pancreatic enzyme replacement therapy

Cost calculations of Pancreatic Enzyme Replacement Therapy (PERT) for Exocrine Pancreatic Insufficiency (EPI) and alternative over the counter enzyme products

by Dana Lewis

I previously wrote about my experience figuring out that I have exocrine pancreatic insufficiency (known as EPI or PEI), and also a little bit about starting on pancreatic enzyme replacement therapy (PERT). I talked briefly about the method I was using to figure out the right amount of PERT for me, but I realize that there’s a lot more detail I could provide about how to titrate enzymes in general, and not just PERT.

Some background first, though. When I write about PERT (pancreatic enzyme replacement therapy), I am talking about the FDA-approved class of drugs (called “pancrelipase”) that contain THREE types of enzymes, which the FDA calls “pancreatic enzyme products” or PEPs. Pancrelipase contains lipase (helps digest fat), protease (helps digest protein), and amylase (helps digest starches and other complex carbohydrates). As of 2010, all pancrelipase products that are marketed for EPI must be FDA approved.

Any time I refer (here or in other blog posts) to other enzyme products (either single enzyme or multi-enzyme), I’m referring to over the counter products that are not FDA approved.

Why does FDA approval matter for PEPs? FDA approval is essentially a rubber stamp saying you can trust the FDA to have validated that the companies making these products are making them as they describe them, meaning if they say they have 25,000 units of lipase, they actually have 25,000 units of lipase in them. (And protease and amylase). FDA-approved PEPs used in PERT are made from ground up pig pancreas (really), which is why they’re expensive. There is no generic PEP or PERT. (FDA also has a nice page here explaining the importance of understanding what is and is not an approved PEP/PERT product, and it also explains the brands that are currently approved and the differences between them.) This matters because when you talk about the cost people will probably suggest a “generic” of PERT, but there isn’t one.

However, there are non-FDA-approved over the counter enzyme products. They do exist, but because they have not been vetted by the FDA, I (and you!) should be wary about trusting them when they say they contain X units of lipase or any other enzyme product. Additionally, there are no studies (that I can find) comparing the efficacy between over the counter enzymes (single or multi-enzyme products) and FDA-approved PERT. (If you have found such a study, please leave a comment!)

So does that mean you can’t take them? No, I’m not saying that. What I am saying is you should only try other products with enzymes if you are willing to carefully test and vet FOR YOURSELF whether they work FOR YOU or not. (P.S. – did I mention I’m not a doctor? This is not medical advice; for medical advice, talk with your doctor. Although, doctors may not be aware of the over the counter enzyme options either, and this post might be worth sharing with them as well).

Three goals for optimally titrating enzymes for exocrine pancreatic insufficiency

I have three goals for getting my PERT dose titrated well.

  • First, get enough enzymes (through PERT) to reduce all symptoms.
  • Second, test and assess my lipase:fat and protease:protein ratios so I can figure out how to optimally dose enzymes for new meals of different amounts of fat and protein.
  • Third, optimize for reducing cost with enzymes, through a combination of supplementing PERT with standalone lipase and/or using lipase for fat-only snacks.

Here’s an example of how you might consider vetting over the counter enzyme products, and using them to supplement your FDA-approved (and hopefully insurance-covered) PERT:

As I mentioned earlier, I titrated and found out that my current dose of PERT covers about 30-40 grams of fat and 30 grams of protein. Some individuals only need support in digesting fat (e.g., need only lipase), but I have found that my body also needs support in digesting protein. (However, I don’t appear to need much amylase for carbohydrates.) Therefore I am tracking what amount of fat and protein I am eating with every meal. A 25,000 (lipase) dose of my PERT also contains enough protease to cover 30 grams of protein. Sometimes, I eat higher (>30-40g) fat meals that mean I need more lipase. So I would need two pills of the current dose of PERT, because 25,000 only covers ~30-40g of fat (FOR ME).

But – what if there was another way to get additional lipase without needing a full second pill of PERT, if I don’t need the additional support for more protein for this meal?

