Pancrelipase

Dosage

PERTZYE is not substitutable with any other pancrelipase products.

PERTZYE is administered orally or via a gastrostomy tube. Therapy should be initiated at the lowest recommended dose and gradually increased. The dosage of PERTZYE should be individualized based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet (see Limitations on Dosing below).

Dosage recommendations for pancreatic enzyme replacement therapy were published following the Cystic Fibrosis Foundation Consensus Conferences.1,2,3 PERTZYE should be administered in a manner consistent with the recommendations of the Conferences provided in the following paragraphs. Patients may be dosed on a fat ingestion-based or actual body weight-based dosing scheme.

Infants may be given 4,000 lipase units (one capsule) per 120 mL of formula or breastfeeding. Do not mix PERTZYE capsule contents directly into formula or breast milk prior to administration [see Administration].

Enzyme dosing should begin with 1,000 lipase units/kg of body weight per meal for children less than age 4 years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day.

Adults Enzyme dosing should begin with 500 lipase units/kg of body weight per meal for those older than age 4 years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day.

Usually, half of the prescribed PERTZYE dose for an individualized full meal should be given with each snack. The total daily dose should reflect approximately three meals plus two or three snacks per day.

Enzyme doses expressed as lipase units/kg of body weight per meal should be decreased in older patients because they weigh more but tend to ingest less fat per kilogram of body weight.

Dosing should not exceed the recommended maximum dosage set forth by the Cystic Fibrosis Foundation Consensus Conferences Guidelines.1,2,3

If symptoms and signs of steatorrhea persist, the dosage may be increased by a healthcare professional. Patients should be instructed not to increase the dosage on their own. There is great inter-individual variation in response to enzymes; thus, a range of doses is recommended. Changes in dosage may require an adjustment period of several days. If doses are to exceed 2,500 lipase units/kg of body weight per meal, further investigation is warranted.

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. Doses greater than 6,000 lipase units/kg of body weight per meal have been associated with colonic strictures, indicative of fibrosing colonopathy, in children with cystic fibrosis less than 12 years of age [see WARNINGS AND PRECAUTIONS]. Patients currently 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.

Administration

PERTZYE should always be taken as prescribed by a healthcare professional.

PERTZYE should be administered to infants immediately prior to each feeding, using a dosage of 4,000 lipase units (one capsule) per 120 mL of formula or per breast-feeding. Contents of the capsule may be mixed with approximately 10 mL of soft acidic food with a pH of 4.5 or less (e.g., applesauce). Contents of the capsule may also be administered directly to the mouth. Administration should be followed by breast milk or formula. Do not mix contents of the capsule directly into formula or breast milk as this may diminish efficacy. Care should be taken to ensure that the PERTZYE microspheres are not crushed or chewed or retained in the mouth, to avoid irritation of the oral mucosa [see WARNINGS AND PRECAUTIONS].

• Administer PERTZYE during meals or snacks, with sufficient fluid.
• Swallow PERTZYE capsules whole.
• If a dose is missed, take the next dose with the next meal or snack as directed. Do not take two doses at one time.
• Do not crush or chew the capsules or the capsule contents.
• For patients who are unable to swallow intact capsules, follow the instructions below for oral administration with soft foods with a pH of 4.5 or less (e.g., applesauce):

1. Place a small amount (approximately 10 mL) of applesauce into a clean container.
2. Carefully open the capsule(s).
3. Sprinkle the intact microspheres on the applesauce.
4. Mix the microspheres with the applesauce being careful not to crush the microspheres when mixing.
5. Consume the entire contents immediately. Do not chew the microspheres. Do not save the applesauce and microspheres for later use.
6. Follow with water or juice to ensure complete ingestion and to ensure nothing is retained in the mouth to avoid mucosal irritation [see WARNINGS AND PRECAUTIONS].

