About Sucraid

What is Sucraid®?

Sucraid® (sacrosidase) Oral Solution is an enzyme replacement that facilitates breakdown of sucrose (sugar) into simpler forms for absorption from the intestine into the blood. It can help relieve the gastrointestinal symptoms associated with congenital sucrase-isomaltase deficiency (CSID) and allow patients with CSID to maintain a more normal diet.

Sucraid® is available in 118 mL translucent plastic bottles, packaged two bottles per box. Each mL of solution contains 8,500 International Units (I.U.) of sacrosidase. A 1 mL measuring scoop is provided with each bottle.

CSID is an autosomal recessive disease of the small intestine first discovered in 1960 by Weijers and colleagues. The disease was originally characterized by undetectable sucrase activity, a decrease of maltase activity to nearly one third of the normal level, and a varying degree of isomaltase activity. Click here for more information: About CSID.

Your doctor has prescribed Sucraid® either because you have been diagnosed with a deficiency of sucrase-isomaltase enzyme or because the doctor suspects you may have some deficiency of the enzyme and wishes to determine if Sucraid® is of benefit.

Sucraid® does not break down starch (potato, bread, pasta) and some CSID patients also have an inability to absorb starch from their diet. Therefore, your doctor may recommend you restrict the amount of starch for two weeks after you first start Sucraid® and gradually reintroduce starch to your diet. If symptoms return, you should consult your doctor. Keeping a dietary diary for the first few weeks of therapy is recommended.

How does Sucraid® work? 

Sucraid® is a sucrase enzyme replacement therapy that catalyzes the hydrolysis of sucrose into glucose and fructose, thereby facilitating absorption from the small intestine into the bloodstream. Sucraid® has been shown to be safe and effective in the treatment of patients with CSID. The sacrosidase in Sucraid® is potent and robust; on a per milliliter basis, Sucraid® is approximately 100-fold more potent than endogenous sucrase. It has been shown to be stable at 4˚C and at pH values as low as 1.0. Sucraid® is more effective if taken with food or milk.

Although Sucraid® provides replacement therapy for deficient sucrase, it does not provide specific replacement therapy for deficient isomaltase.1 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.

Clinical Evidence

Clinical Studies

Robayo-Torres CC et al. 13C-breath tests for sucrose digestion in congenital sucrase isomaltase-deficient and sacrosidase-supplemented patients. J Pediatr Gastroenterol Nutr. 2009;48:412-418.

Study Design
In this study, Robayo-Torres and colleagues examined both the ability of a 13C-labeled breath test to detect CSID without the need for a duodenal biopsy and the effect of sacrosidase supplementation on breath test results. A total of ten CSID patients (diagnosed by low biopsy sucrase activity) and ten control patients who had undergone endoscopy and biopsy because of dyspepsia or chronic diarrhea, but with normal mucosal enzyme activity, were tested. Patients were separately administered uniformly labeled oral 13C-glucose and 13C-sucrose loads. After each administration, 13C-CO2 breath enrichment was assayed using an infrared spectrophotometer. Tests were repeated after adding Sucraid®. Results were measured by calculating the mean percentage coefficient of glucose oxidation (%CGO).

Results

In the control group, an average of 146% ± 45.5% mean percentage coefficient of glucose oxidation (%CGO); in contrast, the %CGO in the CSID group was 25% ± 21% (P<.001), demonstrating that 13C-breath testing clearly distinguished among patients with and without CSID (Figure 2).

The test had 100% sensitivity and 100% specificity for detection of low duodenal sucrase activity. All patients with CSID showed correction of sucrase deficiency with oral Sucraid® supplementation (Figure 3; P=.001).

Conclusions

The 13C-sucrose breath test was accurate and specific as a noninvasive confirmatory test of CSID. All patients with CSID showed correction of sucrase deficiency with oral Sucraid® supplementation.

Treem WR et al. Sacrosidase therapy for congenital sucrase-isomaltase deficiency. J Pediatr Gastroenterol Nutr. 1999;28:137-142.

In a study published in 1999 by Treem and colleagues, the efficacy and safety of sacrosidase oral solution was examined in children with confirmed CSID consuming a normal sucrose- and carbohydrate-containing diet.

Patients
Patients with CSID were recruited from the practices of members of the North American Society for Pediatric Gastroenterology. Criteria for inclusion were:

  • History of chronic, watery diarrhea with an acid pH <6.0
  • Small intestinal biopsy specimens with measurement of tissue disaccharidase levels
  • Sucrase activity <10% of control specimens
  • Normal or decreased maltase activity
  • Normal lactase levels and a normal result in a lactose breath hydrogen test
  • Normal villous architecture of the small intestine

A total of twenty-eight patients with CSID were enrolled in this randomized, multicenter, double-blind, controlled trial. All patients were infants or children (twelve boys) between the ages of 5 months and 11.5 years (mean age, 4 years; median, 2.5 years). At baseline, the mean body weight of subjects was 16.5 kg.

