FDA label ef8ae0f8-41e4-4a2a-9c37-eec8f6570443

WARNING Vinorelbine Injection USP should be administered under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. This product is for intravenous (IV) use only. Intrathecal administration of other vinca alkaloids has resulted in death. Syringes containing this product should be labeled "WARNING - FOR IV USE ONLY. FATAL if given intrathecally." Severe granulocytopenia resulting in increased susceptibility to infection may occur. Granulocyte counts should be ≥ 1,000 cells/mm 3 prior to the administration of Vinorelbine Injection USP. The dosage should be adjusted according to complete blood counts with differentials obtained on the day of treatment. Caution - It is extremely important that the intravenous needle or catheter be properly positioned before Vinorelbine Injection USP is injected. Administration of Vinorelbine Injection USP may result in extravasation causing local tissue necrosis and/or thrombophlebitis (see DOSAGE AND ADMINISTRATION: Administration Precautions ).

WARNINGS Vinorelbine Injection USP should be administered in carefully adjusted doses by or under the supervision of a physician experienced in the use of cancer chemotherapeutic agents. Patients treated with Vinorelbine Injection USP should be frequently monitored for myelosuppression both during and after therapy. Granulocytopenia is dose-limiting. Granulocyte nadirs occur between 7 and 10 days after dosing with granulocyte count recovery usually within the following 7 to 14 days. Complete blood counts with differentials should be performed and results reviewed prior to administering each dose of Vinorelbine Injection USP. Vinorelbine Injection USP should not be administered to patients with granulocyte counts <1,000 cells/mm 3 . Patients developing severe granulocytopenia should be monitored carefully for evidence of infection and/or fever. See DOSAGE AND ADMINISTRATION for recommended dose adjustments for granulocytopenia. Acute shortness of breath and severe bronchospasm have been reported infrequently, following the administration of Vinorelbine Injection USP and other vinca alkaloids, most commonly when the vinca alkaloid was used in combination with mitomycin. These adverse events may require treatment with supplemental oxygen, bronchodilators, and/or corticosteroids, particularly when there is pre-existing pulmonary dysfunction. Reported cases of interstitial pulmonary changes and acute respiratory distress syndrome (ARDS), most of which were fatal, occurred in patients treated with single-agent Vinorelbine Injection USP. The mean time to onset of these symptoms after vinorelbine administration was 1 week (range 3 to 8 days). Patients with alterations in their baseline pulmonary symptoms or with new onset of dyspnea, cough, hypoxia, or other symptoms should be evaluated promptly. Vinorelbine Injection USP has been reported to cause severe constipation (e.g., Grade 3-4), paralytic ileus, intestinal obstruction, necrosis, and/or perforation. Some events have been fatal. Pregnancy: Pregnancy Category D. Vinorelbine Injection USP may cause fetal harm if administered to a pregnant woman. A single dose of vinorelbine has been shown to be embryo- and/or fetotoxic in mice and rabbits at doses of 9 mg/m 2 and 5.5 mg/m 2 , respectively (one third and one sixth the human dose). At nonmaternotoxic doses, fetal weight was reduced and ossification was delayed. There are no studies in pregnant women. If Vinorelbine Injection USP is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Vinorelbine Injection USP.