Alternatively, the contents of one or two 4,000 USP lipase unit capsules can be administered with soft foods with a pH of 4.0 or less (e.g., applesauce) via a gastrostomy tube with a  diameter of 14 French or larger.

Gastrostomy Tube Administration Instructions (14 French Gastrostomy Tube or Larger)

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.

1. Transfer a minimum of 10 mL of applesauce into a small bowl or medicine cup.
2. Carefully open one or two Pertzye 4,000 lipase unit capsules.
3. Mix the capsule contents thoroughly with the transferred applesauce to create a uniform suspension. Once mixed, administer the suspension immediately. Care should be taken not to crush the enzyme microspheres. Discard the empty capsules.
4. Remove the plunger from a 35 mL slip tip syringe. Cover the tip of the syringe with your finger. Transfer the PERTZYE-applesauce mixture into the syringe. Replace the plunger partially back into the syringe.
5. Shake or tap the syringe lightly with the syringe tip facing upward so that the PERTZYE-applesauce mixture will move towards the plunger. Carefully push the plunger slowly until the residual air is removed from the syringe tip.
6. Once the residual air is removed, connect the syringe directly into the gastrostomy tube feeding port.
7. Push the syringe contents into the gastrostomy tube feeding port using steady pressure until empty.
8. Draw up approximately 10 mL of water with the slip tip syringe and flush the gastrostomy tube feeding port with the water.
9. Discard any unused portion of the PERTZYE-applesauce mixture. Do not save for later use.
10. If dose requires more than two capsules, repeat steps 1-9 until prescribed dose is reached.

The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) include fibrosing colonopathy, hyperuricemia and allergic reactions [see WARNINGS AND PRECAUTIONS].

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 short-term safety of PERTZYE was assessed in a randomized, double-blind, placebo-controlled, crossover study of 24 patients, ages 8 to 43 years, with exocrine pancreatic insufficiency due to cystic fibrosis. In this study, patients were randomized to receive PERTZYE at individually titrated doses (not to exceed 2,500 lipase units per kilogram per meal) or matching placebo for 6 to 8 days of treatment, followed by crossover to the alternate treatment for an additional 6 to 8 days. The length of exposure to PERTZYE during this study was 20-28 days, including the treatment period of 6 to 8 days, and the open label titration and transition periods of 7 to 10 days.

The most common adverse reactions ( ≥ 10%) were diarrhea, dyspepsia, and cough. 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.

Table 1: Adverse Reactions Occurring in at Least 2 Patients ( ≥ 10%)

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of PERTZYE. 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.

This formulation of PERTZYE has been marketed since 2004 under the trademark PANCRECARB®. Two product complaints relating to an adverse drug reaction were reported. A mild allergic reaction (itching and red, blotchy rash on face) was reported by a patient with a known history of allergy to another pancrelipase product, and a dull headache was reported by another patient taking concomitant ursodeoxycholic acid. Both events resolved without sequelae after discontinuation of treatment.

Delayed-and immediate-release pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase) have been used for the treatment of patients with exocrine pancreatic insufficiency due to cystic fibrosis and other conditions, such as chronic pancreatitis. The long-term safety profile of these products has been described in the medical literature. The most serious adverse events include fibrosing colonopathy, distal intestinal obstruction syndrome (DIOS), recurrence of pre-existing carcinoma, and severe allergic reactions including anaphylaxis, asthma, hives, and pruritus. The most commonly reported adverse events were gastrointestinal disorders, including abdominal pain, diarrhea, flatulence, constipation and nausea, and skin disorders, including pruritus, urticaria and rash.

Included as part of the PRECAUTIONS section.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if pancrelipase crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using pancrelipase.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• how you respond to this medication
• your diet
• your weight
• your age

The dose of pancrelipase varies with your age, body weight, and the amount of fat in your diet. Do not exceed maximum daily dosage recommendations.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended. Do not switch brands of this medicine without your doctor's advice.

Pancrelipase should be taken with a meal or snack.

