zanosar（streptozocin）说明书

警告

ZANOSAR应在有经验的使用癌症化疗药物的医生的监督下进行。

患者不需要住院治疗，但应该有机会获得实验室和支持性资源，足以监测药物耐受性并保护和维持受药物毒性损害的患者。肾毒性与剂量相关且累积，可能是严重或致命的。其他主要毒性是恶心和呕吐，这可能是严重的并且有时限制治疗。此外，在一些患者中观察到肝功能障碍，腹泻和血液学改变。链脲佐菌素具有致突变性。当肠胃外给药时，已经发现它在某些啮齿类动物中是致瘤的或致癌的。

在考虑ZANOSAR治疗的可取性时，医师必须判断患者对该药物已知毒性作用的可能益处。在作出判断和开始治疗之前，医生应该熟悉以下内容。

描述

每瓶ZANOSAR含有1g活性成分链脲菌素2-脱氧-2 [[（甲基亚硝基氨基）羰基]氨基]-α（和β）-D-吡喃葡萄糖和220mg无水柠檬酸。 ZANOSAR可作为无菌淡黄色冷冻干燥制剂供静脉给药。用氢氧化钠调节pH值。当按照指示重新配制时，溶液的pH值将介于3.5和4.5之间。链脲佐菌素是一种合成的抗肿瘤剂，与化疗中使用的其他亚硝基脲化学相关。 Streptozocin是一种象牙色的晶体粉末，分子量为265.2。它溶于水或生理盐水，易溶于酒精。结构式如下所示：

适应症

ZANOSAR被用于治疗胰腺的转移性胰岛细胞癌。已经对功能性和非功能性癌症进行了响应。由于其固有的肾毒性，该药的治疗应限于有症状或进行性转移性疾病的患者。

剂量和给药

ZANOSAR灭菌粉末应通过快速注射或短时间/长时间输注静脉注射。口头不积极。尽管已经进行了动脉内给药，但在进一步评估这种给药途径可能更迅速地引起不良肾效应的可能性之前，不建议这样做。

ZANOSAR已成功使用两种不同的剂量时间表。

每日计划

每日静脉给药的推荐剂量为每六周连续五天500毫克/平方米的体表面积，直至获得最大益处或观察到治疗限制性毒性。不建议在这个时间表上增加剂量。

每周计划

对于前两个疗程（周），每周静脉内施用的推荐初始剂量为每周一次1000毫克/平方米的体表面积。在随后的课程中，药物剂量可能会升高，但尚未达到治疗反应的患者，以前的治疗过程中没有经历过显着的毒性反应。然而，1500 mg /m²的人体表面面积不得超过1剂，因为更大的剂量可能导致氮质血症。当按照这个时间表施用时，反应发作的中位时间约为17天，最大反应的中位时间约为35天。开始应答的中位总剂量约为2000毫克/平方米体表面积，中位总剂量至最大应答约为4000毫克/平方米体表面积。

对于上述任一计划，ZANOSAR维持治疗的理想持续时间尚未明确确定。

对于功能性肿瘤患者，空腹胰岛素水平的连续监测可以确定对治疗的生化反应。对于患有功能性或非功能性肿瘤的患者，可通过可测量的肿瘤大小减少（减少器官肿大，肿块或淋巴结）来确定对治疗的反应。

用9.5 mL右旋糖注射液，USP或0.9％氯化钠注射液USP重建ZANOSAR。得到的淡金溶液将含有每毫升100毫克链脲霉素和22毫克柠檬酸。如果需要更多稀释的输液，建议在上述载体中进一步稀释。链霉素置于溶液中后的总存放时间不应超过12小时。本产品不含防腐剂，不适用于多剂量小瓶。

