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  • CLASSES

    Pancreatic Enzymes

    DEA CLASS

    Rx

    DESCRIPTION

    Oral porcine-derived pancreatic enzyme replacement
    Contains lipase, amylase, and protease that are capable of digesting fats, starches, and proteins, respectively; more potent than pancreatin
    Available in several different dosage forms that are not therapeutically interchangeable

    COMMON BRAND NAMES

    Creon, Pancrease, Pancreaze, Pertzye, Ultrase MT, Ultresa, Viokace, Zenpep

    HOW SUPPLIED

    Creon/Pancrease/Pancreaze/Pertzye/Ultrase MT/Zenpep Oral Cap DR Pellets: 10000-55000-34000U, 10500-61500-35500U, 12000-39000-39000U, 12000-60000-38000U, 15000-82000-51000U, 16000-60500-57500U, 16800-98400-56800U, 20000-109000-68000U, 20000-84000-63000U, 21000-83900-54700U, 24000-120000-76000U, 24000-90750-86250U, 25000-136000-85000U, 2600-10850-6200U, 3000-15000-9500U, 3000-16000-10000U, 36000-180000-114000U, 4000-15125-14375U, 40000-218000-136000U, 4200-24600-14200U, 5000-27000-17000U, 6000-30000-19000U, 8000-30250-28750U
    Viokace Oral Tab: 10440-39150-39150U, 20880-78300-78300U

    DOSAGE & INDICATIONS

    For the management of exocrine pancreatic insufficiency, such as in patients with cystic fibrosis, chronic pancreatitis, or other conditions.
    NOTE: For patients with cystic fibrosis, the Cystic Fibrosis Foundation (CFF) recommends 500 to 2,500 lipase units per kg body weight per meal. The CFF also recommends limiting the pancrelipase dose to less than or equal to 10,000 lipase units per kg per day or less than 4,000 lipase units per gram dietary fat per day.
    In combination with a proton pump inhibitor in adults with chronic pancreatitis.
    Oral dosage (Viokace 10 or Viokace 20 tablets)

    NOTE: This formulation has been approved by the FDA.
    NOTE: Viokace is not interchangeable with any other pancrelipase product.

    Adults

    Initially, 500 lipase units/kg/meal PO. Titrate dose based on clinical symptoms, steatorrhea, and fat content of diet; do not exceed a maximum of 2,500 lipase units/kg/meal (10,000 lipase units/kg/day or less or less than 4,000 lipase units/gram fat ingested/day). As a general guide, half the mealtime dose should be given with snacks. Doses as high as 125,280 lipase units/meal PO were given in clinical studies; these patients were consuming at least 100 g of fat/day. Older patients may require a decreased dosage expressed as lipase units/kg/meal, as they tend to weigh more but tend to ingest less fat/kg/day.

    Oral dosage (delayed release capsules, Creon, Zenpep, Pancreaze)

    NOTE: These formulations have been approved by the FDA. 
    NOTE: The various pancrelipase brands are not interchangeable with other pancrelipase products, unless the specific manufacturer FDA-approved label notes interchangeability.

    Adults

    Initially, 500 lipase units/kg/meal PO. Titrate dose based on clinical symptoms, steatorrhea, and fat content of diet; do not exceed a maximum of 2,500 lipase units/kg/meal (10,000 lipase units/kg/day or less or less than 4,000 lipase units/gram fat ingested/day). As a general guide, half the mealtime dose should be given with snacks. Doses of 72,000 lipase units/meal PO have been studied in adult patients aged 32 to 75 years with pancreatic insufficiency due to chronic pancreatitis; these patients were consuming at least 100 g of fat/day. Older patients may require a decreased dosage expressed as lipase units/kg/meal, as they tend to weigh more but tend to ingest less fat/kg/day.

    Children and Adolescents 4 years and older

    Initially, 500 lipase units/kg/meal PO. Titrate dosage based on clinical symptoms, steatorrhea, and fat content of diet. Max: 2,500 lipase units/kg/meal or 10,000 lipase units/kg/day or 4,000 lipase units/gram fat ingested/day. As a general guide, half the mealtime dose should be given with snacks.

    Children 1 to 3 years

    Initially, 1,000 lipase units/kg/meal PO. Titrate dosage based on clinical symptoms, steatorrhea, and fat content of diet. Max: 2,500 lipase units/kg/meal or 10,000 lipase units/kg/day or 4,000 lipase units/gram fat ingested/day. As a general guide, half the mealtime dose should be given with snacks.

