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治療オプション:
Militian Inessa Mesropovna 、薬局による医学的評価、 最終更新日:08.04.2022
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同じ成分を持つトップ20の薬:
PANCREAZE(パンクレリパーゼ)は、 ⁇ 胞性線維症または他の状態による外分 ⁇ 不全の治療に適応されます。.
LipaCreon(パンクレリパーゼ)は、 ⁇ 胞性線維症または他の状態による外分 ⁇ 不全の治療に適応されます。.
投与量。
PANCREAZEは他の ⁇ 臓製品と互換性がありません。.
PANCREAZEは経口投与されます。. 治療は最低推奨用量で開始し、徐々に増やす必要があります。. PANCREAZEの投与量は、臨床症状、存在する脂肪質の程度、および食事の脂肪含有量に基づいて個別化する必要があります(参照)。 以下の投与量の制限。).
⁇ 酵素補充療法の投与量の推奨は、 ⁇ 胞性線維症財団コンセンサス会議に続いて発表されました。.1,2,3。 PANCREAZEは、次の段落で提供される会議の推奨事項と一致する方法で管理する必要があります。. 患者は、脂肪摂取ベースまたは実際の体重ベースの投与計画で投与される場合があります。.
幼児(最大12か月)。
乳児には、120 mLの調合乳あたり、または授乳ごとに2,000〜4,000リパーゼ単位を与えることができます。. 投与前にパンクレアゼカプセルの内容物を調合乳または母乳に直接混ぜないでください。.
12か月以上4年未満の子供。
酵素投与は、4歳未満の子供には1,000リパーゼ単位/ kg体重/食から、最大2,500リパーゼ単位/ kg体重/食から開始する必要があります。 (または1日あたり10,000リパーゼ単位/ kg体重以下。) または1日あたり4,000リパーゼ単位/ g脂肪未満が摂取されます。.
4歳児および成人。
酵素投与は、4歳以上の場合、食事あたり500リパーゼ単位/ kg体重から、食事あたり最大2,500リパーゼ単位/ kg体重まで開始する必要があります。 (または1日あたり10,000リパーゼ単位/ kg体重以下。) または1日あたり4,000リパーゼ単位/ g脂肪未満が摂取されます。.
通常、個別化されたフルミールの処方されたパンクリーズ用量の半分は、各スナックと一緒に投与する必要があります。. 1日の総投与量は、約3回の食事と1日あたり2〜3回の軽食を反映する必要があります。.
高齢の患者では体重が多いが体重1キログラムあたりの脂肪摂取量が少ない傾向があるため、リパーゼ単位/食事あたりの体重kgとして表される酵素用量を減らす必要があります。.
投与の制限。
投与量は、 ⁇ 胞性線維症財団コンセンサス会議ガイドラインで規定されている推奨最大投与量を超えてはなりません。.1,2,3。
脂肪症の症状や兆候が続く場合は、医療専門家が投与量を増やすことができます。. 患者は自分で投与量を増やさないように指示されるべきです。. 酵素への反応には個人間の大きなばらつきがあります。したがって、さまざまな用量が推奨されます。. 投与量の変更には、数日間の調整期間が必要になる場合があります。. 用量が食事あたり2,500リパーゼ単位/ kg体重を超える場合は、さらに調査する必要があります。.
食事あたり2,500リパーゼ単位/ kg体重を超える用量。 (または1日あたり10,000リパーゼ単位/ kg体重を超える。) 注意深く使用し、脂肪吸収係数が大幅に改善されたことを示す3日間の ⁇ 便脂肪測定で有効であると文書化されている場合にのみ使用してください。. 12歳未満の ⁇ 胞性線維症の子供では、6,000リパーゼ単位/ kg体重/食事あたりの用量が、結腸管狭 ⁇ と関連しており、結腸症の発症を示します。. 現在、6,000リパーゼ単位/ kg体重/食事よりも高い用量を受けている患者を検査し、用量を直ちに減らすか、より低い範囲まで滴定します。.
管理。
PANCREAZEは常に医療専門家の処方どおりに服用する必要があります。.
