Pancreatin & Ox Bile Extract [Discontinued] by Vital Nutrients

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Celiac disease. Although there has been interest in using oral lipase for celiac disease, there is insufficient reliable information about the clinical effects of lipase for this purpose.
• Dyspepsia. It is unclear if oral lipase is beneficial for improving symptoms of postprandial distress syndrome. Details: A small clinical trial shows that taking a specific acid-resistant lipase (Amano Enzyme USA) 280 mg immediately before a high-fat meal does not reduce postprandial bloating and nausea when compared with placebo in individuals with postprandial distress syndrome (101900).
• Inflammatory bowel disease (IBD). Although there has been interest in using oral lipase for IBD, there is insufficient reliable information about the clinical effects of lipase for this purpose.
• Prematurity. It is unclear if adding a specific form of lipase, recombinant human bile salt-stimulated lipase (rhBSSL), to infant formula improves outcomes in premature infants. Some research suggests a potential increased risk for adverse effects. Details: Human breast milk contains rhBSSL, but it is inactivated when breast milk is pasteurized for donation. Clinical research in infants born before 32 weeks' gestation shows that adding rhBSSL as 8700 units per 100 mL formula or pasteurized breast milk, for 4 weeks does not increase growth velocity, body length, or head circumference over the next 12 months when compared with formula or pasteurized breast milk devoid of lipase. However, the infants who were small for gestational age (SGA), which made up approximately 15% of the study population, grew by an additional 1.9 grams/kg daily on average when compared with placebo (101940). More evidence is needed to rate lipase for these uses.

