Consumer medicine information

Creon Micro

Lipase; Amylase; Protease

BRAND INFORMATION

Brand name

Creon Micro

Active ingredient

Lipase; Amylase; Protease

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Creon Micro.

What is in this leaflet

This leaflet answers some of the common questions about Creon Micro. It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

Please read this leaflet before you start taking Creon Micro.

If you are helping someone else to take Creon Micro, please read this leaflet before you give the first dose.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Creon Micro against the benefits expected for you.

If you have any concerns about taking Creon Micro, ask your doctor or pharmacist. Your doctor and pharmacist have more information.

Keep this leaflet with your Creon Micro. You may need to read it again.

What Creon Micro is used for

Creon Micro is a pancreatic enzyme supplement used in a condition called pancreatic exocrine insufficiency where the body does not make enough enzymes to digest food. This condition appears in a number of different patients including those with cystic fibrosis, chronic pancreatitis, or patients who have had upper gastrointestinal surgery. People with a deficiency of pancreatic enzymes often suffer with symptoms of diarrhoea, steatorrhoea (foul fatty stools which float in the toilet), bloating and weight loss. These symptoms appear because the body is unable to digest food normally. When this happens your body's ability to absorb important nutrients from food is impaired and leads to malnutrition. If left untreated, these symptoms can affect your quality of life and a poor nutritional status could have long term health implications. The supplementation of pancreatic enzymes using Creon helps restore the normal digestive action in your body to relieve abdominal symptoms and improve nutritional status.

The enzymes are extracted from pancreas of pigs.

Creon Micro is approved for the uses listed above. However, your doctor may prescribe this medicine for another use. If you would like more information, ask your doctor.

There is no evidence that Creon Micro is addictive.

Before you take Creon Micro

When you must not take it

Do not take Creon Micro if you are allergic to pork, other pig products or any of the ingredients listed at the end of this leaflet.

Do not take Creon Micro after the expiry date (EXP) printed on the pack. If you take this medicine after the expiry date has passed, it may not work as well.

Do not take Creon Micro if the packaging is torn or shows signs of tampering.

Before you start to take it

You must tell your doctor if you are allergic to any other medicines or any foods, dyes or preservatives.

You must tell your doctor if you are pregnant, planning to become pregnant, are breast feeding or intend to breast feed. Your doctor will discuss whether you should take this product.

If you have not told your doctor about any of the above, tell them before you take Creon Micro.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

You should avoid taking antacids, which are medicines that are used to treat heartburn and indigestion, at the same time as when taking Creon Micro. Antacids may affect how well Creon Micro work by breaking down the special coating used to protect the pancreatic enzymes. If it is necessary to take an antacid, then it should be taken at least one hour before you take your Creon Micro.

How to take Creon Micro

Follow all directions given to you by your doctor carefully. These directions may differ from the information in this leaflet.

How much to take

Your doctor will tell you how much Creon Micro to take or give to your child. Do not increase the number of doses yourself without informing your doctor.

Your doctor has prescribed a dose of Creon for you or your child which is specifically tailored to the severity of the condition.

It is normally not necessary to restrict your diet of fat while you are taking Creon as your symptoms will usually be under control. In people with malnutrition, getting enough fat in the diet will help improve nutrition. If unsure, you should consult your doctor or dietitian regarding your diet whilst on Creon.

The maximum recommended dose of lipase in infants and children with cystic fibrosis is 10,000 units per kilogram body weight in 24 hours.

Patients who use more than 10,000 units per kilogram per day, will probably be monitored closely by their doctor.

When to take it

Take Creon Micro with every meal and snack.

How to take it

The small measuring scoop that is provided with the bottle is designed to contain a dose of 100 mg of granules. This amount provides 5,000 units of lipase.

Creon Micro can be added to small amounts of acidic soft food that do not require chewing such as apple juice or mashed bananas. The mixture of Creon Micro and soft food should be swallowed immediately without crushing or chewing, and followed with water or juice to ensure complete ingestion. Care should be taken to ensure that no drug is retained in the mouth.

In young infants, Creon Micro should be mixed with a small amount of apple juice and given from a spoon directly before the feed. In young infants, granules should be taken with acidic liquids or soft foods (e.g. mixed with apple juice or apple puree), but without chewing, directly before the meal. When giving Creon Micro to young infants the apple juice should not be diluted.

When you are taking Creon Micro, it is important to make sure that you drink plenty of liquid every day.

If you forget to take it

Wait until your next meal or snack and take your usual number of doses.

Do not take a double dose to make up for the dose that you missed.

If you have trouble remembering when to take your medicine, ask your pharmacist for hints.

If you take too much (overdose)

If you, or anybody else, have taken too many Creon Micro drink plenty of water and contact your doctor, pharmacist or the Poisons Information Centre (13 11 26), or go to the casualty department of the hospital nearest to you. Do this even if there are no signs of discomfort or poisoning.