Read all patient information, medication guides, and instruction sheets provided to you. Be especially careful to follow all directions about giving this medicine to a child. Ask your doctor or pharmacist if you have any questions.

Pancrelipase is sometimes given with a stomach acid reducer such as Nexium, Prevacid, Prilosec, or Protonix. Follow your doctor's instructions about taking all medicines needed to treat your condition.

Do not crush, chew, or break a pancrelipase capsule or tablet. Swallow it whole with a full glass of water.

Do not hold the pill in your mouth. Pancrelipase can irritate the inside of your mouth.

You may open the pancrelipase capsule and sprinkle the medicine into a spoonful of applesauce to make swallowing easier. Swallow the mixture right away without chewing. Do not save for later use. Do not mix the medicine with infant formula or breast milk.

Do not inhale the powder from a pancrelipase capsule, or allow it to touch your skin. It may cause irritation, especially to your nose and lungs.

Use pancrelipase regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Store at room temperature, away from moisture and heat. Keep the medicine container tightly closed.

Your medicine bottle may also include a packet or canister of moisture-absorbing preservative. Keep this packet in the bottle at all times.

Call your doctor if you have any worsening of a long-term pancreas problem.

Take the missed dose with your next meal or snack. Do not take extra medicine to make up the missed dose.

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

Usual Adult Dose for Pancreatic Exocrine Dysfunction:

Initial: lipase 500 units/kg orally per meal.

Maintenance: Lipase 400 to 2500 units/kg orally per meal. Give one-half the usual dose with each snack.

Maximum: Total daily dose should not exceed 10,000 lipase units/kg body weight/day.

Usual Adult Dose for Cystic Fibrosis:

Initial: lipase 500 units/kg orally per meal.

Maintenance: Lipase 400 to 2500 units/kg orally per meal. Give one-half the usual dose with each snack.

Maximum: Total daily dose should not exceed 10,000 lipase units/kg body weight/day.

Usual Adult Dose for Chronic Pancreatitis:

8000 to 36,000 lipase USP orally with each meal.

In patients with pancreatectomy or obstruction of pancreatic ducts, lipase 8000 to 16,000 USP orally taken at 2-hour intervals or as directed by physician.

Usual Pediatric Dose for Pancreatic Exocrine Dysfunction:

Less than 1 year:
2000 to 4000 units per 120 mL of formula, breast milk, or per breast-feeding

Greater than 1 to less than 4 years:
Initial dose: 1000 units/kg/meal
Dosage range: 1000 to 2500 units/kg/meal

Greater than or equal to 4 years:
Refer to adult dosing.

In cystic fibrosis, the powder is given as one-fourth teaspoonful (0.7 g) with meals.

Usual Pediatric Dose for Cystic Fibrosis:

Less than 1 year:
2000 to 4000 units per 120 mL of formula, breast milk, or per breast-feeding

Greater than 1 to less than 4 years:
Initial dose: 1000 units/kg/meal
Dosage range: 1000 to 2500 units/kg/meal

Greater than or equal to 4 years:
Refer to adult dosing.

In cystic fibrosis, the powder is given as one-fourth teaspoonful (0.7 g) with meals.

Malabsorption Syndrome

Used as replacement therapy in the symptomatic treatment of malabsorption syndrome caused by established pancreatic insufficiency of organic origin, as in cystic fibrosis of the pancreas, chronic pancreatitis, pancreatectomy, GI bypass surgery (e.g., Billroth II gastroenterostomy), cancer of the pancreas, or other conditions in which pancreatic insufficiency impairs fat digestion.100 101 102 103 104 a

May be used as a presumptive test for pancreatic function (e.g., pancreatic insufficiency associated with chronic pancreatitis).103

Pancreatic exocrine replacement therapy should not delay or supplant treatment of the primary disorder.103 a

Has been used in treating steatorrhea of postgastrectomy syndrome and bowel resection; however, pancreatic extracts are less likely to be effective in this condition and in cases of malabsorption associated with ileitis, tuberculosis, or lymphomas.a

Not effective in the treatment of functional digestive disorders unrelated to pancreatic insufficiency.a

• Catalyzes hydrolysis of fats to glycerol and fatty acids and protein into proteoses and derived substances; converts starch into dextrins and short-chain sugars.100 101 102 103 104

• Reduces fat and nitrogen content in stool.103

• If sufficient pancreatic enzymes are delivered to the small intestine, malabsorption could be corrected.103

In the U.S.

