Re: Creon Forte (long and scientific)

[Guest guest]

Hi Liesbeth,

welcome back to the list! And thanks again for the nice card you sent me after

Kasper arrived. I am not sure, whether you ever got my reply.

Have you moved into your new house already? We did in December and it's great!

Re the Creon forte, well, I think the whole discussion is about the potential

risk of a substance, Eudragit L30D55, which is used as a coating on some enzyme

brands like Ultrase or Panzytrat. There is some speculation, that this substance

might be the culprit for a disease called fibrosing colonopathy. To get more

information, you can follow the link below or read the abstracts I have copied.

http://www.fibrosingcolonopathy.com/library.htm

Solvay, the maker of Creon, claims that Eudragit is dangerous, but it can be a

marketing strategy, because they use a different coating.

Fiona has forever been on Creon 5, and we don't have a reason to change. The

problem I see with the Creon 25 is, that you can't find an easy dosage for

snacks. Whenever Fiona eats some chocolate or drinks a cup of milk, we give a

Creon 5.

And Jen, yep, your math is great :-))) The numbers behind the different enzyme

brands stand for the amount of lipase units in thousands, e.g. one Creon 25

contains 25,000 lipase units.

In a british study the docs have found out, that exceeding the enzyme dosage

above 10,000 units per kg/ per day doesn't help at all. I have copied this

finding below too! Hope some of you find it interesting. We have reduced Fiona's

enzyme dosage over the last half year from 8,000 units per kg/ per day to 6,000

and haven't seen great a difference.

Bye-bye

Torsten, dad of Fiona 3wcf

e-mail: aberdeen95@...

TI: Comparative and experimental pathology of fibrosing colonopathy.

AU: van-Velzen-D; Ball-LM; Dezfulian-AR; Southgate-A; -CV

AD: Department of Fetal and Infant Pathology, University of Liverpool,

UK.

SO: Postgrad-Med-J. 1996 Mar; 72 Suppl 2: S39-48; discussion S49-51

ISSN: 0032-5473

PY: 1996

LA: ENGLISH

CP: ENGLAND

AB: Although the occurrence of fibrosing colonopathy is temporally

associated with the introduction of high-strength pancreatic enzyme

supplements, its pathogenesis remains uncertain. The UK case-control study

showed fibrosing colonopathy to be associated with high doses of

high-strength pancreatic enzyme supplements and with a group of brands which

occupy only 30% of the market. Two alternative hypotheses were proposed to

explain the aetiology of fibrosing colonopathy: exposure to high levels of

enzymes or to as yet unidentified components of the formulation. Comparison

of the anatomical pathology of fibrosing colonopathy with that of previously

encountered forms of obstructive gastrointestinal pathology, such as

stricturing lesions due to potassium chloride preparations and nonsteroidal

anti-inflammatory drugs, confirmed it to be a previously unencountered,

long-segment lesion of the colon. Thus the use of the descriptive term

'stricture' is a misnomer leading to much clinical confusion when discussing

obstructive bowel pathology in cystic fibrosis patients. Gavage studies in

the rat with one of the two monomers (ethyl acrylate) forming the

methacrylic acid copolymer (Eudragit L30D55) used for the enteric coating of

the high-strength pancreatic enzyme supplements, have shown pathology

comparable to fibrosing colonopathy. These findings prompted a series of

exploratory studies in adolescent pigs. After seven days caecal gavage of

Eudragit L30D55 at doses of 10, 50 or 500 mg/kg/day (comparable to human

intake), extensive fibrosing colonopathy-like changes, inclusive of dense

submucosal fibrosis, were noted at all dose levels in seven out of nine

animals. Similar studies of the monomer components of the Eudragit L30D55

copolymer, at dose levels of 0.015 to 50 mg/kg/day, representing possible

residues in Eudragit L30D55, did not produce comparable changes. The

conclusion is that, although the precise mechanisms have not been

elucidated, the role of enteric coatings containing Eudragit L30D55 in the

pathogenesis of fibrosing colonopathy requires urgent further study.

AU: -C-J

CA: Univ.London

LO: London, U.K.

CO: LANCAO

JN: Lancet ( 353, No. 9156, 911-15, 1999 )

TI: Colonic toxicity from pancreatins: a contemporary safety issue.

AB: An unknown form of colonic fibrosis termed fibrosing colonopathy

caused by pancreatin in children with cystic fibrosis is reviewed with

respect to the safety of preparations available. Topics discussed include

evidence implicating high-strength pancreatins, fibrosing colonopathy

outside the U.K., pancreatin products, pancreatin intake, hypotheses on

pathogenesis of fibrosing colonopathy, recent developments, regulatory

responses and toxicological benefits. It appears formulation may have a

role to play in this toxicity. In conclusion, had the use of high-strength

pancreatins been more conservative, their ability to treat cystic fibrosis

might have been continued without restriction.

