MedPath
FDA Approval

Zenpep

FDA-approved pharmaceutical product with comprehensive regulatory information, manufacturing details, and complete labeling documentation.

FDA Approval Summary

Company
Effective Date
February 28, 2024
Labeling Type
HUMAN PRESCRIPTION DRUG LABEL
Pancrelipase amylase(14000 [USP'U] in 1 1)
Pancrelipase lipase(3000 [USP'U] in 1 1)
Pancrelipase protease(10000 [USP'U] in 1 1)

Products8

Detailed information about drug products covered under this FDA approval, including NDC codes, dosage forms, ingredients, and administration routes.

Zenpep

Product Details

NDC Product Code
73562-113
Application Number
BLA022210
Marketing Category
BLA (C73585)
Route of Administration
ORAL
Effective Date
October 27, 2023
Code: YOJ58O116EClass: ACTIBQuantity: 14000 [USP'U] in 1 1
WATERInactive
Code: 059QF0KO0RClass: IACT
Code: 8MYC33932OClass: ACTIBQuantity: 3000 [USP'U] in 1 1
Code: 3560D81V50Class: ACTIBQuantity: 10000 [USP'U] in 1 1
CROSCARMELLOSE SODIUMInactive
Code: M28OL1HH48Class: IACT
MICROCRYSTALLINE CELLULOSEInactive
Code: OP1R32D61UClass: IACT
CARRAGEENANInactive
Code: 5C69YCD2YJClass: IACT
TITANIUM DIOXIDEInactive
Code: 15FIX9V2JPClass: IACT
HYDROGENATED CASTOR OILInactive
Code: ZF94AP8MEYClass: IACT
SILICON DIOXIDEInactive
Code: ETJ7Z6XBU4Class: IACT
MAGNESIUM STEARATEInactive
Code: 70097M6I30Class: IACT
TALCInactive
Code: 7SEV7J4R1UClass: IACT
POTASSIUM CHLORIDEInactive
Code: 660YQ98I10Class: IACT
TRIETHYL CITRATEInactive
Code: 8Z96QXD6UMClass: IACT
HYPROMELLOSE PHTHALATE (31% PHTHALATE, 170 CST)Inactive
Code: 8LDD2V82F5Class: IACT
HYPROMELLOSE, UNSPECIFIEDInactive
Code: 3NXW29V3WOClass: IACT

Zenpep

Product Details

NDC Product Code
73562-111
Application Number
BLA022210
Marketing Category
BLA (C73585)
Route of Administration
ORAL
Effective Date
October 27, 2023
Code: 8MYC33932OClass: ACTIBQuantity: 15000 [USP'U] in 1 1
Code: 3560D81V50Class: ACTIBQuantity: 47000 [USP'U] in 1 1
CROSCARMELLOSE SODIUMInactive
Code: M28OL1HH48Class: IACT
SILICON DIOXIDEInactive
Code: ETJ7Z6XBU4Class: IACT
Code: YOJ58O116EClass: ACTIBQuantity: 63000 [USP'U] in 1 1
HYDROGENATED CASTOR OILInactive
Code: ZF94AP8MEYClass: IACT
MICROCRYSTALLINE CELLULOSEInactive
Code: OP1R32D61UClass: IACT
TRIETHYL CITRATEInactive
Code: 8Z96QXD6UMClass: IACT
TALCInactive
Code: 7SEV7J4R1UClass: IACT
CARRAGEENANInactive
Code: 5C69YCD2YJClass: IACT
MAGNESIUM STEARATEInactive
Code: 70097M6I30Class: IACT
TITANIUM DIOXIDEInactive
Code: 15FIX9V2JPClass: IACT
HYPROMELLOSE, UNSPECIFIEDInactive
Code: 3NXW29V3WOClass: IACT
WATERInactive
Code: 059QF0KO0RClass: IACT
HYPROMELLOSE PHTHALATE (31% PHTHALATE, 170 CST)Inactive
Code: 8LDD2V82F5Class: IACT
POTASSIUM CHLORIDEInactive
Code: 660YQ98I10Class: IACT