    Neonates and Infants

    2,600 lipase units per 120 mL formula or per breastfeeding PO for Pancreaze brand. 3,000 lipase units per 120 mL formula or per breastfeeding PO for Creon and Zenpep brands. Do not mix capsule contents directly into formula or breast milk.

    Oral dosage (delayed-release capsules, Pertyze only)

    NOTE: This formulation has been approved by the FDA.
    NOTE: Pertyze is not interchangeable with other pancrelipase products.

    Adults

    Initially, 500 lipase units/kg/meal PO. Titrate dose based on clinical symptoms, steatorrhea, and fat content of diet; do not exceed a maximum of 2,500 lipase units/kg/meal (10,000 lipase units/kg/day or less or less than 4,000 lipase units/gram fat ingested/day). As a general guide, half the mealtime dose should be given with snacks. Older patients may require a decreased dosage expressed as lipase units/kg/meal, as they tend to weigh more but tend to ingest less fat/kg/day.

    Children and Adolescents 4 years and older weighing 16 kg or more

    Initially, 500 lipase units/kg/meal PO. Titrate dosage based on clinical symptoms, steatorrhea, and fat content of diet. Max: 2,500 lipase units/kg/meal or 10,000 lipase units/kg/day or 4,000 lipase units/gram fat ingested/day. As a general guide, half the mealtime dose should be given with snacks.

    Children 1 to 3 years weighing 8 kg or more

    Initially, 1,000 lipase units/kg/meal PO. Titrate dosage based on clinical symptoms, steatorrhea, and fat content of diet. Max: 2,500 lipase units/kg/meal or 10,000 lipase units/kg/day or 4,000 lipase units/gram fat ingested/day. As a general guide, half the mealtime dose should be given with snacks.

    Neonates and Infants

    4,000 lipase units per 120 mL formula or per breastfeeding PO. Administer immediately prior to each feeding. Do not mix directly in formula or breast milk.

    For the management of exocrine pancreatic insufficiency due to pancreatectomy.
    In combination with a proton pump inhibitor in adults with pancreatectomy.
    Oral dosage (Viokace tablets)

    NOTE: This formulation has been approved by the FDA.
    NOTE: Viokace is not interchangeable with any other pancrelipase product.

    Adults

    Initially, 500 lipase units/kg/meal PO. Titrate dose based on clinical symptoms, steatorrhea, and fat content of diet; do not exceed a maximum of 2500 lipase units/kg/meal (10,000 lipase units/kg/day or less or less than 4000 lipase units/gram fat ingested/day). As a general guide, half the mealtime dose should be given with snacks. Doses as high as 125,280 lipase units/meal PO were given in clinical studies; these patients were consuming at least 100 g of fat/day. Older patients may require a decreased dosage expressed as lipase units/kg/meal, as they tend to weigh more but tend to ingest less fat/kg/day.

    Oral dosage (delayed release capsules, Creon Capsules)

    NOTE: This formulation has been approved by the FDA.
    NOTE: Creon products are not interchangeable with any other pancrelipase product.

    Adults

    Doses of 72,000 lipase units/meal PO have been studied in patients aged 32 to 75 years with pancreatic insufficiency due to pancreatectomy or chronic pancreatitis; these patients were consuming at least 100 grams of fat/day. As a general guide, half the mealtime dose should be given with snacks. Titrate the dose based on clinical symptoms, steatorrhea, and fat content of diet. Do not exceed dosing limits set by the Cystic Fibrosis Foundation Consensus Conference Guidelines (maximum of 2500 lipase units/kg/meal, 10,000 lipase units/kg/day or less, or less than 4000 lipase units/gram fat ingested/day).

    For enteral feeding tube occlusion†.
    Enteral administration dosage (Viokase tablets)
    Adults and Adolescents

    1 Viokase tablet (strength not specified) and one 325-mg sodium bicarbonate tablet crushed and dissolved in 5 mL of warm water. If a clogged Dobbhoff feeding tube (8 Fr) was not able to be cleared using water, then the pancreatic enzyme/sodium bicarbonate solution was instilled into the clogged tube and clamped for 5 minutes. Then, a 50-mL syringe was attached to the feeding tube using an adapter, and the tube was gently flushed with tap water. This procedure was effective in 72% (23 of 32) of the cases, and the authors state that the clearance rate is even higher if the cause of the obstruction is clotted enteral formula and the pancreatic enzyme solution is applied close to clotted formula using a small catheter.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Maximum dosage information is product-specific; individualize dosage. The Cystic Fibrosis Foundation recommends a maximum dose of 10,000 lipase units per kg per day PO or less than 4,000 lipase units per gram dietary fat per day.

