Topical/Local delivery: Induction/Maintenance; Either is best for mild to moderate proctitis and proctosigmoiditis
Suppository (effective to 10-15 cm): Canasa; Enema (effective to splenic flexure): Rowasa
Oral: FDA approved for induction/maintenance of UC, not Crohn’s
Goal of 5ASA is 4-gram equivalent of Sulfasalazine, typically given in BID or TID dosing (Olsalazine rarely used due to ↑ secretary diarrheal side effect); PABA is an inert carrier
Drugs are dose dependant (i.e. more you give, the more they work; No plateau ever demonstrated)
Major side effects: idiosyncratic reaction (i.e. worsening of initial symptoms 5%), N/V, Fever, AIN, Sulfa allergy (except Olsalazine)
Generic | Proprietary | Strength | Sulfasalazine Equivalent | Bond | Action Site |
|---|---|---|---|---|---|
Sulfasalazine | Azulfadine | 500 mg | 8 qd: 4 g | Sulfa (diazo) 5ASA | Cleaved by bacteria in Colon |
Mesalamine Compounds: | |||||
— | Pentasa | 250 mg | 16 qd: 4 g | Coated 5ASA | Time released duodenum to colon |
— | Asacol | 400 mg | 12 qd: 4.8 g | Coated 5ASA | pH released in TI and colon (pH >7.0) |
— | Lialda | 1.2 mg | 4 qd: 4.8 g | Coated 5ASA | MMX technology, pH released TI and Colon |
Balsalazide | Colazal | 750 mg | 9 qd: 6.75 g | PABA (diazo) 5ASA | Cleaved in Colon |
Olsalazine | Dipentum | 250 mg | Not Used | Cleaved in Colon | |
Topical: Cortifoam/Cortenema (Best for mild to moderate proctitis and proctosigmoiditis, not for maintenance)
Budesonide (Entocort): oral, but pH released in TI and right colon and acts as a topical steroid, with low systemic absorption
Oral: Goal is prednisone equivalent of 40-60 mg (no evidence for >60 mg); Taper should be over 1-2 months or longer
IV: Solumedrol 20 q 8 hr, Hydrocortisone 100 q 8 hr (In acute setting, if no response after 3-5 days of steroids, consider next step or a different diagnosis)
Problems include steroid dependence & resistance; Side effects: diabetes, cataracts, osteoporosis, etc. Get baseline DEXA; give Vit Ca/D at same time
Metronidazole (Flagyl) 750-1000 mg/day and Cipro 1000 mg/day: useful in perianal, fistulizing and active colonic CD (caution with pregnancy)
Rifaximin used by some clinicians (no studies yet)
Used as primary or adjuvant therapy mostly with inflammatory CD; Enteral nutrition can help induce remission (not quite as effective as steroids) or be used with resistance or intolerance to meds and/or replete and maintain nutrition status
Data more limited with UC; Enteral nutrition enriched with fish oils, soluble fiber, and antioxidants can reduce steroid use
More studies needed
Bowel rest, stop antidiarrheals, low residue diet
Serial abdominal exams and radiographs/CT to rule out dilation, perforation or abscess
Ulcerative Colitis | Crohn’s Disease | |||||
|---|---|---|---|---|---|---|
Induce | Maintenance | Induce | Maintenance | Side Effects | Cautions | |
6MP (Purinethol) | OK | Yes | Yes (I, F) | Yes (I, F) | Pancreatitis (2-5%), Hepatitis, Allergy/flu like syndrome, BM toxicity | √ WBC, LFTs; Supplement Folate |
–CD & UC: steroid dependant, refractory disease, intolerance/non-response to other meds; CD specific: fistulizing, prevent postop recurrence | ||||||
–MOA: Purine analogs: interfere with DNA synthesis of rapidly dividing cells, such as lymphocytes (T > B) & macrophages; Takes weeks/months to work | ||||||
-Dosage: (See diagram and text on next page) | ||||||
Infliximab | Yes | Yes | Yes | Yes | Infusion reaction, ↑ Lymphoma risk, long term, +AMA | √ TB and HBV before starting |
(Remicade) | (FDA Approved 2005) | (I, F) | (I, F) | |||
–CD & UC: refractory/intolerant steroids & 6 MP/Azathioprine, prominent joint sx; CD specific: significant perianal and/or extensive small bowel disease | ||||||
–MOA: IgG mouse antibody to TNF (binds to soluble and surface membrane TNF), causing lysis | ||||||
-Dosage: Induction 5 mg/kg IV (round to closest 100 mg) 3 doses at 0, 2, 6 wks; Maintenance: 5 mg/kg q 8 wks (See also text on next page) | ||||||
Adalimumab (Hurnira) | ? | ? | Yes (I,F) | Yes (I,F) | √ TB and HBV before starting | |
(FDA approved 2007) | ||||||
-Dosage: 160 mg sq at day 1; then 80 mg sq at day 15; then 40 mg sq every other week; then reassess after several weeks | ||||||
Cyclosporine (Neoral) | Yes | Unlikely | Yes, High doses | ? | Hirsutism, Gingival hyperplasia, HTN, CRF, Opportunistic infections; ↓ Lipids = ↑Seizure risk | √ Lipids, renal function; Bridge to other therapies; There are better options |
-Dosage: 2 mg/kg IV (some use 4 mg/kg); po doses 8 mg/kg/day (See also text on next page) | ||||||
Methotrexate (MTX) | No | ? | OK | Yes | Liver toxicity, infections, teratogenic | Supplement folate |
–MOA: Inhibits dihydrofolate reductase (folate antagonist); Inhibits lymphocyte proliferation | ||||||
-Dosage: 25 mg q wk × 16 wks (give IM as it confirms absorption); reassess and continue 15 mg po or 25 mg IM q wk | ||||||
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