Zenpep

Product Details

NDC Product Code
73562-110
Application Number
BLA022210
Marketing Category
BLA (C73585)
Route of Administration
ORAL
Effective Date
October 27, 2023
CARRAGEENANInactive
Code: 5C69YCD2YJClass: IACT
Code: 8MYC33932OClass: ACTIBQuantity: 10000 [USP'U] in 1 1
MICROCRYSTALLINE CELLULOSEInactive
Code: OP1R32D61UClass: IACT
MAGNESIUM STEARATEInactive
Code: 70097M6I30Class: IACT
TALCInactive
Code: 7SEV7J4R1UClass: IACT
HYPROMELLOSE, UNSPECIFIEDInactive
Code: 3NXW29V3WOClass: IACT
Code: YOJ58O116EClass: ACTIBQuantity: 42000 [USP'U] in 1 1
HYDROGENATED CASTOR OILInactive
Code: ZF94AP8MEYClass: IACT
SILICON DIOXIDEInactive
Code: ETJ7Z6XBU4Class: IACT
Code: 3560D81V50Class: ACTIBQuantity: 32000 [USP'U] in 1 1
CROSCARMELLOSE SODIUMInactive
Code: M28OL1HH48Class: IACT
TRIETHYL CITRATEInactive
Code: 8Z96QXD6UMClass: IACT
HYPROMELLOSE PHTHALATE (31% PHTHALATE, 170 CST)Inactive
Code: 8LDD2V82F5Class: IACT
WATERInactive
Code: 059QF0KO0RClass: IACT
POTASSIUM CHLORIDEInactive
Code: 660YQ98I10Class: IACT
TITANIUM DIOXIDEInactive
Code: 15FIX9V2JPClass: IACT

Zenpep

Product Details

NDC Product Code
73562-115
Application Number
BLA022210
Marketing Category
BLA (C73585)
Route of Administration
ORAL
Effective Date
October 27, 2023
Code: YOJ58O116EClass: ACTIBQuantity: 24000 [USP'U] in 1 1
HYDROGENATED CASTOR OILInactive
Code: ZF94AP8MEYClass: IACT
TALCInactive
Code: 7SEV7J4R1UClass: IACT
HYPROMELLOSE PHTHALATE (31% PHTHALATE, 170 CST)Inactive
Code: 8LDD2V82F5Class: IACT
POTASSIUM CHLORIDEInactive
Code: 660YQ98I10Class: IACT
Code: 8MYC33932OClass: ACTIBQuantity: 5000 [USP'U] in 1 1
Code: 3560D81V50Class: ACTIBQuantity: 17000 [USP'U] in 1 1
CROSCARMELLOSE SODIUMInactive
Code: M28OL1HH48Class: IACT
SILICON DIOXIDEInactive
Code: ETJ7Z6XBU4Class: IACT
MICROCRYSTALLINE CELLULOSEInactive
Code: OP1R32D61UClass: IACT
MAGNESIUM STEARATEInactive
Code: 70097M6I30Class: IACT
TRIETHYL CITRATEInactive
Code: 8Z96QXD6UMClass: IACT
CARRAGEENANInactive
Code: 5C69YCD2YJClass: IACT
TITANIUM DIOXIDEInactive
Code: 15FIX9V2JPClass: IACT
HYPROMELLOSE, UNSPECIFIEDInactive
Code: 3NXW29V3WOClass: IACT
WATERInactive
Code: 059QF0KO0RClass: IACT

Zenpep

Product Details

NDC Product Code
73562-116
Application Number
BLA022210
Marketing Category
BLA (C73585)
Route of Administration
ORAL
Effective Date
October 27, 2023
Code: 8MYC33932OClass: ACTIBQuantity: 25000 [USP'U] in 1 1
CROSCARMELLOSE SODIUMInactive
Code: M28OL1HH48Class: IACT
HYDROGENATED CASTOR OILInactive
Code: ZF94AP8MEYClass: IACT
Code: YOJ58O116EClass: ACTIBQuantity: 105000 [USP'U] in 1 1
TALCInactive
Code: 7SEV7J4R1UClass: IACT
HYPROMELLOSE PHTHALATE (31% PHTHALATE, 170 CST)Inactive
Code: 8LDD2V82F5Class: IACT
POTASSIUM CHLORIDEInactive
Code: 660YQ98I10Class: IACT
HYPROMELLOSE, UNSPECIFIEDInactive
Code: 3NXW29V3WOClass: IACT
Code: 3560D81V50Class: ACTIBQuantity: 79000 [USP'U] in 1 1
SILICON DIOXIDEInactive
Code: ETJ7Z6XBU4Class: IACT
MAGNESIUM STEARATEInactive
Code: 70097M6I30Class: IACT
CARRAGEENANInactive
Code: 5C69YCD2YJClass: IACT
MICROCRYSTALLINE CELLULOSEInactive
Code: OP1R32D61UClass: IACT
WATERInactive
Code: 059QF0KO0RClass: IACT
TRIETHYL CITRATEInactive
Code: 8Z96QXD6UMClass: IACT
TITANIUM DIOXIDEInactive
Code: 15FIX9V2JPClass: IACT

