Fiber Supplement (inulin/sorbitol)

Bulk-forming laxatives are usually administered 1-3 times daily. To reduce the risk of esophageal obstruction in patients receiving large (e.g., the maximum daily dosage recommended by the manufacturer) dosages of bulk-forming laxatives, these laxatives should be administered in divided doses instead of a single daily dose. The usual dosages for the individual bulk-forming laxatives are below; for dosages in children younger than the ages listed, a physician should be consulted.

Bulk-forming laxatives are administered orally. Commercially available powders, flakes, granules, tablets, and liquids should be dissolved and/or diluted according to the instructions of the manufacturer. In the treatment of constipation, at least one full glass (250 mL) of liquid should be administered with each laxative dose. When used to increase the bulk of stools in patients with chronic, watery diarrhea, one manufacturer suggests that one-third of a glass (80 mL) of liquid be administered with each dose.

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There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Laxatives/Trofinetide

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Trofinetide commonly causes diarrhea of mild to moderate severity. Laxatives may increase the incidence or severity of diarrhea.(1)

CLINICAL EFFECTS: Concurrent use of laxatives with trofinetide may increase the risk of severe diarrhea.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients should stop laxatives before starting trofinetide. If diarrhea occurs, consider anti-diarrheal treatment and monitor hydration status. If severe diarrhea or dehydration occurs, interrupt, reduce dose, or discontinue trofinetide.(1)

DISCUSSION: In clinical trials, 85% of patients on trofinetide developed diarrhea. Concurrent use of laxatives may increase this risk.(1)

Laxatives; Stool Softeners/Tenapanor

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Tenapanor commonly causes diarrhea of mild to moderate severity. Laxatives and stool softeners may increase the incidence or severity of diarrhea.(1)

CLINICAL EFFECTS: Concurrent use of laxatives or stool softeners with tenapanor may increase the risk of severe diarrhea.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of tenapanor states that patients should be instructed to avoid stool softeners and laxatives with tenapanor. If severe diarrhea occurs, tenapanor should be discontinued.(1)

DISCUSSION: In clinical trials, 43-53% of CKD patients on dialysis treated with tenapanor developed diarrhea. Diarrhea usually occurred soon after treatment initiation and was severe in 5% of patients.(1)

Sorbitol/Lamivudine

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Sorbitol increases the osmotic pressure in the intestine, resulting in accelerated small intestinal transit time and decreased absorption and bioavailability of lamivudine.

CLINICAL EFFECTS: Concurrent administration of sorbitol and lamivudine may result in decreased clinical efficacy of lamivudine.(1) Reduction in lamivudine exposure is sorbitol dose-dependent.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of lamivudine states that the concurrent use of lamivudine and sorbitol should be avoided.(1) Consider more frequent monitoring of HBV viral load when chronic coadministration cannot be avoided.

DISCUSSION: In an open label, randomized sequence, 4-period, crossover trial in 16 healthy adults, coadministration of a single dose of lamivudine (300 mg) with sorbitol (3.2 grams) resulted in a dose-dependent decrease of lamivudine's area-under-the-curve (AUC(0-24), AUC infinity) and maximum concentration (Cmax) of 20%, 28%, and 28%. A single dose of lamivudine with sorbitol (10.2 grams) resulted in a decrease of lamivudine's AUC and Cmax of 39%, 52%, and 52%. A single dose of lamivudine with sorbitol (13.4 grams) resulted in a decrease of lamivudine's AUC and Cmax of 36%, 55%, and 55%.(1)

Sorbitol/Polystyrene Sulfonate

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Sorbitol may damage the intestinal mucosa, trigger vasospasms in the intestinal vasculature, and increase inflammation.(1) Polystyrene sulfonate crystals may deposit in these areas, resulting in further damage.(2,3)

CLINICAL EFFECTS: Concurrent use of sorbitol and polystyrene sulfonate (either orally or rectally) may result in colonic necrosis, bleeding, ischemic colitis, and perforation of the gastrointestinal tract. Fatalities have been reported.(4)

