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培加帕加司
【英文名】Pegaspargase（Oncaspar）
【结 构
式】本品是L-天门冬酰胺酶的修型（来自大肠杆菌）是由单甲氧基聚乙烯乙二醇（PEG）的共价结合单位产生的酶，分子量约5000。
【作用特点】某些肿瘤细胞本身不能合成L-天门冬酰胺（它是合成蛋白质必需的氨基酸）。本品可使进入肿瘤L-天门冬酰胺水解，肿瘤细胞得不到L-天门冬酰胺，而影响其蛋白质的合成，最终使肿瘤细胞的增长繁殖受到抑制。正常组织细胞自身有合成L-天门冬酰胺的能力，不受本品的影响。本品的抗原性比xxL-天门冬酰胺酶低。血浆半衰期比xx型显著延长。
【功能主治】本品适用于急性淋巴细胞白血病（ALL），这种病人xx中需要L-天门冬酰胺酶，若已对xxL-天门冬酰胺酶产生过敏，可试用本品。一般本品与其它化疗xx并用，如长春新碱、甲氨喋吟，阿糖胞苷，柔红霉素和阿霉素。只有在确认多种化疗xx不适用时才可单用本品。本品的疗效已证实与xxL-天门冬酰胺酶类似。对xxL-天门冬酰胺酶十分严重过敏反应的病人，也能耐受本品。本品也已在非何杰金淋巴瘤和急性骨髓性白血病被评价。然而目前还不是指定的适应症。
【用法用量】本品可肌内注射或静脉滴注。以肌内注射的过敏性或其它不良反应发生率较低。本品每14日1次，2500IU／m2。儿童体表面积小于0.6m2，剂量按每14日82.5IU／kg。本品的作用持续时间长，比用xxL-天门冬酰胺酶的剂量小，给药次数少。本品肌注，单次给药容量应限于2ml，如果＞2ml，应使用多处部位注射。静脉给药时，本品应以100ml生理盐水或5％葡萄糖液稀释后连续滴注l～2／小时。
【注意事项】病人用药后必须严密观察1小时并做好过敏反应的急救准备。有胰腺炎病史的患者禁用本品。并应经常检查血清淀粉酶，以早期发现胰腺炎。有明显出血史的病人禁用本品。如果可能，应当避免使用可能增加出血危险的xx如华法令、肝素、潘生丁、阿斯匹林、非甾体xx药等。对肝功能不良或同时接受其它有强烈肝毒性xx的患者慎用本品。本品作用迅速，并观察到某些病人出现肿瘤溶解综合征。本品可能是接触性刺激剂，溶液必须小心处理，并带手套，必须避免吸入蒸气和接触皮肤、粘膜，尤其眼睛。如果接触，应用大量水冲洗至少15分钟。本品使用时不可振摇。
【制剂规格】注射剂：每小瓶5ml：3750IU。
【贮藏】本品须冷藏，但不可冻结。因为冻结可破坏本品的活性，若已发生冻结应废弃。
Enzon生物制药公司生产
培加帕加司
<外 文 名> Pegaspargase,Oncaspar.
<药理作用>
本品为L-天门冬酰胺酶的修型，是由单氧基聚乙二醇（PEG）的共价结合单位而产生的一种酶。在转化过程中，PEG被结合到天冬酰胺酶的百活性位点上，不影响酶的活性位点。某些肿瘤细胞本身不能合成L-天门冬酰胺，而后者是合成蛋白质所必需的氨基酸。本品可使进入肿瘤细胞内的L-天门冬酰胺水解，而影响其蛋白质合成，使肿瘤细胞的生长繁殖受到抑制。正常组织细胞自身有合成L-天门冬酰胺的能力，故不受本品的影响。
<临床应用>
主要用于急必淋巴细胞白血病。一般常与其化疗药关用，如VCR、MTX、Ara-C、DNR和ADR。
<用法用量>
肌肉注射：每2周1次，每次2500IU/m2，儿童体表面积人小于0.6m2时，剂量按每2周82.5IU/kg.