Zenpep

Product Details

NDC Product Code
73562-114
Application Number
BLA022210
Marketing Category
BLA (C73585)
Route of Administration
ORAL
Effective Date
October 27, 2023
Code: 8MYC33932OClass: ACTIBQuantity: 40000 [USP'U] in 1 1
Code: YOJ58O116EClass: ACTIBQuantity: 168000 [USP'U] in 1 1
Code: 3560D81V50Class: ACTIBQuantity: 126000 [USP'U] in 1 1
CROSCARMELLOSE SODIUMInactive
Code: M28OL1HH48Class: IACT
HYDROGENATED CASTOR OILInactive
Code: ZF94AP8MEYClass: IACT
SILICON DIOXIDEInactive
Code: ETJ7Z6XBU4Class: IACT
MICROCRYSTALLINE CELLULOSEInactive
Code: OP1R32D61UClass: IACT
MAGNESIUM STEARATEInactive
Code: 70097M6I30Class: IACT
TALCInactive
Code: 7SEV7J4R1UClass: IACT
TITANIUM DIOXIDEInactive
Code: 15FIX9V2JPClass: IACT
HYPROMELLOSE PHTHALATE (31% PHTHALATE, 170 CST)Inactive
Code: 8LDD2V82F5Class: IACT
TRIETHYL CITRATEInactive
Code: 8Z96QXD6UMClass: IACT
HYPROMELLOSE, UNSPECIFIEDInactive
Code: 3NXW29V3WOClass: IACT

Zenpep

Product Details

NDC Product Code
73562-112
Application Number
BLA022210
Marketing Category
BLA (C73585)
Route of Administration
ORAL
Effective Date
October 27, 2023
Code: 8MYC33932OClass: ACTIBQuantity: 20000 [USP'U] in 1 1
Code: 3560D81V50Class: ACTIBQuantity: 63000 [USP'U] in 1 1
Code: YOJ58O116EClass: ACTIBQuantity: 84000 [USP'U] in 1 1
MICROCRYSTALLINE CELLULOSEInactive
Code: OP1R32D61UClass: IACT
MAGNESIUM STEARATEInactive
Code: 70097M6I30Class: IACT
CROSCARMELLOSE SODIUMInactive
Code: M28OL1HH48Class: IACT
HYDROGENATED CASTOR OILInactive
Code: ZF94AP8MEYClass: IACT
SILICON DIOXIDEInactive
Code: ETJ7Z6XBU4Class: IACT
TALCInactive
Code: 7SEV7J4R1UClass: IACT
TRIETHYL CITRATEInactive
Code: 8Z96QXD6UMClass: IACT
CARRAGEENANInactive
Code: 5C69YCD2YJClass: IACT
POTASSIUM CHLORIDEInactive
Code: 660YQ98I10Class: IACT
HYPROMELLOSE, UNSPECIFIEDInactive
Code: 3NXW29V3WOClass: IACT
HYPROMELLOSE PHTHALATE (31% PHTHALATE, 170 CST)Inactive
Code: 8LDD2V82F5Class: IACT
TITANIUM DIOXIDEInactive
Code: 15FIX9V2JPClass: IACT
WATERInactive
Code: 059QF0KO0RClass: IACT

Zenpep

Product Details

NDC Product Code
73562-117
Application Number
BLA022210
Marketing Category
BLA (C73585)
Route of Administration
ORAL
Effective Date
October 27, 2023
CROSCARMELLOSE SODIUMInactive
Code: M28OL1HH48Class: IACT
Code: 8MYC33932OClass: ACTIBQuantity: 60000 [USP'U] in 1 1
Code: 3560D81V50Class: ACTIBQuantity: 189600 [USP'U] in 1 1
HYDROGENATED CASTOR OILInactive
Code: ZF94AP8MEYClass: IACT
SILICON DIOXIDEInactive
Code: ETJ7Z6XBU4Class: IACT
MICROCRYSTALLINE CELLULOSEInactive
Code: OP1R32D61UClass: IACT
MAGNESIUM STEARATEInactive
Code: 70097M6I30Class: IACT
TALCInactive
Code: 7SEV7J4R1UClass: IACT
TRIETHYL CITRATEInactive
Code: 8Z96QXD6UMClass: IACT
HYPROMELLOSE PHTHALATE (31% PHTHALATE, 170 CST)Inactive
Code: 8LDD2V82F5Class: IACT
HYPROMELLOSE, UNSPECIFIEDInactive
Code: 3NXW29V3WOClass: IACT
TITANIUM DIOXIDEInactive
Code: 15FIX9V2JPClass: IACT
Code: YOJ58O116EClass: ACTIBQuantity: 252600 [USP'U] in 1 1

Drug Labeling Information

Complete FDA-approved labeling information including indications, dosage, warnings, contraindications, and other essential prescribing details.