Enter over the counter enzyme options. In this example, a single enzyme option for lipase. Here is an example (Amazon affiliate link) to a standalone, single enzyme lipase product that is available as an over the counter product.

I personally have experimented with using standalone over the counter lipase to supplement my PERT dose, for the reason described above (needing more lipase but not necessarily needing more protease or amylase). The reason I would choose standalone lipase has to do with cost.

PERT, being ground up pig pancreas, is expensive. There is no generic for PERT! However, there have been methods to develop lipase from microbes as well as other sources beyond animals. Thus, it is possible to have a standalone source of lipase that is a lot cheaper than PERT. How much cheaper? Well, the bottle linked above when I calculated this was $23.50 for 90 pills. One pill each contains roughly 3,150 units of lipase (again, caveat from above about trusting the amount in over the counter products). That means each pill ($23.50/90 pills) is $0.26 USD, and each 1,000 units of lipase is roughly $0.08.

This math is then helpful to compare the cost of PERT. Depending on the size of prescription PERT, you might see a prescription anywhere from 3,000 to 25,000 to 36,000 units (depending on the brand, they have different amounts, but they are all measured based on units of lipase). Using GoodRx, you can generally compare retail prices of medications, such as this search for 24,000 PERT of one brand (90 capsules) or this search for 25,000 PERT of a different brand (also 90 capsules). Both of them are in the ballpark (for 90 capsules each) of $700-900, so let’s use $800 for 90 capsules for simple math. The per-pill price is $8.89 ($800/90 pills). The per-1,000 unit of lipase cost depends on whether you are using the 24,000 PERT ($8.89/24) or 25,000 PERT ($8.89/25) option, but those are roughly $0.37 and $0.36 per 1000 units of lipase.

So if you were to consume a meal that was ~10g of fat above your current PERT dose, and you didn’t need additional protein support, it would be cheaper to add on additional lipase (at $0.08 per 1000 units of lipase) as a standalone enzyme product instead of an additional PERT (which is, per our estimates, ~$0.36 per 1000 units of lipase). You don’t get to break apart a PERT (It can’t be cut in half, for example), so the per-pill cost is the better comparison. Adding a 3000-ish unit lipase onto your meal to cover an additional 10g of fat costs $0.26, and a second PERT is $8.89.

Therefore, a meal that needs 28,000 lipase is cheaper as 1 PERT and 1 extra standalone lipase rather than 2 PERT.

This of course assumes you have tested the standalone lipase and found that it works for you. I personally have done so and found that standalone lipase of the brand I chose works for this purpose (there are many brands and sizes: again, test what works for you), so I can titrate my meals as PERT+lipase, or even take 1-2 lipase (depending on the fat content) for a snack that’s mainly fat. However, again, a caveat that I personally am sensitive to protein and am tracking everything that I’m eating, so I know my personal math very well. Typical PERT dosing and recommendations is to take “2 or more” for meals or “1-2 for snacks”, but that completely ignores how much fat and protein is in the meals, and might be significantly undertreatment or overtreatment for you.

Why does undertreatment matter? Well, you get symptoms. Those are no fun.

Why does overtreatment matter? Well, you can get constipation. (I haven’t had it, but it also doesn’t sound like fun).
A gif showing a square moving along a spectrum from "too little" to "too much enzyme". Too little enzyme and you have symptoms, not enough and you reduce but don't eliminate symptoms. Enough enzymes and you eliminate symptoms. Too much risks constipation.

My approach was making sure my meals were covered first with prescription PERT, then evaluating additional standalone products that I could use to supplement or replace PERT depending on what I was eating, so I could prioritize reducing symptoms and then for improving the cost required to achieve that.

There are other standalone enzyme products, including products containing multiple enzymes. If you join one of the Facebook groups for EPI, you’ll see people recommencing various names of enzymes for over the counter products. But again, you really should test things and see if they work for you. Read all the ingredients on any product you’re taking. A lot of times you can search for lipase and you’ll get a multiple-enzyme product. And that product may have additional ingredients or fillers that don’t sit well with you. You may even find that one brand of prescription PERT might not work for you, whereas another one does.