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EFFECTIVE

• Pancreatic insufficiency. Oral prescription pancreatic enzyme products improve digestion in patients with exocrine pancreatic insufficiency due to various causes. It is unclear if non-prescription pancreatic enzyme products would be beneficial; their use is not recommended. Details: Prescription pancreatic enzyme products are effective for improving fat, protein, and total energy absorption in patients with exocrine pancreatic insufficiency due to cystic fibrosis, chronic pancreatitis, pancreas resection or removal, or other conditions (67622,67634,67676,67688,67694,67699,67714) (98667,98674,98676,98677,99115,99116,99118,99119,99120,99122)(99124,99125,99126,99127). Improvement in fat absorption and digestion occurs in as little as 1 week. Symptoms such as gas and abdominal discomfort are also improved in most patients (98667,98674,98677). Various prescription products have been approved by the US Food and Drug Administration (FDA) for this indication (95743). These prescription pancreatic enzyme products are typically used at a starting dose of 500-1000 lipase units/kg body weight per meal to a maximum of 2500 lipase units/kg body weight per meal or 10,000 lipase units/kg body weight daily or 4000 lipase units/gram of fat daily (99130). Despite being beneficial for most patients with exocrine pancreatic insufficiency, there is some evidence that prescription pancreatic enzyme products might not be beneficial in all patients. In patients with pancreatic insufficiency following gastrectomy for gastric cancer, research on prescription pancreatic enzyme products shows conflicting results (67617,95744). Also, a small study shows that taking a prescription pancreatic enzyme product for 26-30 days does not improve time to recovery from pancreatic insufficiency related to acute pancreatitis (99117). However, the small size of most of these studies limit the reliability of the results. One large clinical study shows that taking prescription pancreatic enzyme products for pancreatic insufficiency following pancreatoduodenectomy does not improve body weight or serum albumin levels. However, the dose used in this study was lower than recommended in the US guidelines, and adherence to the prescribed regimen was poor (102322). There is no strong evidence that supplemental forms of pancreatic enzyme products help with digestion in patients with pancreatic insufficiency. Non-prescription pancreatic enzyme products are not recommended for this use.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atopic dermatitis (eczema). It is unclear if oral pancreatic enzyme products are beneficial in children with atopic dermatitis. Details: A small clinical study in children with refractory atopic dermatitis and food allergies shows that taking a specific prescription pancreatic enzyme product (Creon, Solvay Pharma) 37,500 or 75,000 protease units with each meal and 18,750 or 37,500 protease units with each snack for 6 weeks reduces the severity of atopic dermatitis when compared with baseline (102321). The validity of this finding is limited by the lack of a comparator group.
• HIV/AIDS. It is unclear if oral pancreatic enzyme products are beneficial in children with HIV. Details: Nutrient malabsorption is common in individuals with HIV/AIDS, possibly leading to malnutrition. Preliminary clinical research in children aged 1-14 years with HIV shows that taking a prescription pancreatic enzyme product (Creon 10,000) 1000 lipase units per gram of digested fat for 2 weeks reduces fecal fat loss when compared with baseline. Although improvement occurred in all of the children, a complete response, resulting in no steatorrhea, occurred in only 33% (99123). The validity of these findings is limited by the lack of a comparator group.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral pancreatic enzyme products are beneficial in patients with NAFLD following pancreaticoduodenectomy. Details: NAFLD is a common complication post-pancreaticoduodenectomy (PD). A small clinical study in patients who developed NAFLD after PD shows that taking a prescription pancreatic enzyme product (LipaCreon, marketed as Creon in the US) 1800 mg daily for 6 months improves the liver-to-spleen attenuation ratio on computed tomography when compared with baseline, suggesting a reduction in hepatic fat content. Liver function was also improved, and most patients showed improvement in symptoms such as diarrhea (99113). The validity of these findings is limited by the lack of a comparator group. Although another preliminary clinical study shows that taking this prescription product for 12 months is as effective for preventing NAFLD after PD as taking specific non-prescription pancreatic enzyme products, including Politose (Takeda Pharmaceutical Co. Ltd) 1800 mg daily or Toughmac-E (Ono Pharmaceutical Co. Ltd) 3 grams daily for 10-12 months (99112), this study was underpowered and was not necessarily designed to detect between-group differences.
• Pancreatic cancer. It is unclear if oral pancreatic enzyme products improve nutrition status and health in patients with clinically overt exocrine pancreatic insufficiency resulting from pancreatic cancer. Details: Exocrine pancreatic insufficiency can be a complication of pancreatic cancer. One clinical study in patients with unresectable pancreatic cancer shows that taking a prescription pancreatic enzyme product (Norzyme, Nordmark Arzneimittel GmbH & Co. KG; not available in the US) 6-9 capsules daily for 8-24 weeks does not increase body weight, global assessment, quality of life, or survival when compared with placebo (99114). Another preliminary clinical study shows that taking a high-dose pancreatic enzyme product providing 48,000 lipase units per meal for 8 weeks during chemotherapy does not improve body mass index, nutritional parameters, or survival when compared with no treatment (99111). However, in both studies, clinically overt exocrine pancreatic insufficiency was absent in most of the patients. In a study in which clinically overt exocrine pancreatic insufficiency was more prevalent, taking a prescription pancreatic enzyme product (Panzytrat 25,000, Nordmark GmbH; not available in the US) 50,000 lipase units per meal three times daily for 8 weeks appears to increase body weight by about 5% when compared with placebo (67708). More evidence is needed to rate pancreatic enzyme products for these uses.

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Proteolytic enzymes represent a wide group of enzymes that are used alone or in combination. See specific monographs for effectiveness information.

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There is insufficient reliable information available about the safety of lipase.

CHILDREN: POSSIBLY UNSAFE
when recombinant human bile salt-stimulated lipase (rhBSSL) is used orally by premature infants. Adding rhBSSL to infant formula or pasteurized breast milk increases the risk for serious gastrointestinal adverse effects in premature infants (101940).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when prescription pancreatic enzyme products are used orally and appropriately under the guidance of a healthcare professional (98667,98674,98676,98677,99115,99116,99118,99120,99122,99124)(99125,99126,99127). Prescription pancreatic enzyme products are typically initiated at a dose of 500-1000 lipase units/kg body weight per meal to a maximum of 2500 lipase units/kg body weight per meal or 4000 lipase units/gram of fat daily. Doses higher than 2500 lipase units/kg body weight per meal are prescribed only if medically necessary (99130).