    Geriatric

    Maximum dosage information is product-specific; individualize dosage. The Cystic Fibrosis Foundation recommends a maximum dose of 10,000 lipase units per kg per day PO or less than 4,000 lipase units per gram dietary fat per day.

    Adolescents

    10,000 lipase units/kg/day or 4,000 lipase units/gram fat ingested/day. In only rare instances, should dosages exceed 2,500 lipase units/kg/meal.

    Children

    10,000 lipase units/kg/day or 4,000 lipase units/gram fat ingested/day. In only rare instances, should dosages exceed 2,500 lipase units/kg/meal.

    Infants

    2,600 lipase units per 120 mL formula or per breast-feeding for Pancreaze; 3,000 lipase units per 120 mL formula or per breast-feeding for Creon and Zenpep; 4,000 lipase units per 120 mL formula or per breast-feeding for Pertzye; do not exceed 4,000 lipase units per gram of ingested fat per day or 10,000 lipase units/kg per day. Safety and efficacy not established for brands not listed.

    Neonates

    Maximum dosage information is product-specific; 2,600 lipase units per 120 mL formula or per breast-feeding for Pancreaze; 3,000 lipase units per 120 mL formula or per breast-feeding for Creon and Zenpep; 4,000 lipase units per 120 mL formula or per breast-feeding for Pertzye; safety and efficacy not established for other brands.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

     
    NOTE: Pancreatic insufficiency products are not clinically interchangeable and are not considered bioequivalent by the FDA. Patients stabilized on one product should remain on that product unless the prescriber orders a specific change.

    Oral Administration

    Follow oral dosage with a glass of water or juice (or formula or breast milk for infants). Administer with meals and snacks or just prior to meals and snacks. Do not retain preparations in the mouth prior to swallowing because the enzyme may cause mucosal irritation and stomatitis.

    Oral Solid Formulations

    Delayed-release capsules
    Administer during meals or snacks with sufficient fluid.
    Do not chew or crush; avoid destruction of enteric coating. The enteric coating will dissolve if in prolonged contact with foods having a pH greater than 5.5. If the enteric coating is destroyed, the enzymes present in pancrelipase may cause ulcerations.
    For patients unable to swallow intact capsules, products containing enteric-coated spheres, microspheres, or microtablets may be opened and the contents sprinkled on a soft acidic food (pH of 4 or 4.5 or less depending on the specific product). Choose a food that does not require chewing (e.g., commercially available preparations of bananas, pears, and applesauce). The soft food mixture should be swallowed immediately and followed with water or juice to ensure complete ingestion.
    Do not mix directly with infant formula or breast-milk; however, in infants, doses should be followed with a feeding of formula or breast milk.
     
    Tablets
    Administer during meals or snacks with sufficient fluid.
    Should be swallowed whole. Do not chew or crush.
    Tablets that are not enteric-coated should be taken with a proton pump inhibitor.

    Other Administration Route(s)

    Administration via Gastrostomy Tube
    Administration of pancrelipase products via a gastrostomy tube presents a complex challenge; the risk of clogging the feeding tube must be balanced with the risk of reducing enzyme effectiveness.
    Consider the feeding tube size, feeding schedule (continuous or intermittent), pancrease product (specifically the size of the microspheres/granules), and other concurrent medications (i.e., medications that suppress gastric acid production) when determining the most appropriate method of administration for a specific patient.
     
    Pertzye 4,000 USP lipase unit capsules (14 Fr gastrostomy tube or larger; no more than 2 capsules may be administered at a time)
    Transfer at least 10 mL of applesauce into a small bowl or medicine cup.
    Mix the capsule contents thoroughly with the transferred applesauce to create a uniform suspension. Do not crush the enzyme microspheres. Use immediately.
    Remove the plunger from a 35 mL slip tip syringe. While covering the tip of the syringe with a finger, transfer the Pertzye-applesauce mixture into the syringe. Replace the plunger partially back into the syringe.
    Shake or tap the syringe lightly with the syringe tip facing upward and carefully push the plunger slowly until the residual air is removed.
    Connect the syringe directly into the gastrostomy tube feeding port and push the syringe contents using steady pressure until empty.
    Flush the gastrostomy tube with approximately 10 mL of water. Discard any unused portion of the mixture.
    If dose requires more than 2 capsules, repeat the above steps until the desired dose is achieved.
     