PREDISPOSING FACTORS: Predisposing factors may include a history of intestinal disease or surgery, hypovolemia, and/or renal insufficiency/failure. Premature infants may also be predisposed to the interaction.(4)

PATIENT MANAGEMENT: The US manufacturer of sodium polystyrene sulfonate states that concurrent use with sorbitol (either orally or rectally) is not recommended.(4) In the event that sorbitol is used as a vehicle to administer polystyrene sulfonate rectally as an enema, particular attention should be given to administering a cleansing enema following the completion of the sodium polystyrene sulfonate enema.(4) Patients who have received concurrent polystyrene sulfonate and sorbitol should be monitored for signs of gastrointestinal complications and instructed to report abdominal pain and/or signs of gastrointestinal bleeding. If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling.

DISCUSSION: There have been numerous case reports of intestinal necrosis following the use of sodium polystyrene sulfonate and sorbitol.(1,5-13) In the majority of these cases, sorbitol was used as a vehicle for rectal administration of sodium polystyrene sulfonate(5-10); however, there have also been reports with oral administration (1,11,12) and in patients who received both oral and rectal sodium polystyrene with sorbitol.(13,14) Fatalities have been reported.(1,5,6)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Bulk Forming Laxatives/Clozapine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Clozapine has potent anticholinergic properties and inhibits serotonin receptors, including 5-HT3.(1-4) Both of these properties may cause inhibition of gastrointestinal (GI) smooth muscle contraction, resulting in decreased peristalsis.(3,4) If fluid intake is inadequate, bulk forming laxatives can increase the risk of gastrointestinal obstruction.(1-6)

CLINICAL EFFECTS: Concurrent use of clozapine and bulk forming laxatives with inadequate fluid intake may increase the risk of constipation (common) and serious bowel complications (uncommon), including complete bowel obstruction, fecal impaction, paralytic ileus and intestinal ischemia or infarction.(1-6)

PREDISPOSING FACTORS: The risk for serious bowel complications is higher with increasing age, higher frequency of constipation, and in patients on higher doses of clozapine or multiple anticholinergic agents.(1,5)

PATIENT MANAGEMENT: Concurrent use of bulk forming laxatives with clozapine may be used with caution in patients who can maintain adequate fluid intake. Evaluate the patient's bowel function regularly. If patient is unable to maintain adequate fluid intake and use bulk forming laxatives as prescribed, avoid the use of bulk forming laxatives with clozapine.(1-6) Monitor for symptoms of constipation and GI hypomotility, including having bowel movements less than three times weekly or less than usual, difficulty having a bowel movement or passing gas, nausea, vomiting, and abdominal pain or distention.(2) Consider a prophylactic laxative in those with a history of constipation or bowel obstruction.(2) Review patient medication list for anticholinergic agents which may have additive effects on decreased GI motility. When possible, decrease the dosage or number of prescribed anticholinergic agents, particularly in the elderly. Counsel the patient about the importance of maintaining adequate hydration. Encourage regular exercise and eating a high-fiber diet.(2)

DISCUSSION: The concurrent use of clozapine and bulk forming laxatives has not been studied. Use of bulk forming laxatives with inadequate fluid intake has been associated with gastrointestinal obstruction.

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• Appendicitis
• Esophageal obstruction
• Gastrointestinal obstruction

• Dysphagia

There are no moderate contraindications for this drug.

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Less Frequent

• Allergic dermatitis
• Esophageal obstruction
• Intestinal impaction
• Pruritus of skin
• Skin rash

Rare or Very Rare

• Anaphylaxis
• Angioedema
• Cardiac arrhythmia
• Dyspnea
• Hypermagnesemia
• Hyponatremia
• Seizure disorder
• Ulceration of colon

Less Frequent

• Abdominal pain with cramps
• Diarrhea
• Flatulence
• Headache disorder
• Nausea
• Polydipsia
• Vomiting

Rare or Very Rare

• Pruritus of skin
• Skin rash
• Urticaria

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