DESCRIPTION SECTION

11 DESCRIPTION

Pancrelipase is a pancreatic enzyme product consisting of a mixture of enzymes including lipases, proteases, and amylases, and is an extract derived from porcine pancreatic glands. The enteric-coated pellets in ZENPEP are formulated to release pancreatic enzymes at an approximate pH of 5.5 or greater.

ZENPEP (pancrelipase) delayed-release capsule for oral administration, include a two-piece shell containing light brown-colored enteric-coated pellets (1.8 to 1.9mm for 3,000 and 5,000 USP units of lipase, 2.2 to 2.5 mm for 10,000, 15,000, 20,000, 25,000, 40,000 and 60,000 USP units of lipase) and are available as follows:

3,000 USP units of lipase; 10,000 USP units of protease; and 14,000 USP units of amylase; delayed-release capsules have a white opaque cap and a white opaque body with imprint “APTALIS 3”. The shells contain carnauba wax or talc, carrageenan, hypromellose, potassium chloride, titanium oxide, and water. The colorant of the printed ink is red iron oxide.

5,000 USP units of lipase; 17,000 USP units of protease; and 24,000 USP units of amylase; delayed-release capsules have a white opaque cap and a white opaque body with imprint “APTALIS 5”. The shells contain carnauba wax or talc, carrageenan, hypromellose, potassium chloride, titanium oxide, and water. The colorant of the printed ink is FD&C Blue 2.

10,000 USP units of lipase; 32,000 USP units of protease; and 42,000 USP units of amylase; delayed-release capsules have a yellow opaque cap and a white opaque body with imprint “APTALIS 10”. The shells contain carnauba wax or talc, carrageenan, hypromellose, potassium chloride, titanium oxide, water and yellow ferric oxide. The colorant of the printed ink is FD&C Blue 2.

15,000 USP units of lipase; 47,000 USP units of protease; and 63,000 USP units of amylase; delayed-release capsules have a red opaque cap and a white opaque body with imprint “APTALIS 15”. The shells contain carnauba wax or talc, carrageenan, hypromellose, potassium chloride, red ferric oxide, titanium oxide, and water. The colorant of the printed ink is FD&C Blue 2.

20,000 USP units of lipase; 63,000 USP units of protease; and 84,000 USP units of amylase; delayed-release capsules have a green opaque cap and a white opaque body with imprint “APTALIS 20”. The shells contain carnauba wax or talc, carrageenan, FD&C Blue #2, hypromellose, potassium chloride, titanium oxide, water, and yellow ferric oxide. The colorant of the printed ink is FD&C Blue 2.

25,000 USP units of lipase; 79,000 USP units of protease; and 105,000 USP units of amylase; delayed-release capsules have a blue opaque cap and a white opaque body with imprint “APTALIS 25”. The shells contain carnauba wax or talc, carrageenan, FD&C Blue #2, hypromellose, potassium chloride, titanium oxide, and water. The colorant of the printed ink is FD&C Blue 2.

40,000 USP units of lipase; 126,000 USP units of protease; and 168,000 USP units of amylase; delayed-release capsules have an orange opaque cap and white opaque body, printed with “APTALIS 40”. The shells contain FD&C Yellow #6, hypromellose, and titanium oxide. The colorant of the printed ink is FD&C Blue 2.

60,000 USP units of lipase; 189,600 USP units of protease; 252,600 USP units of amylase. Capsules have a powder blue opaque cap with two black stripes and white opaque body, printed with "APTALIS 60" The shells contain FD&C Blue #1, hypromellose, and titanium oxide. The colorant of the printed ink is black iron oxide.

ZENPEP (pancrelipase) delayed-release capsules include the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hydrogenated castor oil, hypromellose phthalate, magnesium stearate, microcrystalline cellulose, talc, and triethyl citrate.

CLINICAL PHARMACOLOGY SECTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Pancreatic enzyme products contain a mixture of lipases, proteases, and amylases that catalyze the hydrolysis of fats to monoglycerides, glycerol, and free fatty acids, protein into peptides and amino acids, and starch into dextrins and short chain sugars such as maltose and maltriose in the duodenum and proximal small intestine, thereby acting like digestive enzymes physiologically secreted by the pancreas.