• Creon
• Palcaps
• Pancreaze
• Pancrelipase
• Pangestyme EC
• Panocaps
• Pertzye
• Ultracaps
• Ultresa
• Viokace
• Zenpep

In Canada

• Viokase

Available Dosage Forms:

• Capsule, Delayed Release
• Tablet
• Tablet, Chewable
• Powder
• Capsule

Therapeutic Class: Enzyme Replacement

Pharmacologic Class: Enzyme

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For pancrelipase, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to pancrelipase or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of Creon®, Pancreaze®, Pertzye®, and Zenpep® in children.

Appropriate studies have not been performed on the relationship of age to the effects of Ultresa™ in children younger than 12 months of age, and Viokace™ in children. Safety and efficacy have not been established in these age groups.

Geriatric

No information is available on the relationship of age to the effects of Creon®, Pancreaze®, and Pertzye® in geriatric patients.

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of Ultresa™, Viokace™, and Zenpep® in the elderly. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving these medicines.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of pancrelipase. Make sure you tell your doctor if you have any other medical problems, especially:

• Abnormal blood glucose levels, history of or
• Fibrosing colonopathy (bowel disorder) or
• Gout or
• Hyperuricemia (high uric acid in the blood) or
• Hyperuricosuria (high uric acid in the urine) or
• Intestinal (bowel) blockage, history of or
• Kidney disease or
• Pancreatitis (swelling of the pancreas)—Use with caution. May make these conditions worse.

• Allergy to pork products—Use with caution. Pancrelipase contains pork proteins.

• Lactose intolerance—Viokace™ tablets contains lactose, which can make this condition worse.

It is very important that your doctor check the progress of you or your child at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you or your child should continue to take it.

For patients taking the capsules containing the powder:

• If the capsules are opened to mix with food, be careful not to breathe in the powder. To do so may cause harmful effects, such as stuffy nose, shortness of breath, troubled breathing, or tightness in the chest.

For patients taking the powder form of pancrelipase:

• Avoid breathing in the powder. To do so may cause harmful effects such as stuffy nose, shortness of breath, troubled breathing, or tightness in the chest.

Check with your doctor right away if you or your child have unusual or severe abdominal or stomach pain, trouble passing stool, nausea, or vomiting. These may be symptoms of a rare but serious bowel disorder, called fibrosing colonopathy.

pancrelipase may cause irritation of the inside of your or your child's mouth if it is not swallowed completely, is crushed or chewed, or is mixed into foods that are not recommended. Follow your doctor's instructions carefully to prevent this.

Pancrelipase may increase uric acid levels in the blood. Check with your doctor if you or your child have joint pain, stiffness, or swelling, lower back, side, or stomach pain, or swelling of the feet or lower legs.

pancrelipase is made from the pancreas of pigs. The risk of getting a virus from medicines made of pig organs has been greatly reduced in recent years. This is the result of required testing for certain viruses, and testing during manufacture of these medicines. Although the risk of transmitting certain viruses to people who will use the medicine is low, talk with your doctor if you or your child have concerns.

pancrelipase may cause serious types of allergic reactions, including anaphylaxis, which can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, hives, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, mouth, or throat while you or your child are using pancrelipase.

Tell your doctor if you have a history of abnormal blood glucose levels before taking Zenpep®.