While you are taking Creon Micro

Things you must do

Make sure you tell your doctor if you are still having problems with fatty stools or abdominal pain while you are taking Creon Micro.

Drink plenty of water every day when you are taking Creon Micro.

Follow your doctor's instructions carefully and do not stop taking Creon Micro unless told to do so by your doctor.

If you are about to start taking any new medicines, tell your doctor and pharmacist that you are taking Creon Micro.

Things you must not do

Do not give Creon Micro to anyone else, even if they have the same condition as you.

Do not use this medicine for any purpose other than for the purpose it has been recommended for you.

Do not use more than the recommended amount.

Do not stop taking your medicine until your doctor tells you to do so.

Do not let yourself run out of medicine unless told to do so by your doctor.

Creon Micro has no influence on the ability to drive and use machinery.

Things that may help your condition

Diet should be considered as part of your overall management plan. Talk to your doctor for more information and advice.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Creon Micro.

Creon Micro helps most people whose bodies do not make enough enzymes to digest their food, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

- stomach or bowel problems, including:

  • diarrhoea
  • constipation
  • abnormal stools
  • abdominal discomfort
  • nausea

- skin reactions

Tell your doctor immediately if you have severe or prolonged abdominal pain. If you take too much Creon Micro you may get irritation or inflammation in the anal region.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

The active ingredient in Creon Micro is an extract of pancreatic powder of porcine origin (pigs), therefore the presence of porcine parvovirus or other porcine viruses cannot be totally excluded. However, there is no evidence of transmission of these viruses to humans or of porcine pancreatic powder extracts causing illness in humans.

After taking Creon Micro

Storage

Keep the container tightly closed in order to protect from moisture.

Keep your Creon Micro in a cool dry place where the temperature stays below 25°C. Please note that in warmer climates it may be necessary to store Creon Micro in the refrigerator. After opening use within 3 months.

Do not store it, or any other medicine, in the bathroom or near a sink.

Do not leave it in the car or on a window sill on hot days. Heat and dampness can destroy some medicines.

Keep it where young children cannot reach it. A locked cupboard at least one-and-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking Creon Micro or they passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

Creon® Micro: Round, light brown enteric-coated granules in glass bottles. Each glass bottle contains 20 g of enteric-coated granules. Measuring scoop supplied.

Ingredients

Each dosing unit of 100 mg of Creon® Micro contains Pancreatic Extract 60.12 mg equivalent to not less than 5,000 Ph.Eur. units lipase, 3,600 Ph.Eur. units amylase and 200 Ph. Eur. units protease.

Inactive ingredients in Creon Micro are: macrogol 4000, hypromellose phthalate, cetyl alcohol, triethyl citrate, dimeticone 1000. One dosage unit is measured with a measuring scoop as dosing device.

Sponsor

Creon® Micro is manufactured in Germany for:

Mylan Health Pty Ltd
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point, NSW 2000
Australia
www.mylan.com.au
Phone: 1800 314 527

This leaflet was prepared 9 January 2018

Creon® Micro AUST R 166118

Published by MIMS March 2018

BRAND INFORMATION

Brand name

Creon Micro

Active ingredient

Lipase; Amylase; Protease

Schedule

Unscheduled

 

1 Name of Medicine

Pancreatic extract.

2 Qualitative and Quantitative Composition

Creon Micro is a porcine pancreatic enzyme preparation containing pancreatic extract encapsulated in enteric-coated granules with a pH-sensitive coating.
Each dosing unit of 100 mg of Creon Micro contains pancreatic extract 60.12 mg equivalent to not less than 5,000 Ph.Eur. units lipase, 3,600 Ph.Eur. units amylase and 200 Ph. Eur. units protease.

Excipients with known effect.

Phenylalanine.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Creon Micro.

Round, light brown enteric-coated granules. One dosage unit is measured with a measuring scoop as dosing device.

4 Clinical Particulars

4.1 Therapeutic Indications

Creon Micro is indicated as pancreatic enzyme replacement in paediatric and adult patients with pancreatic exocrine insufficiency (PEI).
Pancreatic exocrine insufficiency is often associated with, but not limited to:
cystic fibrosis;
chronic pancreatitis;
pancreatic surgery;
gastrointestinal bypass surgery (e.g. Bilroth II gastroenterostomy);
ductal obstruction of the pancreas or common bile duct (e.g. from neoplasm).

