Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Fibrosing Colonopathy
Additions and/or
revisions underlined:
Fibrosing colonopathy has been reported following
treatment with pancreatic enzyme products. Fibrosing colonopathy is a rare,
serious adverse reaction initially described in association with use of
high-dose pancreatic enzyme products, usually over a prolonged period of time
and most commonly reported in pediatric patients with cystic fibrosis.
Pancreatic enzyme products exceeding 6,000 lipase units/kg/meal have been
associated with colonic stricture, a complication of fibrosing colonopathy,
in pediatric patients less than 12 years of age. The underlying mechanism of
fibrosing colonopathy remains unknown.
If there is history of fibrosing colonopathy, monitor patients during treatment with CREON
because some patients may be at risk of progressing to colonic stricture
formation. It is uncertain whether regression of fibrosing colonopathy occurs.
Do not exceed the recommended dosage of either 2,500 lipase
units/kg/meal, 10,000 lipase units/kg/day, or 4,000 lipase units/g fat
ingested/day in adult and pediatric patients greater than 12
months of age without further investigation. Higher dosages may be
administered if they are documented to be effective by fecal fat measures or
an improvement in signs or symptoms of malabsorption including measures of
nutritional status. Patients receiving dosages higher than 6,000
lipase units/kg/meal should be frequently monitored for symptoms of
fibrosing colonopathy and the dosage decreased or titrated downward to a
lower range if clinically appropriate [see Dosage and Administration
(2.1)].
5.2 Irritation of the Oral Mucosa
Additions and/or
revisions underlined:
Crushing or chewing
CREON capsules or mixing the capsule contents in foods having a pH
greater than 4.5 can disrupt the protective enteric coating on the capsule
contents and result in early release of enzymes, irritation of the oral
mucosa, and/or loss of enzyme activity.
Instruct the patient or caregiver of the following:
Swallow capsules whole. For patients who cannot swallow the capsules whole, the
capsules can be opened, and the contents sprinkled in a small amount of
acidic soft food with a pH of 4.5 or less (e.g., applesauce, bananas, plain
Greek yogurt).
Do not crush or chew CREON capsules or capsule contents.
Consume sufficient liquids
(juice, water, breast milk, or formula) immediately following
administration of CREON to ensure complete swallowing.
Visually inspect the mouth
of pediatric patients less than 12 months of age and of patients who are unable
to swallow intact capsules to ensure no drug is retained in the mouth and
irritation of the oral mucosa has not occurred [see Dosage and Administration
(2.3)].
5.3 Hyperuricemia
Additions and/or
revisions underlined:
Pancreatic enzyme products contain purines that may
increase blood uric acid levels. High dosages have been associated with
hyperuricosuria and hyperuricemia [see Overdosage (10)]. Consider
monitoring blood uric acid levels in patients with gout, renal impairment, or
hyperuricemia during treatment with CREON.
5.5 Hypersensitivity Reactions
Additions
and/or revisions underlined:
Severe
hypersensitivity
reactions including anaphylaxis, asthma, hives, and pruritus have been reported
with pancreatic enzyme products [see
Adverse Reactions (6.2)]. If symptoms occur, initiate appropriate
medical management.
Monitor
patients with a known hypersensitivity reaction to proteins of porcine origin
for hypersensitivity reactions during treatment with CREON.
The risks and benefits of continued CREON treatment in patients with severe hypersensitivity
reactions should be taken into consideration with the overall clinical
needs of the patient.
6
Adverse Reactions
Additions and/or
revisions underlined:
…
Irritation of the Oral
Mucosa [see Warnings and Precautions (5.2)]
…
Risk of Viral Transmission [see
Warnings and Precautions (5.4)]
…
6.1 Clinical
Trials Experience
Extensive additions and/or revisions; please refer
to label for complete information.
6.2 Postmarketing
Experience
Additions
and/or revisions underlined:
…
Gastrointestinal
Disorders
fibrosing colonopathy and
distal intestinal obstruction syndrome
…
Immune
System Disorders
anaphylaxis, asthma, hives, and pruritus
…
8
Use in Specific Populations
8.4 Pediatric Use
Additions and/or revisions underlined:
The safety and effectiveness of CREON for the
treatment of exocrine pancreatic insufficiency have been established in
pediatric patients.
Use of CREON for this indication is supported by two adequate and well-controlled trials in adult and pediatric
patients 12 years and older (Study 1) and in pediatric patients 7 to 11 years
of age (Study 2) along with supportive data from an open-label,
single-arm, study in 18 pediatric patients 4 months to six years of age (Study
3). All three study populations consisted of patients with exocrine pancreatic
insufficiency due to cystic fibrosis.
