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美国FDA批准POMALYST（泊马度胺胶囊）用于复发性及难治性多发性骨髓瘤治疗
2013年2月8日，美国食品药品管理局FDA批准Pomalyst(pomalidomide)用于其它癌症药物治疗后病情仍有进展的多发性骨髓瘤患者的治疗。
多发性骨髓瘤起因于骨髓中的浆细胞，属血癌的一种，主要影响老年人有。根据美国国家癌症研究所提供的信息，每年大约有21700名美国人被诊断为多发性骨髓瘤，并且会有10710人死于该种疾病。
Pomalyst通过调节人体免疫系统破坏癌细胞，抑制癌细胞的生长。该药物用于先前至少接受过包括来那度胺和硼替佐米在内的两种药物治疗的患者，，患者已对药物没有响应，并在60天的治疗期内病情仍有发展（复发和难以治疗）。
“Pomalyst是包括来那度胺和沙利度胺在内的第三个免疫调节剂类药物， 也是过去一年来第二个被批准用于治疗多发性骨髓瘤的药物，”
FDA药物评价和研究中心血液和肿瘤产品办公室主任Richard Pazdur医学博士说。“对于多发性骨髓瘤的治疗要通过调整以满足个体患者的要求，今天Pomalyst的获批给对其它药物不起响应的患者提供了另一种治疗选择。”
2012年7月，FDA批准Kyprolis(carfilzomib)用于治疗多发性骨髓瘤。和Kyprolis情况类似，Pomalyst也是通过FDA加速审评程序而获得批准，这样可以使患者早日用到这个比较有希望的药物，同时公司要进行额外的研究以确保该药物的临床收益和安全使用。另外该药物由于其用途是治疗罕有疾病而获得了孤儿药资格。
Pomalyst的安全性和有效性通过221名复发或难治性多发性骨髓瘤患者参与的临床试验进行评价。临床试验的目的是检测使用该药物治疗之后（目标反应率，或ORR），癌症完全或部分消失的患者数量。
结果显示，单纯使用Pomalyst治疗的患者目标反应率为7.4%。但患者对该药物的持续响应时间仍未达到中位值。Pomalyst加低剂量地塞米松治疗的患者目标反应率为29.2%，平均响应时间为7.4个月。
Pomalyst有一个黑框警告，提醒患者和医护专业人员该药不能用于孕妇，因为该药物能引起严重致命性的出生缺陷，另外该药物还能引起血血栓。
由于Pomalyst的胚胎-胎儿风险，该药物只能通过Pomalyst风险评估与控制策略(REMS)程序才能使用。该药物处方必须进行登记并符合风险评估与控制策略的要求，并通过Pomalyst REMS鉴定。患者必须签有医患协议并遵守REMS的要求。特别指出的是没有怀孕但能成为孕妇的女性患者必须进行妊娠检查并采取避孕措施，男性必须遵守避孕要求。药房必须通过Pomalyst REMS程序认证，必须把药物配发给获得授权可以使用该药物的患者，必须遵守REMS要求。来那度胺和沙利度胺也有类似的REMS。
该药物常见的副作用包括能使抗击感染的白细胞减少（嗜中性粒细胞减少症）、疲劳和虚弱、红细胞计数降低（贫血）、便秘、腹泻、血小板计数降低（血小板减少症）、上呼吸道感染、背部疼痛和发烧。
Pomalyst、来那度胺和沙利度胺均由新泽西州Summit的塞尔基因公司上市销售，Kyprolis由加利福尼亚州南旧金山的奥尼克斯制药公司上市销售。
POMALYST®(pomalidomide)胶囊为口服使用
美国初次批准：2013
一般描述
POMALYST是一种免疫调节抗肿瘤药。化学名是 (RS)-4-Amino-2-(2,6-dioxo-piperidin-3-yl)-isoindoline-1,3dione和结构式如下：
Pomalidomide的经验式为C13H11N3O4和克分子量为273.24.
