Viokace

The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) that are described elsewhere in the label 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 practice.

The short-term safety of VIOKACE was assessed in a single, multicenter, randomized, parallel, placebo-controlled, double-blind study of 50 patients, ages 24-70 years, with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis or pancreatectomy. VIOKACE Tablets (20,880 USP units of lipase per tablet) or placebo were administered as 22 tablets per day (6 tablets with 3 meals and 2 tablets with 2 of 3 snacks). Duration of exposure ranged from 6 to 7 days. The majority of the subjects were Caucasian (96%) and male (82%).

The most common adverse reactions (greater than or equal to 7%) were biliary tract stones and anal pruritus. Table 1 enumerates adverse reactions that occurred in at least 1 patient (greater than or equal to 3%) treated with VIOKACE at a higher rate than with placebo. Two adverse reactions reported in greater than one patient were biliary tract stones and anal pruritus.

TABLE 1: Adverse Reactions Occurring in at Least 1 Patient (greater than or equal to 3%) in Chronic Pancreatitis or Pancreatectomy

Postmarketing Experience

Post-marketing data for VIOKACE have been available since 2003. The safety data are similar to that described below. 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.

Pancreatic enzyme products (delayed and immediate-release) 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 included 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.

There have been no reports of overdose in clinical trials or post-marketing surveillance with VIOKACE. Chronic high doses of pancreatic enzyme products have been associated with fibrosing colonopathy and colonic strictures [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS]. 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].

You should not take pancrelipase if you are allergic to pork proteins.

Call your doctor at once if you have symptoms of a rare but serious bowel disorder: severe or unusual stomach pain, vomiting, bloating, diarrhea, or constipation.

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• joint pain or swelling; or

• symptoms of a rare but serious bowel disorder--severe or unusual stomach pain, vomiting, bloating, diarrhea, constipation.

Tell your doctor if your child is not growing at a normal rate while using pancrelipase.

Common side effects may include:

• stomach pain, gas, upset stomach;

• diarrhea, frequent or abnormal bowel movements;

• rectal itching;

• headache;

• runny or stuffy nose, sore throat; or

• changes in your blood sugar.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Gas.
• Cough.
• Sore throat.
• Neck pain.
• Stuffy nose.
• Ear pain.
• Heartburn.
• Dizziness.
• Nosebleed.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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.

None.

Mechanism of Action

The pancreatic enzymes in Viokace 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.

Pharmacokinetics

Pancreatic enzymes are not absorbed from the gastrointestinal tract in appreciable amounts.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, genetic toxicology, and animal fertility studies have not been performed with pancrelipase.

Viokace may increase your chance of having a rare bowel disorder called fibrosing colonopathy. This condition is serious and may require surgery. The risk of having this condition may be reduced by following the dosing instructions that your doctor gave you.

Call your doctor right away if you have any unusual or severe:

• stomach area (abdominal) pain
• bloating
• trouble passing stool (having bowel movements)
• nausea, vomiting, or diarrhea

Take Viokace exactly as prescribed by your doctor. Do not take more or less Viokace than directed by your doctor.

Active ingredient: lipase, protease and amylase

Inactive ingredients: colloidal silicon dioxide, crosscarmellose sodium, lactose monohydrate, microcrystalline cellulose, stearic acid and talc.