Sucraid® Description
Chemical Name: B,D fructofuranoside fractohydrolase

Sucraid®(sacrosidase) oral solution is an enzyme replacement therapy for the treatment of the genetically determined sucrase deficiency, which is part of congenital sucrase-isomaltase deficiency (CSID). Sucraid® is a pale yellow, clear solution with a pleasant, sweet taste.

The active ingredient is sacrosidase [enzyme derived from bakers yeast (saccharomyces cerevisiae)]. Sucraid® also contains 50% glycerol in an aqueous solution, with no expected toxicity at recommended Sucraid® dose levels.

The solution is fully soluble with water, milk and infant formula. DO NOT HEAT SOLUTIONS CONTAINING Sucraid®. Do not put Sucraid® in warm or hot liquids. DO NOT MIX WITH SUGARY DRINKS SUCH AS FRUIT JUICES.

Does Sucraid® contain isomaltase?
Sucraid® does not contain isomaltase.

Does Sucraid® contain gluten?
Sucraid® does not contain gluten. (per QA response 3/2/00)

Is a support group available?
Yes. A parent support group is available. Visit www.csidinfo.com

Mechanism of Action
Sucraid® facilitates breakdown and absorption of sucrose (table sugar) from the intestine and can help relieve the gastrointestinal symptoms of CSID.

Sucraid® does not break down starch. Therefore, you may need to restrict the amount of starch in your diet. Your doctor will tell you if you should restrict the amount of starch in your diet.

Medical literature suggests CSID affects up to 0.2% of the population in the United States of America. Studies have found a higher incidence of CSID in Greenland, Alaska, and Northern Canadian Eskimos where the incidence is 10-1000 times greater than the United States of America.

What causes CSID?
Sucrase is a naturally-occurring enzyme that is produced in the brush-border of the small intestine, primarily in the distal duodenum and jejunum. Sucrase hydrolyzes sucrose, a disaccharide, into its component monosaccharides, glucose and fructose. Congenital sucrase-isomaltase deficiency (CSID) is a rare, chronic, autosomal recessive,  phenotypically heterogenous 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.

What are the symptoms of CSID?
Symptoms may include some or all of the following: excessive gas, bloating, abdominal cramps, watery diarrhea, nausea, vomiting, and failure to thrive.

Sucrase is naturally produced in the brush border of the small intestine. Sucrase hydrolyzes the disaccharide sucrose into its component monosaccharides, glucose and fructose. In the absence of endogenous human sucrase, sucrose is not metabolized. This may lead to an osmotic retention of water, which causes 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.

How do you diagnose CSID?
CSID is difficult to diagnose.
Approximately 4 to 10% of pediatric patients with chronic diarrhea of unknown origin have CSID.

The definitive test for diagnosis of CSID is measurement of intestinal disaccharidases following small bowel biopsy.

Less invasive diagnoses are: A positive breath hydrogen test following an oral challenge with sucrose and a negative breath hydrogen test following oral challenge with lactose along with a stool pH of less than 6 provides an acceptable diagnosis of CSID. Due to the high incidence of false - negatives in the breath hydrogen test, a therapeutic challenge with Sucraid® may be warranted. Measurement of expired breath hydrogen under controlled conditions following a sucrose challenge in CSID patients has shown levels as great as six times that in normal subjects.

Alternatively, because of the difficulty in diagnosing CSID a physician may prescribe a short therapeutic trial in patients suspected of having CSID. Therapeutic trial supplies may be ordered by physicians by calling 1-800-370-2510

Laboratory Tests
The definitive test for diagnosis of CSID is the measurement of intestinal disaccharides following small bowel biopsy. A differential urinary disaccharide testing has shown to be in agreement with small bowel biopsy.

Other tests used alone may be inaccurate: e.g. Breath hydrogen test; oral sucrose test often show false readings.

Are there any other treatments available for CSID?
There are no other FDA approved treatments for CSID. Historically the only way to manage CSID was to eat a restricted diet containing very little sucrose.

A two phase (dose-response preceded by a breath hydrogen phase), double blind, multi-site, crossover trial was conducted in 28 patients (aged 4 months to 11.5 years) with confirmed CSID, as published in, Treem WR, Mc Adams L, Stanford L, Kastoff G, Justinich C, Hyams J. Sacrosidase Therapy for Congenital Sucrase-Isomaltase Deficiency. Journal of Pediatric Gastroenterology and Nutrition 1999; 28(2):137-142.