作用机制
Pomalidomide，一种沙利度胺类似物，是一种有抗肿瘤活性.免疫调节剂。在体外细胞学试验，pomalidomide 抑制造血肿瘤细胞增殖和诱导凋亡。此外，pomalidomide 抑制来那度胺-耐药多发性骨髓瘤细胞株的增殖和在来那度胺-敏感和来那度胺-耐药细胞株与地塞米松协同诱导肿瘤细胞凋亡。Pomalidomide增强T细胞-和天然杀伤(NK)细胞介导的免疫和抑制单核细胞促炎性细胞因子的生成(如，TNF-α和IL-6)。在小鼠肿瘤模型和和体外脐带模型中Pomalidomide 显示抗血管生成活性。
适应证和用途
POMALYST是一种沙利度胺类似物适用为有多发性骨髓瘤患者曾接受至少两种既往治疗包括来那度胺[lenalidomide]和硼替佐米[bortezomib]和已证实疾病进展或末次治疗完成60天内。批准是根据反应率。尚未证明临床获益，例如改善活存或症状。
剂量和给药方法
重复28天疗程在第1-21天每天口服4 mg直至疾病进展。
剂型和规格
胶囊：1 mg，2 mg，3 mg和4 mg (3)
禁忌证
妊娠 (4)
警告和注意事项
（1）血液学毒性：中性粒细胞减少是最常报道3/4级不良事件。监视患者血液学毒性，尤其是中性粒细胞减少(5.4)。
不良反应
最常见不良反应(≥30%)包括疲乏和虚弱，中性粒细胞减少，贫血，便秘，恶心，腹泻，呼吸困难，上呼吸道感染，背痛和发热 (6.1).
为报告怀疑不良反应，联系Celgene Corporation电话1-888-423-5436或FDA电话1-800-332-1088或www.fda.gov/medwatch.
在特殊人群中使用
（1）哺乳母亲：终止药物或哺乳考虑药物对母亲的重要性。(8.3)
（2）有血清肌酐 >3.0 mg/dL患者中避免POMALYST。(8.7).
U.S. Food and Drug Administration Approves POMALYST® (pomalidomide) for the Treatment of Patients with Relapsed and Refractory Multiple Myeloma
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today announced the U.S. Food and Drug Administration (FDA) has approved POMALYST® brand therapy (pomalidomide) for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy.
Approval is based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified.
Supporting the approval were the results of MM-002, a phase II, randomized, open-label study evaluating pomalidomide (4 mg once daily on days 1-21 of each 28-day cycle) plus low-dose dexamethasone (40 mg per day given only on Days 1, 8, 15 and 22 of each 28-day cycle for patients 75 years or younger, or 20 mg per day given only on Days 1, 8, 15 and 22 of each 28-day cycle for patients greater than 75 years of age) versus pomalidomide (4 mg once daily on days 1-21 of each 28-day cycle) alone in patients with relapsed multiple myeloma who were refractory to their last myeloma therapy and had received lenalidomide and bortezomib.
Of the 221 patients that were evaluable for response, 29.2% (95% CI 21.0, 38.5) achieved a partial response or better in the pomalidomide plus low-dose dexamethasone arm compared to 7.4% (95% CI 3.3, 14.1) in the pomalidomide-alone arm. Overall Response Rate was based on responses assessed by the Independent Review Adjudication Committee (IRAC) based on the European Group for Blood and Marrow Transplantation (EMBT) criteria. The median duration of response for patients in the pomalidomide plus low-dose dexamethasone arm was 7.4 months (95% CI 5.1, 9.2) while the median has not yet been reached for the pomalidomide alone arm.
POMALYST is an analogue of thalidomide, is contraindicated in pregnancy and is only available through a restricted distribution program called POMALSYT REMSTM. Deep venous thrombosis (DVT) and pulmonary embolism (PE) occur in patients with multiple myeloma treated with POMALYST. Please see full Prescribing Information, including Boxed WARNINGS, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.
