英文商品名： Sucraid R
中文商品名： 酵母轉化酶
主成分： sacrosidase 。
劑型：
口服溶液， 8500IU/ml, 118m l/bot 之 sacrosidase 。
 
適應症：
先天性蔗糖酶-異麥芽糖酶缺乏症 (congenital sucrase-isomaltase deficiency) 。
 
藥理機轉：
Sacrosidase 主要是由啤酒酵母菌 Saccharomyces cerevisiae 中萃取出之轉化酵素，利用 sacrosidase 可將蔗糖分解以提供身體所需的養分。
 
藥動學：
1. Sacrosidase 主要於腸胃道分解成 peptides 及胺基酸，再進一步吸收。
2. 於服用 sacrosidase 時，可併服含蛋白質的食物，以減少胃中之酸度增加及避免胃蛋白酵素將 sacrosidase 分解。
3. 哺乳：安全。
 
禁忌： 對於肝油、酵母菌或其相關產品易過敏者，須小心使用。
 
副作用：
1. 中樞系統方面：失眠、頭痛。
2. 腸胃道方面：腹痛、噁心、嘔吐、腹瀉、便秘、脫水。
 
懷孕分級： Ｃ
 
交互作用： 果汁：由於果汁的酸性會減少 Sacrosidase 的活性，故須避免使用果汁稀釋，而改以冷水、牛奶或嬰兒食品來稀釋。
 
注意事項：
1. 於初次服用時，為避免病患發生嚴重之過敏反應，建議病患於醫療院所內服用初劑量。
2. 病患於日常飲食須限制澱粉的攝取。
3. 糖尿病之病患於服用 sacrosidase 時須特別注意。
4. 於服用 sacrosidase 時，可將 sacrosidase 加於冷水或牛奶中，但避免將該藥加熱或熱飲中，以避免高溫的破壞。
5. 病患於平常忘記服藥時，不須補服該劑量，僅於下次用餐時再服用 sacrosidase 即可。
 
用法用量：
1. 成人：體重超過 15 公斤 者，於每次用餐或點心時，服用 17000 IU 的 sacrosidase ( 相當於 2 毫克及 44 滴之溶液 ) ，將該劑量於用餐前及用餐後服用完畢即可。
2. 小孩：體重低於 15 公斤 者，於每次用餐或點心時，服用 8500 IU 的 sacrosidase ( 相當於 1 毫克及 22 滴之溶液 ) ， 體重超過 15 公斤 者，於每次用餐或點心時，服用 17000 IU 的 sacrosidase ( 相當於 2 毫克及 44 滴之溶液 ) ，將該劑量於用餐前及用餐後服用完畢即可。
 
保存：
由於 sacrosidase 開封後易滋生細菌，故建議 sacrosidase 於開封後須於 2 ℃ 至 8 ℃ 內避光保存，約可保存四週，另外若置於 4°C 內可以保存 6 個月。
 
廠商： 
•  藥　商： 科懋生物科技股份有限公司

SUCRAID-sacrosidase solution
QOL Medical, LLC
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SUCRAID® (sacrosidase) oral solution:

DESCRIPTION
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).

CHEMISTRY
SUCRAID is a pale yellow, 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. 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 glycosolated 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).

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 also contains 50% glycerol (w/w) in an aqueous solution. 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.

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 > 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.

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.

INDICATIONS AND USAGE
SUCRAID (sacrosidase) oral solution is indicated as oral replacement therapy of the genetically determined sucrase deficiency, which is part of congenital sucrase-isomaltase deficiency. (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’ 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. Patients should be instructed 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.

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

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. However, SUCRAID should not be reconstituted or consumed with fruit juice, since its 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 mutogenic potential have not been performed.

PREGNANCY:
Teratogenic effects. Pregnancy Category C. 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
Over dosage with SUCRAID has not been reported.

DOSAGE AND ADMINISTRATION
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 SUCRAID container 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 SUCRAID because heating is likely to decrease potency. SUCRAID should 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 SUCRAID container tip).

HOW SUPPLIED
SUCRAID is 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). Discard four weeks after first opening due to the potential for bacterial growth. Protect from heat and light.