幼児(最大12か月)。
PANCREAZEは、各授乳の直前に、120 mLの処方あたり、または授乳ごとに2,000〜4,000リパーゼ単位の用量を使用して乳児に投与する必要があります。. カプセルの内容物は、pHが4.5以下の少量の酸性ソフトフードに振りかけることができます(例:.、アップルソース)、15分以内に乳児に与えられます。. カプセルの内容物は口に直接投与することもできます。. 投与後には母乳または調合乳を併用する必要があります。. カプセルの内容物は、効能が低下する可能性があるため、処方または母乳に直接混合しないでください。. 口腔粘膜の刺激を避けるために、PANCREAZEが口内で押しつぶされたり、噛まれたり、保持されたりしないように注意する必要があります。.
子供と大人。
PANCREAZEは、十分な水分を補給して、食事やスナックの間に服用する必要があります。. PANCREAZEカプセルとカプセルの内容物は、押しつぶしたり噛んだりしないでください。. カプセルは丸ごと飲み込む必要があります。.
無傷のカプセルを飲み込むことができない患者の場合、カプセルを注意深く開け、pHが4.5以下の少量の酸性ソフトフードに内容物を振りかけることができます(例:.、アップルソース)。. PANCREAZE-soft食品混合物は、粉砕したり噛んだりせずにすぐに飲み込み、その後、水またはジュースを入れて完全に摂取する必要があります。. 口の中に薬物が保持されないように注意する必要があります。.
投与量。
LipaCreonは他の ⁇ 臓製品と互換性がありません。.
LipaCreonは経口投与されます。. 治療は最低推奨用量で開始し、徐々に増やす必要があります。. LipaCreonの投与量は、臨床症状、存在する脂肪質の程度、および食事の脂肪含有量に基づいて個別化する必要があります(参照)。 以下の投与量の制限。).
⁇ 酵素補充療法の投与量の推奨は、 ⁇ 胞性線維症財団コンセンサス会議に続いて発表されました。.1,2,3。 LipaCreonは、次の段落で提供される会議の推奨事項と一致する方法で管理する必要があります。. 患者は、脂肪摂取ベースまたは実際の体重ベースの投与計画で投与される場合があります。.
幼児(最大12か月)。
乳児には、120 mLの調合乳あたり、または授乳ごとに2,000〜4,000リパーゼ単位を与えることができます。. 投与前に、LipaCreonカプセルの内容物を調合乳または母乳に直接混ぜないでください。.
12か月以上4年未満の子供。
酵素投与は、4歳未満の子供には1,000リパーゼ単位/ kg体重/食から、最大2,500リパーゼ単位/ kg体重/食から開始する必要があります。 (または1日あたり10,000リパーゼ単位/ kg体重以下。) または1日あたり4,000リパーゼ単位/ g脂肪未満が摂取されます。.
4歳児および成人。
酵素投与は、4歳以上の場合、食事あたり500リパーゼ単位/ kg体重から、食事あたり最大2,500リパーゼ単位/ kg体重まで開始する必要があります。 (または1日あたり10,000リパーゼ単位/ kg体重以下。) または1日あたり4,000リパーゼ単位/ g脂肪未満が摂取されます。.
通常、個別化されたフルミールの処方されたLipaCreon用量の半分は、各スナックと一緒に投与する必要があります。. 1日の総投与量は、約3回の食事と1日あたり2〜3回の軽食を反映する必要があります。.
高齢の患者では体重が多いが体重1キログラムあたりの脂肪摂取量が少ない傾向があるため、リパーゼ単位/食事あたりの体重kgとして表される酵素用量を減らす必要があります。.
投与の制限。
投与量は、 ⁇ 胞性線維症財団コンセンサス会議ガイドラインで規定されている推奨最大投与量を超えてはなりません。.1,2,3。
脂肪症の症状や兆候が続く場合は、医療専門家が投与量を増やすことができます。. 患者は自分で投与量を増やさないように指示されるべきです。. 酵素への反応には個人間の大きなばらつきがあります。したがって、さまざまな用量が推奨されます。. 投与量の変更には、数日間の調整期間が必要になる場合があります。. 用量が食事あたり2,500リパーゼ単位/ kg体重を超える場合は、さらに調査する必要があります。.
食事あたり2,500リパーゼ単位/ kg体重を超える用量。 (または1日あたり10,000リパーゼ単位/ kg体重を超える。) 注意深く使用し、脂肪吸収係数が大幅に改善されたことを示す3日間の ⁇ 便脂肪測定で有効であると文書化されている場合にのみ使用してください。. 12歳未満の ⁇ 胞性線維症の子供では、6,000リパーゼ単位/ kg体重/食事あたりの用量が、結腸管狭 ⁇ と関連しており、結腸症の発症を示します。. 現在、6,000リパーゼ単位/ kg体重/食事よりも高い用量を受けている患者を検査し、用量を直ちに減らすか、より低い範囲まで滴定します。.