In Study 1, a 10 year-old patient was administered a dose of 10,856 lipase units per kg body weight of Pancrelipase for a period of one day. The patient did not experience any adverse events as a result of the dose increase, nor did this patient experience any adverse events during a 44-day follow-up period. No abnormalities from analyses of safety labs (chemistry, hematology, urinalysis or uric acid) were noted.

Chronic high doses of pancreatic enzyme products have been associated with fibrosing colonopathy and colonic strictures [see Dosage and Administration (2.1) and Warnings and Precautions  (5.1 )]. High doses of pancreatic enzyme products have been associated with hyperuricosuria and hyperuricemia, and should be used with caution in patients with a history of hyperuricemia, gout, or renal impairment [see Warnings and Precautions  (5.3 )].

Pancrelipase is a pancreatic enzyme preparation consisting of Pancrelipase, an extract derived from porcine pancreatic glands. Pancrelipase contains multiple enzyme classes, including porcine-derived lipases, proteases, and amylases.

Pancrelipase is a cream-colored powder. It is miscible in water and practically insoluble or insoluble in alcohol and ether.

Each capsule for oral administration contains enteric-coated beads (1.8-1.9mm for 5,000 USP units of lipase).

The active ingredient evaluated in clinical trials is lipase. Pancrelipase is dosed by lipase units. Other active ingredients include protease and amylase.

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

The imprinting blue ink on the capsules contains dehydrated alcohol, FD&C Blue #2 aluminum lake C.I. 73015-E132, isopropyl alcohol, n-butyl alcohol, propylene glycol, shellac and strong ammonia solution.

5,000 USP units of lipase; 17,000 USP units of protease; 27,000 USP units of amylase. Capsules have a white opaque cap and a white opaque body with imprint “PAN 5”. The shells contain carnauba wax or talc, carrageenan, hypromellose, potassium chloride, titanium oxide, and water.

Mechanism of Action

The pancreatic enzymes in Pancrelipase catalyze the hydrolysis of fats to monoglycerides, glycerol and fatty acids, protein into peptides and amino acids, and starch into dextrins and short chain sugars in the duodenum and proximal small intestine, thereby acting like digestive enzymes physiologically secreted by the pancreas.

Pharmacokinetics

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

Pregnancy

Teratogenic effects

Pregnancy Category C: Animal reproduction studies have not been conducted with Pancrelipase. It is also not known whether Pancrelipase can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Pancrelipase should be given to a pregnant woman only if clearly needed. The risk and benefit of Pancrelipase should be considered in the context of the need to provide adequate nutritional support to a pregnant woman with exocrine pancreatic insufficiency. Adequate caloric intake during pregnancy is important for normal maternal weight gain and fetal growth. Reduced maternal weight gain and malnutrition can be associated with adverse pregnancy outcomes.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Pancrelipase is administered to a nursing woman. The risk and benefit of Pancrelipase should be considered in the context of the need to provide adequate nutritional support to a nursing mother with exocrine pancreatic insufficiency.

Pediatric Use

The short-term safety and effectiveness of Pancrelipase were assessed in 2 clinical studies in pediatric patients, ages 1 to 17 years, with EPI due to CF.

Study 1 was a randomized, double-blind, placebo-controlled, crossover study in 34 patients 26 of whom were children, including 8 children aged 7 to 11 years, and 18 adolescents aged 12 to 17 patients.. The safety and efficacy in pediatric patients in this study were similar to adult patients [see Adverse Reactions  (6.1 ) and Clinical studies  (14 )].

Study 2 was an open-label, single arm study in 19 patients, ages 1 to 6 years, with EPI due to CF. When patient regimen was switched from their usual PEP regimen to Pancrelipase at similar doses, patients showed similar control of their clinical symptoms.

The safety and efficacy of pancreatic enzyme products with different formulations of Pancrelipase consisting of the same active ingredient (lipases, proteases, and amylases) for treatment of children with exocrine pancreatic insufficiency due to cystic fibrosis has been described in the medical literature and through clinical experience.