12.2 Pharmacodynamics

For patients consuming a high fat diet in the clinical trials, the coefficient of fat absorption (CFA) was higher in patients who received ZENPEP compared to the placebo treatment group, indicating improved fat absorption [see Clinical Studies (14)].

12.3 Pharmacokinetics

Following oral administration, the lipases, proteases, and amylases released from ZENPEP are not absorbed from the gastrointestinal tract in appreciable amounts.

Drug Interactions

The lipases, proteases, and amylases of ZENPEP are not substrates of CYP enzymes or transporters. CYP enzymes or transporters mediated drug interactions are not expected.


INDICATIONS & USAGE SECTION

Highlight: ZENPEP® is indicated for the treatment of exocrine pancreatic insufficiency in adult and pediatric patients. (1)

1 INDICATIONS AND USAGE

ZENPEP® is indicated for the treatment of exocrine pancreatic insufficiency in adult and pediatric patients.

DOSAGE FORMS & STRENGTHS SECTION

Highlight: Delayed-Release Capsules (3):

3,000 USP units of lipase; 10,000 USP units of protease; and 14,000 USP units of amylase

5,000 USP units of lipase; 17,000 USP units of protease; and 24,000 USP units of amylase

10,000 USP units of lipase; 32,000 USP units of protease; and 42,000 USP units of amylase

15,000 USP units of lipase; 47,000 USP units of protease; and 63,000 USP units of amylase

20,000 USP units of lipase; 63,000 USP units of protease; and 84,000 USP units of amylase

25,000 USP units of lipase; 79,000 USP units of protease; and 105,000 USP units of amylase

40,000 USP units of lipase; 126,000 USP units of protease; and 168,000 USP units of amylase

60,000 USP units of lipase; 189,600 USP units of protease; and 252,600 USP units of amylase

3 DOSAGE FORMS AND STRENGTHS

Delayed-release capsules are available in the following strengths:

3,000 USP units of lipase; 10,000 USP units of protease; and 14,000 USP units of amylase in a two‑piece hypromellose capsule with a white opaque cap and white opaque body, and red imprint with “APTALIS 3” 

5,000 USP units of lipase; 17,000 USP units of protease; and 24,000 USP units of amylase in a two‑piece hypromellose capsule with a white opaque cap and white opaque body, and blue imprint with “APTALIS 5” 

10,000 USP units of lipase; 32,000 USP units of protease; and 42,000 USP units of amylase in a two-piece hypromellose capsule with a yellow opaque cap and white opaque body, and blue imprint with “APTALIS 10”

15,000 USP units of lipase; 47,000 USP units of protease; and 63,000 USP units of amylase in a two-piece hypromellose capsule with a red opaque cap and white opaque body, and blue imprint with “APTALIS 15”

20,000 USP units of lipase; 63,000 USP units of protease; and 84,000 USP units of amylase in a two-piece hypromellose capsule with a green opaque cap and white opaque body, and blue imprint with “APTALIS 20”

25,000 USP units of lipase; 79,000 USP units of protease; and 105,000 USP units of amylase in a two-piece hypromellose capsule with a blue opaque cap and white opaque body, and blue imprint with “APTALIS 25”

40,000 USP units of lipase; 126,000 USP units of protease; and 168,000 USP units of amylase in a two-piece hypromellose capsule with an orange opaque cap and white opaque body, and blue imprint with “APTALIS 40”

60,000 USP units of lipase; 189,600 USP units of protease; 252,600 USP units of amylase. Capsules have a powder blue opaque cap with two black stripes and white opaque body, black imprint with “APTALIS 60”

CONTRAINDICATIONS SECTION

Highlight: None (4)

4 CONTRAINDICATIONS

None


USE IN SPECIFIC POPULATIONS SECTION

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Published data from case reports with pancrelipase use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Pancrelipase is minimally absorbed systematically; therefore, maternal use is not expected to result in fetal exposure to the drug. Animal reproduction studies have not been conducted with pancrelipase.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

8.2 Lactation

Risk Summary

There are no data on the presence of pancrelipase in either human or animal milk, the effects on the breastfed infant or the effects on milk production. Pancrelipase is minimally absorbed systemically following oral administration, therefore maternal use is not expected to result in clinically relevant exposure of breastfed infants to the drug. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZENPEP and any potential adverse effects on the breastfed infant from ZENPEP or from the underlying maternal conditions.