管理。
LipaCreonは常に医療専門家の処方どおりに服用する必要があります。.
幼児(最大12か月)。
LipaCreonは、各授乳の直前に、120 mLの処方あたり、または授乳ごとに2,000〜4,000リパーゼ単位の用量を使用して乳児に投与する必要があります。. カプセルの内容物は、pHが4.5以下の少量の酸性ソフトフードに振りかけることができます(例:.、アップルソース)、15分以内に乳児に与えられます。. カプセルの内容物は口に直接投与することもできます。. 投与後には母乳または調合乳を併用する必要があります。. カプセルの内容物は、効能が低下する可能性があるため、処方または母乳に直接混合しないでください。. 口腔粘膜の刺激を避けるために、LipaCreonが口の中で押しつぶされたり、噛まれたり、保持されたりしないように注意する必要があります。.
子供と大人。
LipaCreonは、十分な水分を摂取して、食事や軽食の間に服用する必要があります。. LipaCreonカプセルとカプセルの内容物は、押しつぶしたり噛んだりしないでください。. カプセルは丸ごと飲み込む必要があります。.
無傷のカプセルを飲み込むことができない患者の場合、カプセルを注意深く開け、pHが4.5以下の少量の酸性ソフトフードに内容物を振りかけることができます(例:.、アップルソース)。. LipaCreon-soft食品混合物は、粉砕または噛むことなくすぐに飲み込み、その後、水またはジュースを入れて完全に摂取する必要があります。. 口の中に薬物が保持されないように注意する必要があります。.
無し。.
WARNINGS
Included as part of the PRECAUTIONS section.
PRECAUTIONS
Fibrosing Colonopathy
Fibrosing colonopathy has been reported following treatment with different pancreatic enzyme products.4,5 Fibrosing colonopathy is a rare serious adverse reaction initially described in association with high-dose pancreatic enzyme use, usually with use over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis. The underlying mechanism of fibrosing colonopathy remains unknown. Doses of pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with colonic strictures in children less than 12 years of age.1 Patients with fibrosing colonopathy should be closely monitored because some patients may be at risk of progressing to stricture formation. It is uncertain whether regression of fibrosing colonopathy occurs.1 It is generally recommended, unless clinically indicated, that enzyme doses should be less than 2,500 lipase units/kg of body weight per meal (or less than 10,000 lipase units/kg of body weight per day) or less than 4,000 lipase units/g fat ingested per day.
Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorption. Patients receiving higher doses than 6,000 lipase units/kg of body weight per meal should be examined and the dosage either immediately decreased or titrated downward to a lower range.
Potential for Irritation to Oral Mucosa
Care should be taken to ensure that no drug is retained in the mouth. PANCREAZE should not be crushed or chewed or mixed in foods having a pH greater than 4.5. These actions can disrupt the protective enteric coating resulting in early release of enzymes, irritation of oral mucosa, and/or loss of enzyme activity. For patients who are unable to swallow intact capsules, the capsules may be carefully opened and the contents sprinkled to a small amount of acidic soft food with a pH of 4.5 or less, such as applesauce. The PANCREAZE-soft food mixture should be swallowed immediately and followed with water or juice to ensure complete ingestion.
Potential For Risk Of Hyperuricemia
Caution should be exercised when prescribing PANCREAZE to patients with gout, renal impairment, or hyperuricemia. Porcine-derived pancreatic enzyme products contain purines that may increase blood uric acid levels.
Potential Viral Exposure From The Product Source
PANCREAZE is sourced from pancreatic tissue from swine used for food consumption. Although the risk that PANCREAZE will transmit an infectious agent to humans has been reduced by testing for certain viruses during manufacturing and by inactivating certain viruses during manufacturing, there is a theoretical risk for transmission of viral disease, including diseases caused by novel or unidentified viruses. Thus, the presence of porcine viruses that might infect humans cannot be definitely excluded. However, no cases of transmission of an infectious illness associated with the use of porcine pancreatic extracts have been reported.