The
safety in pediatric patients 2 years of age and older in Studies 1
and 2 were similar to that observed adult patients [see Adverse Reactions (6.1) and Clinical Studies
(14)].
In
Study 3, patients received their usual pancreatic enzyme replacement therapy
(mean dose of 7,000 lipase units/kg/day for a mean duration of 18.2 days)
followed by CREON (mean dose of 7,500 lipase units/kg/day for a mean duration
of 12.6 days). The mean daily fat intake was 48 grams during treatment with
usual pancreatic enzyme replacement therapy and 47 grams during treatment with
CREON. Adverse reactions that occurred in patients during treatment with CREON in
Study 3 were vomiting, irritability, and decreased appetite [see Adverse Reactions (6.1)].
Dosages exceeding 6,000
lipase units/kg/meal have been reported postmarketing to be
associated with fibrosing colonopathy and colonic strictures in pediatric
patients less than 12 years of age. If there is a history of fibrosing
colonopathy, monitor patients during treatment with CREON because some patients
may be at risk of progressing to stricture formation. Do not exceed the
recommended dosage of either 2,500 lipase units/kg/meal, 10,000 lipase
units/kg/day, or 4,000 lipase units/g fat ingested/day in pediatric patients
greater than 12 months of age without further investigation [see Dosage and Administration (2.2) and Warnings and Precautions (5.1)].
Crushing
or chewing CREON capsules or mixing the capsule contents in foods having a pH
greater than 4.5 can disrupt the protective enteric coating on the capsule
contents and result in early release of enzymes, irritation of the oral mucosa,
and/or loss of enzyme activity. Instruct the patient or caregiver of the
following: consume sufficient liquids (juice, water, breast milk, or formula)
to ensure complete swallowing, and visually inspect the mouth of pediatric
patients less than 12 months of age to ensure no drug is retained in the mouth
and irritation of the oral mucosa has not occurred [see Dosage and Administration (2.3) and Warnings and Precautions
(5.2)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions
and/or revisions underlined:
…
Fibrosing
Colonopathy
Advise
the patient or caregiver that fibrosing colonopathy has been reported with
high dosages of pancreatic enzyme products, usually with use over a
prolonged period of time and in pediatric patients with cystic fibrosis.
Colonic stricture has been reported in pediatric patients less than 12
years of age. Advise patients and caregivers that if signs and
symptoms of colon stricture formation occur (e.g., stomach area (abdominal)
pain, bloating, trouble passing stool (constipation), nausea, vomiting, diarrhea)
to immediately contact their healthcare provider [see Warnings and Precautions (5.1)].
Hyperuricemia
Advise
the patient or caregiver that hyperuricemia may occur in patients with gout or
renal impairment and to contact the healthcare provider if they experience
pain, stiffness, redness or swelling of their joints [see Warnings and Precautions (5.3)].
Hypersensitivity Reactions
Inform the patient or caregiver that severe
hypersensitivity reactions, including anaphylaxis, asthma,
hives, and pruritus, have been reported with use of pancreatic enzyme products.
Seek medical attention if signs or symptoms of a hypersensitivity reaction
develop [see Warnings and Precautions (5.5)].
Dosage
Advise the patient or caregiver to take or
administer CREON as prescribed, and to contact the healthcare provider if
signs and symptoms of malabsorption persist [see Dosage and Administration
(2.2)].
Administration
Instruct the patient or caregiver as follows:
Take CREON during meals and snacks.
Swallow capsules whole.
For adult and pediatric
patients unable to swallow intact capsules, the capsule
contents may be sprinkled on a small amount of soft acidic food with a pH of
4.5 or less (e.g., applesauce, bananas, plain Greek yogurt). For pediatric
patients birth to 12 months of age, CREON capsules can also be opened, and the
capsule contents sprinkled directly into the infant’s mouth.
Consume sufficient liquids (juice, water, breast
milk, or formula) and visually inspect an infant’s mouth to ensure complete
swallowing of CREON capsules or capsule contents [see Warnings and
Precautions (5.2)].
Do not crush or chew CREON capsules or capsule
contents.
Do not mix the CREON
capsule contents directly into a bottle of breast milk or formula. Storage
Instruct the patient or caregiver as follows:
Keep CREON in a dry place
and protect from heat.
After opening, keep the
bottle tightly closed between uses to protect from moisture.
Keep CREON in the original
container.
If there is a desiccant
packet in the bottle, keep it in the bottle. Do not eat or throw away the
desiccant.
MEDICATION GUIDE
Extensive additions and/or revisions, please refer
to label for complete information.
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