My suggestions include:

  • Carefully test any product, whether it’s PERT or over the counter enzymes. Keep a good log of your post-meal symptoms and next-day symptoms (e.g. bathroom results) and try different meals with different amounts of fat and protein.
  • If you have symptoms regularly with a certain amount of enzymes, it could be either that this particular brand (over the counter or even prescription PERT) does not work well for you, OR that you are not taking enough enzymes to cover your needs.
  • If in doubt, talk with your doctor. They may/not have opinions on over the counter products, especially if they haven’t had other patients reporting back what is working for them or not, since there are no studies on those particular brands (and of course, they’re not FDA approved). But with approved PERT, they should be able to give you some more input on how to increase your dose or change your prescription to adjust. Having the data on how much fat and protein you’re eating and what results you’ve been getting could help you (and them) get to a more optimal dose more quickly.

—

(PS, if you didn’t see them, I have other posts about EPI at DIYPS.org/EPI)

What you should know about starting on Pancreatic Enzyme Replacement Therapy (PERT)

by Dana Lewis

It’s been about two weeks since I started on pancreatic enzyme replacement therapy (PERT) and it’s been really interesting to experience the difference it is making for me.

For context (and you can read more here), I have moderate exocrine pancreatic insufficiency (EPI or PEI), but I have very obvious symptoms following anything I eat for a few hours, as well as next-day bathroom habits. My clinician didn’t think trying PERT would be a problem even though my elastase levels were only borderline low, and it didn’t hurt. It definitely helped in multiple ways.

Here’s what the experience has been like starting on PERT, what I like about it, what I found challenging, what it’s like to scientifically titrate your dosing of PERT, and a handful of random other thoughts.

Here is what I like about Pancreatic Enzyme Replacement Therapy (PERT)

With undiagnosed EPI, for the last almost two years, I would eat food with dread. And not a lot of food (averaging 2 meals a day), because I had to severely limit the kinds of things I was eating to try to reduce my symptoms (with mixed success). With my first few doses of PERT, I ate relatively small, careful and low-FODMAP meals so I could better assess whether PERT was working.

And wow, was it working.

With the first few small (and low-FODMAP, to reduce variables that I was testing) meals, I had an immediate improvement. I didn’t realize until I took PERT how sick I felt every time I ate anything, even when I didn’t have obvious post-meal symptoms of gas, stabbing abdominal pain, or next-day bathroom habits. With PERT, I felt…nothing? Which is apparently how I used to feel after I would eat. There was no sick feeling, no bloating within an hour, and no discomfort for hours. There was no gas after I ate or overnight. In the morning, I didn’t have steatorrhea.

I got braver and experimented with a few bigger meals. In some cases, I still felt not-sick after I ate, but did develop some gas. However, it was significantly reduced.

From tracking the cumulative fat and protein levels in everything I ate, I was able to see that things less than 50 grams of fat and protein (combined) worked exceptionally well with the level of PERT I had started on. PERT has different dosing options, and I had started on a relatively moderate dose. I saw that some of my 70-ish gram meals were fine, but the ones in the 90s definitely needed more PERT.

Even when I could tell I needed more PERT, though, it wasn’t a complete failure. Even for meals with 90+ grams of fat+protein, I had a reduction in feeling sick, way less gas, and improved bathroom habits, even if they weren’t as ideal as what happened when I ate <50g of fat and protein meals.

As I discussed in my previous post, I had felt like a boiling frog where I didn’t really feel good every day, but there was usually nothing obviously wrong (no broken bone, no stabbing pain every day). So it was hard to know what was wrong. Now, taking PERT, I can see a clear difference on the days when the dosing is well-titrated to what I’m eating (no symptoms after I eat, plus I feel a lot better!) compared to when the dosing isn’t optimal (reduced symptoms but still there, sometimes will still feel sick or abdominal discomfort).