In the study, 219 patients were evaluable for safety. The most common grade 3 or 4 adverse reactions (≥15%) in the pomalidomide plus low-dose dexamethasone arm versus pomalidomide alone respectively, were neutropenia (38% and 47%), anemia (21% and 22%), thrombocytopenia (19% and 22%), and pneumonia (23% and 16%).
POMALYST will only be available in the United States through POMALYST REMS™, a restricted distribution program.
POMALYST® is a registered trademark of Celgene Corporation
About POMALYST®
POMALYST® oral therapy comprises pomalidomide, an IMiDs® compound. POMALYST and other IMiDs compounds continue to be evaluated in over 100 clinical trials.
POMALYST® (pomalidomide) is indicated for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval is based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified.
Important Safety Information
WARNING: EMBRYO-FETAL TOXICITY and VENOUS THROMBOEMBOLISM
Embryo-Fetal Toxicity
POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting POMALYST treatment
Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping POMALYST treatment
POMALYST is only available through a restricted distribution program called POMALYST REMSTM.
Venous Thromboembolism
Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE) occur in patients with multiple myeloma treated with POMALYST. Prophylactic anti-thrombotic measures were employed in the clinical trial. Consider prophylactic measures after assessing an individual patient’s underlying risk factors
CONTRAINDICATIONS: Pregnancy
POMALYST can cause fetal harm and is contraindicated in females who are pregnant. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus
Pomalidomide is a thalidomide analogue and is teratogenic in both rats and rabbits when administered during the period of organogenesis.
WARNINGS AND PRECAUTIONS
Embryo-Fetal Toxicity
Females of Reproductive Potential: Must avoid pregnancy while taking POMALYST and for at least 4 weeks after completing therapy. Must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control, beginning 4 weeks prior to initiating treatment with POMALYST, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of POMALYST therapy. Must obtain 2 negative pregnancy tests prior to initiating therapy.
Males: Pomalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 28 days after discontinuing POMALYST, even if they have undergone a successful vasectomy. Males must not donate sperm
Blood Donation: Patients must not donate blood during treatment with POMALYST and for 1 month following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST
POMALYST REMS Program
Because of the embryo-fetal risk,POMALYST is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called “POMALYST REMS.” Prescribers and pharmacists must be certified with the program; patients must sign an agreement form andcomplywith the requirements. Further information about the POMALYST REMS program is available at [celgeneriskmanagement.com] or by telephone at 1-888-423-5436.
Venous Thromboembolism: Patients receiving POMALYST have developed venous thromboembolic events reported as serious adverse reactions. In the trial, all patients were required to receive prophylaxis or antithrombotic treatment. The rate of DVT or PE was 3%. Consider anticoagulation prophylaxis after an assessment of each patient’s underlying risk factors.
Hematologic Toxicity: Neutropenia of any grade was reported in 50% of patients and was the most frequently reported Grade 3/4 adverse event, followed by anemia and thrombocytopenia. Monitor patients for hematologic toxicities, especially neutropenia, with complete blood counts weekly for the first 8 weeks and monthly thereafter. Treatment is continued or modified for Grade 3 or 4 hematologic toxicities based upon clinical and laboratory findings. Dosing interruptions and/or modifications are recommended to manage neutropenia and thrombocytopenia.
Hypersensitivity Reactions: Patients with a prior history of serious hypersensitivity associated with thalidomide or lenalidomide were excluded from studies and may be at higher risk of hypersensitivity.
Dizziness and Confusional State: 18% of patients experienced dizziness and 12% of patients experienced a confusional state; 1% of patients experienced grade 3/4 dizziness, and 3% of patients experienced grade 3/4 confusional state. Instruct patients to avoid situations where dizziness or confusion may be a problem and not to take other medications that may cause dizziness or confusion without adequate medical advice.
Neuropathy: 18% of patients experienced neuropathy (approximately 9% peripheral neuropathy). There were no cases of grade 3 or higher neuropathy adverse reactions reported.