Dosing of pediatric patients should be in accordance with recommended guidance from the Cystic Fibrosis Foundation Consensus Conferences [see Dosage and Administration (2.1)]. Doses of other pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with fibrosing colonopathy and colonic strictures in children less than 12 years of age [see Warnings and Precautions  (5.1 )].

Geriatric Use

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

(pan kre LYE pase)

• Amylase, Lipase, and Protease
• Digestive Enzyme
• Lipancreatin
• Lipase, Protease, and Amylase
• Pancrease MT
• Pancreatic Enzymes
• Pancrecarb MS-16
• Pangestyme
• Panocaps
• Panokase
• Protease, Lipase, and Amylase
• Ultrase

• Creon
• Pancreaze
• Pancrelipase (Lip-Prot-Amyl)
• Pertzye
• Ultresa
• Viokace
• Zenpep

There are no contraindications listed in the manufacturer’s labeling.

There are no dosage adjustments provided in the manufacturer’s labeling. Use with caution.

Animal reproduction studies have not been conducted. Nutrition should be optimized in pregnancy; in cystic fibrosis patients with malabsorption, pancreatic enzyme replacement is not considered to cause a risk to the pregnancy.

• Amylase, Lipase, and Protease
• Digestive Enzyme
• Lipancreatin
• Lipase, Protease, and Amylase
• Pancrease MT
• Pancreatic Enzymes
• Pancrecarb MS-16
• Pangestyme
• Panocaps
• Panokase
• Protease, Lipase, and Amylase
• Ultrase

• Creon
• Pancreaze
• Pancrelipase (Lip-Prot-Amyl)
• Pertzye
• Ultresa
• Viokace
• Zenpep

Pancrelipase is a natural product harvested from the porcine pancreatic glands. It contains a combination of lipase, amylase, and protease. Products are formulated to dissolve in the more basic pH of the duodenum so that they may act locally to break down fats, protein, and starch.

Absorption

None; acts locally in GI tract

Excretion

Feces

Refer to adult dosing.

Avoid heat. Protect from moisture. After opening, keep the container tightly closed between uses to protect from moisture.

Creon: Store at room temperature up to 25°C (77°F); excursions are permitted between 25°C and 40°C (77°F and 104°F) for ≤30 days. Discard if moisture conditions are >70%. Bottles of 3,000 USP units of lipase must be stored and dispensed in the original container.

Pancreaze: Store at ≤25°C (77°F). Store in the original container.

Pancrelipase: Store at 20°C to 25°C (68°F to 77°F); brief excursions are permitted between 15°C and 40°C (59°F and 104°F).

Pertzye: Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 40°C (59°F and 104°F). Store in the original container.

Ultresa: Store at 20°C to 25°C (68°F to 77°F). Store in the original container.

Viokace: Store at 20°C to 25°C (68°F to 77°F); brief excursions are permitted up to 40°C (104°F) for up to 24 hours.

Zenpep:

Original glass container: Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 40°C (59°F and 104°F).

Repackaged HDPE container: Store at ≤30°C (86°F) for up to 6 months; excursions are permitted between 15°C and 40°C (59°F and 104°F) for ≤30 days.

The following adverse reactions were reported in a short-term safety studies; actual frequency varies with different products; adverse events, particularly gastrointestinal events, were often greater with placebo.