应该小心处理和准备粉末和溶液，并建议使用手套。如果ZANOSAR的无菌粉末或由ZANOSAR制备的溶液接触到皮肤或粘膜，请立即用肥皂和水清洗患处。

应考虑正确处理和处置抗癌药物的程序。关于这个问题的几个指导方针已经出版.7没有普遍认为指南中建议的所有程序都是必要的或适当的。

副作用

肾

见警告。

胃肠道

大多数用ZANOSAR治疗的患者经历严重的恶心和呕吐，偶尔需要停止药物治疗。一些患者出现腹泻。许多患者经历肝毒性，其特征在于肝酶（SGOT和LDH）水平升高和低白蛋白血症升高。

血液学

血液学毒性很少见，最常见的是血细胞比容值的轻微下降。但是，已经观察到致命的血液学毒性，其中白细胞和血小板计数显着降低。

新陈代谢

已经在用ZANOSAR治疗的一些患者中注意到轻度至中度的葡萄糖耐量异常。这些通常是可逆的，但观察到低血糖的胰岛素休克。

泌尿生殖系统

已报道两例ZANOSAR治疗后肾性尿崩症。一个有自发恢复，第二个对吲哚美辛有反应。

后期营销经验

产品外渗后自发报告了局部炎症（即水肿，红斑，灼痛，压痛）。在大多数情况下，这些事件在同一天或几天内解决。

药物相互作用

当与其他细胞毒性药物联合使用时，ZANOSAR可能表现出相加毒性。据报道链脲佐菌素可延长阿霉素的消除半衰期并可导致严重的骨髓抑制;同时接受ZANOSAR的患者应考虑减少阿霉素剂量。据报道在一例中同时使用链佐星和苯妥英导致链脲佐菌素细胞毒性降低。

实验室测试

接受ZANOSAR治疗的患者必须密切监测，特别是肾，肝和造血毒性的证据。警告部分描述了肾功能测试。

还应密切监测患者造血和肝脏毒性的证据。全血细胞计数和肝功能检查应至少每周进行一次。取决于所指出的毒性程度，可以指示药物的剂量调整或中断。

警告

肾毒性

用ZANOSAR治疗的许多患者经历肾毒性，如氮质血症，无尿，低磷酸盐血症，糖尿和肾小管酸中毒所证实。这种毒性与剂量有关且累积，可能是严重或致命的。每次治疗前后都必须监测肾功能。在药物施用之前，至少每周一次，以及药物施用后四周，应获得连续尿分析，血尿素氮，血浆肌酸酐，血清电解质和肌酸酐清除率。系列尿分析对早期检测蛋白尿尤其重要，应在检测到蛋白尿时用24小时收集进行定量。轻度蛋白尿是肾毒性的首要征兆之一，可能预示肾功能进一步恶化。建议在存在显着的肾毒性的情况下减少ZANOSAR的剂量或停止治疗。通过降低肾脏和尿液中药物及其代谢物的浓度，充足的水合可能有助于降低肾小管上皮细胞肾毒性的风险。

在患有先前存在的肾脏疾病的患者中使用ZANOSAR需要医生判断潜在的益处，而不是已知的严重肾损害风险。

该药不应与其他潜在的肾毒素联合使用或与其他潜在的肾毒素联合使用。

当皮肤暴露时，一些大鼠在施用链脲霉素的部位产生良性肿瘤。因此，如果处理不当，链脲霉素可能在局部暴露后引起致癌危险。 （请参阅“用法和用法”。）请参阅此插入开始处的其他警告。

注意事项

注入 - 反应

ZANOSAR无菌粉末刺激组织。外渗可能会导致严重的组织损伤和坏死。

链脲霉素在细菌，植物和哺乳动物细胞中具有致突变性。当肠胃外给药时，已经显示其在大鼠中诱导肾肿瘤并诱导仓鼠中的肝肿瘤和其他肿瘤。在用链脲佐菌素口服治疗的大鼠中观察到胃和胰腺肿瘤。链脲佐菌素还显示在小鼠中致癌。

