NURSE-UN 1243 Lecture Notes - Lecture 11: Cystic Fibrosis Foundation, Exocrine Pancreatic Insufficiency, Cystic Fibrosis
29 Apr 2019
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HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
CREON® safely and effectively. See full prescribing information for
CREON.
CREON (pancrelipase) Capsules, Delayed Release for Oral Use
Initial U.S. Approval: _________
------------------------INDICATIONS AND USAGE-------------------------
CREON Capsules is a pancrelipase which is a combination of porcine-
derived lipases, proteases, and amylases indicated for the treatment of
exocrine pancreatic insufficiency due to cystic fibrosis or other
conditions.
--------------------DOSAGE AND ADMINISTRATION--------------------
Dosage (2.1)
CREON is not interchangeable with any other pancrelipase product.
Infants (up to 12 months)
● Infants may be given 2,000 to 4,000 lipase units per 120 mL of
formula or per breast-feeding.
● Do not mix CREON capsule contents directly into formula or breast
milk prior to administration. (2.2)
Children Older than 12 Months and Younger than 4 Years
● Enzyme dosing should begin with 1,000 lipase units/kg of body
weight per meal for children less than age 4 years to a maximum of
2,500 lipase units/kg of body weight per meal (or less than or equal
to 10,000 lipase units/kg of body weight per day), or less than 4,000
lipase units/g fat ingested per day.
Children 4 Years and Older and Adults
● Enzyme dosing should begin with 500 lipase units/kg of body
weight per meal for those older than age 4 years to a maximum of
2,500 lipase units/kg of body weight per meal (or less than or equal
to 10,000 lipase units/kg of body weight per day), or less than 4,000
lipase units/g fat ingested per day.
Limitations on Dosing
● Dosing should not exceed the recommended maximum dosage set
forth by the Cystic Fibrosis Foundation Consensus Conferences
Guidelines.
Administration (2.2)
CREON should be swallowed whole. For infants or patients unable to
swallow intact capsules, the contents may be administered without
crushing or chewing, followed by fluid to ensure complete ingestion.
---------------------DOSAGE FORMS AND STRENGTHS-----------------
● 6,000 USP units of lipase; 19,000 USP units of protease; 30,000 USP
units of amylase capsules have an orange opaque cap with imprint
“CREON 1206” and a blue opaque body. (3)
● 12,000 USP units of lipase; 38,000 USP units of protease; 60,000 USP
units of amylase capsules have a brown opaque cap with imprint “CREON
1212” and a colorless transparent body. (3)
● 24,000 USP units of lipase; 76,000 USP units of protease; 120,000 USP
units of amylase capsules have an orange opaque cap with imprint
“CREON 1224” and a colorless transparent body. (3)
------------------------------CONTRAINDICATIONS-------------------------------
None.
-------------------------WARNINGS AND PRECAUTIONS-----------------------
● Fibrosing colonopathy, a rare, serious adverse reaction has been described
in association with high-dose use of pancreatic enzyme replacement in the
treatment of cystic fibrosis patients. Caution should be exercised when
doses of CREON exceed 2,500 lipase units/kg of body weight per meal
(or greater than 10,000 lipase units/kg of body weight per day). (5.1)
● Care should be taken to ensure that CREON is not chewed or retained in
the mouth to avoid irritation of oral mucosa. (5.2)
● Caution should be exercised when prescribing CREON to patients with
gout, renal impairment, or hyperuricemia. (5.3)
● There is theoretical risk of viral transmission with all pancreatic enzyme
products including CREON. (5.4)
● Caution should be exercised when administering pancrelipase to a patient
with a known allergy to proteins of porcine origin. (5.5)
------------------------------ADVERSE REACTIONS-------------------------------
● Treatment-emergent adverse events occurring in at least 2 patients (greater
than or equal to 6%) receiving CREON or placebo are abdominal pain,
abdominal pain upper, abnormal feces, cough, dizziness, flatulence,
headache, and weight decreased. (6.1)
● There is no postmarketing experience. (6.2)
To report SUSPECTED ADVERSE REACTIONS, contact Solvay Pharmaceuticals, Inc.
at 1-800-241-1643 or FDA at 1-800-FDA-1088 or www.fda.gov/Medwatch.