ADVERSE REACTIONS The pattern of adverse reactions is similar whether Vinorelbine Injection USP is used as a single agent or in combination. Adverse reactions from studies with single-agent and combination use of Vinorelbine Injection USP are summarized in Tables 2-4. Single-Agent Vinorelbine Injection USP: Data in the following table are based on the experience of 365 patients (143 patients with NSCLC; 222 patients with advanced breast cancer) treated with IV Vinorelbine Injection USP as a single agent in 3 clinical studies. The dosing schedule in each study was 30 mg/m 2 Vinorelbine Injection USP on a weekly basis. Table 2: Summary of Adverse Events in 365 Patients Receiving Single-Agent Vinorelbine Injection USP *†: Adverse Event All Patients (n=365) NSCLC (n=143) Bone Marrow Granulocytopenia <2,000 cells/mm 3 90% 80% <500 cells/mm 3 36% 29% Leukopenia <4,000 cells/mm 3 92% 81% <1,000 cells/mm 3 15% 12% Thrombocytopenia <100,000 cells/mm 3 5% 4% <50,000 cells/mm 3 1% 1% Anemia <11 g/dL 83% 77% <8 g/dL 9% 1% Hospitalizations due to granulocytopenic complications 9% 8% All Grades Grade 3 Grade 4 Adverse Event All Patients NSCLC All Patients NSCLC All Patients NSCLC Clinical Chemistry Elevations Total Bilirubin (n = 351) SGOT (n = 346) General Asthenia Injection Site Reactions Injection Site Pain Phlebitis Digestive Nausea Vomiting Constipation Diarrhea Peripheral Neuropathy‡ Dyspnea Alopecia 13% 67% 36% 28% 16% 7% 44% 20% 35% 17% 25% 7% 12% 9% 54% 27% 38% 13% 10% 34% 15% 29% 13% 20% 3% 12% 4% 5% 7% 2% 2% <1% 2% 2% 3% 1% 1% 2% ≤1% 3% 2% 5% 5% 1% 1% 1% 1% 2% 1% 1% 2% 1% 3% 1% 0% 0% 0% 0% 0% 0% 0% 0% <1% 1% 0% 2% 1% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% * None of the reported toxicities were influenced by age. Grade based on modified criteria from the National Cancer Institute. † Patents with NSCLC had not received prior chemotherapy. The majority of the remaining patents had received prior chemotherapy. ‡ Incidence of paresthesia plus hypesthesia. Hematologic: Granulocytopenia is the major dose-limiting toxicity with Vinorelbine Injection USP . Dose adjustments are required for hematologic toxicity and hepatic insufficiency (see DOSAGE AND ADMINISTRATION ). Granulocytopenia was generally reversible and not cumulative over time. Granulocyte nadirs occurred 7 to 10 days after the dose, with granulocyte recovery usually within the following 7 to 14 days. Granulocytopenia resulted in hospitalizations for fever and/or sepsis in 8% of patients. Septic deaths occurred in approximately 1% of patients. Prophylactic hematologic growth factors have not been routinely used with Vinorelbine Injection USP . If medically necessary, growth factors maybe administered at recommended doses no earlier than 24 hours after the administration of cytotoxic chemotherapy. Growth factors should not be administered in the period 24 hours before the administration of chemotherapy. Whole blood and/or packed red blood calls were administered to 18% of patients who received Vinorelbine Injection USP . Neurologic: Loss of deep tendon reflexes occurred in less than 5% of patients. The development of severe peripheral neuropathy was infrequent (1%) and generally reversible. Skin: Like other anticancer vinca alkaloids, Vinorelbine Injection USP is a moderate vesicant. Injection site reactions, including erythema, pain at injection site, and vein discoloration, occurred in approximately one third of patients; 5% were severe. Chemical phlebitis along the vein proximal to the site of injection was reported in 10% of patents. Gastrointestinal: Prophylactic administration of antiemetics was not routine in patients treated with single-agent Vinorelbine Injection USP . Due to the low incidence of severe nausea and vomiting with single-agent Vinorelbine Injection USP , the use of serotonin antagonists is generally not required. Hepatic: Transient elevations of liner enzymes were reported without clinical symptoms. Cardiovascular: Chest pain was reported in 5% of patients. Most reports of chest pain were in patients who had either a history of cardiovascular disease or tumor within the chest. There have been rare reports of myocardial infarction. Pulmonary: Shortness of breath was reported in 3% of patients; it was severe in 2% (see WARNINGS ). Interstitial pulmonary changes were documented. Other: Fatigue occurred in 27% of patients. It was usually mild or moderate but tended to increase with cumulative dosing. Other toxicities that have been reported in less than 5% of patients include jaw pain, myalgia, arthralgia, and