当施用于雄性和雌性大鼠时，链脲佐菌素不利地影响生育力。

怀孕类别D

生殖研究表明，链脲佐菌素在大鼠中是致畸的并且在兔子中具有堕胎作用。当静脉注射给怀孕的猴子时，它在胎儿循环中迅速出现。孕妇没有研究。 ZANOSAR只有在潜在利益证明对胎儿有潜在风险时才应在怀孕期间使用。

护理母亲

目前还不知道链脲菌素是否在人乳中排泄。由于许多药物都在人乳中排泄，并且由于护理婴儿可能出现严重不良反应，因此接受ZANOSAR的患者应该停止护理。

老年人使用

链脲佐菌素的临床研究未包括足够数量的65岁以上的患者，以确定与年轻患者相比是否在功效或毒性方面有差异。其他报道的临床经验尚未发现老年人与年轻患者人群之间疗效或安全性的差异。通常，老年患者的剂量选择应该谨慎，通常从剂量范围的低端开始，反映肝，肾或心脏功能降低的频率较高，并伴有疾病或其他药物治疗。

临床药理学

链脲佐菌素抑制细菌和哺乳动物细胞中的DNA合成。在细菌细胞中，与胞嘧啶部分的特异性相互作用导致DNA降解。导致哺乳动物细胞死亡的生化机制尚未确定;链脲佐菌素抑制细胞增殖的水平远低于抑制前体掺入DNA或抑制几种参与DNA合成的酶所需的水平。尽管链脲佐菌素抑制细胞进入有丝分裂，但细胞周期的特定阶段对其致死效应并不特别敏感。

链脲霉素在L1210白血病小鼠中在相当宽范围的肠胃外给药时间表中有活性。在许多动物物种的实验中，链脲佐菌素诱导类似于人类高血糖非酮症糖尿病的糖尿病。这种已被广泛研究的现象似乎是通过降低β细胞烟酰胺腺嘌呤二核苷酸（NAD）和随后的胰岛β细胞的组织病理学改变而介导的。

尚未广泛研究在生理条件下发生的链脲佐菌素的代谢和化学分解。当静脉注射给各种实验动物时，链脲霉素很快从血液中消失。在所有测试的物种中，它被发现集中在肝脏和肾脏。多达20％的药物（或含有N-亚硝基脲基团的代谢物）被肾代谢和/或排泄。代谢产物尚未确定。

患者信息

有报道称，接受连续静脉输注ZANOSAR 5天的患者数量有限，导致精神错乱，嗜睡和抑郁症。 应告知患者驾驶或使用复杂机器可能存在潜在风险。

Medically reviewed on March 25, 2018

· Streptozotocin

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Zanosar: 1 g (1 ea)

· Zanosar

· Antineoplastic Agent, Alkylating Agent

· Antineoplastic Agent, Alkylating Agent (Nitrosourea)

Streptozocin inhibits DNA synthesis by alkylation and cross-linking the strands of DNA, and by possible protein modification; cell cycle nonspecific

Concentrates in liver, kidney, and pancreatic beta cells

Rapid; primarily hepatic

Urine (primarily; as parent drug and metabolites)

1,500 mg/m2 once weekly: Onset of response: 17 days; median time to maximum response: 35 days

<1 hour (Perry 2012)

Pancreatic neuroendocrine tumors: Treatment of metastatic islet cell carcinoma of the pancreas (symptomatic or progressive disease)

Data from a randomized, controlled, open-label, parallel-group study supports the use of streptozocin in the treatment of metastatic adrenocortical carcinoma. In this phase III study comparing mitotane in combination with etoposide, doxorubicin, and cisplatin (EDP regimen), to streptozocin in combination with mitotane, the response rate and progression free survival were significantly better with the EDP arm, although there was no difference in overall survival between the groups [Fassnacht 2012]. Data from a phase II study evaluating streptozocin (in combination with mitotane) also supports the use of streptozocin in the treatment of metastatic adrenal carcinoma; either complete or partial response occurred in 36.4% of patients resulting in a 2 year survival of 70% and a 5 year survival rate of 32.5% [Khan 2000].