-----------------------------DRUG INTERACTIONS--------------------------------
None known. (7)
-----------------------USE IN SPECIFIC POPULATIONS------------------------
Pediatric Patients
● The safety and effectiveness of CREON have been demonstrated in
pediatric patients 12 years and older. (8.4)
● The safety and efficacy of pancreatic enzyme products with different
formulations of pancrelipase in pediatric patients have been described in
the medical literature and through clinical experience. (8.4)
See 17 for PATIENT COUNSELING INFORMATION and FDA-
approved Medication Guide
1 FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Dosage
2.2 Administration
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Fibrosing Colonopathy
5.2 Potential for Irritation to Oral Mucosa
5.3 Potential for Risk of Hyperuricemia
5.4 Potential Viral Exposure from the Product Source
5.5 Allergic Reactions
6 ADVERSE REACTIONS
6.1 Adverse Reactions in Clinical Trials
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
15 REFERENCES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
17.1 Dosing and Administration
17.2 Fibrosing Colonopathy
17.3 Allergic Reactions
17.4 FDA-Approved Medication Guide
*Sections or subsections omitted from the full prescribing information are
not listed.
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3 1055216 1E Rev Apr 2009
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FULL PRESCRIBING INFORMATION
6 1 INDICATIONS AND USAGE
7 CREON® (pancrelipase) Delayed-Release Capsules is indicated for the treatment of exocrine pancreatic
8 insufficiency due to cystic fibrosis or other conditions.
9 2 DOSAGE AND ADMINISTRATION
2.1 Dosage
11 CREON is not interchangeable with any other pancrelipase product.
12 CREON is orally administered. Therapy should be initiated at the lowest recommended dose and gradually
13 increased. The dosage of CREON should be individualized based on clinical symptoms, the degree of steatorrhea
14 present, and the fat content of the diet (see Limitations on Dosing below).
Dosage recommendations for pancreatic enzyme replacement therapy were published following the Cystic
16 Fibrosis Foundation Consensus Conferences.1, 2, 3 CREON should be administered in a manner consistent with the
17 recommendations of the Conferences provided in the following paragraphs. Patients may be dosed on a fat
18 ingestion-based or actual body weight-based dosing scheme.
19 Infants (up to 12 months)
Infants may be given 2,000 to 4,000 lipase units per 120 mL of formula or per breast-feeding. Do not mix
21 CREON capsule contents directly into formula or breast milk prior to administration [see Dosage and
22 Administration (2.2)].
23 Children Older than 12 Months and Younger than 4 Years
24 Enzyme dosing should begin with 1,000 lipase units/kg of body weight per meal for children less than age 4
years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg
26 of body weight per day), or less than 4,000 lipase units/g fat ingested per day.
27 Children 4 Years and Older and Adults
28 Enzyme dosing should begin with 500 lipase units/kg of body weight per meal for those older than age
29 4 years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase
units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day.
31 Usually, half of the prescribed CREON dose for an individualized full meal should be given with each snack.
32 The total daily dose should reflect approximately three meals plus two or three snacks per day.
33 Enzyme doses expressed as lipase units/kg of body weight per meal should be decreased in older patients
34 because they weigh more but tend to ingest less fat per kilogram of body weight.
Limitations on Dosing
36 Dosing should not exceed the recommended maximum dosage set forth by the Cystic Fibrosis Foundation
37 Consensus Conferences Guidelines.1, 2, 3 If symptoms and signs of steatorrhea persist, the dosage may be increased
38 by the healthcare professional. Patients should be instructed not to increase the dosage on their own. There is great
39 inter-individual variation in response to enzymes; thus, a range of doses is recommended. Changes in dosage may
require an adjustment period of several days. If doses are to exceed 2,500 lipase units/kg of body weight per meal,
41 further investigation is warranted. Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than
42 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be
43 effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorption. Doses
44 greater than 6,000 lipase units/kg of body weight per meal have been associated with colonic stricture, indicative of
fibrosing colonopathy, in children less than 12 years of age [see Warnings and Precautions (5.1)]. Patients currently
46 receiving higher doses than 6,000 lipase units/kg of body weight per meal should be examined and the dosage either
47 immediately decreased or titrated downward to a lower range.
