Optimizing PERT: Dosing, Adjustments, and Managing Non-Responders in EPI

This episode delivers highly practical guidance on PERT optimization—one of the most clinically impactful sections of the series. The panel opens with a frank discussion of naturopathic and over-the-counter enzyme alternatives. These products remain unvalidated, are not equivalent to prescription PERT, often come with inadequate lipase units and higher pill burden, and are not cheap—making transparency with patients about their limitations essential.

On product selection, Jennifer Geremia notes that insurance coverage and access frequently make the choice rather than clinical preference. When there is flexibility, she prefers to start with a product that offers the highest available lipase units per capsule to minimize pill burden, given that patients will already be managing multiple medications.

The panel walks through nuanced dosing considerations. The most common adult starting approach for established PERT products is approximately 2–3 capsules per major meal and 1 with snacks, with increases for larger holiday-type meals. Compliance review is the first step when patients are not responding—specifically: Are they taking PERT with every meal and snack? Are they taking it at the right time relative to eating? Weight changes warrant dose reassessment at every visit. Importantly, patients with uric acid conditions (gout, uric acid renal stones) require slightly lower doses to prevent uric acid overload.

For patients on non-enteric-coated formulations, or those not responding despite adequate dosing, adding a proton pump inhibitor (PPI) can improve PERT efficacy. Sarah Enslin extends this with a split-dosing strategy for extended meals—beginning with 2 capsules and adding a mid-meal dose for long dinners. Empowering patients with a general framework while encouraging them to self-adjust based on meal size and frequency is described as a key adherence strategy.

The panel tackles non-responders systematically. Key questions to ask: Has there been a change in symptoms from a stable baseline? Have new medications been added? Is disease progression occurring? For chronic pancreatitis patients, the 4–6% lifetime risk of pancreatic cancer should prompt surveillance consideration if there is unexplained change. Co-existing conditions such as SIBO should be reconsidered. Patients who ration medication due to cost are another common source of apparent treatment failure, underscoring the role of patient assistance programs.

In the next episode, "Team-Based EPI Care: Why Multidisciplinary Coordination Matters," the discussion transitions from clinical management to systems-based care, exploring why EPI requires a coordinated team approach and which specialties contribute most meaningfully to the patient journey.