SACROSIDASE: 129 Adverse Event Reports & Safety Profile

DESCRIPTION Sacrosidase is an enzyme with the chemical name of β,D-fructofuranoside fructohydrolase. The enzyme is derived from baker’s yeast ( Saccharomyces cerevisiae ). It has been reported that the primary amino acid structure of this protein consists of 513 amino acids with an apparent molecular weight of 100,000 Da for the glycosylated monomer (range 66,000- 116,000 Da). Reports also suggest that the protein exists in solution as a monomer, dimer, tetramer, and octomer ranging from 100,000 Da to 800,000 Da. It has an isoelectric point (pI) of 4.5. Sucraid ® (sacrosidase)

Oral

Solution is an oral enzyme replacement therapy. Sucraid is a pale yellow to colorless, clear solution with a pleasant, sweet taste. Each milliliter (mL) of Sucraid contains 8,500 International Units (I.U.) of the enzyme sacrosidase, the active ingredient. Sucraid may contain small amounts of papain (see WARNINGS). Papain is a protein-cleaving enzyme that is introduced in the manufacturing process to digest the cell wall of the yeast and may not be completely removed during subsequent process steps. Sucraid contains sacrosidase in a vehicle comprised of glycerin, water, citric acid, and sodium hydroxide to maintain the pH at 4.0 to 4.7. Glycerol (glycerin) in the amount consumed in the recommended doses of Sucraid has no expected toxicity. This enzyme preparation is fully soluble with water, milk, and infant formula. DO NOT HEAT SOLUTIONS CONTAINING SUCRAID. Do not put Sucraid in warm or hot liquids (see DOSAGE AND ADMINISTRATION, Administration Instructions).

INDICATIONS AND USAGE Sucraid ® (sacrosidase)

Oral

Solution is indicated for the treatment of sucrase deficiency, which is part of congenital sucrase-isomaltase deficiency (CSID), in adult and pediatric patients 5 months of age and older.

DOSAGE AND ADMINISTRATION Important Administration Information Administer Sucraid with each meal or snack.

Mix

Sucraid with cold or room temperature water, milk or infant formula prior to administration. Administration of Sucraid in liquids other than water, milk, or infant formula has not been studied and is not recommended. Do not mix or consume Sucraid with fruit juice. Do not warm or heat the water, milk, or infant formula before or after addition of Sucraid. Administer half of the dose at the beginning of the meal or snack and the other half of the dose during the meal or snack.

Recommended Dosage

The recommended dosage is: Patients weighing 15 kg and less: 8,500 International Units (1 mL) administered orally with each meal or snack. Patients weighing more than 15 kg: 17,000 International Units (2 mL) administered orally with each meal or snack. Preparation and Administration Instructions for Patients Weighing 15 kg or Less Multiple-Dose Bottle: Using the measuring scoop provided, add 1 scoop of Sucraid (1 mL) to 60 mL of cold or room temperature water, milk, or infant formula. Stir to mix well. Administer half of the mixed Sucraid solution (30 mL) at the beginning of the meal or snack and the other half of the mixed solution (30 mL) during the meal or snack. Do not save any of the mixed Sucraid solution for later use. Rinse the measuring scoop with water. Single-Use Container: Empty the entire contents of the single-use container (2 mL) in 120 mL of cold or room temperature water, milk, or infant formula. Stir to mix well. Divide the mixed Sucraid solution into two separate 60 mL portions. The first portion (60 mL) is for immediate use.

• Administer half of the first portion (30 mL) of the mixed Sucraid solution at the beginning of the meal or snack and the other half of the first portion (30 mL) of the mixed Sucraid solution during the meal or snack. Store the second portion of the mixed Sucraid solution (60 mL) at 2°C to 8°C (36°F to 46°F) for up to 24 hours for administration with the next meal or snack.
• Discard the mixed Sucraid solution if not used within 24 hours. Preparation and Administration Instructions for Patients Weighing More than 15 kg Multiple-Dose Bottle: Using the measuring scoop provided, add 2 scoops of Sucraid (2 mL) to 120 mL of cold or room temperature water, milk, or infant formula. Stir to mix well. Administer half of the mixed Sucraid solution (60 mL) at the beginning of the meal or snack and the other half of the mixed Sucraid solution (60 mL) during the meal or snack. Do not save any of the mixed Sucraid solution for later use. Rinse the measuring scoop with water. Single-Use Container: Empty the entire contents of the single-use container (2 mL) in 120 mL of cold or room temperature water, milk, or infant formula. Stir to mix well. Administer half of the mixed Sucraid solution (60 mL) at the beginning of the meal or snack and the other half of the mixed solution during the meal or snack (60 mL). Do not save any of the mixed Sucraid solution for later use.