    Delayed-release capsules
    Two main methods of administration have been described: 1.) opening the capsules and mixing the contents with a thickened acidic liquid or thin food (e.g., baby food) and 2.) opening the capsule and dissolving the contents in sodium bicarbonate. These methods have different risks and advantages that must be considered on an individual patient basis.
    Mixing with thickened liquid (risk: tube occlusion; benefit: maintaining integrity of enteric coating which may preserve efficacy)
    Using a mildly thickened liquid as the vehicle is thought to reduce the risk of tube occlusion compared to using water or other thin liquid because a thin liquid allows the enteric-coated microspheres/beads to settle and clump together in the feeding tube.
    Adequate flushing of the feeding tube before and after administration is critical. If direct contact occurs between the acidic fruit juice and enteral feedings inside the tube, an interaction can occur that may clog the feeding tube.
    Some dietary experts have proposed the following technique, which can be used for tube sizes 10 Fr and above. However, if sizes 10 Fr or 12 Fr are in place, the use of low-dose enzyme capsules (3,000 to 5,000 units of lipase) are recommended because they contain the smallest sized microspheres/beads.
    Prepare 50 to 100 mL of mildly thickened fruit juice using a thickening agent (e.g., Nectar Thick).
    Open the pancrease capsule(s) into a small clean container.
    Add sufficient mildly thickened liquid to completely coat the microspheres/beads and stir gently to evenly suspend them in the liquid.
    If the patient is receiving continuous feedings, stop the tube feeds.
    Flush the feeding tube with an appropriate amount of water.
    Draw up the mixture with an enteral syringe of appropriate size for the volume and feeding tube size. Administer the mixture slowly through the feeding tube with slow, gentle pressure.
    Flush the feeding tube with water, and resume feeds.
    Mixing with baby food/applesauce (risk: tube occlusion; benefit: maintaining integrity of enteric coating which may preserve efficacy)
    In an in vitro study, Creon capsules were opened and the contents sprinkled onto approximately 15 mL of baby food (applesauce or bananas with a pH less than 4.5) per capsule. The mixture was stirred gently and allowed to sit for 15 minutes. The mixture was then administered slowly through various gastrostomy tubes at a rate of about 15 mL per 10 to 15 seconds using a 35 mL syringe. The tube was then flushed with 10 to 30 mL of water.
    Pancrelipase doses were successfully administered through the following G-tubes: Kimberly-Clark MIC Bolus size 18 Fr or larger, Kimberly-Clark MIC-KEY 16 Fr or larger, Bard Tri-Funnel 18 Fr or larger, and Bard Button 18 Fr or larger. The tubes that were sizes smaller than those indicated as having successful administration became clogged with at least one of the baby foods tested. Administration was successful if there was no clogging of the tube and no visible pellet damage.
    Mixing with sodium bicarbonate solution (risk: reduced efficacy because enteric coat is removed; benefit: lower risk of tube occlusion)
    When pancreatic enzyme products are administered into a feeding tube that is placed duodenally or jejunally, some experts recommend opening the capsules, crushing the enteric coated beads, and then mixing with sodium bicarbonate. For each 10,000 units of lipase, 10 mL of 8.4% sodium bicarbonate is recommended. Alternatively, the uncrushed bead/microspheres can be mixed with the sodium bicarbonate and allowed to dissolve (about 20 to 30 minutes). Administer the solution slowly through the feeding tube, and flush the tube with water before and after each dose.
    Although there is debate about using this method of administration for feeding tubes placed in the stomach because of the risk for enzyme inactivation, some centers use this method to avoid feeding tube occlusion. Monitor efficacy carefully.

