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.

PERTZYE (BLA-022175)

(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-10)

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 with use 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 a history of fibrosing colonopathy, monitor patients during treatment with PERTZYE 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). The 4,000 USP lipase unit capsule may also be administered with applesauce via a gastrostomy tube with a diameter of 14 French or larger
Do not crush or chew PERTZYE capsules or capsule contents.
Consume sufficient liquids (juice, water, breast milk, or formula) immediately following administration of PERTZYE 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 PERTZYE.

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 PERTZYE. The risks and benefits of continued PERTZYE 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:

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)]
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
…
The data described below reflect exposure to PERTZYE in 21 patients, aged 8 to 43 years, with exocrine pancreatic insufficiency due to cystic fibrosis in a placebo-controlled clinical trial [see Clinical Studies (14)].
Table 1 enumerates adverse reactions that occurred in at least 2 patients (greater than or equal to
10%) treated with PERTZYE at a higher rate than with placebo.
Please refer to label to view Table 1.
6.2 Postmarketing Experience
Additions and/or revisions underlined:
The following adverse reactions have been identified during post-approval use of PERTZYE 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 PERTZYE for the treatment of exocrine pancreatic insufficiency have been established in pediatric patients.

Use of PERTZYE for this indication is supported by a randomized, double-blind, placebo- controlled, crossover study of 24 pediatric patients, 8 years and older with exocrine pancreatic insufficiency due to cystic fibrosis. The safety in pediatric patients was similar to that observed in adult patients [see Adverse Reactions (6.1) 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 PERTZYE because some patients may be at risk of progressing to stricture formation. Do not exceed the 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 (2.1) and Warnings and Precautions (5.1)].

Crushing or chewing PERTZYE 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 that 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 PERTZYE 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:

…

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)].

…

Dosage

Advise the patient or caregiver to take or administer PERTZYE 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 PERTZYE with meals or snacks.
Swallow capsules whole.
For 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). The 4,000 USP lipase unit capsule may also be administered with applesauce via gastrostomy tube 14 French or larger.
For pediatric patients birth to 12 months of age, PERTZYE capsules can be opened, and the capsule contents sprinkled directly into the infant’s mouth.
See the Instructions for Use for a description of all preparation and administration instructions.

Consume sufficient liquids (juice, water, breast milk, or formula) and visually inspect an infant’s mouth to ensure complete swallowing of PERTZYE capsules or capsule contents [see Warnings and Precautions (5.2)].
Do not crush or chew PERTZYE capsules or capsule contents.
Do not mix the PERTZYE capsule contents directly into a bottle of breast milk or formula.

Storage

Instruct the patient or caregiver as follows:

Keep PERTZYE in a dry place and protect from moisture and heat.
After opening, keep the container tightly closed between uses to protect from moisture.
The desiccant packet should not be eaten or thrown away.
MEDICATION GUIDE
Extensive additions and/or revisions, please refer to label for complete information.

09/28/2022 (SUPPL-8)

Approved Drug Label (PDF)

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

MEDICATION GUIDE

Additions and/or revisions underlined

…

How should I take PERTZYE?

…

Always take PERTZYE with a meal or snack and plenty of fluid. If you eat a lot of meals or snacks in a day, be careful not to go over your total daily dose.
…

07/12/2017 (SUPPL-4)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Potential for Irritation to Oral Mucosa

(Additions and/or revisions are underlined)

… For patients who are unable to swallow intact capsules, the capsules may be carefully opened and the contents mixed with a small amount of acidic soft food with a pH of 4.5 or less, such as applesauce, or administered with applesauce via a gastrostomy tube with a diameter of 14 French or larger (only for the 4,000 USP lipase unit capsule strength). If administered orally, the PERTZYE-soft food mixture should be swallowed immediately and followed with water or juice to ensure complete ingestion.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions are underlined)

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Dosing and Administration Instruct patients and caregivers:

Administer PERTZYE during meals or snacks, with sufficient fluid.
Swallow PERTZYE capsules whole.
Do not crush or chew the capsules or the capsule contents.
For patients who are unable to swallow intact capsules, follow the instructions in the Medication Guide for:

oral administration with soft foods with a pH of 4.5 or less (e.g., applesauce); or
via a gastrostomy tube with a diameter of 14 French or larger with soft foods with a pH of 4.0 or less (e.g., applesauce). Only perform gastrostomy tube administration with the contents of the 4,000 USP lipase unit capsule of PERTZYE. The contents of no more than two capsules may be administered at a time.

If a dose is missed the next dose should be taken with the next meal or snack as directed. Do not take two doses at one time.
After opening the bottle containing PERTZYE, keep it tightly closed between uses. Do not eat or throw away the desiccant packet.

Fibrosing Colonopathy

High doses of pancreatic enzyme products have been associated with colonic strictures in children below the age of 12 years. Advise patients and caregivers that if signs and symptoms of stricture formation occur (e.g., stomach area (abdominal) pain, bloating, trouble passing stool (constipation), nausea, vomiting, diarrhea) to immediately contact their healthcare provider.

Allergic Reactions

Allergic reactions, including anaphylaxis, asthma, hives and pruritus may occur. Advise patients and caregivers to immediately contact their healthcare provider if symptoms occur.

MEDICATION GUIDE

(Additions and/or revisions are underlined)

What is the most important information I should know about PERTZYE?

PERTZYE may increase the risk of having a rare bowel disorder called fibrosing colonopathy, especially if taken at a high dose in children with cystic fibrosis who are less than 12 years of age…

Before taking PERTZYE, tell your doctor about all of your medical conditions, including if you:

are pregnant or plan to become pregnant. It is not known if PERTZYE can harm your unborn baby. It is not known if PERTZYE can affect your ability to become pregnant.
are breastfeeding or plan to breastfeed. It is not known if PERTZYE passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take PERTZYE.

How should I take PERTZYE?

See the Instructions for Use at the end of this Medication Guide for detailed instructions about how to give PERTZYE by mouth and through a gastrostomy tube.

Throw away the PERTZYE capsule contents-food mixture that is not used. Do not save this mixture for later use.
If you miss a dose of PERTZYE , wait until your next meal or snack and take your prescribed dose. Take your next dose at your usual time. Do not take two doses at one time.

What are the possible side effects of PERTZYE?

Irritation of the inside of your mouth. This can happen if PERTZYE is not swallowed completely, is crushed or chewed, or is mixed in foods that are not recommended.

Allergic reactions, including trouble swallowing or breathing, skin rash, itching, or swelling of your face, eyes, lips, tongue, or throat.