Sacrosidase

Sacrosidase
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aparna Vuppala, M.B.B.S. [2]

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Overview

Sacrosidase is a gastrointestinal agent that is FDA approved for the treatment of of oral replacement therapy of the genetically determined sucrase deficiency, which is part of congenital sucrase-isomaltase deficiency (CSID).. Common adverse reactions include abdominal pain, constipation, diarrhea, nausea, vomiting, headache, insomnia, dehydration.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Sucrase deficiency

• sacrosidase oral solution is indicated as oral replacement therapy of the genetically determined sucrase deficiency, which is part of congenital sucrase-isomaltase deficiency (CSID).

Dosage

• The recommended dosage is 1 or 2 mL (8,500 to 17,000 I.U.) or 1 or 2 full measuring scoops (each full measuring scoop equals 1mL; 28 drops from the sacrosidasecontainer tip equals 1mL) taken orally with each meal or snack diluted with 2 to 4 ounces of water, milk or infant formula. The beverage or infant formula should be served cold or at room temperature. The beverage or infant formula should not be warmed or heated before or after addition of sacrosidasebecause heating is likely to decrease potency. sacrosidaseshould not be reconstituted or consumed with fruit juice since its acidity may reduce the enzyme activity.
• It is recommended that approximately half of the dosage be taken at the beginning of the meal or snack and the remainder be taken during the meal or snack.
• 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 in body weight.
• 2mL (17,000 I.U.) (two full measuring scoops or 56 drops) per meal or snack for patients over 15 kg in body weight.
• Dosage may be measured with the 1 mL measuring scoop (provided) or by drop count method (1mL equals 28 drops from the sacrosidasecontainer tip).

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Sacrosidase in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Sacrosidase in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Sacrosidase in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Sacrosidase in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Sacrosidase in pediatric patients.

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 sacrosidase.

Precautions

• Care should be taken to administer initial doses of sacrosidasenear (within a few minutes’ travel) a facility where acute hypersensitivity reactions can be adequately treated. Alternatively, the patient may be tested for hypersensitivity to sacrosidase 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 sacrosidaseprovides 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 sacrosidaseshould 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 sacrosidaseto assess response in a patient suspected of sucrase deficiency.

• The effects of sacrosidasehave not been evaluated in patients with secondary (acquired) disaccharidase deficiencies

USE IN DIABETICS:

The use of sacrosidasewill 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 sacrosidase.

Adverse Reactions

Clinical Trials Experience

• Adverse experiences with sacrosidasein 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 sacrosidase. 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 . The event resulted in withdrawal of the patient from the trial but resolved with no sequelae.

Postmarketing Experience

There is limited information regarding Sacrosidase Postmarketing Experience in the drug label.

Drug Interactions

• Neither drug-drug nor drug-food interactions are expected or have been reported with the use of sacrosidase. However, sacrosidaseshould not be reconstituted or consumed with fruit juice, since its acidity may reduce the enzyme activity.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

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

Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Sacrosidase in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Sacrosidase during labor and delivery.

Nursing Mothers

• The sacrosidaseenzyme is broken down in the stomach and intestines and the component amino acids and peptides are then absorbed as nutrients.

Pediatric Use

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

Geriatic Use

There is no FDA guidance on the use of Sacrosidase with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Sacrosidase with respect to specific gender populations.

Race

There is no FDA guidance on the use of Sacrosidase with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Sacrosidase in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Sacrosidase in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Sacrosidase in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Sacrosidase in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

Monitoring

• 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.

IV Compatibility

There is limited information regarding IV Compatibility of Sacrosidase in the drug label.

Overdosage

• Overdosage with sacrosidasehas not been reported.

Pharmacology

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Mechanism of Action

• 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.

Structure

• 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).

CHEMISTRY

• sacrosidaseis a pale yellow, clear solution with a pleasant sweet taste. Each milliliter (mL) of sacrosidase contains 8,500 International Units (I.U.) of the enzyme sacrosidase, the active ingredient. The chemical name of this enzyme is ß,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 g/mole for the glycosylated monomer (Range 66,000-116,000 g/mole). Reports also suggest that the protein exists in solution as a monomer, dimer, tetramer, and octomer ranging from 100,000 g/mole to 800,000 g/mole. It has an isoelectric point of 4 (pl=4.093).

• sacrosidasemay 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.

• sacrosidasealso contains 50% glycerol (w/w) in an aqueous solution. Glycerol (glycerin) in the amount consumed in the recommended doses of sacrosidasehas no expected toxicity.

• This enzyme preparation is fully soluble with water, milk, and infant formula (DO NOT HEAT SOLUTIONS CONTAINING sacrosidase). Do not put sacrosidasein warm or hot liquids.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Sacrosidase in the drug label.

Pharmacokinetics

• 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. sacrosidasedoes 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 > 10ppm 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.

Nonclinical Toxicology

CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY:

• Long-term studies in animals with sacrosidasehave not been performed to evaluate the carcinogenic potential. Studies to evaluate the effect of sacrosidaseon fertility or its mutagenic potential have not been performed.

Clinical Studies

• 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. During the dose response phase the patients were challenged with an ordinary sucrose containing diet while receiving each of four doses of sacrosidase; full strength (9000 I.U./mL) and three dilutions (1:10 [900 I.U./mL], 1:100 [90 I.U./mL], and 1:1000 [9 I.U./mL]) in random order for a period of 10 days. Patients who weighed no more than 15 kg received 1 mL per meal; those weighing more than 15 kg received 2 mL per meal. The dose did not vary with age or sucrose intake.

• A 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 end-points. In addition, 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 end-points.

• 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.

• A second study of similar design and execution as the first used 4 different dilutions of sacrosidase 1:100 (90 I.U./mL), 1:1000 (9 I.U./mL), 1:10,000 (0.9 I.U./mL), and 1:100,000 (0.09 I.U./mL). There were inconsistent results with regards to the primary efficacy parameters.

• In both trials however, patients showed a marked decrease in breath hydrogen output when they received sacrosidase in comparison to placebo.

How Supplied

• sacrosidaseis available in 118 mL (4 fluid ounces) 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. A full measuring scoop is 1 mL.

• Store in a refrigerator at 2°- 8°C (36°- 46°F). Product is sterile until opened. Discard four weeks after first opening due to the potential for bacterial growth. Protect from heat and light.

Storage

There is limited information regarding Sacrosidase Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

• Patients should be instructed to discard bottles of sacrosidase4 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.

sacrosidaseis fully soluble with water, milk and infant formula, but it is important to note that this product is sensitive to heat. sacrosidaseshould not be reconstituted or consumed with fruit juice, since its acidity may reduce the enzyme activity.

Precautions with Alcohol

• Alcohol-Sacrosidase interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Sacrosidase Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Sacrosidase Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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