Risk of Second Primary Malignancies: Cases of acute myelogenous leukemia have been reported in patients receiving POMALYST as an investigational therapy outside of multiple myeloma.
ADVERSE REACTIONS
In the clinical trial of 219 patients who received POMALYST alone (n=107) or POMALYST + low-dose dexamethasone (low-dose dex) (n=112), all patients had at least one treatment-emergent adverse reaction.
In the POMALYST alone versus POMALYST + low dose dexamethasone arms, respectively, most common adverse reactions (≥30%) included fatigue and asthenia (55%, 63%), neutropenia (52%, 47%), anemia (38%, 39%), constipation (36%, 35%), nausea (36%,22%), diarrhea (34%, 33%), dyspnea (34%, 45%), upper respiratory tract infection (32%, 25%), back pain (32%, 30%), and pyrexia (19%, 30%)
90% of patients treated with POMALYST alone and 88% of patients treated with POMALYST + low-dose dex had at least one treatment-emergent NCI CTC Grade 3 or 4 adverse reaction
In the POMALYST alone versus POMALYST + low dose dexamethasone arms, respectively, most common Grade 3/4 adverse reactions (≥15%) included neutropenia (47%, 38%), anemia (22%, 21%), thrombocytopenia (22%, 19%), and pneumonia (16%, 23%). For other Grade 3 or 4 toxicities besides neutropenia and thrombocytopenia, hold treatment and restart treatment at 1 mg less than the previous dose when toxicity has resolved to less than or equal to Grade 2 at the physician’s discretion67% of patients treated with POMALYST and 62% of patients treated with POMALYST + low-dose dex had at least one treatment-emergent serious adverse reactionIn the POMALYST alone versus POMALYST + low dose dexamethasone arms, respectively, most common serious adverse reactions (≥5%) were pneumonia (14%, 19%), renal failure (8%, 6%), dyspnea (5%, 6%), sepsis (6%, 3%), pyrexia (3%, 5%) dehydration (5%, 3%), hypercalcemia (5%, 2%), urinary tract infection (0%, 5%), and febrile neutropenia (5%, 1%)
DRUG INTERACTIONS
No formal drug interaction studies have been conducted with POMALYST. Pomalidomide is primarily metabolized by CYP1A2 and CYP3A. Pomalidomide is also a substrate for P-glycoprotein (P-gp). Coadministration of POMALYST with drugs that are strong inhibitors or inducers of CYP1A2, CYP3A, or P-gp should be avoided. Cigarette smoking may reduce pomalidomide exposure due to CYP1A2 induction. Patients should be advised that smoking may reduce the efficacy of pomalidomide.
USE IN SPECIFIC POPULATIONS
Pregnancy:If pregnancy does occur during treatment, immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Report any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-332-1088 and also to Celgene Corporation at 1-888-423-5436.
Nursing Mothers: It is not known if pomalidomide is excreted in human milk. Pomalidomide was excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from POMALYST, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use: Safety and effectiveness of POMALYST in patients under the age of 18 have not been established.
Geriatric Use: No dosage adjustment is required for POMALYST based on age. Patients greater than or equal to 65 years of age were more likely than patients less than or equal to 65 years of age to experience pneumonia.
Renal and Hepatic Impairment: Pomalidomide is metabolized in the liver. Pomalidomide and its metabolites are primarily excreted by the kidneys. The influence of renal and hepatic impairment on the safety, efficacy, and pharmacokinetics of pomalidomide has not been evaluated. Avoid POMALYST in patients with a serum creatinine >3.0 mg/dL. Avoid POMALYST in patients with serum bilirubin >2.0 mg/dL and AST/ALT >3.0 x ULN.
Please see full Prescribing Information, including Boxed WARNINGS, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.
POMALYST (pomalidomide) is indicated for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval is based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified.
POMALYST Rx
Pharmacological Class:
Immunomodulator.
