No Separation Required Between Xifaxan and Mylanta
You do not need to separate Xifaxan (rifaximin) from Mylanta (aluminum/magnesium hydroxide antacid). The FDA-approved prescribing information for Xifaxan explicitly states that "XIFAXAN can be taken with or without food," and there are no documented drug interactions requiring separation from antacids 1.
Rationale for Concurrent Administration
Minimal systemic absorption: Rifaximin has a bioavailability of less than 0.4% after oral ingestion, meaning virtually none of the drug enters the bloodstream 2. This extremely low absorption eliminates the typical concern about antacids interfering with drug absorption in the gastrointestinal tract.
No documented interactions: The FDA label for Xifaxan does not list antacids as requiring dose separation or caution, and only specifically mentions monitoring when used with warfarin or P-glycoprotein inhibitors like cyclosporine 1.
Gut-selective mechanism: Rifaximin works locally in the gastrointestinal tract rather than systemically, so alterations in gastric pH from antacids do not meaningfully affect its therapeutic activity 2.
Context for Diabetes and GI Symptoms
Since your question mentions acute onset diabetes with gastrointestinal symptoms, it's important to note:
GI symptoms are common in diabetes: All 16 measured gastrointestinal symptoms occur significantly more frequently in patients with diabetes compared to controls, and this is strongly associated with poor glycemic control 3.
Metformin considerations: If the patient is on metformin (the preferred first-line agent for type 2 diabetes), this medication is independently associated with chronic diarrhea and should be considered as a potential cause of GI symptoms 4, 5.
Severe hyperglycemia requires immediate attention: If the patient has blood glucose >300 mg/dL or HbA1c ≥10%, insulin therapy should be initiated immediately alongside metformin, as this represents a medical urgency 6, 7.
Important Caveats
Monitor for worsening symptoms: If diarrhea persists more than 24-48 hours or worsens while on Xifaxan, discontinue the medication and seek alternative treatment, as this may indicate a pathogen other than noninvasive E. coli 1.
Clostridium difficile risk: Although rare, antibacterial agents including Xifaxan can cause C. difficile-associated diarrhea; if diarrhea develops or worsens during or after therapy, evaluate for this complication 1.