48 2.2 Administration
49 CREON should always be taken as prescribed by a healthcare professional.
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50 Infants (up to 12 months)
51 CREON should be administered to infants immediately prior to each feeding, using a dosage of 2,000 to
52 4,000 lipase units per 120 mL of formula or per breast-feeding. Contents of the capsule may be administered directly
53 to the mouth or with a small amount of applesauce. Administration should be followed by breast milk or formula.
54 Contents of the capsule should not be mixed directly into formula or breast milk as this may diminish efficacy. Care
55 should be taken to ensure that CREON is not crushed or chewed or retained in the mouth, to avoid irritation of the
56 oral mucosa.
57 Children and Adults
58 CREON should be taken during meals or snacks, with sufficient fluid. CREON capsules and capsule contents
59 should not be crushed or chewed. Capsules should be swallowed whole.
60 For patients who are unable to swallow intact capsules, the capsules may be carefully opened and the
61 contents added to a small amount of acidic soft food with a pH of 4 or less, such as applesauce, at room temperature.
62 The CREON-soft food mixture should be swallowed immediately without crushing or chewing, and followed with
63 water or juice to ensure complete ingestion. Care should be taken to ensure that no drug is retained in the mouth.
64 3 DOSAGE FORMS AND STRENGTHS
65 The active ingredient in CREON evaluated in clinical trials is lipase. CREON is dosed by lipase units.
66 Other active ingredients include protease and amylase. Each CREON capsule strength contains the specified
67 amounts of lipase, protease, and amylase as follows:
68
69 ● 6,000 USP units of lipase; 19,000 USP units of protease; 30,000 USP units of amylase capsules have an
70 orange opaque cap with imprint “CREON 1206” and a blue opaque body.
71 ● 12,000 USP units of lipase; 38,000 USP units of protease; 60,000 USP units of amylase capsules have a
72 brown opaque cap with imprint “CREON 1212” and a colorless transparent body.
73 ● 24,000 USP units of lipase; 76,000 USP units of protease; 120,000 USP units of amylase capsules have
74 an orange opaque cap with imprint “CREON 1224” and a colorless transparent body.
75 4 CONTRAINDICATIONS
76 None.
77 5 WARNINGS AND PRECAUTIONS
78 5.1 Fibrosing Colonopathy
79 Fibrosing colonopathy has been reported following treatment with different pancreatic enzyme products. 4, 5
80 Fibrosing colonopathy is a rare, serious adverse reaction initially described in association with high-dose pancreatic
81 enzyme use, usually over a prolonged period of time and most commonly reported in pediatric patients with cystic
82 fibrosis. The underlying mechanism of fibrosing colonopathy remains unknown. Doses of pancreatic enzyme
83 products exceeding 6,000 lipase units/kg of body weight per meal have been associated with colonic stricture in
84 children less than 12 years of age.1 Patients with fibrosing colonopathy should be closely monitored because some
85 patients may be at risk of progressing to stricture formation. It is uncertain whether regression of fibrosing
86 colonopathy occurs.1 It is generally recommended, unless clinically indicated, that enzyme doses should be less than
87 2,500 lipase units/kg of body weight per meal (or less than 10,000 lipase units/kg of body weight per day) or less
88 than 4,000 lipase units/g fat ingested per day [see Dosage and Administration (2.1)].
89 Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of
90 body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat
91 measures that indicate a significantly improved coefficient of fat absorption. Patients receiving higher doses than
92 6,000 lipase units/kg of body weight per meal should be examined and the dosage either immediately decreased or
93 titrated downward to a lower range.
94 5.2 Potential for Irritation to Oral Mucosa
95 Care should be taken to ensure that no drug is retained in the mouth. CREON should not be crushed or
96 chewed or mixed in foods having a pH greater than 4. These actions can disrupt the protective enteric coating
97 resulting in early release of enzymes, irritation of oral mucosa, and/or loss or enzyme activity [see Dosage and
98 Administration (2.2) and Patient Counseling Information (17.4)]. For patients who are unable to swallow intact
99 capsules, the capsules may be carefully opened and the contents added to a small amount of acidic soft food with a
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