rash. Hemorrhagic cystitis and the syndrome of inappropriate ADH secretion were each reported in <1% of patients. Combination Use: Adverse events for combination use are summarized in Tables 3 and 4. Vinorelbine Injection USP in Combination with Cisplatin: Vinorelbine Injection USP plus Cisplatin versus Single-Agent Cisplatin (Table 3): Myelosuppression was the predominant toxicity in patients receiving combination therapy, Grade 3 and 4 granulocytopenia of 82% compared to 5% in the single-agent cisplatin arm. Fever and/or sepsis related to granulocytopenia occurred in 11% of patients on Vinorelbine Injection USP and cisplatin compared to 0% on the cisplatin arm. Four patients on the combination died of granulocytopenia-related sepsis. During this study, the use of granulocyte colony-stimulating factor [(G-CSF) filgrastim) was permitted, but not mandated, after the first course of treatment for patients who experienced Grade 3 or 4 granulocytopenia (xl,000 cells/mm 3 ) or in those who developed neutropenic fever between cycles of chemotherapy. Beginning 24 hours after completion of chemotherapy, G-CSF was started at a dose of 5 mcg/kg per day and continued until the total granulocyte count was >1000 cells/mm 3 on 2 successive determinations. G-CSF was not administered on the day of treatment. Grade 3 and 4 anemia occurred more frequently in the combination arm compared to control, 24% vs. 8%, respectively. Thrombocytopenia occurred in 6% of patients treated with Vinorelbine Injection USP plus cisplatin compared to 2% of patients treated with cisplatin. The incidence of severe non-hematologic toxicity was similar among the patients in both treatment groups. Patients receiving Vinorelbine Injection USP plus cisplatin compared to single-agent cisplatin experienced more Grade 3 and/or 4 peripheral numbness (2% vs. <1%), phlebitis/thrombosis/embolism (3% vs. <1%), and infection (6% vs. <1%). Grade 3-4 constipation and/or ileus occurred in 3% of patients treated with combination therapy and in 1% of patients treated with cisplatin. Seven deaths were reported on the combination arm; 2 were related to cardiac ischemia, 1 massive cerebrovascular accident, 1 multisystem failure due to an overdose of Vinorelbine Injection USP, and 3 from febrile neutropenia. One death, secondary to respiratory infection unrelated to granulocytopenia, occurred with single-agent cisplatin. Vinorelbine Injection USP plus Cisplatin versus Vindesine plus Cisplatin versus Single-Agent Vinorelbine (Table 4): Myelosuppression, specifically Grade 3 and 4 granulocytopenia, was significantly greater with the combination of Vinorelbine Injection USP plus cisplatin (79%) than with either single-agent Vinorelbine Injection USP (53%) or vindesine plus cisplatin (48%), P<0.0001. Hospitalization due to documented sepsis occurred in 4.4% of patients treated with Vinorelbine Injection USP plus cisplatin: 2% of patients treated with vindesine and cisplatin, and 4% of patients treated with single-agent Vinorelbine Injection USP . Grade 3 and 4 thrombocytopenia was infrequent in patients receiving combination chemotherapy and no events were reported with single-agent Vinorelbine Injection USP . The incidence of Grade 3 and/or 4 nausea and vomiting, alopecia, and renal toxicity were reported more frequently in the cisplatin-containing combinations compared to single-agent Vinorelbine Injection USP . Severe local reactions occurred in 2% of patients treated with combinations containing Vinorelbine Injection USP ; none were observed in the vindesine plus cisplatin arm. Grade 3 and 4 neurotoxicity was significantly more frequent in patents receiving vindesine plus cisplatin (17%) compared to Vinorelbine Injection USP plus cisplatin (7%) and single-agent vinorelbine (9%) (P<0.005). Cisplatin did not appear to increase the incidence of neurotoxicity observed with single-agent Vinorelbine Injection USP . Table 3: Selected Adverse Events From a Comparative Trial of Vinorelbine Injection USP plus Cisplatin versus Single-Agent Cisplatin* Vinorelbine Injection USP 25 mg/m 2 plus Cisplatin 100 mg/m 2 (n = 212) Cisplatin 100 mg/m 2 (n = 210) Adverse Event All Grades Grade 3 Grade 4 All Grades Grade 3 Grade 4 Bone Marrow Granulocytopenia Anemia Leukopenia Thrombocytopenia Febrile neutropenia Hepatic Elevated transaminase Renal Elevated creatinine Non-Laboratory Malaise/fatigue/lethargy Vomiting Nausea Anorexia Constipation Alopecia Weight loss Fever without infection Hearing Local (injection site reactions) Diarrhea Paresthesias Taste alterations Peripheral