I also now have back the lab results of the bloodwork I asked my gastroenterologist to run on fat-soluble vitamins (A, D, E) and iron, to make sure I didn’t have any deficiencies that need addressing. Thankfully, I didn’t – which is probably influenced by the fact that I am absorbing some of what I eat without PERT, but is also likely due to the fact that I take two multivitamins daily plus additional vitamin D supplements. I can imagine that I would have much lower levels without the supplementation, so I’m glad I had built the habit in the last two years of making sure I was taking my vitamins. (Which I wasn’t doing before two years ago consistently, and intuitively was worried about getting the right nutrients given the changes I was making to what I was eating, so that was a good habit to have built up!)

As a pleasant result of taking PERT, I’m also seeing improvements in symptoms that I did not think were correlated with EPI.

For example, in October I developed severely dry eyes, which I’ve never had before. I’ve been using lubricating eye drops several times a day and gel drops at night ever since. After about a week of PERT, I realized that I was waking up in the morning and my first thought wasn’t about putting drops in my eyes because they weren’t painfully dry. And then on days following when my PERT dosing wasn’t optimal (as evidenced by post-meal gas or abdominal discomfort, etc), my eyes are more dry than they are on the other days.

Another thing I’ve noticed is the skin on my face improving. In the last year, I started having more acne breakouts and changes to my skin tone. This, like the eye dryness, has started to noticeably improve in the last week or so (with no other changes to routine or the weather: it’s still winter here!).

What I find challenging about Pancreatic Enzyme Replacement Therapy (PERT)

There’s not a lot of guidance to patients regarding PERT titration (changing dosing levels as needed). My GI doc wrote a script for one size and said we could size up if it wasn’t working. That was it.

Thankfully, I have 19 years of experience with titrating insulin dosing for everything I’m eating, and I have an inclination to use spreadsheets to track things, so I began to take PERT and write down the relevant details of what I was eating (date, timing, what it was, how much fat and protein it had, what PERT dose I took), the result (any post-meal symptoms including timing) and whether it caused steatorrhea or other bathroom-related changes. From this, I was able to very quickly group meals into “wow that worked awesome”, “hmm, this reduced symptoms but it wasn’t perfect”, and “wow that needed more PERT”. For me, those roughly ended up being <50 grams combined of fat and protein (“wow that worked awesome”), around 70 grams (“hmm, this reduced symptoms but it wasn’t perfect on every front”), and more than 90 grams (“wow that needed more PERT”).

Interestingly, a lot of the medical literature I read about PERT indicates that most people are not taking enough. Given my analysis of my own data, that’s currently true. (Personally I’m currently trying to collect more data in each category before I discuss dosing with my clinician, to figure out what dosing or prescription I might need).

I’m only two weeks in, so I can’t yet give solid advice to anyone else taking PERT, but I imagine in the future I would likely feel more confident saying the following to someone else starting on PERT:

  • If you can, write down the date, timing, what you eat, and the nutrients (e.g. fat, protein, and carb) of what you’re eating, and track what symptoms you have when following a meal. Also make sure to note how many and what dose of PERT you took.
  • See if you can group the data between which meals turned out well, which could be improved, and what didn’t work. That may help you discuss with your doctor what level of enzyme you need for what type of meal.

Anecdotally in the EPI communities, people discuss taking 3-4 of the largest dose PERT for meals, vs 1-2 for their snacks. It seems to be very, very individual about what people need. Some people (like me with moderate EPI) have symptoms, others can have severe insufficiency (severe EPI) but have fewer symptoms. As a result, we may need more or less PERT, depending on how our bodies are generating symptoms.

One frustration I have about GI-related conditions, whether that’s those that result in people using the low FODMAP diet or EPI resulting in the need for PERT – and even in the diabetes community where insulin is needed – is that there’s very much a perception of individual blame in the day-to-day operations. If you have symptoms, you probably did something wrong. You ate a high FODMAP thing, or you ‘stacked’ FODMAPs…or for EPI, you didn’t take enough PERT or you ate the wrong thing. In diabetes, you didn’t take enough insulin, or you did it at the wrong time, or you forgot, or you ate too much, or you ate the wrong thing…. There is SO much blame and shame going around, and it’s frustrating to see (and experience).