Allergic Reactions
Caution should be exercised when administering pancrelipase to a patient with a known allergy to proteins of porcine origin. Rarely, severe allergic reactions including anaphylaxis, asthma, hives, and pruritus, have been reported with other pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase). The risks and benefits of continued PANCREAZE treatment in patients with severe allergy should be taken into consideration with the overall clinical needs of the patient.
Patient Counseling Information
See Medication Guide
Dosing And Administration
- Instruct patients and caregivers that PANCREAZE should only be taken as directed by their healthcare professional. Patients should be advised that the total daily dose should not exceed 10,000 lipase units/kg body weight/day unless clinically indicated. This needs to be especially emphasized for patients eating multiple snacks and meals per day. Patients should be informed that if a dose is missed, the next dose should be taken with the next meal or snack as directed. Doses should not be doubled.
- Instruct patients and caregivers that PANCREAZE should always be taken with food. Patients should be advised that PANCREAZE delayed-release capsules and the capsule contents must not be crushed or chewed as doing so could cause early release of enzymes and/or loss of enzymatic activity. Patients should swallow the intact capsules with adequate amounts of liquid at mealtimes. If necessary, the capsule contents can also be sprinkled on soft acidic foods..
- Instruct patients to notify their healthcare professional if they are pregnant or are thinking of becoming pregnant during treatment with PANCREAZE.
- Instruct patients to notify their healthcare professional if they are breastfeeding or are thinking of breastfeeding during treatment with PANCREAZE.
Fibrosing Colonopathy
Advise patients and caregivers to follow dosing instructions carefully, as doses of pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal (10,000 lipase units/kg of body weight/day) have been associated with colonic strictures in children below the age of 12 years.
Allergic Reactions
Advise patients and caregivers to contact their healthcare professional immediately if allergic reactions to PANCREAZE develop.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Carcinogenicity, genetic toxicology, and animal fertility studies have not been performed with pancrelipase.
Use In Specific Populations
Pregnancy
Teratogenic effects
Pregnancy Category C: Animal reproduction studies have not been conducted with pancrelipase. It is not known whether pancrelipase can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. PANCREAZE should be given to a pregnant woman only if clearly needed. The risk and benefit of pancrelipase should be considered in the context of the need to provide adequate nutritional support to a pregnant woman with exocrine pancreatic insufficiency. Adequate caloric intake during pregnancy is important for normal maternal weight gain and fetal growth. Reduced maternal weight gain and malnutrition can be associated with adverse pregnancy outcomes.
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when PANCREAZE is administered to a nursing woman. The risk and benefit of pancrelipase should be considered in the context of the need to provide adequate nutritional support to a nursing mother with exocrine pancreatic insufficiency.
Pediatric Use
The short-term safety and effectiveness of PANCREAZE were assessed in two clinical studies in pediatric patients with EPI due to CF; one study included patients ages 6 to 30 months, and the other included patients ages 8 years to 17 years.
Study 1 was a randomized, double-blind, placebo-controlled study in 40 patients, 14 of whom were pediatric patients, including 7 children aged 8 to 11 years, and 7 adolescents aged 12 to 17 years. The safety and efficacy in pediatric patients in this study were similar to adult patients.
Study 2 was a randomized, investigator-blinded, dose-ranging study in 17 pediatric patients aged 6 to 30 months. When patient regimen was switched from their usual PEP regimen to PANCREAZE, patients showed similar control of their fat malabsorption.
The safety and efficacy of pancreatic enzyme products with different formulations of pancrelipase consisting of the same active ingredients (lipases, proteases, and amylases) for treatment of children with exocrine pancreatic insufficiency due to cystic fibrosis has been described in the medical literature and through clinical experience.
Dosing of pediatric patients should be in accordance with recommended guidance from the Cystic Fibrosis Foundation Consensus Conferences. Doses of other pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with fibrosing colonopathy and colonic strictures in children less than 12 years of age.
REFERENCES
4.Smyth RL, Ashby D, O'Hea U, et al. Fibrosing colonopathy in cystic fibrosis: results of a case-control study. Lancet. 1995; 346: 1247-1251.
5.FitzSimmons SC, Burkhart GA, Borowitz DS, et al. High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis. New England Journal of Medicine. 1997; 336: 1283-1289.
WARNINGS
Included as part of the PRECAUTIONS section.
