Exocrine pancreatic enzyme deficiency as in cystic fibrosis, chronic pancreatitis, post pancreatectomy, post gastro-intestinal bypass surgery (eg Billroth II gastroenterostomy), and ductal obstruction from neoplasm (eg of the pancreas or common bile duct).

For oral administration.

Patients with pancreatic insufficiency should undergo regular nutritional assessments as a component of routine care and additionally, when dosing of pancreatic enzyme replacement is altered.

Dosage should be individualised to each patient, with therapy being initiated at the lowest possible dose and gradually increase until the desired control of steatorrhoea is obtained.

Adults and children

One or two capsules during each meal and one capsule with snacks. The inter-individual response to pancreatin supplements is variable and the number of capsules may need to be titrated to the individual based upon parameters of steatorrhoea, the fat content of the diet and symptomatology. Further dose increases, if required, should be added slowly, with careful monitoring of response and symptomatology. Patients should be instructed not to increase the dosage on their own. Changes in dosage may require an adjustment period of several days.

Where patients are already in receipt of lower unit dose enteric coated pancreatin supplements, Pancrease HL Capsules may be substituted at one-third of the number of capsules of the previous preparation.

Where swallowing of capsules is difficult, they may be opened and the minitablets taken with acidic liquid or soft foods (pH of 4.5 or less such as apple sauce) which do not require chewing. To protect the enteric coating, the minitablets should not be crushed or chewed.

Contact of the minitablets with food having a pH higher than 4.5 (e.g., milk, custard, ice cream, and many other dairy products) can dissolve the protective coating and will reduce the efficacy of the product.

It is important to ensure adequate hydration of patients at all times whilst dosing Pancrease HL Capsules.

Patients who are taking or have been given in excess of 10,000 units of lipase/kg/day are at risk of developing colon damage. The dose of Pancrease HL should usually not exceed this dose. If malabsorption is not controlled at this dosage, further investigation is warranted to rule out other causes of malabsorption.

Pancrease HL Capsules are not interchangeable with other pancreatin products.

.

Children aged 15 or under with cystic fibrosis.

Fibrosing colonopathy has been reported following treatment with different pancreatic enzyme products. Fibrosing colonopathy is a rare serious adverse reaction initially described in association with high-dose pancreatic enzyme use, usually with use over a prolonged period of time and most commonly reported in paediatric patients with cystic fibrosis. The underlying mechanism of fibrosing colonopathy remains unknown.

If symptoms suggestive of gastrointestinal obstruction occur, the possibility of bowel strictures should be considered. In some cases surgery including resection of the bowel is required and the need for this should also be considered.

It is uncertain whether regression of fibrosing colonopathy occurs.

Any change in pancreatic enzyme replacement therapy (e.g., dose or brand of medication) should be made cautiously and only under medical supervision. It is recommended that therapy be initiated at a low dose, followed by titration to an effective dose. The titration schedule should be guided by measured changes in 3-day faecal fat excretion. (See section 4.2)

Potential for irritation to oral mucosa

Care must be taken to ensure that no drug is retained in the mouth. Pancrease HL Capsules must not be crushed or chewed or mixed in foods having a pH greater than 4.5. These actions can disrupt the protective enteric coating resulting in early release of enzymes, irritation of oral mucosa, and/or loss of enzyme activity. For patients who are unable to swallow intact capsules, the capsules may be carefully opened and the contents sprinkled on a small amount of acidic soft food with a pH of 4.5 or less.

Potential for risk of hyperuricaemia

Caution should be exercised when prescribing Pancrease HL Capsules to patients with gout, renal impairment, or hyperuricaemia. Porcine-derived pancreatic enzyme products contain purines that may increase blood uric acid levels.

Potential viral exposure from the product source

Pancrease HL Capsules is sourced from pancreatic tissue from swine used for food consumption. Although the risk that Pancrease HL Capsules will transmit an infectious agent to humans has been reduced by testing for and inactivating certain viruses during manufacture, there is a theoretical risk for transmission of viral disease, including diseases caused by novel or unidentified viruses. Therefore, the presence of porcine viruses that might infect humans cannot be definitely excluded. However, no cases of transmission of an infectious illness associated with the use of porcine pancreatic extracts have been reported.

Allergic reactions

Caution should be exercised when administering pancreatin to a patient with a known allergy to proteins of porcine origin. Rarely, severe allergic reactions including anaphylaxis, asthma, hives, and pruritus have been reported with other pancreatic enzyme products with different formulations of the same active ingredient (pancreatin). The risks and benefits of continued Pancrease HL Capsules treatment in patients with severe allergy must be taken into consideration with the overall clinical needs of the patient.