Having tracked my data for two weeks now, I can see very clear cause and effect in the data: when I feel great, my PERT dosing has been well-matched to what I was eating. When I have some symptoms, the PERT dosing was not-optimal, and sometimes as a result I have a lot of symptoms and don’t feel well. It’s a very clear cause and effect relationship between having sufficient enzymes or not having enough enzymes. I am working to not feel guilty, e.g. I did something ‘wrong’ by choosing the wrong sized meal to go with the PERT dosing, and instead frame it as data that I’m collecting to inform the future prescription I need of PERT.

(My point here is that I don’t like the blame/shame that goes around, and yet, I still feel it, too. I’m trying to remove myself from those patterns of thinking, because it’s not at all helpful.)

It’s helpful instead for me to think “Wow, that was not enough PERT this time! Next time I should take 2 of this dose, or supplement my single PERT with standalone lipase” rather than feel shame or guilt because I ate a “big” meal. This is in part why I’m trying to stay away from thinking and using words like “big” or “small” meal, because the size is so arbitrary, depending on whether you’re looking at volume of food on a plate, thinking about calories, carbohydrates (to take insulin for it), or the fat and protein amounts (to dose PERT for it).

Also, everyone with EPI is likely VERY different from one another, and so my cutoffs of 70 or 90g of fat+protein may be numerically more or less than what someone else needs. (Those who take PERT will also notice I am very careful to not specify what PERT dose my one pill is, because everyone’s needs are different, and I don’t want anyone to accidentally anchor on my dose numbers, because what I need may not be what everyone else needs.)

And I can imagine some folks without EPI reading this with their own perceptions of fat and protein levels thinking judgmental thoughts about the numerical amounts of what I’m eating at different times.

Having to track fat and protein makes me grumpy, for a few reasons. In part, because it’s “one more thing” to track (in addition to general carbohydrate estimates to be able to dose insulin or inform my automated insulin delivery system about what I’m eating). In part, because I set up a spreadsheet to learn from what I’m doing, so I need to count it, input it into my spreadsheet, and then analyze the data later. I know I won’t always need to do this, and eventually I’ll learn intuitively what dosing I need for different types of meals.

But, I now have to remember to get out my PERT, take it “with the first bite” (which I interpret as swallow the PERT and then immediately try to put a bite of food in my mouth so I match the timing of the food with the PERT), then write down the timing of when I took my PERT and input the fat and protein and details of the meal into my spreadsheet…and then remember to also enter carbohydrates into my automated insulin delivery system (which I don’t have to do, but I get better outcomes with a meal announcement so I want to do so. When I’m not working on PERT titration, it doesn’t feel like a burden.).

—

Although I am grumbling about the titration learning curve and process of figuring out my dosing and what I am eating, I know it’s like any learning curve: I will figure it out soon, and the routine of taking PERT will become as easy as remembering to enter carbs or take insulin for what I’m eating.

And as a short-term benefit and reward of learning to dose PERT for what I’m eating, I feel so much better. Immediately, after every meal, as well as the next day, and I also feel better overall while improving other ‘symptoms’ that I didn’t realize were correlated with my EPI. Hooray!

What it’s like to start on Pancreatic Enzyme Replacement Therapy (PERT)

PS – make sure to check out my other posts about EPI at DIYPS.org/EPI, including the one about  PERT Pilot, the first iOS app for Exocrine Pancreatic Insufficiency that I built! It’s an iOS app that allows you to record as many meals as you want, the PERT dosing and outcomes, to help you visualize and review more of your PERT dosing data!

—
You can also contribute to a research study and help us learn more about EPI/PEI – take this anonymous survey to share your experiences with EPI-related symptoms!

—