>10%:

Central nervous system: Headache (3% to 15%)

Gastrointestinal: Abdominal pain (3% to 18%)

Hematologic & oncologic: Lymphadenopathy (11%)

Infection: Streptococcal infection (beta-hemolytic streptococcus: 11%)

Neuromuscular & skeletal: Neck pain (14%)

Otic: Otalgia (11%)

Respiratory: Nasal congestion (14%)

1% to 10%:

Cardiovascular: Peripheral edema (3%)

Central nervous system: Dizziness (4% to 6%)

Dermatologic: Skin rash (3%)

Endocrine & metabolic: Hyperglycemia (4% to 8%), weight loss (3% to 6%), exacerbation of diabetes mellitus (4%), hypoglycemia (4%)

Gastrointestinal: Dyspepsia (10%), diarrhea (≤10%), flatulence (3% to 9%), choledocholithiasis (7%), pruritus ani (7%), early satiety (6%), vomiting (6%), upper abdominal pain (≤5%), abnormal stools (≤4%)

Hematologic & oncologic: Anemia (3%)

Hepatic: Ascites (3%), hydrocholecystis (3%)

Infection: Viral infection (3%)

Renal: Renal cyst (3%)

Respiratory: Cough (4% to 10%), epistaxis (7%), pharyngolaryngeal pain (7%), nasopharyngitis (4%)

<1% (Limited to important or life-threatening; reported with various formulations of pancrelipase): Anaphylaxis, asthma, blurred vision, carcinoma (recurrence), constipation, duodenitis, fibrosing colonopathy, gastritis, hyperuricemia, increased serum transaminases (asymptomatic), intestinal obstruction (distal intestinal obstruction syndrome [DIOS]), muscle spasm, myalgia, nausea, neutropenia (transient), pruritus, severe hypersensitivity, urticaria

Concerns related to adverse effects:

• Fibrosing colonopathy: Fibrosing colonopathy, advancing to colonic strictures, has been reported (rarely). Risk may be increased with high doses, prolonged use, and in pediatric patients with cystic fibrosis; however, the mechanism is unknown. Doses of lipase >6,000 units/kg/meal have been associated with colonic stricture in children <12 years. Patients taking doses of lipase >6,000 units/kg/meal should be examined and the dose decreased. Doses of lipase >2,500 units/kg/meal, lipase >10,000 units/kg/day, or lipase >4,000 units/g fat daily should be used with caution and only with documentation of effectiveness by 3-day fecal fat measures indicating a significantly improved coefficient of fat absorption.

• Hypersensitivity: Severe, allergic reactions (eg anaphylaxis, asthma, hives, pruritus) have rarely been observed; use with caution in patients hypersensitive to pork proteins, taking into consideration the patient's overall clinical needs.

• Mucosal irritation: Crushing or chewing the contents of the capsules or tablets, or mixing the capsule contents with foods outside of product labeling, may cause early release of the enzymes, causing irritation of the oral mucosa and/or loss of enzyme activity. When mixing the contents of capsules with food, the mixture should be swallowed immediately and followed with water or juice to ensure complete ingestion. Pancrelipase should not be mixed in foods with pH >4.5.

• Pork: Products are derived from porcine pancreatic glands. Transmission of porcine viruses, and diseases caused by novel or unidentified viruses, is theoretically a risk; however, testing and/or inactivation or removal of certain viruses, reduces the risk. There have been no cases of transmission of an infectious illness reported.

Disease-related concerns:

• Gout, hyperuricemia: Use caution in patients with gout or hyperuricemia; porcine-derived products contain purines which may increase uric acid concentrations.

• Pancreatic cancer: According to guidelines from the American Society of Clinical Oncology, patients with pancreatic cancer (potentially curable, locally advanced, or metastatic) who experience exocrine pancreatic insufficiency may require pancreatic enzyme replacement therapy to improve digestion and nutrient absorption (Balaban 2016; Khorana 2016; Sohal 2016). A retrospective study in patients with metastatic pancreatic cancer suggests that pancreatic enzyme replacement therapy is underutilized (Landers 2016).

• Renal impairment: Use caution in patients with renal impairment; porcine-derived products contain purines which may increase uric acid concentrations.

Dosage form specific issues:

• Brand interchangeability: Available brand products are not interchangeable.

• Lactose: Viokace tablets may contain lactose; use with caution in patients with lactose intolerance.

Abdominal symptoms, nutritional intake, weight, growth (in children), stool character, fecal fat