POSSIBLY UNSAFE ...when prescription pancreatic enzyme products are used orally at doses over 2500 lipase units/kg body weight per meal or 10,000 lipase units/kg body weight daily. Higher doses, especially those greater than 6000 lipase units/kg body weight per meal, have been associated with fibrosing colonopathy (99130). There is insufficient reliable information available about the safety of supplemental forms of pancreatic enzyme products.

CHILDREN: LIKELY SAFE
when prescription pancreatic enzyme products are used orally and appropriately under the guidance of a healthcare professional (99118,99119,99120,99121,99122,99124,99125,99126). Prescription pancreatic enzyme products are usually initiated at a dose of 500-1000 lipase units/kg body weight per meal to a maximum of 2500 lipase units/kg body weight per meal or 4000 lipase units/gram fat daily. Doses higher than 2500 lipase units/kg body weight per meal are prescribed only if medically necessary (99130).

CHILDREN: POSSIBLY UNSAFE
when prescription pancreatic enzyme products are used orally at doses over 2500 lipase units/kg body weight per meal or 10,000 lipase units/kg body weight daily. Higher doses, especially those greater than 6000 lipase units/kg body weight per meal, have been associated with fibrosing colonopathy (99130). There is insufficient reliable information available about the safety of supplemental forms of pancreatic enzyme products.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using unless essential for replacement therapy (15).

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POSSIBLY SAFE ...when used orally and appropriately. Various proteolytic enzymes have been safely used orally in clinical research (716,964,965,968,969,6252,6253,10622,11457,18281,18284) (91104,91105,91106,91111,96449). Side effects are typically mild to moderate and most often include gastrointestinal effects. See specific monographs for more detailed information related to the safety of individual proteolytic enzymes. ...when used topically and appropriately. Various proteolytic enzymes have been safely used topically in clinical research (67835,67843,67845,91113). Some proteolytic enzymes might cause allergic reactions when used topically. See specific monographs for more detailed information related to the safety of individual proteolytic enzymes.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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ACARBOSE (Precose, Prandase) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, pancreatic enzyme products may reduce the effects of acarbose.  Details The digestive enzymes present in pancreatic enzyme products may break down acarbose, reducing its effects (9).

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General ...No adverse effects have been reported in adults. However, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Gastrointestinal adverse effects, such as necrotizing enterocolitis, when recombinant human bile salt-stimulated lipase is used in premature infants.

Gastrointestinal ...Orally, when added to the formula or pasteurized breast milk consumed by premature infants, recombinant human bile salt-stimulated lipase (rhBSSL) can cause gastrointestinal adverse effects, including abdominal distension, flatulence, constipation, colic, abdominal pain, gastroenteritis, vomiting, regurgitation, and rectal bleeding (101940). Premature infants receiving rhBSSL also had a slightly higher rate of necrotizing enterocolitis (NEC) when compared with those receiving placebo. After review by a panel of experts, it was determined that the rate of confirmed or suspected NEC in infants consuming rhBSSL was 3.3%, compared with 0.5% in those receiving placebo. Although this rate of NEC is lower than the historical rate of occurrence in premature infants (11%), a possible increased risk for NEC cannot be ruled out (101940).

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General ...Orally, prescription pancreatic enzyme products are generally well tolerated when used at prescribed doses in adults and children.
Most Common Adverse Effects:
Orally: Prescription pancreatic enzyme products can cause abdominal pain, constipation, diarrhea, dry mouth, flatulence, irritation of the skin around the mouth and anus, nausea, steatorrhea, and vomiting.
Topically: Pancreatic enzyme product powder is irritating to the skin, eyes, mucus membranes, and respiratory tract. Pancreatic enzyme products that are held in the mouth prior to swallowing can cause irritation of the mucosa, including ulceration and stomatitis.
Serious Adverse Effects (Rare):
Orally: Prescription pancreatic enzyme products can worsen glucose control. Extremely high doses have been associated with fibrosing colonopathy and high uric acid levels in blood and urine.
Topically: Inhalation of dust containing pancreatic enzyme products has been associated with asthma, bronchospasm, and pulmonary hypersensitivity reactions.

