Viokace

VIOKACE- pancrelipase lipase, pancrelipase protease and pancrelipase amylase tablet
Nestle Healthcare Nutrition, Inc.

1 INDICATIONS AND USAGE

VIOKACE tablets, in combination with a proton pump inhibitor, is indicated in adults for the treatment of exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy.

2 DOSAGE AND ADMINISTRATION

VIOKACE is not interchangeable with any other pancrelipase product.

VIOKACE is orally administered. Therapy should be initiated at the lowest recommended dose and gradually increased. The dosage of VIOKACE should be individualized based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet as described in the Limitations on Dosing below [see Dosage and Administration (2.2) and Warnings and Precautions (5.1)].

2.1 Administration

Since VIOKACE is not enteric-coated, it should be taken in combination with a proton pump inhibitor [see Indications and Usage (1)].

VIOKACE should be taken during meals or snacks, with sufficient fluid. Tablets should be swallowed whole. Do not crush or chew tablets. Care should be taken to ensure that no drug is retained in the mouth to avoid mucosal irritation.

2.2 Dosage

Dosage recommendations for pancreatic enzyme replacement therapy were published following the Cystic Fibrosis Foundation Consensus Conferences.^{1, 2, 3} VIOKACE should be administered in a manner consistent with the recommendations of the Conferences provided in the following paragraph. Only the adult dosing guidelines are shown below. Patients may be dosed on a fat ingestion-based or actual body weight-based dosing scheme.

Additional recommendations for pancreatic enzyme therapy in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy are based on a clinical trial conducted in these populations.

Enzyme dosing should begin with 500 lipase units/kg of body weight per meal 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 VIOKACE dose for an individualized full meal should be given with each snack. The total daily dosage should reflect approximately three meals plus two or three snacks per day.

In one clinical trial, patients received VIOKACE at a dose of 125,280 lipase units per meal while consuming 100 g of fat per day [see Clinical Studies (14)]. Lower starting doses recommended in the literature are consistent with the 500 lipase units/kg of body weight per meal lowest starting dose recommended for adults in the Cystic Fibrosis Foundation Consensus Conferences Guidelines.^{1, 2, 3, 4} The initial starting dose and increases in the dose per meal should be individualized based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet.

Limitations on Dosing

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 the 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 stricture, indicative of fibrosing colonopathy, in children less than 12 years of age [see Warnings and Precautions (5.1)]. 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.

3 DOSAGE FORMS AND STRENGTHS

The active ingredient in VIOKACE evaluated in clinical trials is lipase. VIOKACE is dosed in lipase units.

Other active ingredients include protease and amylase. Each VIOKACE tablet strength contains the specified amounts of lipase, protease, and amylase as follows:

•

10,440 USP units of lipase; 39,150 USP units of protease; 39,150 USP units of amylase tablets are tan, round, biconvex and have VIO9111 engraved on one side and 9111 on the other side.

•

20,880 USP units of lipase; 78,300 USP units of protease; 78,300 USP units of amylase tablets are tan, oval, biconvex with V¹⁶ engraved on one side and 9116 on the other side.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Fibrosing Colonopathy

Fibrosing colonopathy has been reported following treatment with different pancreatic enzyme products.^{5, 6} Fibrosing colonopathy is a rare, serious adverse reaction initially described in association with high-dose pancreatic enzyme use, usually 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 stricture 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 (2.2)].

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.

5.2 Potential for Irritation to Oral Mucosa

Care should be taken to ensure that no drug is retained in the mouth to avoid irritation of oral mucosa, and/or loss of enzyme activity. VIOKACE should not be crushed or chewed [see Dosage and Administration (2.1) and Patient Counseling Information (17.1)].

5.3 Potential for Risk of Hyperuricemia

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

5.4 Potential for Viral Exposure from the Product Source

VIOKACE is sourced from pancreatic tissue from pigs used for food consumption. Although the risk that VIOKACE 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.

5.5 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 VIOKACE treatment in patients with severe allergy should be taken into consideration with the overall clinical needs of the patient.