    STORAGE

    Generic:
    - Do not refrigerate
    - Store below 77 degrees F
    - Store in a dry place
    Creon:
    - Protect from moisture
    - Store at room temperature (up to 77 degrees F)
    - Store below 104 degrees F
    Creon 10:
    - Do not refrigerate
    - Store between 59 to 77 degrees F
    Creon 20:
    - Do not refrigerate
    - Store between 59 to 77 degrees F
    Creon 5:
    - Do not refrigerate
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Dygase:
    - Avoid excessive humidity
    - Store at room temperature (between 59 to 86 degrees F)
    Kutrase:
    - Avoid excessive humidity
    - Store at room temperature (between 59 to 86 degrees F)
    Ku-Zyme :
    - Avoid excessive humidity
    - Store at room temperature (between 59 to 86 degrees F)
    Ku-Zyme HP:
    - Avoid excessive humidity
    - Store below 77 degrees F
    Lapase :
    - Avoid excessive humidity
    - Store at room temperature (between 59 to 86 degrees F)
    Lipram:
    - Do not refrigerate
    - Store below 77 degrees F
    - Store in a dry place
    Lipram-CR:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Lipram-PN:
    - Do not refrigerate
    - Store below 77 degrees F
    - Store in a dry place
    Lipram-UL:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Palcaps :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Pancrease:
    - Avoid exposure to heat
    - Protect from moisture
    - Store below 77 degrees F
    - Store in original container
    Pancrease MT:
    - Do not refrigerate
    - Store below 77 degrees F
    - Store in a dry place
    Pancreaze:
    - Avoid exposure to heat
    - Protect from moisture
    - Store below 77 degrees F
    - Store in original container
    Pancrecarb MS:
    - Avoid excessive humidity
    - Do not refrigerate
    - Store at 77 degrees F
    - Store in a dry place
    Pancron:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Pangestyme CN:
    - Do not refrigerate
    - Store between 59 to 77 degrees F
    Pangestyme EC:
    - Do not refrigerate
    - Store below 77 degrees F
    - Store in a dry place
    Pangestyme MT:
    - Do not refrigerate
    - Store below 77 degrees F
    - Store in a dry place
    Pangestyme UL:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Panocaps:
    - Do not refrigerate
    - Store below 77 degrees F
    - Store in a dry place
    Panocaps MT:
    - Do not refrigerate
    - Store below 77 degrees F
    - Store in a dry place
    Panokase :
    - Store below 77 degrees F
    Pertzye:
    - Dispense in original container or USP equivalent tight container
    - Protect from light
    - Protect from moisture
    - Store at room temperature (68 to 77 degrees F); brief excursions permitted to 59 to 104 degrees F
    - Store in original container
    Plaretase:
    - Store below 77 degrees F
    Ultracaps MT:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Ultrase:
    - Do not refrigerate
    - Store below 77 degrees F
    - Store in a dry place
    Ultrase MT:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Ultresa:
    - Avoid excessive heat (above 104 degrees F)
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in a dry place
    - Store in original container
    Viokace:
    - Avoid exposure to heat
    - Protect from moisture
    - Store between 68 to 77 degrees F; brief excursions permitted to 104 degrees F
    - Store in a dry place
    - Store in original container
    Viokase:
    - Protect from moisture
    - Store below 77 degrees F
    Viokase 16:
    - Protect from moisture
    - Store below 77 degrees F
    Viokase 8:
    - Protect from moisture
    - Store below 77 degrees F
    Zenpep:
    - Avoid excessive heat (above 104 degrees F)
    - Do not refrigerate
    - Protect from moisture
    - Store at room temperature (68 to 77 degrees F); brief excursions permitted to 59 to 104 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Porcine protein hypersensitivity

    Pancrelipase is produced from porcine pancreatic enzyme concentrate; therefore, it should be used with caution in patients with porcine protein hypersensitivity. Discontinue pancrelipase if hypersensitivity occurs during treatment. Rarely, severe allergic reactions including anaphylaxis, asthma, hives, and pruritus, have been reported with some pancreatic enzyme products.

    Viral infection

    Pancrelipase is sourced from the pancreatic tissue of swine used for food consumption. In order to minimize the risk of viral transmission to humans, certain steps (including testing for and inactivating known viruses) are taken throughout the manufacturing process of pancrelipase. There is, however, a theoretical risk for transmission of a viral infection caused by a novel or unidentified virus. Although there have not been any reported cases of viral transmission associated with the use of porcine pancreatic extracts, the presence of porcine viruses that might infect humans cannot be definitely excluded.