Active Ingredient(s):
Pomalidomide 1mg, 2mg, 3mg, 4mg; capsules.
Company
Celgene Corp
Indication(s):
Multiple myeloma, in patients who have received at least two prior therapies (including lenalidomide and bortezomib), and have shown disease progression on or within 60 days of completion of the last therapy. Clinical benefit, such as improvement in survival or symptoms, has not been verified.
Pharmacology:
Pomalidomide is a thalidomide analogue that inhibits proliferation and induces apoptosis of hematopoietic tumor cells. Pomalidomide also enhances T cell- and NK cell-mediated immunity and inhibits production of pro-inflammatory cytokines (eg, TNF-α, IL-6) by monocytes.
Clinical Trials:
The safety and efficacy of Pomalyst were evaluated in a Phase 2, multicenter, randomized, open-label study in patients with relapsed multiple myeloma who were refractory to their last myeloma therapy and had received lenalidomide and bortezomib. Patients were considered relapsed if they had achieved at least stable disease for at least one cycle of treatment to at least one prior regimen and then developed progressive disease. Patients were considered refractory if they experienced disease progression on or within 60 days of their last therapy. A total of 221 patients were randomized to receive Pomalyst alone or Pomalyst with low dose dexamethasone (Dex). In this trial, patients given Pomalyst 4mg, once daily for 21 of 28 days, until disease progression, were evaluated alone and in combination with low dose Dex (40mg/day for patients ≤75 years or 20mg/day for patients >75 years) given only on Days 1, 8, 15 and 22 of each 28-day cycle.
Results showed that overall response rate was achieved in the Pomalyst alone arm (7.4%; 95% CI 3.3, 14.1) vs. Pomalyst plus low-dose Dex arm (29.2%; 95% CI 21.0, 38.5) with a 7.4 month median duration of response. Also, partial response was demonstrated with 7.4% in the Pomalyst alone (n=8) arm vs. 28.3% in the Pomalyst with low-dose Dex (n=32) treatment arm.
Legal Classification:
Rx
Adults:
Swallow whole; may be taken with water. Take without food. 4mg once daily on Days 1–21 of repeated 28-day cycles until disease progression; may give with dexamethasone. Dose modification for hematologic and other Grade 3/4 toxicities: see full labeling.
Children:
<18 years: not established.
Contraindication(s):
Pregnancy (Category X): avoid during and for at least 4 weeks after completing therapy.
Warnings/Precautions:
Females of reproductive potential must commit either to abstain from heterosexual sex or to use two methods of reliable contraception, beginning 4 weeks prior to initiating, during therapy, dose interruptions and for 4 weeks after discontinuation. Obtain two negative pregnancy tests prior to initiating therapy: perform first test within 10–14 days, and second test within 24 hours prior to prescribing, and then weekly during first month, then monthly thereafter in women with regular menstrual cycles or every 2 weeks if irregular cycles. Males: must use latex or synthetic condom during therapy and up to 28 days after discontinuing, even after successful vasectomy; do not donate sperm. Patients must not donate blood during therapy and for 1 month after discontinuation. Venous thromboembolism; consider anticoagulation prophylaxis. Monitor for hematologic toxicities (esp. neutropenia); obtain CBCs weekly for first 8 weeks and monthly thereafter; may need dose interruption and/or modification. Renal impairment (serum creatinine >3mg/dL) or hepatic impairment (serum bilirubin >2mg/dL and AST/ALT >3x ULN): avoid. Risk of hypersensitivity or second primary malignancies. Nursing mothers: not recommended.
Interaction(s)
May be potentiated by strong CYP1A2, CYP3A (eg, ketoconazole), or P-gp inhibitors; avoid. May be antagonized by strong CYP1A2, CYP3A (eg, rifampin), or P-gp inducers; avoid. Smoking may reduce efficacy.
Adverse Reaction(s)
Fatigue, asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, pyrexia; venous thromboembolism, dizziness, confusion, neuropathy, pneumonia, thrombocytopenia.
