Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

PANCREAZE (BLA-022523)

(PANCRELIPASE (AMYLASE;LIPASE;PROTEASE))

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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02/28/2024 (SUPPL-19)

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 strictures, 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 a history of fibrosing colonopathy, monitor patients during treatment with PANCREAZE 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 and 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:

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 on a small amount of acidic soft food with a pH of 4.5 or less (e.g., applesauce).
Do not crush or chew PANCREAZE capsules or capsule contents.
Consume sufficient liquids (juice, water, breast milk, or formula) immediately following administration of PANCREAZE 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 that 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 PANCREAZE.

5.5 Hypersensitivity Reactions

Additions and/or revisions underlined:

Serious hypersensitivity reactions including anaphylaxis, asthma, hives, and pruritus have been reported with pancreatic enzyme products [see Adverse Reactions (6)]. 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 PANCREAZE. The risks and benefits of continued PANCREAZE treatment in patients with serious hypersensitivity reactions should be taken into consideration with the overall clinical needs of the patient.

6 Adverse Reactions

Additions and/or revisions underlined:

The following serious or otherwise important adverse reactions are described elsewhere in the labeling:

Fibrosing Colonopathy [see Warnings and Precautions (5.1)]
Irritation of the Oral Mucosa [see Warnings and Precautions (5.2)]
Hyperuricemia [see Warnings and Precautions (5.3)]
Risk of Viral Transmission [see Warnings and Precautions (5.4)]
Hypersensitivity Reactions [see Warnings and Precautions (5.5)]

The data described below reflect exposure to PANCREAZE in 57 adult and pediatric patients with exocrine pancreatic insufficiency due to cystic fibrosis in two clinical trials. Study 1 was conducted in 40 patients, aged 8 years to 57 years; Study 2 was conducted in 17 pediatric patients, aged 6 months to 30 months [see Clinical Studies (14)]. The most common adverse reactions were gastrointestinal, including diarrhea and vomiting.
The following adverse reactions have been identified during post-approval use of PANCREAZE or other pancreatic enzyme products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Eye Disorders
blurred vision
Gastrointestinal Disorders
fibrosing colonopathy, distal intestinal obstruction syndrome
abdominal pain, flatulence, constipation, and nausea
Immune System Disorders
anaphylaxis, asthma, hives, and pruritus
Investigations
asymptomatic elevations of liver enzymes
Musculoskeletal System
myalgia, muscle spasm
Skin and Subcutaneous Tissue Disorders
urticaria and rash

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

The safety and effectiveness of PANCREAZE for the treatment of exocrine pancreatic insufficiency have been established in pediatric patients.

Use of PANCREAZE for this indication is supported by an adequate and well-controlled trial in adult and pediatric patients 8 to 17 years of age (Study 1) along with supportive data from a randomized, investigator-blinded, dose-ranging study in 17 pediatric patients aged 6 to 30 months (Study 2). Both study populations consisted of patients with exocrine pancreatic insufficiency due to cystic fibrosis. The safety in pediatric patients in these studies was similar to that observed in adult patients [see Adverse Reactions (6) and Clinical Studies (14)].

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 PANCREAZE 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 PANCREAZE 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)].

8.5 Geriatric Use

New subsection added:

Clinical studies of PANCREAZE did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between patients aged 65 years and over and younger adult patients.

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 PANCREAZE 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 to:

Take PANCREAZE with meals or snacks.
Swallow capsules whole.
For adult and pediatric patients unable to swallow intact capsules, the capsule contents may be sprinkled on a small amount soft acidic food with a pH of 4.5 or less (e.g., applesauce). For pediatric patients birth to 12 months of age, PANCREAZE 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 PANCREAZE capsules or capsule contents [see Warnings and Precautions (5.2)].
Do not crush or chew PANCREAZE capsules or capsule contents.
Do not mix the PANCREAZE capsule contents directly into a bottle of breast milk or formula.

Storage

Instruct the patient or caregiver as follows:

Keep PANCREAZE in a dry place and protect from moisture and heat.
After opening, keep bottle tightly closed between uses to protect from moisture.
Keep PANCREAZE in the original container.
Do not eat or throw away the desiccant canister in the bottle.
MEDICATION GUIDE
Extensive additions and/or revisions, please refer to label for complete information.