PRECAUTIONS
Fibrosing Colonopathy
Fibrosing colonopathy has been reported following treatment with different pancreatic enzyme products.4,5 Fibrosing colonopathy is a rare serious adverse reaction initially described in association with high-dose pancreatic enzyme use, usually with use over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis. The underlying mechanism of fibrosing colonopathy remains unknown. Doses of pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with colonic strictures in children less than 12 years of age.1 Patients with fibrosing colonopathy should be closely monitored because some patients may be at risk of progressing to stricture formation. It is uncertain whether regression of fibrosing colonopathy occurs.1 It is generally recommended, unless clinically indicated, that enzyme doses should be less than 2,500 lipase units/kg of body weight per meal (or less than 10,000 lipase units/kg of body weight per day) or less than 4,000 lipase units/g fat ingested per day.
Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorption. Patients receiving higher doses than 6,000 lipase units/kg of body weight per meal should be examined and the dosage either immediately decreased or titrated downward to a lower range.
Potential for Irritation to Oral Mucosa
Care should be taken to ensure that no drug is retained in the mouth. LipaCreon should not be crushed or chewed or mixed in foods having a pH greater than 4.5. These actions can disrupt the protective enteric coating resulting in early release of enzymes, irritation of oral mucosa, and/or loss of enzyme activity. For patients who are unable to swallow intact capsules, the capsules may be carefully opened and the contents sprinkled to a small amount of acidic soft food with a pH of 4.5 or less, such as applesauce. The LipaCreon-soft food mixture should be swallowed immediately and followed with water or juice to ensure complete ingestion.
Potential For Risk Of Hyperuricemia
Caution should be exercised when prescribing LipaCreon to patients with gout, renal impairment, or hyperuricemia. Porcine-derived pancreatic enzyme products contain purines that may increase blood uric acid levels.
Potential Viral Exposure From The Product Source
LipaCreon is sourced from pancreatic tissue from swine used for food consumption. Although the risk that LipaCreon will transmit an infectious agent to humans has been reduced by testing for certain viruses during manufacturing and by inactivating certain viruses during manufacturing, there is a theoretical risk for transmission of viral disease, including diseases caused by novel or unidentified viruses. Thus, the presence of porcine viruses that might infect humans cannot be definitely excluded. However, no cases of transmission of an infectious illness associated with the use of porcine pancreatic extracts have been reported.
Allergic Reactions
Caution should be exercised when administering pancrelipase to a patient with a known allergy to proteins of porcine origin. Rarely, severe allergic reactions including anaphylaxis, asthma, hives, and pruritus, have been reported with other pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase). The risks and benefits of continued LipaCreon treatment in patients with severe allergy should be taken into consideration with the overall clinical needs of the patient.
Patient Counseling Information
See Medication Guide
Dosing And Administration
- Instruct patients and caregivers that LipaCreon should only be taken as directed by their healthcare professional. Patients should be advised that the total daily dose should not exceed 10,000 lipase units/kg body weight/day unless clinically indicated. This needs to be especially emphasized for patients eating multiple snacks and meals per day. Patients should be informed that if a dose is missed, the next dose should be taken with the next meal or snack as directed. Doses should not be doubled.
- Instruct patients and caregivers that LipaCreon should always be taken with food. Patients should be advised that LipaCreon delayed-release capsules and the capsule contents must not be crushed or chewed as doing so could cause early release of enzymes and/or loss of enzymatic activity. Patients should swallow the intact capsules with adequate amounts of liquid at mealtimes. If necessary, the capsule contents can also be sprinkled on soft acidic foods..
- Instruct patients to notify their healthcare professional if they are pregnant or are thinking of becoming pregnant during treatment with LipaCreon.
- Instruct patients to notify their healthcare professional if they are breastfeeding or are thinking of breastfeeding during treatment with LipaCreon.
Fibrosing Colonopathy
Advise patients and caregivers to follow dosing instructions carefully, as doses of pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal (10,000 lipase units/kg of body weight/day) have been associated with colonic strictures in children below the age of 12 years.
Allergic Reactions
Advise patients and caregivers to contact their healthcare professional immediately if allergic reactions to LipaCreon develop.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Carcinogenicity, genetic toxicology, and animal fertility studies have not been performed with pancrelipase.