Data from a phase II/III randomized study supports the use of streptozocin (in combination with fluorouracil) in the treatment of gastrointestinal neuroendocrine (carcinoid) tumors [Sun 2005 [LOE B]]. Additionally, a small number of patients with gastrointestinal neuroendocrine tumors (GiNETs) were included in a study evaluating response to streptozocin (in combination with fluorouracil, leucovorin, and cisplatin) in patients with neuroendocrine tumors (including pancreatic and GI tumors); while patients with pancreatic neuroendocrine tumors had a higher response rate, patients with GiNETs also demonstrated objective responses and stable disease [Turner 2010 [LOE C]].

There are no contraindications listed within the manufacturer's labeling.

Note: Streptozocin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Hesketh 2017; Roila 2016).

Adrenocortical carcinoma, metastatic (off-label use): IV: 1,000 mg once daily for 5 days (cycle 1) followed by 2,000 mg on day 1 (subsequent cycles) every 3 weeks until disease progression or unacceptable toxicity (in combination with mitotane) (Fassnacht 2012; Khan 2000).

Gastrointestinal neuroendocrine tumors (off-label use): IV: 500 mg/m2 on days 1 to 5 every 10 weeks (in combination with fluorouracil) until disease progression or unacceptable toxicity (Sun 2005) or1,000 mg/m2 once every 3 weeks for 3 cycles, if no progression may continue for up to a total of 6 cycles in the absence of unacceptable toxicity (in combination with leucovorin, fluorouracil and cisplatin) (Turner 2010).

Pancreatic neuroendocrine tumors (metastatic): IV:

Daily schedule: 500 mg/m2 once daily for 5 consecutive days every 6 weeks (in combination with either doxorubicin or fluorouracil) until disease progression or unacceptable toxicity (Moertel 1992)

Weekly schedule: 1,000 mg/m2 once weekly; if therapeutic response not achieved after 2 weeks, may escalate dose to a maximum of 1,500 mg/m2 weekly

Alternate schedules (off-label dosing): 1,000 mg/m2 once every 3 weeks for up to 6 cycles (in combination with leucovorin, fluorouracil and cisplatin) (Turner 2010) or 400 mg/m2 days 1 to 5 every 4 weeks (in combination with fluorouracil and doxorubicin) until disease progression or unacceptable toxicity (Kouvaraki 2004) or 500 mg/m2 on days 1 to 5 every 5 or 6 weeks (in combination with fluorouracil) for up to 1 year if best response is stable disease (Dilz 2015)

Refer to adult dosing. Select dose cautiously, beginning at the lower end of dosing range.

Bone marrow suppression: May require dosage reduction or discontinuation.

ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs 2012).

Reconstitute powder with 9.5 mL D5W or NS to a concentration of 100 mg/mL. May further dilute for infusion in D5W or NS.

IV: Streptozocin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011; Hesketh 2017; Roila 2016).

Administer as either a rapid IV injection or as short or prolonged infusion.

Irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity.

Store intact vials at 2°C to 8°C (36°F to 46°F). Protect from light. The manufacturer recommends use within 12 hours of reconstitution; vial does not contain a preservative.

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents.Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy.Consider therapy modification

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Frequency not defined.