Study Design and Treatments

The trial consisted of two phases. The breath hydrogen phase, which consisted of three single-dose treatments (placebo, sacrosidase, and sacrosidase with milk). Patients were subsequently randomized to one of four doses of sacrosidase for a 10-day treatment period, and crossed over to other dosages in random order until a 40-day treatment period was completed. Dosing of sacrosidase was weight-dependent: 1 mL/meal if weight was ≤15 kg; 2 mL/meal if >15 kg.

Assessments and End Points
Stool frequency and consistency measures, symptoms, and dietary data were recorded daily and compared with a baseline period in which patients had consumed a sucrose-free diet without sacrosidase. Dietary assessment of sucrose and carbohydrate consumption was summarized for each treatment period during the dose-response phase to verify whether patients were compliant with a “normal” diet (2 g/kg/d sucrose and 5 g/kg/d carbohydrate).

The primary efficacy variables included total stools and total symptoms scores collected during the dose-response phase. All other measurements were secondary. During the dose-response phase, the number of stools and severity of symptoms (gas, bloating, nausea, vomiting, and abdominal cramps) were recorded daily by each patient and assigned values ranging from 0 (none) to 3 (severe). A post hoc responder assessment (asymptomatic yes/no) was also determined.

Results
Of the twenty-eight patients in this trial who received ≥1 dose of sacrosidase, twenty-six (93%) completed the trial. Significant differences were observed between the two higher concentrations (undiluted and 1:10 dilution) and the two lower concentrations (1:100 and 1:1,000 dilution) for both of the primary outcome variables—total stools and total symptoms score.

Number of stools in 10 days
Sacrosidase treatment Stools/d (mean ± SEM) Watery Soft Formed Hard Total symptoms score ≤7 (%)
Full strength 1.82 ± 1.6* 3.8 ± 1.7 6.1 ± 1.4 7.9 ± 1.2 0.4 ± 0.2 70*
1:10 2.20 ± 2.5 7.0 ± 2.8 7.0 ± 1.2 7.7 ± 1.7 0.1 ± 0.1 63
1:100 2.58 ± 2.9 12.0 ± 3.3 8.3 ± 1.3 5.1 ± 1.1 0.1 ± 0.1 54
1:1000 2.44 ± 2.5 9.7 ± 2.3 9.0 ± 1.5 5.4 ± 1.1 0.3 ± 0.3 54
Baseline 2.31 ± 2.2 82

Table 1. Effect of sacrosidase on stools and stool consistency while consuming a sucrose-containing diet. *Significant differences were shown between the two higher and two lower
concentrations for total stools (P≤.001) and total symptoms score (P=.003).

Overall, 81% of patients were asymptomatic while receiving full-strength sacrosidase. 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 aged ≥3 years, 77% became asymptomatic, suggesting that therapeutic response does not differ significantly according to age (Figure 5).13

Of the twenty-eight patients in the trial who consumed a sucrose-free diet, the percentage reporting severe or moderate gastrointestinal symptoms was as follows: 75% diarrhea, 67% gas, 60% stomach pain, and 20% nausea.13

Conclusions

The results of this trial indicate that sacrosidase is an effective and well-tolerated treatment for CSID. By taking a small amount of sacrosidase with each meal, patients were able to eat a normal carbohydrate- and sucrose-containing diet without developing major gastrointestinal symptoms. Long-term sacrosidase therapy may reduce the high incidence of GI complaints in this patient population.

Treem WR et al. Evaluation of the liquid yeast-derived sucrase enzyme replacement in patients with sucrase-isomaltase deficiency. Gastroenterology. 1993;105:1061-1068.

In this study, published by Treem and colleagues in 1993, the ability of sacrosidase to reduce the breath hydrogen response to an oral sucrose test was examined. Additionally, the ability of sacrosidase to reduce symptoms of sucrose malabsorption was assessed.

Study Design
A variety of methods were used to examine the enzymatic quality and stability of sacrosidase. The clinical activity of sacrosidase was evaluated in patients with a positive diagnosis of CSID who underwent double-blind, placebo-controlled breath hydrogen tests, followed by an eight-week dose-response study conducted while consuming a diet containing a moderate amount of sucrose. During this period patients were treated with four different concentrations of sacrosidase for fourteen days each.

Results
Sacrosidase was found to be stable at 4˚C and retains full activity between pH 1.0 and 6.2. Pepsin digestion of the enzyme in vitro was completely eliminated by bovine serum albumin.

A total of fourteen patients with CSID (five male; mean age 7.6 years) were enrolled in the study. All patients had normal lactose breath H2 test results and abnormal sucrose breath H2 tests. Overall, there was a significant reduction in cumulative breath H2 (P<.001) and peak breath H2 (P<.002) when sucrose was ingested with sacrosidase compared with placebo. Twelve patients completed an eight-week field trial of four different concentrations of sacrosidase, ranging from a 1:100 dilution to a 1:100,000 dilution. Of note, there was a strong dose-response relationship, with patients who received the lowest dilution experiencing the fewest symptoms.