Use In Specific Populations
Pregnancy
Teratogenic effects
Pregnancy Category C: Animal reproduction studies have not been conducted with pancrelipase. It is not known whether pancrelipase can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. LipaCreon should be given to a pregnant woman only if clearly needed. The risk and benefit of pancrelipase should be considered in the context of the need to provide adequate nutritional support to a pregnant woman with exocrine pancreatic insufficiency. Adequate caloric intake during pregnancy is important for normal maternal weight gain and fetal growth. Reduced maternal weight gain and malnutrition can be associated with adverse pregnancy outcomes.
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when LipaCreon is administered to a nursing woman. The risk and benefit of pancrelipase should be considered in the context of the need to provide adequate nutritional support to a nursing mother with exocrine pancreatic insufficiency.
Pediatric Use
The short-term safety and effectiveness of LipaCreon were assessed in two clinical studies in pediatric patients with EPI due to CF; one study included patients ages 6 to 30 months, and the other included patients ages 8 years to 17 years.
Study 1 was a randomized, double-blind, placebo-controlled study in 40 patients, 14 of whom were pediatric patients, including 7 children aged 8 to 11 years, and 7 adolescents aged 12 to 17 years. The safety and efficacy in pediatric patients in this study were similar to adult patients.
Study 2 was a randomized, investigator-blinded, dose-ranging study in 17 pediatric patients aged 6 to 30 months. When patient regimen was switched from their usual PEP regimen to LipaCreon, patients showed similar control of their fat malabsorption.
The safety and efficacy of pancreatic enzyme products with different formulations of pancrelipase consisting of the same active ingredients (lipases, proteases, and amylases) for treatment of children with exocrine pancreatic insufficiency due to cystic fibrosis has been described in the medical literature and through clinical experience.
Dosing of pediatric patients should be in accordance with recommended guidance from the Cystic Fibrosis Foundation Consensus Conferences. Doses of other pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with fibrosing colonopathy and colonic strictures in children less than 12 years of age.
REFERENCES
4.Smyth RL, Ashby D, O'Hea U, et al. Fibrosing colonopathy in cystic fibrosis: results of a case-control study. Lancet. 1995; 346: 1247-1251.
5.FitzSimmons SC, Burkhart GA, Borowitz DS, et al. High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis. New England Journal of Medicine. 1997; 336: 1283-1289.
The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) include fibrosing colonopathy, hyperuricemia and allergic reactions
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The short-term safety of PANCREAZE was assessed in two clinical trials conducted in 57 patients with exocrine pancreatic insufficiency (EPI) due to CF. Study 1 was conducted in 40 patients, ages 8 years to 57 years; Study 2 was conducted in 17 patients, ages 6 months to 30 months. In Study 1, PANCREAZE was administered in a dose of approximately 6,300 lipase units per kilogram per day for lengths of treatment ranging from 8 to 26 days; in Study 2, PANCREAZE was administered in four treatment arms (doses of 1,375, 2,875, 4,735, and 5,938 lipase units per kilogram per day) for lengths of treatment ranging from 6 to 11 days. The population was nearly evenly distributed in gender, and approximately 96% of patients were Caucasian.
Study 1 was a randomized, double-blind, placebo-controlled study of 40 patients, ages 8 to 57 years, with EPI due to CF. In this study, patients received PANCREAZE at individually titrated doses (not to exceed 2,500 lipase units per kilogram per meal) for 14 days, followed by randomization to PANCREAZE or matching placebo for 7 days of treatment. The mean exposure to PANCREAZE during this study, including titration period and randomized withdrawal period, was 18 days.
The incidence of adverse events (regardless of causality) was higher during placebo treatment (60%) than during PANCREAZE treatment (40%). The most common adverse events reported during the study were gastrointestinal complaints, which were reported more commonly during placebo treatment (55%) than during PANCREAZE treatment (30%). The type and incidence of adverse events were similar in children (8 to 11 years), adolescents (12 to 17 years), and adults (greater than 18 years).
Table 1 enumerates treatment-emergent adverse events that occurred in at least 2 patients (greater than or equal to 10%) treated with either PANCREAZE or placebo in Study 1. Adverse events were classified by Medical Dictionary for Regulatory Activities (MedDRA) terminology.