静脉滴注：剂量同上，以100ml生理盐水或5%葡萄糖液稀释后连续滴注1~2小时。
<不良反应>
（1）过敏反应：本品肌肉注射时，过敏反应发生率为xxL-天门冬酰胺酶过敏者的30%，而对xxL-天门冬酰胺酶不过敏的病人为11%。
（2）胰腺炎：约1%的患者发生胰腺炎，有时胰腺炎暴发是致命的。
（3）血栓形成：约4%的患者可发生血栓形成。
（4）可发生轻度到重度高血糖，约3%的患者需用胰岛素控制。
（5）肝功能损害：恶心、呕吐、发热不适、接触性刺激、肿瘤溶解综合征。
<禁 忌 证>
（1）有胰腺炎病史，出血史的患者禁用。
（2）肝功能不良或同时接受其他有强烈肝毒性xx的患者慎用。
<注意事项>
（1）本品的抗原性比xx的L-门冬酰胺酶低。
（2）只有在确认多种化陪xx不适用时方可使用本品。
（3）本品肌肉注射，单次给药剂量应小于2ml,若大于2ml,则应多部位注射。
（4）使用本品后，必须严格密切观察1小时，并做好处理过敏反应的各种急救药品。
（5）在使用本品过程中，应避免使用可能增加血危险的xx如肝素、潘生丁、阿斯匹林、非甾体xx药等。
（6）在xx期间，应经常检查血清淀粉酶、血糖，以尽早发现胰腺炎与高血糖症，及时处理。
（7）本品溶液必须小心处理，并带手套，必须避免吸入蒸汽和接触皮肤、粘膜，尤其是眼睛。若不慎接触，应用大量水冲洗至少15分钟。
（8）本品冷藏而不可冻结，使用时不可振荡。
<制剂规格> 注射剂：5ml/支（含本品3750国际单位）。
发布时间：2002年07月31日
Oncaspar (pegaspargase)
Vials: 750 IU/ml (5 ml)
Manufacturer: Enzon
Manufacturer's website: www.enzon.com
Indications/Dosage/Administration
Acute lymphoblastic leukemia in patients who need L-asparaginase in
their treatment regimen but who have developed hypersensitivity to
native forms of L-asparaginase: 2,500 IU/m2 IM or IV every 14 days,
alone or in addition to other chemotherapeutic agents. In children
with a BSA > 0.6 m2, give above recommended dose;
for children with a BSA < 0.6 m2, 82.5 IU/kg IM or
IV every 14 days, alone or in addition to other chemotherapeutic
agents.
Single-agent therapy: Use as a single agent only when multiagent
chemotherapy is inappropriate or if patient is refractory to other
therapy.
Combination therapy: Drug is generally used with other
chemotherapeutic agents, such as vincristine, methotrexate,
cytarabine, daunorubicin, and doxorubicin. Pegaspargase may
interfere with enzymatic detoxification of other drugs, especially
in the liver.
Maintenance: When remission is obtained, institute appropriate
maintenance therapy; mitoxantrone may be used as part of a
maintenance program.
Administration: Preferred administration route is IM because of
lower incidence of hepatotoxicity, coagulopathy, and GI and renal
disorders compared to IV route. Limit IM injection at a single
injection site to 2 ml. When using IV, give over a 1- to 2-h period
in 100 ml of sodium chloride or 5% dextrose inj through an infusion
that is already running.
Patient Monitoring
Blood: Monitor peripheral blood count and bone marrow function to
guide therapy, and determine fibrinogen, PT, and PTT, if needed.
Obtain frequent serum amylase determinations to detect early
evidence of pancreatitis. Monitor blood sugar levels during
therapy.
Liver function: If using other hepatotoxic agents, monitor patient
for liver dysfunction.
Patient instructions: Inform patients of possibility of
hypersensitivity reactions, including immediate anaphylaxis.
Instruct patients to avoid simultaneous use of other drugs that may
increase risk of bleeding; also advise patient that pegaspargase
may increase toxicity of other medications. Advise patients that
use of drug may predispose to infection, and that they should
report any adverse reactions.
General Considerations
Patient selection: Drug is indicated for treatment of patients with
acute lymphoblastic leukemia who require L-asparaginase but have
developed hypersensitivity to native forms of this drug.
Hypersensitivity: Contraindicated in patients who have had previous
serious allergic reactions (eg, generalized urticaria,
bronchospasm, laryngeal edema, hypotension, or other unacceptable
adverse reactions) to pegaspargase. Hypersensitivity reaction to
pegaspargase may occur during therapy, especially in patients with
known hypersensitivity to other forms of L-asparaginase; observe
patient for 1 h after administration with resuscitation equipment
and available antihistamines, epinephrine, oxygen, and IV
steroids.
Pancreatitis: Contraindicated in patients with pancreatitis or a
history of pancreatitis.
Blood dyscrasias: Contraindicated in patients who have had
significant hemorrhagic events associated with prior L-asparaginase
therapy. Patients are at higher than usual risk for bleeding
problems, especially when other drugs with anticoagulant properties
are used. A fall in circulating lymphoblasts that may be
accompanied by a marked rise in serum uric acid is often seen after
initiation of therapy.
Accidental contact: Avoid inhalation of vapors and contact with
skin or mucous membranes, especially the eyes. If accidental
contact occurs, wash affected area with copious amounts of water
for at least 15 min.
Immunosuppression: Drug may have immunosuppressive properties; use
may predispose patient to infection.
Hepatic or neurologic toxicity: Severe hepatic and CNS toxicity may
occur following multiagent therapy including pegaspargase.
Pregnancy: Use only if clearly needed (Pregnancy Category C).
Breast-feeding: Do not use in nursing mothers.
Pediatric use: See indications and dosage recommendations.
Adverse Reactions
The most frequent reactions are italicized. Adult patients have had
a somewhat higher incidence of known L-asparaginase toxicities,
except for hypersensitivity reactions, than have pediatric
patients.
Cardiovascular: Hypotension, tachycardia, and peripheral edema
(1-5%), endocarditis, hypertension, chest pain, and edema
(< 1%); in patients with hematologic malignancies:
chest pain, subacute bacterial endocarditis, hypertension, severe
hypotension, tachycardia.
