PANOZYME

Dosage Form: Capsule

Generic Name: Pancreatin

Strength: 150 mg.

For the treatment of pancreatic exocrine insufficiency.

Posology

Adults (including the elderly) and children:

Initially one or two capsules during or immediately after each meal. Dose increases, if required, should be added slowly, with careful monitoring of response and symptomatology.

The daily dose of pancreatic enzymes for most patients should remain below 2500 units of lipase per kilogram per meal (10,000 units per kilogram per day), and that higher doses should be used with caution and only if quantitative measures demonstrate substantially improved absorption with such treatment. This particularly applies to young children.

It is important to ensure adequate hydration of patients at all times whilst dosing PANOZYME.

The capsules can be swallowed whole, or for ease of administration they may be opened and the granules taken with acidic fluid [pH<5.5] or acidic soft food [pH<5.5]. This could be apple sauce or yoghurt or fruit juice with a pH less than 5.5, e.g. apple, orange or pineapple juice. Crushing and chewing of the Mini microspheres or mixing with food or fluid with a pH greater than 5.5 can disrupt the protective enteric coating. This can result in the early release of enzymes in the oral cavity and may lead to reduced efficacy and irritation of the mucous membranes. Care should be taken so that no product is retained in the mouth. If the granules are mixed with food, it is important that they are taken immediately and the mixture should not be stored, otherwise dissolution of the enteric coating may result. To protect the enteric coating, it is important that the granules are not crushed or chewed.

Colonic damage has been reported in patients with cystic fibrosis taking high doses of pancreatic enzyme supplements.

Hypersensitivity to the active substance or to any of the excipients.

Strictures of the ileo-caecum and large bowel (fibrosing colonopathy) have been reported in patients with cystic fibrosis taking high doses of pancreatin preparations. As a precaution, unusual abdominal symptoms or changes in abdominal symptoms should be medically assessed to exclude the possibility of fibrosing colonopathy, especially if the patient is taking more than 10000 units of lipase/kg/day.

This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, essentially 'sodium-free'.

Traceability

To improve the traceability of biological medicinal products, the name and the batch number of the administered products should be clearly recorded.

No interaction studies have been performed.

Fertility And Pregnancy

For pancreatic enzymes no clinical data on exposed pregnancies is available.

Animal studies show no evidence for any absorption of porcine pancreatic enzymes. Therefore, no reproductive or developmental toxicity is to be expected.

Caution should be exercised when prescribing to pregnant women.

Lactation

No effects on the breast-fed newborns/infants are anticipated since animal studies suggest no systemic exposure of the breast-feeding woman to pancreatic enzymes. Pancreatic enzymes can be used during breast-feeding.

If required during pregnancy or lactation PANOZYME should be used in doses sufficient to provide adequate nutritional status.

PANOZYME has no or negligible influence on the ability to drive and use machines.

In clinical trials, more than -900 patients were exposed to PANOZYME.

The most reported adverse reactions were gastrointestinal disorders and were primarily mild or moderate in severity.

The following adverse reactions have been observed during clinical trials with the below indicated frequencies.

*Gastrointestinal disorders are mainly associated with the underlying disease. Similar or lower incidences compared to placebo were reported for abdominal pain and diarrhea.

Strictures of the ileo-caecum and large bowel (fibrosing colonopathy) have been reported in patients with cystic fibrosis taking high doses of pancreatin preparations, see section 4.4 Special warnings and precautions for use.

Allergic reactions mainly but not exclusively limited to the skin have been observed and identified as adverse reactions during post approval use. Because these reactions were reported spontaneously from a population of uncertain size, it is not possible to reliably estimate their frequency.

Pediatric Population

No specific adverse reactions were identified in the pediatric population. Frequency, type and severity of adverse reactions were similar in children with cystic fibrosis as compared to adults.

Extremely high doses of pancreatin have been reported to be associated with hyperuricosuria and hyperuricemia.

Supportive measures including stopping enzyme therapy and ensuring adequate rehydration are recommended.

Pharmacodynamics Properties

Multienzymes (Amylase, Lipase, Protease)

PANOZYME contains porcine pancreatin formulated as enteric coated (acid-resistant) Mini microspheres within gelatin capsules. The capsules dissolve rapidly in the stomach releasing plenty of Mini microspheres, a multi-dose principle which is designed to achieve good mixing with the chyme, emptying from the stomach together with the chyme and after release, good distribution of enzymes within the chyme.

When the Mini microspheres reach the small intestine, the coating rapidly disintegrates (at pH > 5.5) to release enzymes with lipolytic, amylolytic and proteolytic activity to ensure the digestion of fats, starches and proteins. The products of pancreatic digestion are then either absorbed directly, or following further hydrolysis by intestinal enzymes.

Clinical Efficacy

Overall, 30 studies investigating the efficacy of PANOZYME (PANOZYME capsules with 10000, 25000 or 40000 Ph. Eur units of lipase and PANOZYME 5000) in patients with pancreatic exocrine insufficiency have been conducted. Ten of these were placebo-controlled studies performed in patients with cystic fibrosis, chronic pancreatitis or post-surgical conditions.

In all randomized, placebo-controlled, efficacy studies, the pre-defined primary objective was to show superiority of PANOZYME over placebo on the primary efficacy parameter, the coefficient of fat absorption (CFA).

The coefficient of fat absorption determines the percentage of fat that is absorbed into the body considering fat intake and fecal fat excretion. In the placebo-controlled PEI studies, the mean CFA (%) was higher with PANOZYME treatment (83.0%) as compared to placebo (62.6%). In all studies, irrespective of the design, the mean CFA (%) at the end of the treatment period with PANOZYME was similar to the mean CFA values for PANOZYME in the placebo-controlled studies.

Treatment with PANOZYME improves the symptoms of pancreatic exocrine insufficiency including stool consistency, abdominal pain, flatulence and stool frequency, independent of the underlying disease.

Pediatric Population

In cystic fibrosis (CF) the efficacy of PANOZYME was demonstrated in 288 pediatric patients covering an age range from newborns to adolescents. In all studies, the mean end-of-treatment CFA values exceeded 80% on PANOZYME compared to all pediatric age groups.

Pharmacokinetic data is not available as the enzymes act locally in the gastrointestinal tract. After exerting their action, the enzymes are digested in the intestine.

Store protected from light, moisture and temperature not exceeding 30°C.