Pancreaze

Dosage Forms & Strengths

lipase/protease/amylase

(KU=1000 units)

capsule, delayed-release (contains enteric-coated microspheres)

• Creon
• 6KU/19KU/30KU
• 12KU/38KU/60KU
• 24KU/76KU/120KU
• 36KU/114KU/180KU

capsule, delayed-release (contains enteric-coated microtablets)

• Pancreaze
• 4.2KU/10KU/17.5KU
• 10.5KU/25KU/43.75KU
• 16.8KU/40KU/70KU
• 21KU/37KU/61KU

capsule, delayed-release (contains enteric-coated minitablets)

• Ultresa
• 13.8KU/27.6KU/27.6KU
• 20.7KU/41.4KU/41.4KU
• 23KU/46KU/46KU

tablet

• Viokace
• 10.44KU/39.15KU/39.15KU  
• 20.88KU/78.3KU/78.3KU

capsule, delayed-release (contains enteric-coated microspheres)

• Pertzye
• 8KU/28.75KU/30.25KU
• 16KU/57.5KU/60.5KU
• 24KU/86.25KU/90.75KU

capsule, delayed-release (contains enteric-coated beads)

• Zenpep
• 5KU/17KU/27KU
• 10KU/34KU/55KU
• 15KU/51KU/82KU
• 20KU/68KU/109KU
• 25KU/85KU/136KU

Exocrine Pancreatic Insufficiency

Creon, Ultresa, Pertzye, Zenpep, Pancreaze are indicated for pancreatic insufficiency due to cystic fibrosis, pancreatitis, pancreatectomy, or other conditions

• Cystic fibrosis guidelines: Generally, start 500 lipase units/kg PO per meal; can titrate up to 2500 units/kg/meal based on response; not to exceed 10,000 lipase units/kg/day or <4000 lipase units/g fat ingested per day  
• Administer 50% of meal dose with snacks
• High-dose Creon: In 1 clinical trial described in the prescribing information, adults received a dose of 72,000 lipase units/meal while consuming at least 100 g of fat/day for chronic pancreatitis or pancreatectomy; lower starting doses (ie, 500 lipase units/kg/meal) are consistent with Cystic Fibrosis guidelines

Viokace

• Only indicated in adults for the treatment of exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy (and not cystic fibrosis)
• Generally, start 500 lipase units/kg PO per meal; can titrate up to 2500 units/kg/meal based on response; not to exceed 10,000 lipase units/kg/day or <4000 lipase units/g fat ingested per day  
• Administer 50% of meal dose with snacks
• Viokace should be administered with a PPI

Dosing Considerations

For patients who are unable to swallow intact capsules, may carefully open capsules and 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 mixture should be swallowed immediately and followed with water or juice to ensure complete ingestion

Dosage Forms & Strengths

lipase/protease/amylase

(KU=1000 units)

capsule, delayed-release (enteric-coated microspheres)

• Creon
• 3KU/9.5KU/15KU
• 6KU/19KU/30KU
• 12KU/38KU/60KU
• 24KU/76KU/120KU

capsule, delayed-release (enteric-coated microtablets)

• Pancreaze
• 4.2KU/10KU/17.5KU
• 10.5KU/25KU/43.75KU
• 16.8KU/40KU/70KU
• 21KU/37KU/61KU

capsule, delayed-release (contains enteric-coated minitablets)

• Ultresa
• 13.8KU/27.6KU/27.6KU
• 20.7KU/41.4KU/41.4KU
• 23KU/46KU/46KU

tablet

• Viokace
• 10.44KU/39.15KU/39.15KU  
• 20.88KU/78.3KU/78.3KU

capsule, delayed-release (contains enteric-coated microspheres)

• Pertzye
• 4KU/14.375KU/15.125KU
• 8KU/28.75KU/30.25KU
• 16KU/57.5KU/60.5KU
• 24KU/86.25KU/90.75KU

capsule, delayed-release (contains enteric-coated beads)