Digestive: Nausea and/or vomiting (> 5%), abdominal
pain, anorexia, and diarrhea (1-5%), clinical pancreatitis (1%),
constipation, flatulence, GI pain, increased appetite, liver fatty
deposits, increased amylase, and weight loss (< 1%);
in patients with hematologic malignancies: pancreatitis (sometimes
fulminant and fatal), increased serum amylase and lipase, weight
loss, anorexia, constipation, decreased appetite, diarrhea,
indigestion, flatulence, gas, GI pain, mucositis, hepatomegaly,
elevated GGTP, increased appetite, mouth tenderness, severe
colitis, nausea and/or vomiting.
Hematologic: Thrombosis (4%), hyperglycemia requiring insulin
therapy (3%), decreased anticoagulant effect, disseminated
intravascular coagulation, decreased fibrinogen, hemolytic anemia,
leukopenia, pancytopenia, thrombocytopenia, increased
thromboplastin, hyperglycemia, hyperuricemia, hypoglycemia, and
hypoproteinemia (1-5%), coagulation disorder, increased coagulation
time, decreased platelet count, purpura, hyperammonemia, and
hyponatremia (< 1%); in patients with hematologic
malignancies: mild to severe hyperglycemia, hypoglycemia,
hyponatremia, hyperammonemia, hyperuricemia, hypoproteinemia,
hypoalbuminemia, hypofibrinogenemia, prolonged PT, prolonged PTT,
decreased antithrombin III, superficial deep-vein thrombosis,
sagittal sinus thrombosis, venous catheter thrombosis, atrial
thrombosis, leukopenia, agranulocytosis, pancytopenia,
thrombocytopenia, disseminated intravascular coagulation, severe
hemolytic anemia, anemia, easy bruisability, ecchymosis.
Hepatic: Increased SGPT (> 5%), jaundice, abnormal
liver function test, bilirubinemia, and increased SGOT (1-5%),
hepatomegaly (< 1%); in patients with hematologic
malignancies: jaundice, ascites, hypoalbuminemia, fatty changes in
liver, liver failure, increased SGOT, SGPT, and bilirubin (direct
and indirect).
Hypersensitivity/dermatologic: Allergic reactions (which may have
included rash, erythema, edema, pain, fever, chills, urticaria,
dyspnea, or bronchospasm)(> 5%), anaphylactic
reactions, injection site hypersensitivity, lip edema, rash,
urticaria, and injection site reaction (1-5%), petechial rash,
facial edema, lesional edema, and pruritus, (< 1%);
in patients with hematologic malignancies: acute or delayed
reactions, including acute anaphylaxis, bronchospasm, dyspnea,
urticaria, arthralgia, erythema, induration, edema, pain,
tenderness, hives, swelling, lip edema, chills, fever, skin
reactions, itching, alopecia, fever blister, purpura, hand
whiteness, fungal changes, nail whiteness and ridging, erythema
simplex, jaundice, petechial rash.
Neurologic/musculoskeletal: Pain in extremities, injection site
pain, arthralgia, myalgia, convulsion, headache, and paresthesia
(1-5%), bone pain, joint disorder, confusion, dizziness, emotional
lability, and somnolence (<1%); in patients with
hematologic malignancies: status epilepticus, temporal lobe
seizures, somnolence, coma, malaise, mental status changes,
dizziness, emotional lability, headache, lip numbness, finger
paresthesia, mood changes, night sweats, Parkinson-like syndrome,
mild to severe confusion, disorientation, paresthesia, diffuse and
local musculoskeletal pain, arthralgia, joint stiffness,
cramps.
Miscellaneous: Fever and malaise (> 5%), chills,
dyspnea, and night sweats (1-5%), bronchospasm, sepsis, septic
shock, excessive thirst, increased cough, epistaxis, upper
respiratory infection, erythema simplex, hematuria, increased
urinary frequency, and abnormal kidney function (<
1%); in patients with hematologic malignancies: thirst, uric acid
nephropathy, peripheral edema, proteinuria, metabolic acidosis,
increased BUN, increased creatinine, increased urinary frequency,
hematuria due to thrombopenia, severe hemorrhagic cystitis, renal
dysfunction, renal failure, cough, epistaxis, severe bronchospasm,
upper respiratory infection, localized edema, injection site
reactions (including pain, swelling, or redness), malaise,
infection, sepsis, fatigue, and septic shock.
Drug Interactions
Anticoagulants (eg, coumadin, heparin, dipyridamole, aspirin, or
NSAIDs): Use caution; imbalances in coagulation factors seen with
use of pegaspargase, predisposing to bleeding and/or
thrombosis.
Antitumor agents: Unfavorable reactions seen.
Drugs that require cell replication for lethal effects (eg,
methotrexate): Interference with action of interacting drug.
Hepatotoxic agents: Increased risk of hepatotoxicity; use caution,
especially when liver dysfunction is present.
Protein-bound drugs: Increased toxicity of protein-bound
drugs.
The information provided above is based on the manufacturer's
official US labeling for this product, last updated February
1994.
1996-2000 by PRR, Inc. All rights reserved
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