Notes:
Available only through Pomalyst REMS program.
How Supplied:
Caps—21, 100
LAST UPDATED:
5/24/2013
美国食品药品管理局核准POMALYST®（泊马度胺）用于治疗复发性及难治性多发性骨髓瘤患者
·新泽西州萨米特-- (美国商业资讯) -- Celgene Corporation (NASDAQ: CELG)今天宣布，美国食品药品管理局(FDA)已核准品牌药物POMALYST®（泊马度胺）用于既往接受过至少2种药物（包括来那度胺和硼替佐米）且最近治疗进行中或治疗完成60天内疾病进展的多发性骨髓瘤患者。
核准的依据是缓解率。生存或症状改善等临床收益尚未得到验证。
该核准得到MM-002试验结果的支持，该试验为II期随机开放研究，评估泊马度胺（每28天周期的第1-21天4毫克每天一次）联合低剂量地塞米松（≤75岁的患者仅在每28天周期的第1、8、15和22天每天给药40毫克，>75岁的患者仅在每28天周期的第1、8、15和22天每天给药20毫克）vs泊马度胺（每28天周期的第1-21天4毫克每天一次）单药用于最近骨髓瘤治疗难治且已用过来那度胺和硼替佐米的复发性多发性骨髓瘤患者。
221例可评估缓解的患者中，获得部分缓解或更佳的患者，泊马度胺联合低剂量地塞米松组vs泊马度胺单药组分别为29.2% (95% CI 21.0, 38.5) vs 7.4% (95% CI 3.3, 14.1)。由独立评审裁定委员会(IRAC)按欧洲血液和骨髓移植组(EMBT)标准评定缓解，据此计算总缓解率。缓解的中位持续时间，泊马度胺联合低剂量地塞米松组为7.4个月(95% CI 5.1, 9.2)，而泊马度胺单药组尚未达到中位持续时间。
POMALYST是沙利度胺的类似物，妊娠期禁用，仅通过一项名为POMALSYT REMSTM的限制性分销计划供药。接受POMALYST治疗的多发性骨髓瘤患者可发生深静脉血栓形成(DVT)和肺栓塞(PE)。请参阅完整的处方信息，包括黑框“警示”、“禁忌症”、“警示与注意事项”和“不良反应”。
该研究中，219例患者可评估安全性。泊马度胺联合低剂量地塞米松组vs泊马度胺单药组最常见的3度或4度不良反应(≥15%)分别为中性粒细胞减少（38%和47%）、贫血（21%和22%）、血小板减少（19%和22%）和肺炎（23%和16%）。
POMALYST在美国仅通过一项名为POMALSYT REMSTM的限制性分销计划供药。
POMALYST® 是Celgene Corporation的注册商标
关于POMALYST®
POMALYST® 口服药含有IMiDs® 化合物泊马度胺。POMALYST和其他IMiDs化合物仍在一百多项临床试验中接受评估。
POMALYST®（泊马度胺）适用于既往接受过至少2种药物（包括来那度胺和硼替佐米）且最近治疗进行中或治疗完成60天内疾病进展的多发性骨髓瘤患者。核准的依据是缓解率。生存或症状改善等临床收益尚未得到验证。
重要安全性信息
警示：胚胎-胎儿毒性和静脉血栓栓塞
胚胎-胎儿毒性
•POMALYST妊娠期禁用。POMALYST是沙利度胺的类似物。已知沙利度胺可导致人类畸胎，可导致重度出生缺陷或胚胎-胎儿死亡。育龄女性在启用POMALYST治疗之前须经2次妊娠试验显示阴性。
•育龄女性在POMALYST治疗期间及治疗停止4周内须使用2种避孕方法或坚持杜绝异性性交。
POMALYST仅通过一项名为POMALSYT REMSTM的限制性分销计划供药。