• Zenpep
• 3KU/10KU/16KU
• 5KU/17KU/27KU
• 10KU/34KU/55KU
• 15KU/51KU/82KU
• 20KU/68KU/109KU
• 25KU/85KU/136KU

Exocrine Pancreatic Insufficiency

Creon, Ultresa, Pertzye, Zenpep, Pancreaze are indicated for pancreatic insufficiency due to cystic fibrosis, pancreatitis, pancreatectomy, or other conditions

Creon/Zenpep

• ≤12 months: 3000 lipase units/kg/120 mL of formula or per breastfeeding; administer prior to feeding; capsule contents should not be mixed directly in formula or breast milk  
• 1-3 years: Initiate at 1000 lipase units/kg/meal; not to exceed 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day
• ≥4 years: Initiate at 500 lipase units/kg/meal; not to exceed 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day

Pancreaze

• ≤12 months: 2000-4000 lipase units/kg/120 mL of formula or per breastfeeding; administer prior to feeding; capsule contents should not be mixed directly in formula or breast milk  
• 1-3 years: Initiate at 1000 lipase units/kg/meal; not to exceed 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day
• ≥4 years: Initiate at 500 lipase units/kg/meal; not to exceed 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day
• Not to exceed 10,000 unit lipase/kg/day or <4,000 lipase unites/g fat ingested daily

Pertzye

• ≤12 months: 4000 lipase units/kg/120 mL of formula or per breastfeeding; administer prior to feeding; capsule contents should not be mixed directly in formula or breast milk  
• 1-4 years and weight ≥8 kg: Initiate at 1000 lipase units/kg/meal; not to exceed 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day
• ≥4 years and weight ≥16 kg: Initiate at 500 lipase units/kg per meal; not to exceed 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day

Ultresa

• 1-4 years and weight >14 kg: Initiate at 1000 lipase units/kg/meal; not to exceed 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day  
• ≥4 years and weight >28 kg: Initiate at 500 lipase units/kg/meal; not to exceed 2500 lipase units/kg/meal (or 10,000 lipase units/kg/day) or <4000 lipase units/g fat ingested per day

Viokace

• Safety and effectiveness not established

Recommendations from Cystic Fibrosis Foundation Consensus Report

• Infants <2 years is 2000-5000 lipase units/120 mL feeding; as infant grows, adjust dose not to exceed 2500 lipase units/kg/feeding (or 10,000 lipase units/kg/day)
• In general, daily requirements of 500-4000 lipase units/g of fat are required
• J Pediatr 2009;155(6 Suppl):S73-S93

• Janssen Pharmaceuticals, Inc.

Pancrelipase is a combination of three enzymes (proteins): lipase, protease, and amylase. These enzymes are normally produced by the pancreas and are important in the digestion of fats, proteins, and sugars.

Pancrelipase is used to replace these enzymes when the body does not have enough of its own. Certain medical conditions can cause this lack of enzymes, including cystic fibrosis, chronic inflammation of the pancreas, or blockage of the pancreatic ducts.

Pancrelipase may also be used following surgical removal of the pancreas.

Pancrelipase may also be used for purposes not listed in this medication guide.

You should not take pancrelipase if you are allergic to pork proteins.

To make sure pancrelipase is safe for you, tell your doctor if you have ever had:

• kidney disease;

• gout;

• diabetes;

• a blockage or scarring in your intestines;

• trouble swallowing pills; or

• lactose intolerance.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether pancrelipase passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, genetic toxicology, and animal fertility studies have not been performed with pancrelipase.

NDC 50458-342-60

Pancreaze®
(pancrelipase)
Delayed-Release Capsules

Each capsule contains:
Lipase 10,500 USP Units
Amylase 61,500 USP Units
Protease 35,500 USP Units

DOSE BY LIPASE UNITS

Each capsule contains enteric coated
pancrelipase microtablets.

Attention Pharmacist:
Dispense the accompanying
Medication Guide to each patient.

Rx only.

100 capsules

Fibrosing Colonopathy

Fibrosing colonopathy has been reported following treatment with different pancreatic enzyme products.4,5 Fibrosing colonopathy is a rare serious adverse reaction initially described in association with high-dose pancreatic enzyme use, usually with use over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis. The underlying mechanism of fibrosing colonopathy remains unknown. Doses of pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with colonic strictures in children less than 12 years of age.1 Patients with fibrosing colonopathy should be closely monitored because some patients may be at risk of progressing to stricture formation. It is uncertain whether regression of fibrosing colonopathy occurs.1 It is generally recommended, unless clinically indicated, that enzyme doses should be less than 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 than 4,000 lipase units/g fat ingested per day [see Dosage and Administration (2.1)].

Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorption. Patients receiving higher doses than 6,000 lipase units/kg of body weight per meal should be examined and the dosage either immediately decreased or titrated downward to a lower range.

Potential for Irritation to Oral Mucosa

Care should be taken to ensure that no drug is retained in the mouth. Pancreaze should not be crushed or chewed or mixed in foods having a pH greater than 4.5. These actions can disrupt the protective enteric coating resulting in early release of enzymes, irritation of oral mucosa, and/or loss of enzyme activity [see Dosage and Administration (2.2) and Patient Counseling Information (17)]. For patients who are unable to swallow intact capsules, the capsules may be carefully opened and the contents sprinkled to a small amount of acidic soft food with a pH of 4.5 or less, such as applesauce. The Pancreaze-soft food mixture should be swallowed immediately and followed with water or juice to ensure complete ingestion.

Potential for Risk of Hyperuricemia

Caution should be exercised when prescribing Pancreaze to patients with gout, renal impairment, or hyperuricemia. Porcine-derived pancreatic enzyme products contain purines that may increase blood uric acid levels.

Potential Viral Exposure from the Product Source

Pancreaze is sourced from pancreatic tissue from swine used for food consumption. Although the risk that Pancreaze will transmit an infectious agent to humans has been reduced by testing for certain viruses during manufacturing and by inactivating certain viruses during manufacturing, there is a theoretical risk for transmission of viral disease, including diseases caused by novel or unidentified viruses. Thus, the presence of porcine viruses that might infect humans cannot be definitely excluded. However, no cases of transmission of an infectious illness associated with the use of porcine pancreatic extracts have been reported.

Allergic Reactions

Caution should be exercised when administering pancrelipase to a patient with a known allergy to proteins of porcine origin. Rarely, severe allergic reactions including anaphylaxis, asthma, hives, and pruritus have been reported with other pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase). The risks and benefits of continued Pancreaze treatment in patients with severe allergy should be taken into consideration with the overall clinical needs of the patient.

Mechanism of Action

The pancreatic enzymes in Pancreaze catalyze the hydrolysis of fats to monoglyceride, glycerol and free fatty acids, proteins into peptides and amino acids, and starches 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.

Pharmacokinetics

The pancreatic enzymes in Pancreaze are enteric-coated to minimize destruction or inactivation in gastric acid. Pancreaze is expected to release most of the enzymes in vivo at pH greater than 5.5. Pancreatic enzymes are not absorbed from the gastrointestinal tract in appreciable amounts.

See Medication Guide

Dosing and Administration

Instruct patients and caregivers that Pancreaze should only be taken as directed by their healthcare professional. Patients should be advised that the total daily dose should not exceed 10,000 lipase units/kg body weight/day unless clinically indicated. This needs to be especially emphasized for patients eating multiple snacks and meals per day. Patients should be informed that if a dose is missed, the next dose should be taken with the next meal or snack as directed. Doses should not be doubled [see Dosage and Administration (2)].

Instruct patients and caregivers that Pancreaze should always be taken with food. Patients should be advised that Pancreaze delayed-release capsules and the capsule contents must not be crushed or chewed as doing so could cause early release of enzymes and/or loss of enzymatic activity. Patients should swallow the intact capsules with adequate amounts of liquid at mealtimes. If necessary, the capsule contents can also be sprinkled on soft acidic foods. [see Dosage and Administration (2)].

Instruct patients to notify their healthcare professional if they are pregnant or are thinking of becoming pregnant during treatment with Pancreaze [see Use in Specific Populations (8.1)].

Instruct patients to notify their healthcare professional if they are breastfeeding or are thinking of breastfeeding during treatment with Pancreaze [see Use in Specific Populations (8.3)].

Fibrosing Colonopathy

Advise patients and caregivers to follow dosing instructions carefully, as doses of pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal (10,000 lipase units/kg of body weight/day) have been associated with colonic strictures in children below the age of 12 years [see Dosage and Administration (2)].

