Pancreatic Enzyme Replacement Therapy

Indications for Use

Pancreatic Exocrine Insufficiency (PEI) occurs when the pancreas does not release enough digestive enzymes leading to poor digestion and malnutrition. Digestive enzymes include lipase, amylase and protease, which help digest fats, carbohydrates and proteins respectively. Common symptoms of PEI include diarrhoea, abdominal cramps, steatorrhoea (fatty stools) and fat soluble vitamin deficiency (vitamins A,D,E and K). 

PEI can be caused by a range of conditions, often affecting the pancreas:

• Chronic pancreatitis
• Cystic fibrosis
• Pancreatic cancer
• Coeliac disease
• Surgery affecting the gut or pancreas

The main treatment for PEI is pancreatic enzyme replacement therapy (PERT), also known as pancreatin. PERT is the provision of pancreatic enzymes required for digestion; lipase, amylase and protease. 

By TeachMeSeries Ltd (2026)

Fig 1: Breakdown of fats, carbohydrates and proteins by pancreatic enzymes

Pharmacokinetics

Pancreatin is released in the small intestine and acts locally to help digest foods. Pancreatin is not absorbed systemically. Peak enzyme activity occurs at ~30 minutes.

Creon and Nutrizym 22 capsules are formulated as enteric-coated (acid-resistant) mini-microspheres/minitablets within gelatine capsules – the mini-microspheres/minitablets should not be chewed or crushed. The enteric coating helps to protect pancreatin from deactivation from stomach acid.

It is common practise for non enteric-coated formulations such as Pancrex V Powder to be administered via enteral tubes, when the oral route is inaccessible.

Acid reducing drugs such as proton pump inhibitors (PPIs) may be prescribed alongside PERT to increase effectiveness.

• For enteric coated formulations – increased effectiveness is due to an increase in the pH of the duodenum (where PERT is released) via a reduction in acid flowing into the duodenum from the stomach.
• For non enteric-coated formulations, such as Pancrex V Powder and Pancrex V granules, PPIs increase the pH of the stomach, reducing deactivation of PERT by stomach acid. 

Common formulations are shown in the table below:

By TeachMeSeries Ltd (2026)

Fig. 2: Available formulations of pancreatic enzyme replacement therapy.

Patient counselling

PERT should be taken with meals and snacks, spreading out the dosage throughout the meal is beneficial. PERT does not need to be taken with fat free snacks or meals e.g. jelly.  

Doses usually start at 2 capsules with meals and 1 capsule with snacks. The dose is adjusted to symptoms, starting with a lower dose and increasing as necessary. Maximum doses are quoted as 10,000 units/kg/day of lipase, doses above this range may cause colonic damage and if symptoms are not controlled at higher doses, then alternative diagnoses should be considered. Acid suppressing medications should be considered, if not already prescribed, for patients are reaching higher doses of PERT.

Pancreatin is destroyed by heat, so patients should be counselled not to take PERT with hot food or drink. Furthermore, PERT should be taken with food or drink with a pH < 5.5 such as apple sauce or yoghurt or any fruit juice, or plain water, to avoid enzyme release prior to reaching the small intestine (pancreatin is inactivated in stomach acid which can reduce the efficacy). Pancreatic enzymes released prior to the small intestine can also cause irritation of the gastrointestinal tract. 

PERT may be required alongside enteral feeds administered via enteral tubes. If the patient is unable to take capsules, then often Pancrex V powder is administered via the enteral feed at prescribed intervals throughout the duration of the enteral feed. Pancrex powder can also be swallowed dry or mixed with a little water or milk before each snack or meal. Pancrex V Powder and Pancrex V Granules are not enteric-coated, therefore are more susceptible to deactivation in the stomach.

Pancreatin is derived from a porcine source therefore permission is given for Jewish and Muslim patients to take PERT, as there are no porcine-free alternatives. 

Cautions

Irritation of the anus may occur with PERT, this could be an indication of taking too much PERT, but symptoms should be taken into account during assessment. 

References

1. Exocrine pancreatic insufficiency | Treatment summaries | BNF | NICE Accessed 5/5/26
2. Creon 25000 Capsules – Summary of Product Characteristics (SmPC) – (emc) | 1168  Accessed 5/5/26
3. Pancrex V Powder – Summary of Product Characteristics (SmPC) – (emc) | 1056  Accessed 5/5/26
4. Nutrizym 22 – Summary of Product Characteristics (SmPC) – (emc) | 11883  Accessed 7/5/26