2.1 Important Dosing Information

VIOKACE is a mixture of enzymes including lipases, proteases, and amylases. VIOKACE dosing is based on lipase units.

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Administer VIOKACE with a proton pump inhibitor.

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Use either an actual body weight or fat ingestion‑based dosing scheme.

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Start at the lowest recommended dosage and individualize the dosage based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet. Changes in dosage may require an adjustment period of several days.

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Do not exceed 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or 4,000 lipase units/g fat ingested/day without further investigation [see Warnings and Precautions (5.1)]. Higher dosages may be administered if they are documented to be effective by fecal fat measures or an improvement in signs or symptoms of malabsorption including measures of nutritional status.

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The total daily dosage should reflect approximately three meals plus two or three snacks per day. With each snack, administer approximately half the prescribed VIOKACE dose for a meal.

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Do not substitute other pancreatic enzyme products for VIOKACE. When switching from another pancreatic enzyme product to VIOKACE, monitor patients for clinical symptoms of exocrine pancreatic insufficiency and titrate the dosage as needed.

2.2 Recommended Dosage

Adult Patients:

The recommended oral initial starting dosage of VIOKACE is 500 lipase units/kg/meal.

If signs and symptoms of malabsorption persist, increase the dosage. Titrate to a maximum of either 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or 4,000 lipase units/grams of fat ingested/day.

2.3 Preparation and Administration Instructions

Adult Patients:

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Take VIOKACE with meals or snacks. If a dose is missed, take the next dose with the next meal or snack.

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Swallow tablets whole. Do not crush or chew VIOKACE tablets.

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Consume sufficient liquids (water) to ensure complete swallowing of VIOKACE tablets [see Warnings and Precautions (5.2)].

5.1 Fibrosing Colonopathy

Fibrosing colonopathy has been reported following treatment with pancreatic enzyme products. Fibrosing colonopathy is a rare, serious adverse reaction initially described in association with use of high-dose pancreatic enzyme products, usually over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis. Pancreatic enzyme products exceeding 6,000 lipase units/kg/meal have been associated with colonic stricture, a complication of fibrosing colonopathy, in pediatric patients less than 12 years of age. The underlying mechanism of fibrosing colonopathy remains unknown.

If there is a history of fibrosing colonopathy, monitor patients during treatment with VIOKACE because some patients may be at risk of progressing to colonic stricture formation. It is uncertain whether regression of fibrosing colonopathy occurs. Do not exceed the recommended dosage of either 2,500 lipase units/kg/meal, 10,000 lipase units/kg/day, or 4,000 lipase units/g fat ingested/day without further investigation. Higher dosages may be administered if they are documented to be effective by fecal fat measures or an improvement in signs or symptoms of malabsorption including measures of nutritional status. Patients receiving dosages higher than 6,000 lipase units/kg/meal should frequently monitored for symptoms of fibrosing colonopathy and the dosage decreased or titrated downward to a lower range if clinically appropriate [see Dosage and Administration (2.1)].

5.2 Irritation of the Oral Mucosa

Crushing or chewing VIOKACE tablets can result in irritation of the oral mucosa, and/or loss of enzyme activity. Instruct the patient to swallow tablets whole. Do not crush or chew VIOKACE tablets. Consume sufficient liquids immediately following administration of VIOKACE to ensure complete swallowing [see Dosage and Administration (2.3)].

5.3 Hyperuricemia

Pancreatic enzyme products contain purines that may increase blood uric acid levels. High dosages have been associated with hyperuricosuria and hyperuricemia [see Overdosage (10)].

Consider monitoring blood uric acid levels in patients with gout, renal impairment, or hyperuricemia during treatment with VIOKACE.

5.4 Risk of Viral Transmission

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 Hypersensitivity Reactions

Severe hypersensitivity reactions including anaphylaxis, asthma, hives, and pruritus have been reported with pancreatic enzyme products [see Adverse Reactions (6.2)]. If symptoms occur, initiate appropriate medical management.

Monitor patients with a known hypersensitivity reaction to proteins of porcine origin for hypersensitivity reactions during treatment with VIOKACE. The risks and benefits of continued VIOKACE treatment in patients with severe hypersensitivity reactions should be taken into consideration with the overall clinical needs of the patient.

5.6 Potential for Exacerbation of Symptoms of Lactose Intolerance

VIOKACE tablets contain lactose monohydrate [see Description (11)]. Patients who have lactose intolerance may not be able to tolerate VIOKACE.

6.1 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 practice.

The data described below reflect exposure to VIOKACE in 30 adult patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy in a single, multicenter, randomized, parallel, placebo-controlled, double-blind study [see Clinical Studies (14)].

Adverse reactions that were reported in at least 2 VIOKACE-treated patients (greater than or equal to 7%) are shown in Table 1. There were no adverse reactions reported in two or more patients in the placebo group (N=20).

The following adverse reactions were reported in one VIOKACE-treated patient each: anemia, abdominal pain, ascites, flatulence, headache, hydocholecystis, peripheral edema, rash, renal cyst, and viral infection.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of VIOKACE or other pancreatic enzyme products. 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.

Eye Disorders

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blurred vision

Gastrointestinal Disorders

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fibrosing colonopathy and distal intestinal obstruction syndrome

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abdominal pain, diarrhea, flatulence, constipation, and nausea

Immune System Disorders

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anaphylaxis, asthma, hives and pruritis

Investigations

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asymptomatic elevations of liver enzymes

Musculoskeletal System

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myalgia, muscle spasm

Skin and Subcutaneous Tissue Disorders

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urticaria and rash

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

The safety and effectiveness of VIOKACE in pediatric patients have not been established.

Use of VIOKACE in pediatric patients may increase the risk of inadequate treatment of pancreatic insufficiency and result in suboptimal weight gain, malnutrition and/or need for larger doses of pancreatic enzyme replacement due to tablet degradation in the gastric environment of the stomach.

High dosages of pancreatic enzyme products have been associated with fibrosing colonopathy and colonic strictures in pediatric patients less than 12 years of age [see Warnings and Precautions (5.1)].

8.5 Geriatric Use

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

12.1 Mechanism of Action

Pancreatic enzyme products contain a mixture of lipases, proteases, and amylases that catalyze the hydrolysis of fats to monoglycerides, glycerol and free fatty acids, proteins into peptides and amino acids, and starches into dextrins and short chain sugars such as maltose and maltriose in the duodenum and proximal small intestine, thereby acting like digestive enzymes physiologically secreted by the pancreas.

12.2 Pharmacodynamics

For patients consuming a high fat diet in the clinical trial, the coefficient of fat absorption (CFA) was higher in patients who received VIOKACE compared to the placebo treatment group, indicating improved fat absorption [see Clinical Studies (14)].

12.3 Pharmacokinetics

Following oral administration, the lipases, proteases, and amylases released from VIOKACE are not absorbed from the gastrointestinal tract in appreciable amounts.

Drug Interactions

The lipases, proteases, and amylases of VIOKACE are not substrates of CYP enzymes or transporters. CYP enzymes or transporters mediated drug interactions are not expected.