• Dose did not vary with age or sucrose intake;
• Dose-response relationship was shown between the two higher and the two lower doses;
• The two higher doses of sacrosidase were associated with significantly fewer total stools and higher proportions of patients having lower total symptom scores, the primary efficacy endpoints;
• Higher doses of sacrosidase were associated with a significantly greater number of hard and formed stools as well as with fewer watery and soft stools, the secondary efficacy endpoints; and
• Analysis of the overall symptomatic response as a function of age indicated that in CSID patients up to 3 years of age, 86% became asymptomatic. In patients over 3 years of age, 77% became asymptomatic. Thus, the therapeutic response did not differ significantly according to age.

Off-label Uses
The effects of Sucraid® have not been evaluated in patients with secondary (acquired) disaccharidase deficiencies.

Pediatrics
Sucraid® has been used in patients as young as 5 months of age.

Evidence from one placebo-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.

Pregnancy
Pregnancy category C. Animal reproduction studies have not been conducted.

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
Sucraid® is not going to be excreted in the breast milk. The Sucraid® enzyme is broken down in the stomach and intestines and the component amino acids and peptides are then absorbed as nutrients (it is metabolized just like the food that we eat).

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®.

General
Sucraid® provides replacement therapy for the deficient sucrase, but 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.

Patient Information

Do I need to restrict my diet and watch my carbohydrate intake?
Patients in the clinical trial consumed a normal diet consisting of 2g/kg sucrose (table sugar) and 5 g/kg carbohydrates.

What precautions should be discussed with my physician before starting Sucraid® therapy?

• Tell your doctor if you are allergic to, have ever had a reaction to, or have ever had difficulty taking yeast, yeast products, or glyercin (glycerol).
• Tell your doctor if you have diabetes. With Sucraid®, sucrose (table sugar) can be absorbed from your diet and your blood glucose levels may change. Your doctor will tell you if your diet or diabetes medicines need to be changed.

Drug Interactions
Neither drug-drug nor drug-food interactions are expected or have been reported with the use of Sucraid®. However, Sucraid® should not be reconstituted or consumed with fruit juice, since it's acidity may reduce the enzyme activity.

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.

Warnings
See AE Section on next page for details*. Sucraid® may cause serious allergic reactions. If you notice swelling or have difficulty breathing, get emergency help right away. Before taking your first and second doses, be sure that there are health professionals nearby (within a few minutes travel) just in case there is an allergic reaction.

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

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

Are there any tests available to determine if a patient is allergic to Sucraid®?
The patient may be tested for hypersensitivity to Sucraid® through skin abrasion testing. The patient should discuss this with the primary care physician or allergist.

What should I do if I have a reaction to Sucraid®?
Some patients may have worse abdominal pain, vomiting, nausea, or diarrhea. Constipation, difficulty sleeping, headache, nervousness, and dehydration have also occurred. If you notice these or any other side effects during treatment with Sucraid®, check with your doctor. Stop taking Sucraid® and get emergency help immediately if any of the following side effects occur: Difficulty breathing, wheezing, or swelling of the face.

Overdosage

No overdosages with Sucraid® have been reported.

How do you treat an overdose?
No incidents of overdose have been reported. Glycerin, a component of Sucraid®, is an osmotic laxative; so dehydration may occur if too much Sucraid® is ingested. If an overdose should occur, adequate hydration should be maintained.

Dosing Instructions

1 mL (one full measuring scoop or 22 drops) per meal or snack for patients up to 15 kg in body weight. 2 mL (two full measuring scoops or 44 drops) per meal or snack for patient over 15 kg in body weight. It is suggested that half of the dose be taken before the meal and the other half be taken after the meal.

Can I put Sucraid® in other drinks such as water or milk?

Sucraid® is completely soluble in water, milk, and infant formula. Beverages containing Sucraid® should be consumed cold or at room temperature. Heating beverages containing Sucraid®, or adding Sucraid® to hot beverages, will likely decrease the potency. Sucraid® should not be reconstituted or consumed with fruit juice, since its acidity may reduce the enzyme activity. KEEP Sucraid® REFRIGERATED

Stability

How long will Sucraid® be stable once it is put into another liquid such as water or baby formula?
We recommend preparation immediately prior to the meal or snack, with half of the dosage taken before the meal or snack and the remainder of the dosage at the end.

We just received a new shipment of Sucraid® and it was not refrigerated right away. Is it still good?
Sucraid® is an enzyme product and needs to be maintained at refrigerated conditions. However, brief exposure to ambient room temperature should not affect the potency.