Conclusions
Sacrosidase was highly effective in reducing high stool frequency, diarrhea, abdominal pain, and excessive gas in this small population of patients with CSID. There was a clear dose-response relationship in the higher concentrations of sacrosidase which provided greater efficacy. Sacrosidase was stable at temperatures achievable in domestic refrigerators.

Open-label, long-term study of sucrase enzyme therapy for congenital sucrase-isomaltase deficiency

Study Design
This open-label, long-term trial evaluated the safety, patient acceptability, and effectiveness of Sucraid® in treating patients with CSID consuming a sucrose-containing diet.13 Upon completion of the previous controlled trials involving Sucraid®, thirty-four CSID patients from 6 months to 28 years of age were allowed to continue treatment with Sucraid® for two to fifty-four months.

Results

The thirty-four patients treated in the trial represent a total of over 900 patient-months of Sucraid® therapy. A total of thirty-one adverse events were recorded in fourteen patients (41%). Most adverse events were attributed to concurrent illnesses and not considered related to Sucraid®. Although some adverse events were considered as possibly related to treatment, many of these events were also symptoms of sucrose malabsorption typical of patients with CSID and not unexpected for this patient population.

No patients discontinued due to adverse events. Three patients experienced serious adverse events, and all three continued treatment with Sucraid®.

Conclusions

The results of this trial indicate that Sucraid® is a safe, well-tolerated, and effective treatment for the gastrointestinal symptoms of CSID. Sucraid® allowed CSID patients of a broad range of ages to consume a normal diet over the long term by attenuating the characteristic gastrointestinal symptoms of CSID.

Safety Considerations

Sucraid® is contraindicated in patients known to be hypersensitive to yeast, yeast products, glycerin (glycerol), or papain. Care should be taken to administer initial doses of Sucraid® near (within a few minutes’ travel) a facility where acute hypersensitivity reactions can be adequately treated.1 Alternatively, patients can be tested for hypersensitivity to Sucraid® through skin abrasion testing. Should symptoms of hypersensitivity appear, discontinue medication and initiate symptomatic and supportive therapy.

As with all prescribed therapies, patients should review proper use, potential contraindications, and read the patient insert completely.

Dosage and Administration

Please follow the dosing instructions carefully. The recommended dosage is as follows:

1 mL (8,500 I.U.) (one full measuring scoop or 28 drops) per meal or snack for patients up to 15 kg (33.07 lbs.) in body weight.

2mL (17,000 I.U.) (two full measuring scoops or 56 drops) per meal or snack for patients over 15 kg (33.07 lbs.) in body weight.

Dosage should be diluted in 2 to 4 ounces of water, milk or infant formula, and may be measured with the 1 mL measuring scoop (provided) or by drop count method (1mL equals 28 drops from the Sucraid®container tip).

The following should be noted in regards to administration, storage and expiration of Sucraid®:

  • It is suggested that half of each dose be taken before the meal and the other half be taken during the meal. The divided dose is important as the first half of the dose is used to decoy pepsin which is in the stomach and could otherwise reduce Sucraid®’s effectiveness.
  • The beverage or infant formula should be served cold or at room temperature. Do not heat beverages containing Sucraid®, or add Sucraid® to hot beverages, as the heated fluid could decrease the potency of the enzyme.
  • Sucraid® should be refrigerated at 36°F-46°F (2°C-8°C) and should be protected from heat and light.
  • Sucraid® should not be reconstituted or consumed with fruit juices as the acidity may reduce the enzyme activity.
  • Discard bottles of Sucraid® four weeks after first opening due to the potential for bacterial growth.
  • Your doctor may recommend avoiding starch for two weeks then gradually adding starch back into the diet while monitoring symptoms.

Important Safety Information

For a complete discussion of indications, usage, contraindications, warnings, precautions, adverse reactions, and overdosage, please see full prescribing information attached. Do not use Sucraid® with patients known to be hypersensitive to yeast, yeast products, or glycerin (glycerol). Sucraid may contain papain which can cause allergic reactions in some patients. Adverse experiences with Sucraid in clinical trials were generally minor and were frequently associated with 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 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. The effects of Sucraid have not been evaluated in patients with secondary (acquired) disaccharidase deficiency. In one clinical trial, one patient, a four year old boy who was being treated for asthma, experienced severe wheezing necessitating admission into the ICU. While reported reactions are extremely rare, care should be taken when administering initial doses of Sucraid to observe any signs of acute hypersensitivity reaction. Care should be taken to administer initial doses of Sucraid near a facility where acute hypersensitivity reactions can be adequately treated.1