Allergic Reactions

Advise patients and caregivers to contact their healthcare professional immediately if allergic reactions to Pancreaze develop [see Warnings and Precautions (5.5)].

Product of Germany

Finished Product Manufactured by:
Nordmark Arzneimittel GmbH & Co. KG
25436 Uetersen, Germany.

Manufactured for:
Janssen Pharmaceuticals, Inc.
Titusville, NJ 08560.

© Janssen Pharmaceuticals, Inc. 2010

Before taking Pancreaze, 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. It is not known if Pancreaze will harm your unborn baby.
• are breast-feeding or plan to breast-feed. It is not known if Pancreaze passes into your breast milk. You and your doctor should decide if you will take Pancreaze or breast-feed.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, or 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.

Take Pancreaze exactly as your doctor tells you.

• Do not take more capsules in a day than the number your doctor tells you to take (total daily dose).
• Always take Pancreaze 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.
• Your doctor may change your dose based on the amount of fatty foods you eat or based on your weight.
• Do not crush or chew the Pancreaze capsules or their contents, and do not hold the capsule or contents in your mouth. Crushing, chewing or holding the Pancreaze Capsules in your mouth may cause irritation in your mouth or change the way Pancreaze works in your body.

Giving Pancreaze to infants (children up to 12 months):

1. Give Pancreaze right before each feeding of formula or breast milk.
2. Do not mix Pancreaze capsule contents directly into formula or breast milk.
3. Open the capsules and sprinkle the contents directly into your infant's mouth or mix the contents in a small amount of soft food such as applesauce. These foods should be the kind found in baby food jars that you buy at the store, or other food recommended by your doctor.
4. If you sprinkle the Pancreaze on food, give the Pancreaze and food mixture to your child right away. Do not store Pancreaze that is mixed with food.
5. Give your child enough liquid to completely swallow the Pancreaze contents or the Pancreaze and food mixture.
6. Look into your child’s mouth to make sure that all of the medicine has been swallowed.

Giving Pancreaze to children and adults:

1. Swallow Pancreaze capsules whole and take them with enough liquid to swallow them right away.
2. If you have trouble swallowing capsules, open the capsules and sprinkle the contents on a small amount of acidic food such as applesauce. Ask your doctor about other foods you can mix with Pancreaze.
3. If you sprinkle Pancreaze on food, swallow it right after you mix it and drink plenty of water or juice to make sure the medicine is swallowed completely. Do not store Pancreaze that is mixed with food.
4. If you forget to take Pancreaze, call your healthcare provider or wait until your next meal and take your usual number of capsules. Take your next dose at your usual time. Do not make up for missed doses.

Applies to pancrelipase: oral capsule, oral capsule delayed release, oral powder, oral tablet, oral tablet chewable

Along with its needed effects, pancrelipase (the active ingredient contained in Pancreaze) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking pancrelipase:

• Skin rash or hives

• Bowel blockage
• diarrhea
• nausea
• stomach cramps or pain

• Blood in the urine
• joint pain
• swelling of the feet or lower legs

• Stuffy nose
• tightness in the chest
• trouble breathing

• Irritation of the mouth

• Cough
• difficulty with swallowing
• dizziness
• fast heartbeat
• itching
• noisy breathing
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• redness of the skin
• severe stomach pain
• unusual tiredness or weakness

Some side effects of pancrelipase may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Blurred vision
• dry mouth
• flushed, dry skin
• fruit-like breath odor
• headache
• increased hunger
• increased thirst
• increased urination
• sweating
• unexplained weight loss
• vomiting

• Abnormal feces
• anxiety
• bloated feeling
• chills
• cold sweats
• confusion
• cool, pale skin
• depression
• excess air or gas in the stomach or intestines
• feeling of fullness
• fever
• frequent bowel movements
• loss of consciousness
• muscle aches
• nightmares
• passing gas
• runny nose
• seizures
• shakiness
• slurred speech
• sore throat

• Difficulty having a bowel movement
• difficulty with moving
• muscle aching or cramping
• muscle pains or stiffness
• muscle spasm
• swollen joints