No drug interactions with pancreatin have been identified.

Pregnancy

No adequate, well-controlled studies have been conducted in pregnant women. Pancrease HL capsules should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Pancrease HL should not be used in pregnancy unless clearly necessary but if required should be used in doses sufficient to provide adequate nutritional status (see warnings about high dose sections 4.2 & 4.8).

Breast-feeding

It is not known whether pancreatin is excreted in human milk. The possibility of protein constituents appearing in the breast milk cannot be excluded; therefore caution should be exercised when prescribing Pancrease HL capsules to lactating women.

Fertility

No fertility or peri/postnatal studies have been performed in animals.

It is not known if Pancrease HL Capsules has an effect on motor skills; however, there is no evidence that Pancrease HL Capsules alters a patient's ability to drive and use machines.

The following table displays adverse reactions that have been reported with the use of pancreatin from postmarketing experience. The displayed frequency categories use the following convention:

Very common (≥ 1/10); common (≥ 1/100 to <1/10); uncommon (≥ 1/1,000 to <1/100); rare (≥ 1/10,000 to <1/1,000); very rare (<1/10,000); and not known (cannot be estimated from the available clinical trial data).

Table: Adverse Reactions Reported in Postmarketing Experience for Pancrease HL (Pancreatin) Delayed-release Capsules

* Mainly cases of fibrosing colonopathy in paediatric subjects with cystic fibrosis.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

Symptoms and signs

Chronic high doses of pancreatic enzyme products have been associated with fibrosing colonopathy and colonic strictures (see Section 4.4). High doses of pancreatic enzyme products have been associated with hyperuricosuria and hyperuricaemia, and should be used with caution in patients with a history of hyperuricaemia, gout or renal impairment. (see Section 4.4).

Treatment

In the event of overdose, Pancrease HL Capsules should be temporarily discontinued and general supportive treatment given until symptoms resolve.

Pharmacotherapeutic group: Enzyme preparations, ATC code: A09AA02.

Mechanism of action

The porcine-derived pancreatic enzymes (lipases, proteases, and amylases) catalyse the hydrolysis of fats to monoglyceride, glycerol and free fatty acids, proteins into peptides and amino acids, and starches into dextrins and short chain sugars such as maltose and maltriose in the duodenum and proximal small intestine, thereby acting like digestive enzymes physiologically secreted by the pancreas..

Absorption

The enzymes are present in the form of pH-sensitive enteric-coated minitablets, which are filled into hard gelatin capsules. The minitablets, which are released from the capsule into the stomach, are enteric coated to resist inactivation at low pH. Once released, the minitablets are distributed into the stomach and pass into the duodenum where the enteric coating begins to dissolve and the enzymes are released when the pH reaches 5.5. Duodenal availability studies in adults indicate that following oral administration of Pancrease HL capsules, measurable levels of enzymes are present in the duodenum. Pancreatin is not absorbed from the gastro-intestinal tract in appreciable amounts.

Metabolism

Once they have accomplished their digestive function, the enzymes may be digested in the intestine.

Elimination

The constituents may be partially absorbed and subsequently excreted in the urine. Any undigested enzymes are excreted in the faeces.

Special populations

Paediatrics

The pharmacokinetics of pancreatin in paediatric subjects have not been investigated.

Elderly

The pharmacokinetics of pancreatin in elderly subjects have not been investigated.

Renal impairment

The pharmacokinetics of pancreatin in renally impaired subjects have not been investigated.

Hepatic impairment

The pharmacokinetics of pancreatin in hepatically impaired subjects have not been investigated.

No relevant information additional to that contained elsewhere in the Summary of Product Characteristics.

Castor oil, hydrogenated

Silica Colloidal Anhydrous

Magnesium stearate

Croscarmellose Sodium

Cellulose microcrystalline

Coat composition:

Simethicone emulsion

Methacryllic acid-ethyl acrylate copolymer (1:1)

Talc

Triethyl citrate

Purified water

Capsule composition (body and cap):

Titanium dioxide

Gelatin

Ink composition:

Shellac

Red iron oxide (E172)

Dehydrated AlcoholStrong Ammonia Solution Propylene Glycol

Isopropyl Alcohol

Butyl Alcohol

OR

Shellac

Red Iron Oxide (E172)

Dehydrated Alcohol

Propylene Glycol

Isopropyl Alcohol

Butyl Alcohol

Strong Ammonia Solution

Potassium Hydroxide

Purified Water.

None stated.

2 years.

Do not store above 25° C. Keep bottle tightly closed. Do not refrigerate or freeze.

High density polyethylene bottles with a low density polyethylene snap top lid, containing 100 or 500 capsules.

Not applicable.