静脉血栓栓塞
•接受POMALYST治疗的多发性骨髓瘤患者可发生深静脉血栓形成(DVT)和肺栓塞(PE)。临床试验中采取了预防性的抗血栓形成措施。可考虑预防性措施，事先必须评估个体患者的基础危险因素
禁忌症：妊娠
•POMALYST可引起胎儿损伤，禁用于妊娠女性。如果在妊娠期使用了该药，或患者在使用该药期间妊娠，患者必须了解胎儿可能面临的危害
•泊马度胺是沙利度胺的类似物，大鼠和兔子试验均显示，在器官发生阶段给药，可引起畸胎。
警示与注意事项
胚胎-胎儿毒性
•育龄女性：POMALYST治疗期间及治疗完成至少4周内必须避免妊娠。在启用POMALYST之前4周起、治疗期间、中断给药期间及POMALYST停药后至少4周内，必须坚持杜绝异性性交或使用2种可靠的避孕方法。在启用治疗之前须经2次妊娠试验显示阴性。
•男性：泊马度胺用药患者的精液中可检出该药。POMALYST治疗期间及POMALYST停药后28天内，用药男性在与育龄女性的任何性交中必须始终使用乳胶或合成避孕套，即使该男性已成功结扎输精管。用药男性不得捐赠精液。
•献血：POMALYST治疗期间及停药后1个月内，患者不得献血，因为该血液可能输给妊娠女性患者，而此类女性的胎儿不应暴露于POMALYST。
POMALYST REMS计划
由于胚胎-胎儿风险，POMALYST仅在风险评估和减少策略(REMS)下通过一项名为“POMALYST REMS”的限制性分销计划供药。处方者和药剂师必须通过该计划的认证；患者必须签署一份协议表格并满足要求。有关POMALYST REMS计划的进一步信息，请访问[celgeneriskmanagement.com]或拨打电话1-888-423-5436。
静脉血栓栓塞: 接受POMALYST的患者曾发生静脉血栓栓塞，并报告为严重不良反应。该试验要求所有患者均接受预防性治疗或抗血栓治疗。DVT或PE发生率为3%。可考虑抗凝预防性治疗，事先必须评估个体患者的基础危险因素。
血液学毒性：50%的患者报告任何程度的中性粒细胞减少，中性粒细胞减少是最常报告的3/4度不良事件，其次是贫血和血小板减少。患者须监测血液学毒性，尤其是中性粒细胞减少，最初8周须每周检查一次全血细胞计数，然后每月一次。对于3度或4度血液学毒性，须根据临床和实验室结果继续治疗或调整治疗。处治中性粒细胞减少和血小板减少时，建议中断给药和/或调整剂量。
超敏反应：各研究均剔除了既往史中有沙利度胺或来那度胺相关严重超敏反应的患者，这些患者发生超敏反应的风险较高。
头晕和意识模糊状态：18%的患者出现头晕，12%的患者出现意识模糊状态；1%的患者出现3/4度头晕，3%的患者出现3/4度意识模糊状态。告知患者回避头晕或意识模糊可能构成问题的场合，在没有充分医嘱时不要服用其他可能引起头晕或意识模糊的药物。
神经病变：18%的患者发生神经病变（近9%为外周神经病变）。3度或更严重的神经病变不良反应病例未见报道。
第二种原发性恶性肿瘤的风险：POMALYST作为研究用药治疗多发性骨髓瘤以外的其他疾病时曾有报道发生急性粒细胞白血病。
不良反应
在219例接受POMALYST单药（107例）或POMALYST + 低剂量地塞米松（低剂量地松）（112例）患者的临床试验中，所有患者均出现至少一次治疗中发生的不良反应。
•POMALYST单药vs POMALYST +低剂量地塞米松组，常见不良反应(≥30%)分别包括疲乏和无力(55%, 63%)、中性粒细胞减少(52%, 47%)、贫血(38%, 39%)、便秘(36%, 35%)、恶心(36%,22%)、腹泻(34%, 33%)、呼吸困难(34%, 45%)、上呼吸道感染(32%, 25%)、背痛(32%, 30%)和发热(19%, 30%)