EX: Colonic fibrosis has been identified in young children with cystic

fibrosis. Symptoms include failure to thrive (distal intestinal obstructive

syndrome, DIOS), persistent abdominal pain with obstruction or distention,

bloody diarrhea, chylous ascites, thickened bowel wall, reduced peristalsis,

foreshortening of the colon, loss of haustrations, " lead pipe " colon and

dilation of the terminal ileum. An association was made between intake of

high-strength pancreatins and fibrosing colonopathy. Different

high-strength pancreatins have different enteric coatings and it is thought

colonic fibrosis is due to high-intake of Eudragit L30D-55-coated

pancreatin. One possibility is a direct toxic effect of Eudragit L30D-55 on

the intestinal wall. This agent delivered to pigs via an intracecal fistula

produces colonic lumenal narrowing, abscess formation and a fibrosing

reaction in the lamina propria. However, the detergent and polysorbate-80

containing vehicle alone used in the study causes mucosal erosion and

atrophy of the distal colon. Toxicology studies of a monomer of Eudragit

L30D-55, ethyl acrylate show p.o. administration causes edema, ulceration

and acanthosis of the rodent forestomach. Distal small-intestine damage has

been caused by enteric coated KCl supplements for patients taking K-wasting

diuretics. There were reports of small-bowel stenosis with perforations.

In some patients, lesions may also involve the terminal ileum with severe

fibrosing colonopathy. Creon 25000 has been less frequently associated with

colonic fibrosis which may be due to the phthalate-based enteric coating

which has a more rapid dissolution in the small intestine. 2 Fig. 1 Tab. 37

Ref. (IG)

Toxicology Department, St. Bartholemew's and Royal London Hospital, School

of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, England.

(e-mail: C.J.@...)

TI: The pathology of fibrosing colonopathy of cystic fibrosis: a study

of 12 cases and review of the literature.

AU: Pawel-BR; de-Chadarevian-JP; Franco-ME

AD: Department of Pathology, St 's Hospital for Children and

Allegheny University of the Health Sciences, MCP-Hahnemann School of

Medicine, Philadelphia, PA 19134-1095, USA.

SO: Hum-Pathol. 1997 Apr; 28(4): 395-9

ISSN: 0046-8177

PY: 1997

LA: ENGLISH

CP: UNITED-STATES

AB: The authors studied eight colectomy and eight biopsy specimens from

12 patients with cystic fibrosis who had developed fibrosing colonopathy, a

complication observed in patients receiving high-strength enzyme

replacement. The colectomies originated from five male and three female

patients ranging in age from 18 months to 6 years. Five individuals had

localized strictures of the right colon and three had stenosing fibrosis of

the entire colon. The affected colon had a cobblestone appearance,

submucosal fibrosis, thickening of the muscularis propria and chronic

mucosal inflammation in all patients, with active cryptitis in four.

Moderate to severe infiltration by eosinophils, with increase in the number

of mast cells, and widespread interruption of the muscularis mucosa were

present in every case. Four colectomies were preceded by endoscopic

biopsies; four patients who have not undergone surgery also underwent

biopsy. All the biopsies showed evidence of active or chronic inflammation,

and all had increased mucosal eosinophils. Prolonged colonic mucosal contact

with either the enzymes and/or the enteric coating itself may lead to

mucosal colonic ulceration and inflammation. Topical allergy may then

promote the stenosing fibroplasia.

Date: Wed, 1 Dec 1999 13:45:15 GMT0BST

Subject: CF: Pancreatic Insufficiency and Enzymes

Hi

We and others have found that increasing the intake of pancreatic

supplement above 10,000units/Kg body weight/day gives no

improvement in clinical status (weight and height). Further more

excessive amounts of pancreatic supplement have been linked to

the development of a stricture of the colon known as fibrosing

colonopathy. The condition is not common and therefore the risk

is probably low. However I can understand why a clinician might

recommend against taking elevated levels where the clinical

benefits are not clear and there is a possible associated risk albeit

remote.

Henry Ryley

Dr Henry C Ryley

Dept of Medical Microbiology

University of Wales College of Medicine

Cardiff CF4 4XN

Wales, UK

Tel: 01222 743521(office) or 744472 (lab)

Fax: 01222 744123 or 742161

RyleyH@...