s 3 months; after this course, discontinue treatment or change to thiopurine or methotrexate • Mesalamine (5-ASA) rectal and/or oral preferred Moderate-severe disease* • Anti-TNF agents** • Adalimumab (Humira) • Infliximab (Remicade) • Golimumab (Simponi) • Thiopurine (azathioprine, mercaptopurine) • Cyclosporine • IL receptor antagonist O Ustekinumab (Stelara) • Janus kinase inhibitor Tofacitinib (Xeljanz) - not first-line • Anti-TNF agents** • Adalimumab (Humira)| • Infliximab (Remicade) • Certolizumab (Cimzia) | • Thiopurine (azathioprine, mercaptopurine) • Methotrexate • IL receptor antagonist • Ustekinumab (Stelara)| Refractory to above treatments and/or steroid dependent • Integrin receptor antagonists • Vedolizumab (Entyvio) • Natalizumab (Tysabri) Moderate-severe disease* Refractory to above treatments and/or steroid dependent • Integrin receptor antagonists • Vedolizumab (Entyvio) "Agents can be used as monotherapy or in combination. *Select anti-TNF biosimilars are also FDA-approved for IBD. STEROIDS DRUG DOSING SAFETY/SIDE EFFECTS/MONITORING 5-60 mg PO daily CONTRAINDICATIONS Systemic fungal infections, live vaccines SIDE EFFECTS Short-term: † appetite/weight gain, emotional instability (euphoria, mood swings, irritability), insomnia, fluid retention, indigestion, higher doses can cause an t in BP and blood glucose Long-term: adrenal suppression/Cushing's syndrome, impaired wound healing. 1 BP, T blood glucose, cataracts, osteoporosis, others; refer to the Systemic Steroids & Autoimmune Conditions chapter NOTES All Steroids Oral Steroids Prednisone Tablet (Deltasone*) Oral solution (Prednisone Intensol) Delayed-release tablet (Rayos) Budesonide (Entocort EC, Uceris) Entocort EC: 3 mg extended release capsule (for CD only) Uceris: 9 mg extended release tablet (for UC only) Induction (CD and UC): 9 mg PO once daily in the morning for up to 8 weeks Maintenance (CD only): 6 mg PO once daily for 3 months, then taper For management of acute flares; avoid long-term use if possible Can use alternate day therapy (ADT) to ½ adrenal suppression and other adverse effects If used longer than 2 weeks, must taper to avoid withdrawal symptoms If long-term use is required, assess bone density (optimize calcium and vitamin D intake and consider bisphosphonates if needed) Budesonide Undergoes extensive first-pass metabolism: 4 systemic exposure than other oral steroids Swallow whole - do not crush or chew; can open Entocort EC capsules and sprinkle on applesauce Induction and/or Maintenance Cortenema: 1 enema (100 mg) QHS for 21 days or until remission, then taper Cortifoam: 1 applicatorful (90 mg) 1-2 times daily for 2-3 weeks, then every other day thereafter; taper after long-term therapy CONTRAINDICATIONS Cortifoam: obstruction, abscess, perforation, peritonitis, fresh intestinal anastomoses, extensive fistulas and sinus tracts Cortenema: ileocolostomy in immediate/early post-op period NOTES Rectal steroids are indicated for UC only Not proven effective for maintenance of remission; maintenance use is limited to mild-moderate distal UC as an alternative to rectal and/or oral aminosalicylates Rectal Steroids Hydrocortisone (Cortenema, Cortifoam) Enema, rectal foam Budesonide rectal foam (Uceris) Induction Budesonide rectal foam: propellant is flammable; 1 metered dose PR BID × avoid fire and smoking during and after use 2 weeks, then 1 metered dose daily x 4 weeks (1 metered dose = 2 mg budesonide) *Brand discontinued but name still used in practice. AMINOSALICYLATES DRUG DOSING SAFETY/SIDE EFFECTS/MONITORING Mesalamine ER ER capsules (Pentasa, Apriso, Delzicol) ER tablets (Asacol HD, Lialda) Enema (Rowasa) Suppository (Canasa) Induction (oral therapy for 6-8 weeks and/or rectal therapy for 3-6 weeks) Asacol HD: 1.6 g PO TID Delzicol: 800 mg PO TID Lialda: 2.4-4.8 g PO daily Pentasa: 1 g PO QID Suppository: 1 g rectally QHS, retain for at least 1-3 hours Enema: 4 g rectally QHS, retain in the rectum overnight for approximately 8 hours Maintenance Apriso: 1.5 g PO daily Delzicol: 1.6 g PO in 2-4 divided doses Lialda: 2.4 g PO daily Pentasa: 1 g PO QID