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.

ZENPEP (BLA-022210)

(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-26)

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 ZENPEP 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 measuresor 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:

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., commercially available preparations of applesauce, bananas or pears).
Do not crush or chew ZENPEP capsules or capsule contents.
Consume sufficient liquids (juice, water, breast milk, or formula) immediately following administration of ZENPEP 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 ZENPEP.

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 ZENPEP. The risks and benefits of continued ZENPEP 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 ZENPEP in 53 adult and pediatric patients with exocrine pancreatic insufficiency due to cystic fibrosis in two clinical trials conducted [see Clinical Studies (14)]. In both trials, ZENPEP was administered at dosages of approximately 5,000 lipase units/kg/day for 19 to 42 days.
Study 1 was a randomized, double-blind, placebo-controlled, crossover study of 34 adult and pediatric patients, aged 7 to 23 years. Adverse reactions that were reported in at least 2 ZENPEP-treated patients (greater than or equal to 6%) and at a higher rate than in placebo-treated patients in Study 1 are shown in Table 1.
Please refer to label to view Table 1.
Study 2 was an open-label, uncontrolled study of ZENPEP in 19 pediatric patients aged 1 to 6 years. The most commonly reported adverse reactions were gastrointestinal, including abdominal pain and steatorrhea.
The type and incidence of adverse reactions in Studies 1 and 2 were similar between pediatric patients and adults.
6.2 Postmarketing Experience
Additions and/or revisions underlined:
The following adverse reactions have been identified during post-approval use of ZENPEP 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 and distal intestinal obstruction syndrome
abdominal distension, abdominal pain, diarrhea, flatulence, constipation, and nausea

Immune System Disorders
anaphylaxis, asthma, hives and pruritis
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 ZENPEP for the treatment of exocrine pancreatic insufficiency have been established in pediatric patients.

Use of ZENPEP for this indication is supported by an adequate and well-controlled trial in adult and pediatric patients 7 to 17 years of age (Study 1) along with supportive data from an open-label, single arm study in 19 pediatric patients 1 to 6 years of age (Study 2). Both study populations consisted of patients with exocrine pancreatic insufficiency due to cystic fibrosis. The safety in pediatric patients in

Studies 1 and 2 were 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 ZENPEP 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 ZENPEP 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)].

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 ZENPEP 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 ZENPEP with meals or snacks.
Swallow capsules whole.
For adult and pediatric patients who are unable to swallow intact capsules, the capsule contents may be sprinkled on a small amount of acidic soft food with a pH of 4.5 or less (e.g., commercially available preparations of applesauce, bananas, or pears). For pediatric patients birth to 12 months of age, ZENPEP 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 ZENPEP capsules or capsule contents [see Warnings and Precautions (5.2)].
Do not crush or chew ZENPEP capsules or capsule contents.
Do not mix the ZENPEP capsule contents directly into a bottle of breast milk or formula.
Storage
Instruct the patient or caregiver as follows:
Keep ZENPEP in a dry place and protect from moisture and heat.
After opening, keep bottle 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-24)

Approved Drug Label (PDF)

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

MEDICATION GUIDE

Additions and/or revisions underlined

…

What are possible side effects of ZENPEP?

ZENPEP may cause serious side effects, including:

…

These are not all the possible side effects of ZENPEP. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA- 1088.

You may also report side effects to Nestlé HealthScience at 1-833-920-2178.

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General information about ZENPEP

…

This Medication Guide summarizes the most important information about ZENPEP. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about ZENPEP that is written for health professionals. For more information, go to www.ZENPEP.com or call

1-833-920-2178.

…

General information about the safe and effective use of VIOKACE

…

This Medication Guide summarizes the most important information about VIOKACE. If you would like more information, talk to your doctor. You can ask your pharmacist or doctor for information about VIOKACE that is written for healthcare providers.

For more information, go to www.viokace.com or call toll-free 1-833-920-2178.

…