The goals of pharmacologic therapy include inhibition of intestinal motility, reduction in intestinal secretions, and promotion of absorption. Absorbents include agents that form a gelatinous mass that gives density to fecal material. Methylcellulose and pectin are most commonly used, with little data to support their efficacy. These bulk-forming agents may not be well tolerated in some patients because of the large volume required for therapeutic effect and the associated abdominal discomfort and bloating. Adsorbents such as kaolin, clays, and activated charcoals have been used extensively, but no data support their use. Furthermore, they may inhibit absorption of other oral antidiarrheals that may be administered.
Opioids bind to receptors within the gastrointestinal tract and reduce diarrhea by reducing transit time. Loperamide is the most common opioid used, due to its availability and reduced effect on cognition, although codeine and other opioids can also be effective. Common loperamide doses begin with 4 mg, followed by 2 mg after each unformed stool with a maximum of approximately 12 mg/day.[5,26] Regardless of the dose, however, loperamide may be less effective in patients with grade 3 or 4 diarrhea.[Level of evidence: I]
Mucosal prostaglandin inhibitors, also referred to as antisecretory agents, include aspirin, bismuth subsalicylate, corticosteroids, and octreotide. Aspirin may be useful for radiation-induced diarrhea. Bismuth subsalicylate is believed to have direct antimicrobial effects on Escherichia coli, hence its prophylactic use in traveler's diarrhea. This agent is contraindicated in patients who should not be taking aspirin, and large doses can produce toxic salicylate levels. Corticosteroids reduce edema associated with obstruction and radiation colitis and can reduce hormonal influences of some endocrine tumors.
Other pharmacologic therapies for the relief of diarrhea may be specific to the underlying mechanism. Delayed diarrhea (>24 hours) occurs with irinotecan and can be severe in 25% of patients. In a small study of seven patients, six patients obtained relief with oral neomycin, 1,000 mg 3 times daily. This relief occurred without reduction in the active metabolite of irinotecan, SN-38; thus, the poorly metabolized antibiotic did not alter efficacy of the chemotherapeutic agent.[Level of evidence: II] In another small study of 37 patients with non-small cell lung cancer receiving irinotecan, investigators alkalized the feces through oral administration of sodium bicarbonate, basic water, and ursodeoxycholic acid, while speeding transit time of the drug metabolites (thought to reduce damage to the intestinal lumen by reducing stasis of the drug) through the use of magnesium oxide. The incidence of delayed diarrhea was significantly reduced in this group when compared to 32 patients receiving the same chemotherapeutic regimen without oral alkalization and controlled defecation.[Level of evidence: III]
In addition to antidiarrheal agents and immunosuppressive medications, a specialized five-phase dietary regimen should be instituted to effectively manage the diarrhea associated with GVHD. Phase 1 consists of total bowel rest until the diarrhea is reduced. Nitrogen losses associated with diarrhea can be severe and are compounded by the high-dose corticosteroids used to treat GVHD. Phase 2 reintroduces oral feedings consisting of beverages that are isotonic, low-residue, and lactose-free to compensate for the loss of intestinal enzymes secondary to alterations in the intestinal villi and mucosa. If these beverages are well tolerated, phase 3 may reintroduce solids containing minimal lactose, low fiber, low fat, low total acidity, and no gastric irritants. In phase 4, dietary restrictions are progressively reduced as foods are gradually reintroduced and tolerance is established. Phase 5 includes the resumption of the patient's regular diet; however, most patients usually remain lactose intolerant.