Enema: 2 g rectally QHS, or 4 g QHS every 2-3 days CONTRAINDICATIONS Hypersensitivity to salicylates or aminosalicylates WARNINGS Acute intolerance syndrome (cramping, acute abdominal pain, bloody diarrhea): caution in patients with renal or hepatic impairment; delayed gastric retention (e.g., due to pyloric stenosis) can delay release of oral products in the colon; hypersensitivity reactions (including myocarditis, pericarditis, nephritis, hematologic abnormalities and other internal organ damage) - more likely with sulfasalazine than mesalamine: 1 risk of blood dyscrasias in patients > 65 years of age, photosensitivity Apriso contains phenylalanine; do not use in patients with phenylketonuria (PKU) Rowasa enema contains potassium metabisulfite, may cause an allergic-type reaction SIDE EFFECTS Abdominal pain, nausea, headache, flatulence, eructation (belching), nasopharyngitis MONITORING Renal function, CBC, hepatic function, s/sx of IBD NOTES Mesalamine is better tolerated than other aminosalicylates Rectal mesalamine is more effective than oral mesalamine and rectal steroids for distal disease/proctitis in UC; can use oral and topical formulations together Asacol and Delzicol: can leave a ghost tablet in the stool Swallow capsules/tablets whole; do not crush, chew or break due to delayed-release coating Apriso: do not use with antacids (dissolution is ph-dependent) Sulfasalazine Tablets (Azulfidine) ER tablets (Azulfidine EN-tabs) Induction 3-4 g PO divided TID or QID, titrate to 4-6 g PO daily divided QID Maintenance Refer to the Systemic Steroids & Autoimmune Conditions chapter CONTRAINDICATIONS Salicylate allergy, sulfa allergy, intestinal or urinary obstruction, porphyria NOTES Doses should be taken at ≤ 8 hour intervals Can reduce dose if Gl intolerance occurs 2 g PO daily divided TID or OID Balsalazide (Colazal) Capsule Induction Colazal: 2.25 g (three 750 mg capsules) PO TID for 8-12 weeks CONTRAINDICATION Salicylate allergy WARNINGS Gastric retention (e.g., due to pyloric stenosis) can delay release of drug in the colon; acute intolerance syndrome; caution in patients with renal or hepatic impairment, photosensitivity SIDE EFFECTS Headache, abdominal pain, N/V/D MONITORING Renal function, LFTs, S/sx of IBD NOTES Colazal capsule can be opened and sprinkled on applesauce; beads are not coated, so mixture can be chewed if needed; when used this way, it can cause staining of the teeth/tongue Olsalazine| (Dipentum) Capsule Maintenance 500 mg PO BID Take with food CONTRAINDICATION Salicylate allergy SIDE EFFECTS Diarrhea, abdominal pain MONITORING CBC, LFTs, renal function, symptoms of IBD THIOPURINES DRUG Azathioprine (Azasan, Imuran) | Tablet, injection DOSING SAFETY/SIDE EFFECTS/MONITORING 1.5-2.5 mg/kg/day IV or PO CrCl < 50 mL/min: adjustment required PO: taking after meals or in divided doses may I Gl side effects BOXED WARNINGS Chronic immunosuppression T risk of malignancy in patients with IBD (especially lymphomas); mutagenic potential; risk for hematologic toxicities WARNINGS Hematologic toxicities (e.g., leukopenia, thrombocytopenia, anemia): patients with a genetic deficiency of thiopurine methyltransferase (TPMT) are at 1 risk for myelosuppression GI hypersensitivity reactions (severe N/V/D, rash, fever, T LFTs), serious infections, hepatotoxicity SIDE EFFECTS N/V/D, rash, T LFTs MONITORING LFTs, CBC (weekly for 1st month), renal function, s/sx of malignancy NOTES Consider TPMT genetic testing before starting (see Pharmacogenomics chapter) Azathioprine is metabolized to mercaptopurine; do not use the thiopurines in combination Aminosalicylates inhibit TPMT; caution with use in combination Allopurinol inhibits a pathway for inactivation of azathioprine; azathioprine dose reduction required if used in combination Mercaptopurine (Purixan) Tablet, oral suspension 1-1.5 mg/kg/day CrCl ≤ 50 mL/min: adjustment required Same as azathioprine above (except no boxed warning) plus: NOTES Take on an empty stomach Avoid old terms "6-mercaptopurine" and "6-MP"; they 1 the risk of overdose due to administration of doses 6-fold higher than normal