numbness Myalgia/arthralgia Phlebitis/thrombosis/embolism Weakness Dizziness/vertigo Infection Respiratory infection 89% 88% 88% 29% N/A 1% 37% 67% 60% 58% 46% 35% 34% 34% 20% 18% 17% 17% 17% 17% 11% 12% 10% 12% 9% 11% 10% 22% 21% 39% 4% N/A 0% 2% 12% 7% 14% 0% 3% 0% 1% 2% 4% <1% 2% <1% 0% 2% <1% 3% 2% <1% 5% 4% 60% 3% 19% 1% 11% 0% 2% 0% 6% 0% 0% 0% 0% 0% 0% 0% 0% <1% 0% 0% 0% 0% 0% <1% 0% <1% <1% 26% 72% 31% 21% N/A <1% 28% 49% 60% 57% 37% 16% 14% 21% 4% 18% 1% 11% 10% 15% 7% 3% <1% 7% 3% <1% 3% 4% 7% <1% 1% N/A <1% 4% 8% 10% 12% 0% 1% 0% <1% 0% 3% 0% 1% <1% 0% <1% <1% 0% 2% <1% <1% 3% 1% <1% 0% <1% 0% 0% <1% 0% 4% 0% 0% 0% 0% 0% 0% <1% 0% <1% 0% 0% 0% 0% <1% 0% 0% 0% 0% *Graded according to the standard SWOG criteria. Table 4. Selected Adverse Events from a Comparative Trial of Vinorelbine Injection USP Plus Cisplatin versus Vindesine Plus Cisplatin versus Single-Agent Vinorelbine Injection USP * Vinorelbine Injection USP /Cisplatin† Vindesine/Cisplatin‡ Vinorelbine Injection USP § Adverse Event All Grades Grade 3 Grade 4 All Grades Grade 3 Grade 4 All Grades Grade 3 Grade 4 Bone Marrow Neutropenia Leukopenia Thrombocytopenia Febrile neutropenia Hepatic Elevated bilirubin Renal Elevated creatinine Non-Laboratory Nausea/vomiting Alopecia Ototoxicity Local reactions Diarrhea Neurotoxicity ¶ 95% 94% 15% N/A 6% 46% 74% 51% 10% 17% 25% 44% 20% 40% 3% N/A N/A N/A 27% 7% 1% 2% 1.5% 7% 58% 17% 1% 4% N/A N/A 3% 0.5% 1% 0.5% 0% 0% 79% 82% 10% N/A 5% 37% 72% 56% 14% 7% 24% 58% 26% 24% 3% N/A N/A N/A 24% 14% 1% 0% 1% 16% 22% 3% 0.5% 2% N/A N/A 1% 0% 0% 0% 0% 1% 85% 83% 3% N/A 5% 13% 31% 30% 1% 22% 12% 44% 25% 26% 0% N/A N/A N/A 1% 2% 0% 2% 0% 8% 28% 6% 0% 4% N/A N/A 1% 0% 0% 0% 0.5% 0.5% *Grade based on criteria from the World Health Organization (WHO). † n=194 to 207; all patients receiving Vinorelbine Injection USP /cisplatin with laboratory and non-laboratory data. ‡ n=173 to 192; all patients receiving vindesine/cisplatin with laboratory and non-laboratory data. § n =165 to 201; all patients receiving Vinorelbine Injection USP with laboratory and non-laboratory data. ¶ Neurotoxicity includes peripheral neuropathy and constipation. Observed During Clinical Practice: in addition to the adverse events reported from clinical trials, the following events have been identified during post-approval use of Vinorelbine Injection USP. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Vinorelbine Injection USP . Body as a Whole: Systemic allergic reactions reported as anaphylaxis, pruritus, urticaria, and angioedema; flushing; and radiation recall events such as dermatitis and esophagitis (see PRECAUTIONS ) have been reported. Hematologic: Thromboembolic events, including pulmonary embolus and deep venous thrombosis, have been reported primarily in seriously ill and debilitated patients with known predisposing risk factors for these events. Neurologic: Peripheral neurotoxicities such as, but not limited to, muscle weakness and disturbance of gait; have been observed in patients with and without prior symptoms. There may be increased potential for neurotoxicity in patients with pre-existing neuropathy, regardless of etiology, who receive Vinorelbine Injection USP . Vestibular and auditory deficits have been observed with Vinorelbine Injection USP , usually when used in combination with cisplatin. Skin: Injection site reactions, including localized rash and urticaria, blister formation, and skin sloughing have been observed in clinical practice. Some of these reactions may be delayed in appearance. Gastrointestinal: Dysphagia, mucositis, and pancreatitis have been reported. Cardiovascular: Hypertension, hypotension, vasodilation, trichycardia, and pulmonary edema have been reported. Pulmonary: Pneumonia has been reported. Musculoskeletal: Headache has been reported, with and without other musculosketetal aches and pains. Other: Pain in tumor-containing tissue, back pain, and abdominal pain have been reported. Electrolyte abnormalities, including hyponatremia with or without the syndrome of inappropriate ADH secretion, have been reported in seriously ill and debilitated patients. Combination Use: Patients with prior exposure to paclitaxel and who have demonstrated neuropathy should he monitored closely for new or worsening neuropathy. Patients who have experienced neuropathy with previous drug regimens should be monitored for symptoms of neuropathy while receiving Vinorelbine Injection USP. Vinorelbine Injection USP may result in radiosensitizing effects with prior or concomitant radiation therapy (see PRECAUTIONS ).