CONTRAINDICATIONS Sucraid is contraindicated in patients known to be hypersensitive to yeast, yeast products, glycerin (glycerol), or papain (see WARNINGS).

ADVERSE REACTIONS The following adverse reactions associated with the use of sacrosidase were identified in clinical studies or postmarketing reports. Because some of these reactions were 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. In clinical studies of up to 54 months duration, a total of 52 patients were treated with Sucraid. The reported adverse reactions (number of patients) were as follows: abdominal pain (4), vomiting (3), nausea (2), diarrhea (2), constipation (2), insomnia (1), headache (1), nervousness (1), and dehydration (1). Hypersensitivity reactions (wheezing, rash, and pruritis) have been reported (see WARNINGS).

WARNINGS Severe Hypersensitivity Reactions Severe hypersensitivity reactions, including wheezing, rash, and pruritis, have been reported with administration of Sucraid. Sucraid contains papain, which is associated with hypersensitivity reactions (see DESCRIPTION). A pediatric patient in the clinical trials experienced a hypersensitivity reaction of severe wheezing that required hospitalization. Postmarketing cases of cutaneous hypersensitivity reactions have also been reported. Instruct patients or caregivers to stop Sucraid and seek medical attention if symptoms suggestive of a hypersensitivity reaction occur. Sucraid is contraindicated in patients who have had a known hypersensitivity reaction (see CONTRAINDICATIONS).

PRECAUTIONS Increased Blood Glucose Concentrations in Patients with Diabetes Mellitus Sucraid enables the products of sucrose hydrolysis, glucose and fructose, to be absorbed and may increase blood glucose concentrations. Monitor blood glucose concentrations and adjust the diet accordingly for patients with diabetes mellitus.

Dietary Starch Restriction

Sucraid does not replace isomaltase. Therefore, patients may still experience symptoms of CSID while taking Sucraid. Consider dietary starch restriction in addition to Sucraid, especially in patients in whom symptoms are not adequately controlled by Sucraid. Information for Patients See Patient Package Insert and the Instructions for Use.

Drug Interactions Fruit Juice

The acidity in fruit juice may reduce the enzyme activity in Sucraid. Administration of Sucraid with liquids other than water, milk, or infant formula has not been studied and is not recommended (see DOSAGE AND ADMINISTRATION, Administration Instructions). Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals with Sucraid have not been performed to evaluate the carcinogenic potential. Studies to evaluate the effect of Sucraid on fertility or its mutagenic potential have not been performed.

Pregnancy Teratogenic Effects

Animal reproduction studies have not been conducted with Sucraid. Sucraid is not expected to cause fetal harm when administered to a pregnant woman or to affect reproductive capacity. Sucraid should be given to a pregnant woman only if clearly needed.

Nursing Mothers The

Sucraid enzyme is broken down in the stomach and intestines, and the component amino acids and peptides are then absorbed as nutrients.

Pediatric Use

The safety and effectiveness of Sucraid for the treatment of sucrase deficiency, which is part of congenital sucrase-isomaltase deficiency (CSID), have been established in pediatric patients aged 5 months and older. Use of Sucraid for this indication is supported by evidence from adequate and well-controlled studies in pediatric patients (see CLINICAL STUDIES and ADVERSE REACTIONS).

Geriatric Use

Clinical trials of Sucraid did not include patients 65 years of age and older to determine if they respond differently from younger adult patients.

Drug Interactions Fruit Juice The acidity in fruit juice may reduce the enzyme activity in Sucraid. Administration of Sucraid with liquids other than water, milk, or infant formula has not been studied and is not recommended (see DOSAGE AND ADMINISTRATION, Administration Instructions).