Endocrine & metabolic: Decreased glucose tolerance, glycosuria, hyperglycemia, hypoalbuminemia, hypoglycemia, hypophosphatemia, increased lactate dehydrogenase

Gastrointestinal: Diarrhea, nausea, vomiting

Genitourinary: Anuria, azotemia, nephrotoxicity, proteinuria

Hepatic: Increased serum transaminases

Local: Injection site reaction (includes burning sensation at injection site, erythema at injection site, inflammation at injection site, irritation at injection site, swelling at injection site, tenderness at injection site)

Renal: Increased blood urea nitrogen, increased serum creatinine, renal insufficiency, renal tubular acidosis

<1%, postmarketing, and/or case reports: Anemia, bone marrow depression (nadir: 2 to 3 weeks), confusion, depression, diabetes insipidus, hepatic insufficiency, lethargy, leukopenia, metastases, thrombocytopenia

Experienced physician:

Streptozocin should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. A patient need not be hospitalized but should have access to a facility with a laboratory and supportive resources sufficient to monitor drug tolerance and to protect and maintain a patient compromised by drug toxicity. The physician must judge the possible benefit to the patient against the known toxic effects of this drug in considering the advisability of therapy with streptozocin. The physician should be familiar with the following text before making a judgment and beginning treatment.

Drug toxicities:

Renal toxicity is dose-related and cumulative and may be severe or fatal. Other major toxicities are nausea and vomiting, which may be severe and at times treatment-limiting. In addition, liver dysfunction, diarrhea and hematological changes have been observed in some patients.

Secondary malignancy:

Streptozocin is mutagenic. When administered parenterally, it has been found to be tumorigenic or carcinogenic in some rodents.

Concerns related to adverse effects:

• Bone marrow suppression: [US Boxed Warning]: Hematologic toxicity has been observed. Mild bone marrow suppression (rare) may occur (usually mild anemia); monitor blood counts weekly. May require dosage reduction or discontinuation.

• CNS effects: May cause confusion, lethargy or depression; caution patients about performing tasks that require mental alertness (eg, operating machinery or driving).

• Extravasation/tissue irritation: Streptozocin is an irritant with vesicant-like properties. Avoid extravasation. Local tissue irritation or inflammation (burning, edema, erythema, tenderness) may occur, but usually resolves within a few days.

• Gastrointestinal events: [US Boxed Warning]: Diarrhea has been observed. May cause severe nausea and vomiting. Streptozocin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011; Hesketh 2017; Roila 2016).

• Glucose intolerance: Mild-to-moderate glucose intolerance may occur; generally is reversible. Insulin shock with hypoglycemia has been observed.

• Hepatotoxicity: [US Boxed Warning]: Liver dysfunction has been observed. Hepatotoxicity may be characterized by elevated transaminases and LDH, or by hypoalbuminemia; monitor liver function weekly. Hepatic dysfunction may require dosage reduction or discontinuation.

• Renal toxicity: [US Boxed Warning]: Renal toxicity is dose-related and cumulative; may be severe or fatal. Azotemia, anuria, hypophosphatemia, glycosuria and renal tubular acidosis have been reported. Adequate hydration may reduce the risk for nephrotoxicity. Monitor renal function (BUN, serum creatinine, and serial urinalysis) and electrolytes prior to, weekly during, and after each treatment course. Mild proteinuria is an early sign of renal toxicity; if proteinuria is detected with urinalysis, obtain 24-hour urine collection. Avoid use in combination with other nephrotoxic medications. Use with caution in patients with pre-existing renal disease.

• Secondary malignancy: [US Boxed Warning]: Streptozocin is mutagenic; parenteral use is tumorigenic and carcinogenic in animals.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician. Administer in a facility with sufficient access to lab and supportive resources for monitoring toxicities.

Renal function tests, including BUN, serum creatinine, and serial urinalysis, and serum electrolytes (at baseline, weekly during, and for 4 weeks after treatment); 24-hour urine collection if proteinuria is detected on urinalysis; liver function tests (weekly), CBC with differential and platelets (weekly), blood glucose; monitor infusion site

D

Adverse events have been observed in animal reproduction studies.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea. Have patient report immediately to prescriber signs of infection, signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating), severe nausea, vomiting, depression, confusion, severe loss of strength and energy, or severe injection site redness, pain, edema, or irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.