•出现至少一次治疗中发生的NCI CTC 3度或4度不良反应的患者，POMALYST单药组为90%，POMALYST +低剂量地松组为88%
•POMALYST单药vs POMALYST +低剂量地塞米松组，最常见的3/4度不良反应(≥15%)分别包括中性粒细胞减少(47%, 38%)、贫血(22%, 21%)、血小板减少(22%, 19%)和肺炎(16%, 23%)。若出现中性粒细胞减少和中性粒细胞减少以外的其他3度或4度毒性，则暂停治疗，待毒性消退至≤2度，由医生酌情重启治疗，剂量比前次剂量低1毫克
•出现至少一次治疗中发生的严重不良反应的患者，POMALYST单药组为67%，POMALYST +低剂量地松组为62%
•POMALYST单药vs POMALYST +低剂量地塞米松组，最常见的严重不良反应(≥5%)分别包括肺炎(14%, 19%)、肾功能衰竭(8%, 6%)、呼吸困难(5%, 6%)、脓毒血症(6%, 3%)、发热(3%, 5%)、脱水(5%, 3%)、高钙血症(5%, 2%)、尿路感染(0%, 5%)和发热性中性粒细胞减少 (5%, 1%)
药物相互作用
POMALYST尚未正式开展过药物相互作用研究。泊马度胺主要由CYP1A2和CYP3A代谢。泊马度胺同时是P糖蛋白(P-gp)的底物。POMALYST应避免与强效抑制或诱导CYP1A2、CYP3A或 P-gp的药物合用。吸烟可降低CYP1A2诱导所致的泊马度胺暴露量。应告知患者，吸烟可能降低泊马度胺的有效性。
特殊人群用药
妊娠：治疗期间如果妊娠，立即停药，将患者转诊至有生殖毒性经验的产科医生/妇科医生，接受进一步评估和咨询。任何疑似的POMALYST胎儿暴露须通过 MedWatch计划上报FDA，电话是1-800-332-1088，同时上报Celgene Corporation，电话是1-888-423-5436。
哺乳母亲：泊马度胺是否在人类乳汁中有分泌尚属未知。泊马度胺在哺乳期大鼠乳汁中有分泌。由于许多药物在人类乳汁中有分泌、且由于哺乳婴儿可能出现POMALYST所致的不良反应，在决定是否停止哺乳或停药时必须考虑该药对母亲的重要性。
儿科用药：POMALYST在18岁以下患者中的安全性和有效性尚未确立。
老年用药：POMALYST剂量无需按年龄调整。与≤65岁的患者相比，≥65岁的患者较易发生肺炎。
肝肾功能损害：泊马度胺通过肝脏代谢。泊马度胺及其代谢产物主要经肾脏排泄。肝肾功能损害对泊马度胺的安全性、有效性和药代动力学的影响尚未评估。血清肌酐>3.0毫克/分升的患者应避免使用POMALYST。血清胆红素>2.0毫克/分升且AST/ALT >正常值上限3.0倍的患者应避免使用POMALYST。
请参阅完整处方信息，包括黑框“警示”、“禁忌症”、“警示与注意事项”和“不良反应”。
POMALYST（泊马度胺）适用于既往接受过至少2种药物（包括来那度胺和硼替佐米）且最近治疗进行中或治疗完成60天内疾病进展的多发性骨髓瘤患者。核准的依据是缓解率。生存或症状改善等临床收益尚未得到验证。
关于多发性骨髓瘤
多发性骨髓瘤（又名骨髓瘤或浆细胞骨髓瘤）是一种血液癌症，表现为骨髓中恶性浆细胞增生。浆细胞属于白细胞，可帮助生成名为免疫球蛋白的抗体，以对抗感染和疾病。但多数多发性骨髓瘤患者中出现一些细胞，生成一种名为病变蛋白（又名M蛋白）的免疫球蛋白，对机体无益。此外，恶性浆细. |