Table 1: Treatment-Emergent Adverse Events Occurring in at Least 2 Patients (Greater Than or Equal to 10%) in Either Treatment Group of the Placebo-Controlled, Clinical Study of PANCREAZE
MedDRA Primary System Organ Class Preferred Term | PANCREAZE (N=20) n (%) | Placebo (N=20) n (%) |
Gastrointestinal Disorders | ||
Abdominal pain | 2 (10%) | 3 (15%) |
Abdominal pain upper | 1 (5%) | 3 (15%) |
Flatulence | 1 (5%) | 3 (15%) |
Diarrhea | 0 (0%) | 4 (20%) |
Abnormal feces | 0 (0%) | 3 (15%) |
General Disorders and Administration Site Conditions | ||
Fatigue | 0 (0%) | 2 (10%) |
Study 2 was a randomized, investigator-blinded, dose-ranging study of 17 patients, ages 6 months to 30 months, with EPI due to CF. All patients were transitioned from their usual PEP treatment to PANCREAZE at 375 lipase units per kilogram body weight per meal for a 6 day run-in period. Patients were then randomized to receive PANCREAZE at one of four doses (375, 750, 1,125, and 1,500 lipase units per kilogram body weight per meal) for 5 days. Adverse events were collected on patient diary entries and at each study visit.
The most commonly reported adverse events were gastrointestinal, including diarrhea and vomiting, and were similar in type and frequency across treatment arms and to those reported in the double-blind, placebo-controlled trial (Study 1).
Postmarketing Experience
Postmarketing data for PANCREAZE have been available since 1988. The safety data are similar to those described below.
Delayed-and immediate-release pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase) have been used for the treatment of patients with exocrine pancreatic insufficiency due to cystic fibrosis and other conditions, such as chronic pancreatitis. The long-term safety profile of these products has been described in the medical literature. The most serious adverse events included fibrosing colonopathy, distal intestinal obstruction syndrome (DIOS), recurrence of pre-existing carcinoma, and severe allergic reactions including anaphylaxis, asthma, hives, and pruritus. The most commonly reported adverse events were gastrointestinal disorders, including abdominal pain, diarrhea, flatulence, constipation and nausea, and skin disorders including pruritus, urticaria and rash. In general, these products have a well-defined and favorable risk-benefit profile in exocrine pancreatic insufficiency.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) include fibrosing colonopathy, hyperuricemia and allergic reactions
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The short-term safety of LipaCreon was assessed in two clinical trials conducted in 57 patients with exocrine pancreatic insufficiency (EPI) due to CF. Study 1 was conducted in 40 patients, ages 8 years to 57 years; Study 2 was conducted in 17 patients, ages 6 months to 30 months. In Study 1, LipaCreon was administered in a dose of approximately 6,300 lipase units per kilogram per day for lengths of treatment ranging from 8 to 26 days; in Study 2, LipaCreon was administered in four treatment arms (doses of 1,375, 2,875, 4,735, and 5,938 lipase units per kilogram per day) for lengths of treatment ranging from 6 to 11 days. The population was nearly evenly distributed in gender, and approximately 96% of patients were Caucasian.
Study 1 was a randomized, double-blind, placebo-controlled study of 40 patients, ages 8 to 57 years, with EPI due to CF. In this study, patients received LipaCreon at individually titrated doses (not to exceed 2,500 lipase units per kilogram per meal) for 14 days, followed by randomization to LipaCreon or matching placebo for 7 days of treatment. The mean exposure to LipaCreon during this study, including titration period and randomized withdrawal period, was 18 days.
The incidence of adverse events (regardless of causality) was higher during placebo treatment (60%) than during LipaCreon treatment (40%). The most common adverse events reported during the study were gastrointestinal complaints, which were reported more commonly during placebo treatment (55%) than during LipaCreon treatment (30%). The type and incidence of adverse events were similar in children (8 to 11 years), adolescents (12 to 17 years), and adults (greater than 18 years).
Table 1 enumerates treatment-emergent adverse events that occurred in at least 2 patients (greater than or equal to 10%) treated with either LipaCreon or placebo in Study 1. Adverse events were classified by Medical Dictionary for Regulatory Activities (MedDRA) terminology.