8.4 Pediatric Use

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)].

8.5 Geriatric Use

Clinical studies of ZENPEP 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.


ADVERSE REACTIONS SECTION

Highlight: Most common adverse reactions (≥6%) are: headache, contusion, cough, and early satiety. (6.1)

**To report SUSPECTED ADVERSE REACTIONS, contactAimmune Therapeutics, Inc at 1-833-AIM2KNO (1-833-246-2566) or FDA at 1-800-FDA-1088 or **www.fda.gov/medwatch.

6 ADVERSE REACTIONS

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

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

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.

Table 1: Adverse Reactions* in a Clinical Trial of Adult and Pediatric Patients 7 Years of Age and Older with Exocrine Pancreatic Insufficiency due to Cystic Fibrosis (Study 1)
  • Reported in at least 2 ZENPEP-treated patients (greater than or equal to 6%) and at a higher rate than placebo-treated patients.

Adverse
Reaction

ZENPEP
N=34
n (%)

Placebo
N=32
n (%)

Headache

5 (15%)

0

Contusion

2 (6%)

0

Cough

2 (6%)

0

Early Satiety

2 (6%)

0

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

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

CLINICAL STUDIES SECTION

14 CLINICAL STUDIES

Adult and Pediatric Patients 7 Years of Age and Older

Study 1 was a randomized, double-blind, placebo-controlled, crossover study of 34 patients, aged 7 to 23 years, with exocrine pancreatic insufficiency due to cystic fibrosis. The final analysis population was limited to 32 patients, who completed both double-blind treatment periods, and were included in the efficacy analysis population. Patients were randomized to receive ZENPEP or matching placebo for 6 to 7 days of treatment, followed by crossover to the alternate treatment for an additional 6 to 7 days. The mean exposure to ZENPEP during this study, including titration period and open label transition, was 30 days. The mean dosage during the controlled treatment periods ranged from a mean dose of 3,900 lipase units/kg/day to 5,700 lipase units/kg/day. All patients consumed a high-fat diet (greater than or equal to 100 grams of fat per day) during the treatment period. The population was nearly evenly distributed in biological sex, and approximately 96% of patients were White.

Coefficient of Fat Absorption Endpoint and Results

The primary efficacy endpoint was the mean difference in the coefficient of fat absorption (CFA) between ZENPEP and placebo treatment. The CFA was determined by a 72-hour stool collection during both treatments, when both fat excretion and fat ingestion were measured. Each patient’s CFA during placebo treatment was used as their no-treatment CFA value.

Mean CFA was 88% with ZENPEP treatment compared to 63% with placebo treatment. The mean difference in CFA was 26 percentage points in favor of ZENPEP treatment with 95% Confidence Interval of (19, 32) and p≤0.001.

Subgroup analyses of the CFA results showed that mean change in CFA was greater in patients with lower no-treatment (placebo) CFA values than in patients with higher no-treatment (placebo) CFA values. There were similar responses to ZENPEP by age and biological sex.

Pediatric Patients 1 to 6 Years of Age

Study 2 was an open-label, uncontrolled study of 19 pediatric patients, aged 1 to 6 years (mean age 4 years), with exocrine pancreatic insufficiency due to cystic fibrosis. Approximately half of the patients were aged 1 to 3 years. Study 2 compared a measurement of fat malabsorption, spot fecal fat testing, before (while receiving therapy with another pancreatic enzyme product) and after oral administration of ZENPEP capsules with each meal or snack.

After a 4 to 14 day screening period during which patients remained on their current pancreatic enzyme product, patients were switched to ZENPEP at individually titrated dosages ranging between 2,300 and 10,000 lipase units/kg/day (not to exceed 2,500 lipase units/kg/meal) for 14 days. The mean ZENPEP dosage was approximately 5,000 lipase unit/kg/day. There was no wash- out period. Overall, patients showed similar control of fat malabsorption by spot fecal fat testing when switched from their current pancreatic enzyme product to ZENPEP treatment at a similar dosage.


SPL MEDGUIDE SECTION

Medication Guide

MEDICATION GUIDE
ZENPEP**®**** (ZEN-pep)**
(pancrelipase)
delayed-release capsules, for oral use

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

ZENPEP may increase your chance of having a rare bowel disorder called fibrosing colonopathy especially if taken at a high dose for a long time in children with cystic fibrosis. This condition is serious and may require surgery. The risk of having this condition may be reduced by following the dosing instructions that your doctor gave you.Call your doctor right away if you have any unusual or severe:

Stomach area (abdominal) pain

Bloating

Trouble passing stool (having bowel movements)

Nausea, vomiting, or diarrhea

Take ZENPEP exactly as prescribed by your doctor.Do not take more ZENPEP than directed by your doctor.