4.2 Dose and Method of Administration

The granules can be added to small amounts of acidic soft food [pH < 5.5] that do not require chewing, such as apple sauce, mashed bananas or yoghurt, or be taken with liquid such as fruit juice with a pH less than 5.5 for example apple, orange or pineapple juice. The small measuring scoop that is provided with the bottle is designed to contain a dose of 100 mg of granules. This amount provides 5,000 units of lipase.
The mixture of Creon Micro and soft food should be swallowed immediately without crushing or chewing, and followed with water or juice to ensure complete ingestion. Crushing and chewing of the minimicrospheres or mixing with food or fluid with a pH greater than 5.5 can disrupt the protective enteric coating. This can result in early release of enzymes in the oral cavity and may lead to reduced efficacy and irritation of the mucous membranes. Care should be taken to ensure that no drug is retained in the mouth.
Any mixture of the granules with food or liquids should be used immediately and should not be stored.
Based upon Australasian Clinical Practice Guidelines for nutrition in Cystic Fibrosis 2006, the key goal of pancreatic enzyme replacement therapy is to improve the patient's nutritional status and growth as well as controlling the symptoms of maldigestion (e.g. steatorrhoea). This is achieved through optimal dietary intake using a diet without restriction of fat content (> 100 g fat per day if over five years of age), unless the patient is overweight. The dose of Creon required is adjusted according to the fat content of the meal and the severity of the disease.
See Tables 1 and 2.
Agents which increase gastric pH, such as H2-antagonists and proton pump inhibitors, have been reported to increase the activity of administered pancreatic lipase and may be helpful in patients who do not achieve adequate response to pancreatic enzyme therapy.
This is not an approved indication for these agents. Prescribers should decide, on the basis of published evidence, whether or not to use them in this way.
It is important to ensure adequate hydration at all times, especially during periods of increased loss of fluids. Inadequate hydration may aggravate constipation.

4.3 Contraindications

Creon Micro is contraindicated in those patients who are known to be hypersensitive to porcine protein or any of the ingredients.

4.4 Special Warnings and Precautions for Use

Fibrosing colonopathy.

Fibrosing colonopathy has been reported in cystic fibrosis patients treated with some high potency enzyme supplements. The mechanism of injury is unknown. Doses in excess of 10,000 Ph. Eur. units lipase/kg/day should be used with caution. Patients who use doses in excess of 10,000 Ph. Eur. units lipase/kg/day and who develop new symptoms or have a medical history of gastrointestinal complications should be reviewed regularly (e.g. by ultrasound).

Use in the elderly.

No data available.

Paediatric use.

No data available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Antacids should not be taken concomitantly with Creon Micro as the alkaline pH may break down the enteric coating. Should antacid administration be considered necessary, it is recommended that at least one hour elapse between the intake of antacids and any Creon Micro.
No interaction studies have been performed.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
For pancreatic enzymes, no clinical data on exposed pregnancies are available.
Animal studies show no evidence for any absorption of porcine pancreatic enzymes.
Although no reproductive or developmental toxicity would be expected, caution should be exercised when prescribing to pregnant women. If required during pregnancy, Creon should be used in doses sufficient to provide adequate nutritional status.
 Animal studies suggest no systemic exposure of the breastfeeding women to porcine pancreatic enzymes, and no effects on the suckling child are anticipated. If required during lactation, Creon should be used in doses sufficient to provide adequate nutritional status.

4.7 Effects on Ability to Drive and Use Machines

Creon Micro has no influence on the ability to drive and use machinery.

4.8 Adverse Effects (Undesirable Effects)

In clinical trials, more than 1000 patients with pancreatic exocrine insufficiency due to cystic fibrosis, chronic pancreatitis, and pancreatic surgery were exposed to Creon.

Adverse events reported from clinical trials.

See Table 3.

Adverse reactions.

The most commonly 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 indicated frequencies. See Table 4.
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).

Post-marketing.

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

Other patient populations.

Multiple clinical trials were conducted in other patient populations: HIV, acute pancreatitis, diabetes mellitus. No additional adverse drug reactions were identified compared to the above 3 patient groups.

Paediatric population.

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

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Extremely high doses of pancreatin have been reported to be associated with hyperuricosuria and hyperuricaemia.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Administered orally, pancreatic extract assists in the digestion of proteins, carbohydrates and fats.
Creon Micro has been specially formulated to combine the features of rapid homogeneous distribution with the chyme in the stomach, with resistance to inactivation by gastric acid and rapid dissolution in the alkaline pH of the duodenum. When the granules 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. The granules are similar in size to food particles (0.7-1 mm in diameter), and mix homogeneously with the chyme while being protected from inactivation by gastric acid (pH 1) for up to 2 hours. They pass into the alkaline pH of the duodenum at least as quickly as the food they are intended to digest; here the enteric coating rapidly dissolves releasing enzymes at the appropriate site.

Clinical trials.

Efficacy studies.