    Dysphagia, esophageal stricture

    Pancrelipase delayed release capsules are enteric-coated to resist inactivation by gastric acid, and to release most of the enzymes in the duodenum at a pH greater than 5.5. Therefore, delayed release capsules should not be crushed or chewed or mixed in foods having a pH greater than 4. If the protective coating is disrupted irritation of oral mucosa, and/or loss or enzyme activity can occur. For patients with dysphagia, specifically difficulty swallowing capsules, the capsules may be carefully opened and the contents added to a small amount of acidic soft food with a pH of < 4 or 4.5 depending on the specific product, such as applesauce, at room temperature (see Administration). Care should be taken when administering pancrelipase to patients with esophageal stricture or abnormalities to prevent the retention of the dosage within the esophagus and subsequent mucosal irritation.

    Gout, hyperuricemia, renal impairment

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

    Fibrosing colonopathy, GI obstruction, inflammatory bowel disease, surgery

    Fibrosing colonopathy is a rare, serious adverse effect associated with high doses of pancreatic enzyme replacement therapy (PERT). It was initially described in patients taking high doses of pancreatic enzymes for prolonged periods of time, and it is most commonly reported among pediatric patients with cystic fibrosis. In its most advanced form, fibrosing colonopathy leads to colonic stricture. Consider fibrosing colonopathy in patients who have evidence of GI obstruction, bloody diarrhea, or chylous ascites and in patients who have a combination of abdominal pain with continuing diarrhea, poor weight gain, or both. Patients at highest risk include those who are < 12 years old, have taken > 6000 lipase units/kg/meal for more than 6 months, have a history of meconium ileus or distal intestinal obstruction syndrome, have had any intestinal surgery, or have a diagnosis of inflammatory bowel disease. The underlying mechanism of fibrosing colonopathy is unknown and once present regression is uncertain. Should signs or symptoms of GI obstruction occur, the possibility of GI strictures should be considered, and pancrelipase therapy should be reevaluated.The Cystic Fibrosis Foundation Consensus Conferences Guidelines has set forth dosing recommendations that should not be exceeded. If a patient’s dose of pancreatic enzyme exceeds 2,500 lipase units/kg/meal (or greater than 10,000 lipase units/kg/day), further investigation is necessary. Response to enzyme treatment varies among patients, therefore if steatorrhea persists, the dosage may be increased by a healthcare professional; patients must not increase their own dose. Furthermore, the efficacy of doses greater than 2,500 lipase units/kg/meal (or greater than 10,000 lipase units/kg/day) must be confirmed by a 3-day fecal fat measure indicating a significantly improved coefficient of fat absorption. An adjustment period of several days may be required for dosage changes.

    Pregnancy

    Use pancrelipase during pregnancy only when clearly needed. Animal reproduction studies have not been conducted and adequate studies in humans are not available. 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.

    Breast-feeding

    Use pancrelipase with caution during breast-feeding; patients should notify their healthcare professional if they are intending to breast-feed. 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. Pancreatic enzymes act locally in the gastrointestinal tract and are unlikely to be systemically absorbed; however, some of the constituent amino acids and proteins in the pancrelipase product may be absorbed systemically along with normal dietary proteins. It is not known if pancrelipase or these constituents is distributed into breast milk. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Diabetes mellitus

    In patients with diabetes mellitus or at risk for abnormal blood glucose levels, glycemic control may be affected by administration of pancrelipase. Consideration should be given to additional glucose monitoring in these patients.

    ADVERSE REACTIONS

    Severe

    bronchospasm / Rapid / 0-1.0
    anaphylactoid reactions / Rapid / 0-1.0
    fibrosing colonopathy / Delayed / Incidence not known
    GI obstruction / Delayed / Incidence not known
    cholecystitis / Delayed / Incidence not known

    Moderate

    lymphadenopathy / Delayed / 11.0-11.0
    cholelithiasis / Delayed / 7.0-7.0
    ascites / Delayed / 3.0-3.0
    peripheral edema / Delayed / 3.0-3.0
    anemia / Delayed / 3.0-3.0
    hyperglycemia / Delayed / 2.0-2.0
    hypoglycemia / Early / 2.0-2.0
    constipation / Delayed / Incidence not known
    stomatitis / Delayed / Incidence not known
    oral ulceration / Delayed / Incidence not known
    gastritis / Delayed / Incidence not known
    esophagitis / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    hyperuricemia / Delayed / Incidence not known