What is ZENPEP?

ZENPEP is a prescription medicine used to treat people who cannot digest food normally because their pancreas does not make enough enzymes.

ZENPEP contains a mixture of digestive enzymes including lipases, proteases, and amylases from pig pancreas.

ZENPEP is safe and effective in adults and children.

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

are allergic to pork (pig) products.

have a history of blockage of your intestines, or scarring or thickening of your bowel wall (fibrosing colonopathy) 

have gout, kidney disease, or high blood uric acid (hyperuricemia)

have trouble swallowing capsules

have any other medical condition

are pregnant or plan to become pregnant 

are breastfeeding or plan to breastfeed. It is not known if ZENPEP passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take ZENPEP.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine.

How should I take ZENPEP?

**Take ZENPEP exactly as your doctor tells you.** Contact your doctor if you continue to have signs and symptoms of malabsorption (not absorbing nutrients from food) such as abdominal pain, abdominal distention, bloating, fatty stools, or weight loss. Your dose may need to be changed.

You should not switch ZENPEP with any other pancreatic enzyme product without first talking to your doctor.

Do not take more capsules in a day than the number your doctor tells you (total daily dose).

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

**ZENPEP capsules should be swallowed whole. Do not crush or chew the ZENPEP capsules or its contents and do not hold the capsule contents in your mouth.**Crushing or chewing the ZENPEP capsules may cause irritation in your mouth or change the way ZENPEP works in your body.

Giving ZENPEP to Adults and Children 12 Months of Age and Older:

Swallow ZENPEP capsules whole and take them with enough liquid (water or juice) to swallow them right away.

If you have trouble swallowing capsules, open the capsules and sprinkle the entire contents on a small amount of acidic soft food such as applesauce, bananas or pears. Ask your doctor about other foods you can mix with ZENPEP.

If you sprinkle ZENPEP on food,**swallow it right after you** mix it. Do not store ZENPEP that is mixed with food. 

Swallow the ZENPEP and food mixture right away followed with water or juice. Make sure the medicine is swallowed completely. 

If you forget to take ZENPEP, call your doctor or wait until your next meal and take your usual number of capsules.**Do not make up for missed doses.** Take your next dose at the usual time.

Giving ZENPEP to Infants**(Children from Birth to 12 Months of Age):**

The 2 ways to give ZENPEP to infants (children from birth to 12 months of age), which are described below:

a) Giving with an Acidic Soft Food

Before each breastfeeding session or each time you give 120 mL of formula, carefully open the capsule and sprinkle the entire contents of the capsule in a small amount of acidic soft food (such as, store bought preparations of applesauce, bananas or pears)
Mix the capsule contents evenly through the food. Be careful not to crush the ZENPEP capsule contents while mixing.
Give the entire mixture to the infant right away.**Do not** store the ZENPEP mixture or save for later use.
**Do not** mix the ZENPEP capsule contents directly into a bottle of breast milk or formula.
Give your infant enough formula or breastfeed your infant**right away** to completely swallow the ZENPEP food mixture.
Look into your infant’s mouth to make sure that all of the medicine has been swallowed.
Throw away the empty ZENPEP capsule.

b) Giving Directly Into the Infant’s Mouth Before Breastfeeding or Formula Feeding

Before each breastfeeding session or each time you give 120 mL of formula, carefully open the ZENPEP capsule and sprinkle the capsule contents directly into the infant’s mouth. 
**Do not** mix the ZENPEP capsule contents directly into a bottle of breast milk or formula.
Give your infant additional breast milk or formula**right after** ZENPEP to completely swallow the ZENPEP capsule contents.
Look in your infant’s mouth to make sure that all the medicine has been swallowed.
Throw away the empty ZENPEP capsule.

If a dose is missed, give the next dose with the next feeding.

What are possible side effects of ZENPEP?

ZENPEP may cause serious side effects, including:

See**“What is the most important information I should know about ZENPEP?”**

**Irritation of the inside of your mouth.** This can happen if ZENPEP is not swallowed completely.

**Increase in blood uric acid levels (hyperuricemia).**This may happen in people with gout, kidney problems, or those who take high doses of pancrelipase, the active ingredient in ZENPEP. Call your doctor if you have pain, stiffness, redness or swelling of your joints. 