<table ID="_RefID53" width="101%"> <caption>Table 2: Summary of Adverse Events in 365 Patients Receiving Single-Agent Vinorelbine Injection USP *&#x2020;:</caption> <col width="44%"/> <col width="11%"/> <col width="8%"/> <col width="11%"/> <col width="8%"/> <col width="11%"/> <col width="8%"/> <tbody> <tr> <td align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph> <content styleCode="bold">Adverse Event</content> </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">All Patients (n=365)</content> </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">NSCLC (n=143)</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Bone Marrow Granulocytopenia </paragraph> </td> <td colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph> &lt;2,000 cells/mm³ </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph> 90% </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph> 80% </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"/> <td colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>&lt;500 cells/mm³ </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>36% </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>29% </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Leukopenia </paragraph> </td> <td colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>&lt;4,000 cells/mm³ </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>92% </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>81% </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"/> <td colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>&lt;1,000 cells/mm³ </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>15% </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>12% </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Thrombocytopenia </paragraph> </td> <td colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>&lt;100,000 cells/mm³ </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>5% </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>4% </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"/> <td colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>&lt;50,000 cells/mm³ </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>1% </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>1% </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph>Anemia </paragraph> </td> <td colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>&lt;11 g/dL </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>83% </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>77% </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="top"> <paragraph> </paragraph> </td> <td colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>&lt;8 g/dL </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>9% </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph>1% </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Hospitalizations due to granulocytopenic complications </paragraph> </td> <td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"/> <td align="center" colspan="2" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> 9% </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> 8% </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule " valign="middle"/> <td align="center" colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>All Grades </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Grade 3 </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Grade 4 </paragraph> </td> </tr> <tr> <td align="center" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>Adverse Event </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>All Patients </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>NSCLC </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>All Patients </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>NSCLC </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>All Patients </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>NSCLC </paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule " valign="top"> <paragraph>Clinical Chemistry Elevations Total Bilirubin (n = 351) SGOT (n = 346) General Asthenia Injection Site Reactions Injection Site Pain Phlebitis Digestive Nausea Vomiting Constipation Diarrhea Peripheral Neuropathy&#x2021; Dyspnea Alopecia </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 13% 67% 36% 28% 16% 7% 44% 20% 35% 17% 25% 7% 12% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 9% 54% 27% 38% 13% 10% 34% 15% 29% 13% 20% 3% 12% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 4% 5% 7% 2% 2% &lt;1% 2% 2% 3% 1% 1% 2% &#x2264;1% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 3% 2% 5% 5% 1% 1% 1% 1% 2% 1% 1% 2% 1% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 3% 1% 0% 0% 0% 0% 0% 0% 0% 0% &lt;1% 1% 0% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 2% 1% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% 0% </paragraph> </td> </tr> </tbody> </table>