Table 1: Treatment-Emergent Adverse Events Occurring in at Least 2 Patients (Greater Than or Equal to 10%) in Either Treatment Group of the Placebo-Controlled, Clinical Study of LipaCreon
MedDRA Primary System Organ Class Preferred Term | LipaCreon (N=20) n (%) | Placebo (N=20) n (%) |
Gastrointestinal Disorders | ||
Abdominal pain | 2 (10%) | 3 (15%) |
Abdominal pain upper | 1 (5%) | 3 (15%) |
Flatulence | 1 (5%) | 3 (15%) |
Diarrhea | 0 (0%) | 4 (20%) |
Abnormal feces | 0 (0%) | 3 (15%) |
General Disorders and Administration Site Conditions | ||
Fatigue | 0 (0%) | 2 (10%) |
Study 2 was a randomized, investigator-blinded, dose-ranging study of 17 patients, ages 6 months to 30 months, with EPI due to CF. All patients were transitioned from their usual PEP treatment to LipaCreon at 375 lipase units per kilogram body weight per meal for a 6 day run-in period. Patients were then randomized to receive LipaCreon at one of four doses (375, 750, 1,125, and 1,500 lipase units per kilogram body weight per meal) for 5 days. Adverse events were collected on patient diary entries and at each study visit.
The most commonly reported adverse events were gastrointestinal, including diarrhea and vomiting, and were similar in type and frequency across treatment arms and to those reported in the double-blind, placebo-controlled trial (Study 1).
Postmarketing Experience
Postmarketing data for LipaCreon have been available since 1988. The safety data are similar to those described below.
Delayed-and immediate-release pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase) have been used for the treatment of patients with exocrine pancreatic insufficiency due to cystic fibrosis and other conditions, such as chronic pancreatitis. The long-term safety profile of these products has been described in the medical literature. The most serious adverse events included fibrosing colonopathy, distal intestinal obstruction syndrome (DIOS), recurrence of pre-existing carcinoma, and severe allergic reactions including anaphylaxis, asthma, hives, and pruritus. The most commonly reported adverse events were gastrointestinal disorders, including abdominal pain, diarrhea, flatulence, constipation and nausea, and skin disorders including pruritus, urticaria and rash. In general, these products have a well-defined and favorable risk-benefit profile in exocrine pancreatic insufficiency.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
研究1では、10歳の患者に、非盲検および無作為化離脱期間中、1日あたり1キログラムあたり12,399リパーゼ単位のPANCREAZE用量を投与しました。. 患者は両方の研究期間を通じて軽度の腹痛を経験しました。. 研究終了時の異常な化学データには、アスパラギン酸アミノトランスフェラーゼ(AST)、アラニンアミノトランスフェラーゼ(ALT)、および血清リン酸塩の穏やかな上昇が含まれていました。. 研究の終わりの異常な血液学データには、ヘマトクリットの穏やかな上昇が含まれていました。. 尿検査または尿酸の分析による異常は認められなかった。.
慢性的な高用量の ⁇ 酵素製品は、線維性結腸症および結腸狭 ⁇ と関連しています。. 高用量の ⁇ 酵素製品は高尿酸血症および高尿酸血症と関連しており、高尿酸血症、痛風、または腎障害の病歴のある患者には注意して使用する必要があります。.
研究1では、10歳の患者に、非盲検および無作為化離脱期間中、1日あたり1キログラムあたり12,399リパーゼ単位のLipaCreon用量を投与しました。. 患者は両方の研究期間を通じて軽度の腹痛を経験しました。. 研究終了時の異常な化学データには、アスパラギン酸アミノトランスフェラーゼ(AST)、アラニンアミノトランスフェラーゼ(ALT)、および血清リン酸塩の穏やかな上昇が含まれていました。. 研究の終わりの異常な血液学データには、ヘマトクリットの穏やかな上昇が含まれていました。. 尿検査または尿酸の分析による異常は認められなかった。.
慢性的な高用量の ⁇ 酵素製品は、線維性結腸症および結腸狭 ⁇ と関連しています。. 高用量の ⁇ 酵素製品は高尿酸血症および高尿酸血症と関連しており、高尿酸血症、痛風、または腎障害の病歴のある患者には注意して使用する必要があります。.
PANCREAZEの ⁇ 酵素は腸溶性コーティングされており、胃酸の破壊や不活化を最小限に抑えます。. PANCREAZEは、5.5を超えるpHでほとんどの酵素をin vivoで放出すると予想されます。. ⁇ 酵素は、消化管からかなりの量で吸収されません。.
LipaCreonの ⁇ 酵素は腸溶性コーティングされており、胃酸の破壊や不活化を最小限に抑えます。. LipaCreonは、5.5を超えるpHでほとんどの酵素をin vivoで放出すると予想されます。. ⁇ 酵素は、消化管からかなりの量で吸収されません。.