**Severe allergic reactions.**Severe allergic reactions have happened in people taking pancreatic enzyme products like ZENPEP. Stop taking ZENPEP and get emergency treatment right away if you have any of these symptoms:trouble with breathing, skin rashes, swollen lips, or itching. 

The most common side effects of ZENPEP include:

Headache

Bruising

Cough

Feeling full after eating a small amount of food

Other Possible Side Effects:

ZENPEP and other pancreatic enzyme products are made from the pancreas of pigs, the same pigs people eat as pork. These pigs may carry viruses. Although it has never been reported, it may be possible for a person to get a viral infection from taking pancreatic enzyme products that come from pigs.

Tell your doctor if you have any side effect that bothers you or does not go away.

These are not all the possible side effects of ZENPEP.

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 Aimmune Therapeutics, Inc at 1-833-AIM2KNO (1-833-246-2566).

How do I store ZENPEP?

Store ZENPEP at room temperature between 68ºF to 77ºF (20°C to 25°C). Avoid heat.

After opening the bottle, keep it closed tightly between uses to protect from moisture.

Do not eat or throw away the packet (desiccant) in your medicine bottle. This packet will protect your medicine from moisture. 

Store ZENPEP in a dry place.

Keep ZENPEP and all medicines out of the reach of children.

General information about the safe and effective use of ZENPEP.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ZENPEP for a condition for which it was not prescribed. Do not give ZENPEP to other people, even if they have the same symptoms you have. It may harm them.

You can ask your pharmacist or doctor for information about ZENPEP that is written for health professionals.

What are the ingredients in ZENPEP?

Active ingredients: lipase, protease, amylase

Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hydrogenated castor oil, hypromellose phthalate, magnesium stearate, microcrystalline cellulose, talc, and triethyl citrate in hypromellose capsules.

The red radial imprinting on the 3,000 capsule strength contains, antifoam DC 1510, industrial methylated spirit, iron oxide red C.I. 77491-E172, n-butyl alcohol, shellac and soya lecithin.

The blue radial imprinting on the 5,000, 10,000, 15,000, 20,000, 25,000, and 40,000 capsule strengths contains FD&C Blue #2 as colorant.

The black radial imprinting on the 60,000 capsule strength contains black iron oxide as colorant.

Capsule shell ingredients:

3,000 USP units and 5,000 USP units of lipase contain carnauba wax or talc, carrageenan, hypromellose, potassium chloride, titanium oxide, and water.

10,000 USP units of lipase contain carnauba wax or talc, carrageenan, hypromellose, potassium chloride, titanium oxide, water and yellow ferric oxide.

15,000 USP units of lipase contain carnauba wax or talc, carrageenan, hypromellose potassium chloride, red ferric oxide, titanium oxide, and water.

20,000 USP units of lipase contain carnauba wax or talc, carrageenan, FD&C Blue #2, hypromellose, potassium chloride, titanium oxide, water, and yellow ferric oxide.

25,000 USP units of lipase contain carnauba wax or talc, carrageenan, FD&C Blue #2 hypromellose, potassium chloride, titanium oxide, and water.

40,000 USP units of lipase contain FD&C Yellow #6, hypromellose, and titanium oxide.

60,000 USP units of lipase contain FD&C Blue #1, hypromellose and titanium oxide.

Manufactured by:
****Zenpep LLC
1007 US Highway 202/206
Bridgewater, NJ 08807, USA

Product of Germany

US License No. 2198

Manufactured for:
****Aimmune Therapeutics, Inc.
Bridgewater, NJ 08807, USA

For further information, please call Aimmune Therapeutics at 1-833-AIM2KNO (1-833-246-2566)

©2023 Nestlé

For further information, please go to www.ZENPEP.com or call Aimmune Therapeutics, Inc at 1-833-AIM2KNO (1-833-246-2566)

©2024 Nestlé

All trademarks are owned by Société des Produits Nestlé S.A., Vevey, Switzerland or used with permission.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Revised 02/2024


SPL UNCLASSIFIED SECTION

Manufactured by:
****Zenpep LLC
1007 US Highway 202/206,
Bridgewater, NJ 08807, USA

US License No. 2198

Manufactured for:
****Aimmune Therapeutics, Inc.
Bridgewater, NJ 08807, USA

For further information, please call Aimmune Therapeutics at 1-833-AIM2KNO (1-833-246-2566).

©2024 Nestlé

All trademarks are owned by Société des Produits Nestlé S.A., Vevey, Switzerland or used with permission.

Patented. See www.nestlehealthscience.us/patents.


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