In total, 33 studies investigating the efficacy of Creon in patients with pancreatic exocrine insufficiency have been conducted, among which 11 were placebo controlled studies performed in patients with cystic fibrosis, chronic pancreatitis or postsurgical conditions.
In all randomised, placebo controlled, efficacy studies, the predefined primary objective was to show superiority of Creon 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 taking into account fat intake and faecal fat excretion. In the placebo controlled PEI studies, the mean CFA (%) was higher with Creon treatment (83.0%) as compared to placebo (59.1%). The mean CFA (%) at the end of the treatment period with Creon was similar in all studies, irrespective of the trial design.
In all studies performed, irrespective of the underlying disease, marked improvement was also noted with symptomatology associated with pancreatic enzyme insufficiency (e.g. stool frequency, stool consistency, flatulence and abdominal pain).
In cystic fibrosis (CF) the efficacy of Creon was demonstrated in 43 paediatric patients in randomised, placebo controlled studies, and investigated in 340 paediatric patients in all studies combined. The mean end-of-treatment CFA values in all studies exceeded 80% on Creon comparably in all paediatric age groups ranging from newborns to adolescents.
Two double blind placebo controlled studies in 74 CF patients on individualised doses of Creon showed statistically significant (p < 0.001) and clinically relevant results after Creon treatment of 5-7 days. The mean CFAs in the placebo groups were 52.2% and 50.9% respectively as compared to those in Creon treated patients which were 84.1% and 87.2% respectively.
The third placebo controlled study, a crossover study, was performed in 32 paediatric and young adult CF patients. Patients on Creon achieved a mean CFA of 88.6% compared with 49.8% for patients on placebo (p < 0.0001). The treatment duration was 5 days on a preplanned dose of 4000 lipase units/g fat intake.
The baseline controlled study in 12 CF infants showed a mean CFA increase from 58.0% at baseline to 84.7% after 8 weeks treatment with Creon on a dose of 2000 lipase units/g fat intake.
In chronic pancreatitis and pancreatic surgery three placebo controlled studies in 161 adult patients were conducted and were each designed with a placebo run-in period followed by a double blind parallel group placebo or Creon treatment phase of 7 to 14 days. On average, patients in the Creon group achieved CFA values between 81.5% and 86.6% compared with CFA values between 56.3% and 68% for patients on placebo (statistically significant differences).

Studies in other diseases.

Two double blind, placebo controlled studies were performed in patients after acute pancreatitis (AP). One study in patients in a refeeding status after AP was stopped prematurely due to low recruitment. No treatment difference between Creon and placebo was found on the primary endpoint (time to normalisation of faecal elastase > 200 microgram/g stool) in 56 patients. However, only a subgroup of 20 patients had low faecal elastase values at baseline. The other study in 21 subjects after AP was not sufficiently powered to detect any relevant treatment differences in terms of QoL and gastrointestinal symptoms between Creon and placebo.
One double blind, multicentre, placebo controlled, randomised, parallel group aimed at proving superior efficacy of Creon in patients with PEI caused by total or partial gastrectomy. The study was stopped prematurely due to a too low recruitment rate with only seven patients evaluable for efficacy. No conclusion on the efficacy of Creon in gastrectomized patients could be drawn.
Two double blind, placebo controlled studies were performed to investigate the efficacy of Creon in 29 type 1 or 2 diabetes mellitus patients with mild PEI. Both studies were stopped prematurely because of poor recruitment. The pooled analysis of the limited data revealed no significant difference between the groups for the primary endpoint CFA. The change to baseline for stool fat reached statistical significance in favour of Creon (p = 0.010, -1.0 g fat/day in placebo and -6.5 g fat/day for Creon).
All studies confirmed the safe administration of Creon in the respective patient populations.

5.2 Pharmacokinetic Properties

Animal studies showed no evidence for absorption of intact enzymes and therefore classical pharmacokinetic studies have not been performed. Pancreatic enzyme supplements do not require absorption to exert their effects. On the contrary, their full therapeutic activity is exerted from within the lumen of the gastrointestinal tract. Furthermore, they are proteins, and as such undergo proteolytic digestion while passing along the gastrointestinal tract before being absorbed as peptides and amino acids.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Inactive ingredients include macrogol 4000, hypromellose phthalate, dimeticone 1000, triethyl citrate, cetyl alcohol.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.
In warmer climates it may be necessary to store the product in the refrigerator.
Keep the container tightly closed in order to protect from moisture.
Use within 3 months after opening.
Keep out of reach of children.

6.5 Nature and Contents of Container

Container type: Glass bottle with LDPE closure. Measuring scoop supplied.
Pack sizes: 20 g bottle.
Some strengths, pack sizes and/or pack types may not be marketed.

Australian Register of Therapeutic Goods (ARTG).

AUST R 166118 - Creon Micro pancreatic extract 20 g enteric coated granules bottle.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking it to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

No data available.

CAS number.

8049-47-6.

7 Medicine Schedule (Poisons Standard)

Not scheduled.

Summary Table of Changes