Dermatologic ...Orally, rash or skin conditions have been reported rarely in individuals taking prescription pancreatic enzyme products (67709,98667). A pruritic rash occurred in one patient taking a prescription pancreatic enzyme product in one clinical trial; this event was considered by the investigators to be possibly related to treatment (98667). Erythema also occurred in an 84-year-old patient who had taken a digestive enzyme supplement containing pancreatic enzymes and other enzymes (67709). In a case report, taking a supplemental form of pancreatic enzymes also containing hemicellulose and dried ox bile extract powder (Festal, Handok Inc) was thought to be the cause of an acute generalized exanthematous pustulosis (AGEP). The patient required an antihistamine and an oral and topical corticosteroid. Since this product contained more than one ingredient, the role of the pancreatic enzymes in this specific adverse event is unclear (98675).
Topically, exposure to pancreatic enzyme product powder is irritating to the skin. Hypersensitivity reactions such as skin rash have been reported (15).

Endocrine ...Orally, prescription pancreatic enzyme products may cause hypoglycemia or hyperglycemia in some patients (67622,98676,98677). In a double-blind trial of a prescription pancreatic enzyme product compared with placebo in patients with unresectable pancreatic cancer and associated pancreatic duct obstruction, one patient developed diabetes during the study period (67708).

Gastrointestinal ...Orally, prescription pancreatic enzyme products can cause abdominal pain, constipation, diarrhea, dry mouth, irritation of the skin around the mouth and anus, flatulence, nausea, steatorrhea, and vomiting. However, these symptoms can be controlled by following prescription dosing recommendations (67617,67618,67645,67648,67651,67653,67657,67666,67714,98667)(98676,99115,99117,99123,99130). Doses of higher than 2500 lipase units/kg body weight per meal are not recommended unless medically necessary in order to prevent serious side effects, including fibrosing colonopathy and colonic strictures. These side effects are associated with the higher doses of lipase in prescription pancreatic enzyme products (2382,67677,67678,67679,67680,67682,67689,67690,67696,67701,99130).
Topically, pancreatic enzyme products that are held in the mouth prior to swallowing can cause irritation of the mucosa, including ulceration and stomatitis (15).

Hematologic ...Orally, severe neutropenia has been reported with a pancreatic enzyme product. In one case report, a 61-year-old patient taking a prescription pancreatic enzyme product for chronic pancreatitis developed agranulocytosis that persisted despite a trial of filgrastim. Upon discontinuation of the pancreatic enzyme product, marked improvement in neutropenia occurred within 7 days, with full resolution within 6 weeks (107411).

Neurologic/CNS ...Orally, headache and dizziness have been reported rarely in individuals taking prescription pancreatic enzyme products (67618,98667,99120).

Ocular/Otic ...Topically, exposure to pancreatic enzyme product powder is irritating to the eyes. Hypersensitivity reactions such as watery eyes have been reported (15).

Pulmonary/Respiratory ...Topically, exposure to pancreatic enzyme product powder is irritating to the respiratory tract. Hypersensitivity reactions such as sneezing have been reported (15). Inhalation of dust containing pancreatic enzyme products has been associated with allergic rhinitis, asthma, bronchospasm, and pulmonary hypersensitivity reactions (11768,11769,67641).

Renal ...Orally, extremely high doses of pancreatic enzyme products containing more than 10,000 lipase units/kg body weight daily have been associated with high uric acid levels in blood and urine (67673,67693,67705). Rarely, kidney pain has been reported (98667).

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General ...Orally, proteolytic enzymes are generally well tolerated. See specific monographs for detailed safety information related to individual proteolytic enzymes.
Most Common Adverse Effects:
Orally: Gastrointestinal upset.
Serious Adverse Effects (Rare):
Topically: Allergic reactions.

Gastrointestinal ...Orally, some patients taking proteolytic enzymes may have gastrointestinal complaints (101517).

Immunologic ...Proteolytic enzymes are commonly found in laundry detergents and pre-spotter products. Rarely, protease specific IgE positive tests possibly related to these products have occurred. Exposure may be airborne or topical (102705). In addition, in case reports, occupational exposure to the airborne proteolytic enzyme pepsin has resulted in allergic rhinoconjunctivitis or asthma (102706,102707).

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