Contents

Sucraid® (sacrosidase) Oral Solution

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 enzyme replacement therapy for the treatment of genetically determined sucrase deficiency, which is part of congenital sucrase-isomaltase deficiency (CSID).

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. Papain is known to cause allergic reactions in some people. 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.

INDICATIONS AND USAGE

Sucraid® (sacrosidase) Oral Solution is indicated as oral replacement therapy of the genetically determined sucrase deficiency, which is part of congenital sucrose-isomaltase deficiency (CSID).

CLINICAL PHARMACOLOGY

Congenital sucrase-isomaltase deficiency (CSID) is a chronic, autosomal recessive, inherited, phenotypically heterogeneous disease with very variable enzyme activity. CSID is usually characterized by a complete or almost complete lack of endogenous sucrase activity, a very marked reduction in isomaltase activity, a moderate decrease in maltase activity, and normal lactase levels.

Sucrase is naturally produced in the brush border of the small intestine, primarily the distal duodenum and jejunum. Sucrase hydrolyzes the disaccharide sucrose into its component monosaccharides, glucose and fructose. Isomaltase breaks down disaccharides from starch into simple sugars. Sucraid does not contain isomaltase.

In the absence of endogenous human sucrase, as in CSID, sucrose is not metabolized. Unhydrolyzed sucrose and starch are not absorbed from the intestine and their presence in the intestinal lumen may lead to osmotic retention of water. This may result in loose stools.

Unabsorbed sucrose in the colon is fermented by bacterial flora to produce increased amounts of hydrogen, methane, and water. As a consequence, excessive gas, bloating, abdominal cramps, nausea, and vomiting may occur.

Chronic malabsorption of disaccharides may result in malnutrition. Undiagnosed/untreated CSID patients often fail to thrive and fall behind in their expected growth and development curves. Previously, the treatment of CSID has required the continual use of a strict sucrose-free diet.

CSID is often difficult to diagnose. Approximately 4% to 10% of pediatric patients with chronic diarrhea of unknown origin have CSID. Measurement of expired breath hydrogen under controlled conditions following a sucrose challenge (a measurement of excess hydrogen excreted in exhalation) in CSID patients has shown levels as great as 6 times that in normal subjects.

A generally accepted clinical definition of CSID is a condition characterized by the following: stool pH <6, an increase in breath hydrogen of > 10 ppm when challenged with sucrose after fasting and a negative lactose breath test. However, because of the difficulties in diagnosing CSID, it may be warranted to conduct a short therapeutic trial (e.g., one week) to assess response in patients suspected of having CSID.

CONTRAINDICATIONS

Patients known to be hypersensitive to yeast, yeast products, glycerin (glycerol), or papain.

WARNINGS

Severe wheezing, 90 minutes after a second dose of sacrosidase, necessitated admission into the ICU for a 4-year-old boy. The wheezing was probably caused by sacrosidase. He had asthma and was being treated with steroids. A skin test for sacrosidase was positive. Other serious events have not been linked to Sucraid.

PRECAUTIONS

Care should be taken to administer initial doses of Sucraid near (within a few minutes of travel) a facility where acute hypersensitivity reactions can be adequately treated. Alternatively, the patient may be tested for hypersensitivity to Sucraid through skin abrasion testing. Should symptoms of hypersensitivity appear, discontinue medication and initiate symptomatic and supportive therapy.

Skin testing as a rechallenge has been used to verify hypersensitivity in one asthmatic child who displayed wheezing after oral sacrosidase.

GENERAL

Although Sucraid provides replacement therapy for the deficient sucrase, it does not provide specific replacement therapy for the deficient isomaltase. Therefore, restricting starch in the diet may still be necessary to reduce symptoms as much as possible. The need for dietary starch restriction for patients using Sucraid should be evaluated in each patient.

It may sometimes be clinically inappropriate, difficult, or inconvenient to perform a small bowel biopsy or breath hydrogen test to make a definitive diagnosis of CSID. If the diagnosis is in doubt, it may be warranted to conduct a short therapeutic trial (e.g., one week) with Sucraid to assess response in a patient suspected of sucrase deficiency.