<table ID="_RefID72" width="100%"> <caption>Table 3: Selected Adverse Events From a Comparative Trial of Vinorelbine Injection USP plus Cisplatin versus Single-Agent Cisplatin*</caption> <col width="23%"/> <col width="19%"/> <col width="17%"/> <col width="16%"/> <col width="9%"/> <col width="8%"/> <col width="8%"/> <tbody> <tr> <td styleCode="Rrule Lrule Toprule " valign="middle"/> <td align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph> <content styleCode="bold">Vinorelbine Injection USP </content>25 mg/m² plus Cisplatin 100 mg/m²(n = 212) </paragraph> </td> <td align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph>Cisplatin 100 mg/m² (n = 210) </paragraph> </td> </tr> <tr> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Adverse Event </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>All Grades </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Grade 3 </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Grade 4 </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>All Grades </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Grade 3 </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Grade 4 </paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> <content styleCode="bold">Bone Marrow</content> Granulocytopenia Anemia Leukopenia Thrombocytopenia <content styleCode="bold">Febrile neutropenia</content> <content styleCode="bold">Hepatic</content> Elevated transaminase <content styleCode="bold">Renal</content> Elevated creatinine <content styleCode="bold">Non-Laboratory</content> Malaise/fatigue/lethargy Vomiting Nausea Anorexia Constipation Alopecia Weight loss Fever without infection Hearing Local (injection site reactions) Diarrhea Paresthesias Taste alterations Peripheral numbness Myalgia/arthralgia Phlebitis/thrombosis/embolism Weakness Dizziness/vertigo Infection Respiratory infection </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 89% 88% 88% 29% N/A 1% 37% 67% 60% 58% 46% 35% 34% 34% 20% 18% 17% 17% 17% 17% 11% 12% 10% 12% 9% 11% 10% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 22% 21% 39% 4% N/A 0% 2% 12% 7% 14% 0% 3% 0% 1% 2% 4% &lt;1% 2% &lt;1% 0% 2% &lt;1% 3% 2% &lt;1% 5% 4% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 60% 3% 19% 1% 11% 0% 2% 0% 6% 0% 0% 0% 0% 0% 0% 0% 0% &lt;1% 0% 0% 0% 0% 0% &lt;1% 0% &lt;1% &lt;1% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 26% 72% 31% 21% N/A &lt;1% 28% 49% 60% 57% 37% 16% 14% 21% 4% 18% 1% 11% 10% 15% 7% 3% &lt;1% 7% 3% &lt;1% 3% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 4% 7% &lt;1% 1% N/A &lt;1% 4% 8% 10% 12% 0% 1% 0% &lt;1% 0% 3% 0% 1% &lt;1% 0% &lt;1% &lt;1% 0% 2% &lt;1% &lt;1% 3% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 1% &lt;1% 0% &lt;1% 0% 0% &lt;1% 0% 4% 0% 0% 0% 0% 0% 0% &lt;1% 0% &lt;1% 0% 0% 0% 0% &lt;1% 0% 0% 0% 0% </paragraph> </td> </tr> </tbody> </table>

<table ID="_RefID73" width="99%"> <caption>Table 4. Selected Adverse Events from a Comparative Trial of Vinorelbine Injection USP Plus Cisplatin versus Vindesine Plus Cisplatin versus Single-Agent Vinorelbine Injection USP *</caption> <col width="17%"/> <col width="12%"/> <col width="10%"/> <col width="10%"/> <col width="10%"/> <col width="8%"/> <col width="8%"/> <col width="10%"/> <col width="8%"/> <col width="8%"/> <tbody> <tr> <td styleCode="Rrule Lrule Toprule " valign="middle"/> <td align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph> <content styleCode="bold">Vinorelbine Injection USP </content>/Cisplatin&#x2020; </paragraph> </td> <td align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph>Vindesine/Cisplatin&#x2021; </paragraph> </td> <td align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph> <content styleCode="bold">Vinorelbine Injection USP </content>&#xA7; </paragraph> </td> </tr> <tr> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Adverse Event </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>All Grades </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Grade 3 </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Grade 4 </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>All Grades </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Grade 3 </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Grade 4 </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>All Grades </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Grade 3 </paragraph> </td> <td align="center" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Grade 4 </paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> <content styleCode="bold">Bone Marrow</content> Neutropenia Leukopenia Thrombocytopenia <content styleCode="bold">Febrile neutropenia</content> <content styleCode="bold">Hepatic</content> Elevated bilirubin <content styleCode="bold">Renal</content> Elevated creatinine <content styleCode="bold">Non-Laboratory</content> Nausea/vomiting Alopecia Ototoxicity Local reactions Diarrhea Neurotoxicity^&#xB6; </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 95% 94% 15% N/A 6% 46% 74% 51% 10% 17% 25% 44% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 20% 40% 3% N/A N/A N/A 27% 7% 1% 2% 1.5% 7% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 58% 17% 1% 4% N/A N/A 3% 0.5% 1% 0.5% 0% 0% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 79% 82% 10% N/A 5% 37% 72% 56% 14% 7% 24% 58% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 26% 24% 3% N/A N/A N/A 24% 14% 1% 0% 1% 16% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 22% 3% 0.5% 2% N/A N/A 1% 0% 0% 0% 0% 1% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 85% 83% 3% N/A 5% 13% 31% 30% 1% 22% 12% 44% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 25% 26% 0% N/A N/A N/A 1% 2% 0% 2% 0% 8% </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule " valign="middle"> <paragraph> 28% 6% 0% 4% N/A N/A 1% 0% 0% 0% 0.5% 0.5% </paragraph> </td> </tr> </tbody> </table>