    Mild

    abdominal pain / Early / 3.0-18.0
    headache / Early / 3.0-15.0
    nasal congestion / Early / 14.0-14.0
    otalgia / Early / 11.0-11.0
    infection / Delayed / 3.0-11.0
    diarrhea / Early / 10.0-10.0
    dyspepsia / Early / 10.0-10.0
    cough / Delayed / 4.0-10.0
    flatulence / Early / 3.0-9.0
    pruritus ani / Early / 7.0-7.0
    epistaxis / Delayed / 7.0-7.0
    vomiting / Early / 6.0-6.0
    dizziness / Early / 4.0-6.0
    pharyngitis / Delayed / 4.0-4.0
    pruritus / Rapid / 0-1.0
    urticaria / Rapid / 0-1.0
    maculopapular rash / Early / 0-1.0
    rash (unspecified) / Early / 0-1.0
    nausea / Early / Incidence not known
    muscle cramps / Delayed / Incidence not known
    myalgia / Early / Incidence not known
    lactose intolerance / Early / Incidence not known

    DRUG INTERACTIONS

    Alpha-glucosidase Inhibitors: (Major) Digestive enzyme preparations containing carbohydrate-splitting enzymes may reduce the pharmacologic effect of alpha-glucosidase inhibitors and should not be administered concurrently. Separating the timing of administration should limit an interaction, but is not usually feasible given the usual timing of administration around meals for both drugs.
    Antacids: (Major) The effectiveness of gastrointestinal enzymes can be diminished with concurrent administration of antacids. In-vitro studies suggest that calcium and magnesum cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.
    Calcium Carbonate: (Major) The effectiveness of gastrointestinal enzymes can be diminished with concurrent administration of antacids. In-vitro studies suggest that calcium and magnesum cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.
    Calcium Carbonate; Magnesium Hydroxide: (Major) The effectiveness of gastrointestinal enzymes can be diminished with concurrent administration of antacids. In-vitro studies suggest that calcium and magnesum cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.
    Calcium Carbonate; Risedronate: (Major) The effectiveness of gastrointestinal enzymes can be diminished with concurrent administration of antacids. In-vitro studies suggest that calcium and magnesum cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.
    Calcium; Vitamin D: (Major) The effectiveness of gastrointestinal enzymes can be diminished with concurrent administration of antacids. In-vitro studies suggest that calcium and magnesum cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.
    Omeprazole; Sodium Bicarbonate: (Major) The effectiveness of gastrointestinal enzymes can be diminished with concurrent administration of antacids. In-vitro studies suggest that calcium and magnesum cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.
    Sodium Bicarbonate: (Major) The effectiveness of gastrointestinal enzymes can be diminished with concurrent administration of antacids. In-vitro studies suggest that calcium and magnesum cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.

    PREGNANCY AND LACTATION

    Pregnancy

    Use pancrelipase during pregnancy only when clearly needed. Animal reproduction studies have not been conducted and adequate studies in humans are not available. 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.

    Use pancrelipase with caution during breast-feeding; patients should notify their healthcare professional if they are intending to breast-feed. 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. Pancreatic enzymes act locally in the gastrointestinal tract and are unlikely to be systemically absorbed; however, some of the constituent amino acids and proteins in the pancrelipase product may be absorbed systemically along with normal dietary proteins. It is not known if pancrelipase or these constituents is distributed into breast milk. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: Following activation in the alkaline pH of the duodenum, pancrelipase releases high levels of lipase, amylase, and protease, which facilitate the hydrolysis of fats into glycerol and fatty acids, starches into dextrins and sugars, and proteins into peptides. Factors that influence the effectiveness of pancrelipase are those that affect the quantity of enzymatic activity reaching the small intestine, such as dose, gastrointestinal pH, and the microsphere size of the product.

    PHARMACOKINETICS

    Pancrelipase is administered orally; pancrelipase products are not interchangeable due to differences in pancreatic enzyme contents and release mechanisms. Pancrelipase is excreted in the feces.

    Oral Route

    Pancrelipase is not absorbed following oral administration but exerts its action locally in the GI tract. Enzymatic activity of pancrelipase formulations can show considerable individual variation dependent on gastric pH. Some pancrelipase preparations contain enteric-coated microspheres of pancreatic enzyme, which inhibit gastric inactivation during gastric passage and deliver more of the enzymes to the duodenum where they are active.