The effects of Sucraid have not been evaluated in patients with secondary (acquired) disaccharidase deficiencies.

INFORMATION FOR PATIENTS

See Patient Package Insert. Instruct patients to discard bottles of Sucraid 4 weeks after opening due to the potential for bacterial growth. For the same reason, patients should be advised to rinse the measuring scoop with water after each use.

Administer Sucraid with water, milk, or infant formula. Do not warm or heat the beverage or infant formula before or after addition of Sucraid. Do not mix or consume Sucraid with fruit juice.

USE IN DIABETICS

The use of Sucraid will enable the products of sucrose hydrolysis, glucose and fructose, to be absorbed. This fact must be carefully considered in planning the diet of diabetic CSID patients using Sucraid.

LABORATORY TESTS

The definitive test for diagnosis of CSID is the measurement of intestinal disaccharidases following small bowel biopsy. Other tests used alone may be inaccurate: for example, the breath hydrogen test (high incidence of false negatives) or oral sucrose tolerance test (high incidence of false positives).

Differential urinary disaccharide testing has been reported to show good agreement with small intestinal biopsy for diagnosis of CSID.

DRUG INTERACTIONS

Neither drug-drug nor drug-food interactions are expected or have been reported with the use of Sucraid. Do not mix or consume Sucraid with fruit juice, since acidity may reduce the enzyme activity.

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

Sucraid has been used in patients as young as 5 months of age. Evidence in one controlled trial in primarily pediatric patients shows that Sucraid is safe and effective for the treatment of the genetically acquired sucrase deficiency, which is part of CSID.

ADVERSE REACTIONS

Adverse experiences with Sucraid in clinical trials were generally minor and were frequently associated with the underlying disease.

In clinical studies of up to 54 months duration, physicians treated a total of 52 patients with Sucraid. The adverse experiences and respective number of patients reporting each event (in parenthesis) were as follows: abdominal pain (4), vomiting (3), nausea (2), diarrhea (2), constipation (2), insomnia (1), headache (1), nervousness (1), and dehydration (1).

Note: diarrhea and abdominal pain can be a part of the clinical presentation of the genetically determined sucrase deficiency, which is part of congenital sucrase-isomaltase deficiency (CSID).

One asthmatic child experienced a serious hypersensitivity reaction (wheezing) probably related to sacrosidase (see Warnings). The event resulted in withdrawal of the patient from the trial but resolved with no sequelae.

OVERDOSAGE

Overdosage with Sucraid has not been reported.

DOSAGE AND ADMINISTRATION

Dosage

Patients weighing 15 kg and less: The recommended dosage is 1 mL (8,500 International Units) administered orally with each meal or snack.
Patients weighing more than 15 kg: The recommended dosage is 2 mL (17,000 International Units) administered orally with each meal or snack.

Preparation Instructions

1 mL (8,500 International Units) dose for patients weighing 15 kg or less:

Multiple-Dose Bottle: Measure 1 scoop (provided) or 28 drops using the multiple-dose bottle in 60 mL of water, milk, or infant formula and mix well. Rinse the measuring scoop with water after each use.

2 mL (17,000 International Units) dose for patients weighing more than 15 kg:

Multiple-Dose Bottle: Measure 2 scoops (provided) or 56 drops using the multiple-dose bottle in 120 mL of water, milk, or infant formula and mix well. Rinse the measuring scoop with water after each use.
Single-Use Container: Empty the entire contents of the 2 mL single-use container in 120 mL of water, milk, or infant formula and mix well.

Administration Instructions

Administer half of the mixed solution at the beginning of the meal or snack and the other half during the meal or snack.
Serve the beverage or infant formula cold or at room temperature. Do not warm or heat the beverage or infant formula before or after addition of Sucraid.
Administration of Sucraid with 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.

Sucraid® (sacrosidase) Oral Solution

Sucraid® (sacrosidase) Oral Solution