FDA label 00fb7845-664a-44fe-986e-eb370ee7ece9

NOT FOR INTRATHECAL USE PHARMACY BULK PACKAGE IS NOT FOR DIRECT INFUSION

WARNINGS SEVERE ADVERSE EVENTS-INADVERTENT INTRATHECAL ADMINISTRATION: Serious adverse reactions have been reported due to the inadvertent intrathecal administration of iodinated contrast media that are not indicated for intrathecal use. These serious adverse reactions include: death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema. Special attention must be given to insure that this drug product is not administered intrathecally. Nonionic iodinated contrast media inhibit blood coagulation, in vitro , less than ionic contrast media. Clotting has been reported when blood remains in contact with syringes containing nonionic contrast media. The use of plastic syringes in place of glass syringes has been reported to decrease but not eliminate the likelihood of in vitro clotting. Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angiographic procedures with both ionic and nonionic contrast media. Therefore, meticulous intravascular administration technique is necessary, particularly during angiographic procedures, to minimize thromboembolic events. Numerous factors, including length of procedure, catheter and syringe material, underlying disease state, and concomitant medications may contribute to the development of thromboembolic events. For these reasons, meticulous angiographic techniques are recommended including close attention to guidewire and catheter manipulation, use of manifold systems and/or three way stopcocks, frequent catheter flushing with heparinized saline solutions, and minimizing the length of the procedure. Serious or fatal reactions have been associated with the administration of iodine-containing radiopaque media. It is of utmost importance to be completely prepared to treat any contrast agent reaction. Caution must be exercised in patients with severely impaired renal function, combined renal and hepatic disease, combined renal and cardiac disease, severe thyrotoxicosis, myelomatosis, or anuria, particularly when large doses are administered. (See PRECAUTIONS .) Intravascularly administered iodine-containing radiopaque media are potentially hazardous in patients with multiple myeloma or other paraproteinacious diseases, who are prone to disease-induced renal insufficiency and/or failure. Although neither the contrast agent nor dehydration has been proven to be the cause of renal insufficiency (or worsening renal insufficiency) in myelomatous patients, it has been speculated that the combination of both may be causative. Special precautions, including maintenance of normal hydration and close monitoring, are required. Partial dehydration in the preparation of these patients prior to injection is not recommended since this may predispose the patient to precipitation of the myeloma protein. Reports of thyroid storm following the intravascular use of iodinated radiopaque agents in patients with hyperthyroidism, or with an autonomously functioning thyroid nodule, suggest that this additional risk be evaluated in such patients before use of any contrast agent. Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions (SCAR) may develop from 1 hour to several weeks after intravascular contrast agent administration. These reactions include Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS). Reaction severity may increase and time to onset may decrease with repeat administration of contrast agent; prophylactic medications may not prevent or mitigate severe cutaneous adverse reactions. Avoid administering Oxilan to patients with a history of severe cutaneous adverse reaction to Oxilan. Administration of radiopaque materials to patients with known or suspected pheochromocytoma should be performed with extreme caution. If, in the opinion of the physician, the possible benefits of such procedures outweigh the considered risks, the procedures may be performed; however, the amount of radiopaque medium injected should be kept to an absolute minimum. The blood pressure should be assessed throughout the procedure and measures for treatment of a hypertensive crisis should be available. These patients should be monitored very closely during contrast enhanced procedures. Contrast agents may promote sickling in individuals who are homozygous for sickle cell disease when administered intravascularly.

ADVERSE REACTIONS For demographics, see CLINICAL TRIALS section. The following table of incidence of reactions is based upon controlled clinical studies in which OXILAN® was compared with a nonionic contrast agent (iohexol) in 531 patients. It includes all reported adverse events, regardless of attribution. Adverse reactions are listed by body system and in decreasing order of occurrence greater than 0.5% in the OXILAN® group. Body System Adverse Event Ioxilan (n = 531) Comparator (n = 542) Body as a Whole Headache 19 (3.6%) 15 (2.8%) Fever 9 (1.7%) 11 (2.0%) Hematoma at Injection Site 4 (0.8%) 0 (0%) Chills 3 (0.6%) 0 (0%) Cardiovascular Angina Pectoris 7 (1.3%) 11 (2.0%) Hypertension 6 (1.1%) 3 (0.6%) Bradycardia 4 (0.8%) 0 (0%) Hypotension 5 (0.9%) 3 (0.6%) Digestive Nausea 8 (1.5%) 7 (1.3%) Diarrhea 5 (0.9%) 4 (0.7%) Nausea with Vomiting 5 (0.9%) 5 (0.9%) Vomiting 3 (0.6%) 4 (0.7%) Nervous Dizziness 4 (0.8%) 1 (0.2%) Skin Urticaria 4 (0.8%) 4 (0.7%) Rash 3 (0.6%) 4 (0.7%) One or more adverse reactions were reported in 76 of 531 (14.3%) of patients in the clinical trials, coincidental with the administration of OXILAN® or within the study follow-up period of 24 to 72 hours. The incidence and type of adverse reactions were similar to those associated with the nonionic comparator (iohexol) used in the clinical trials. OXILAN®, as do other iodinated contrast agents, often causes warmth and/or pain on injection. The rates are similar to that of the iohexol comparator. Serious, life threatening and fatal reactions have been associated with the administration of iodine-containing contrast media. In all clinical trials 3/835 (0.3%) patients given OXILAN® and 3/542 (0.6%) given iohexol died 4 days or later after drug administration. In the controlled trials 8/531 (1.5%) patients given OXILAN® and 6/542 (1.1%) given iohexol had serious adverse events. The following adverse reactions were observed ≤ 0.5% of patients receiving OXILAN® Injection: BODY: allergic reaction, asthenia, chest and back pain, edema of the neck, facial edema, pain, peripheral edema; CARDIOVASCULAR: atrial fibrillation, syncope, tachycardia, vasodilation, ventricular extrasystole; DIGESTIVE: anorexia, constipation, dyspepsia, dysphagia, GI hemorrhage, ileus, liver failure; NERVOUS: hypotonia, nystagmus, paresthesia, somnolence, vertigo; RESPIRATORY: dyspnea, pharyngitis, rhinitis; SKIN: pruritus, sweating; SPECIAL SENSES: amblyopia, conjunctivitis, taste perversion, vision abnormality; UROGENITAL: anuria, dysuria, hematuria, infection of urinary tract, impairment of urination, kidney failure. Additional adverse events reported in postmarketing surveillance with the use of OXILAN® Injection include: bronchospasm.

<table ID="table2" width="80%"> <colgroup> <col styleCode="Lrule Rrule" align="left"/> <col styleCode="Lrule Rrule" align="center"/> <col styleCode="Lrule Rrule" align="center"/> <col styleCode="Lrule Rrule" align="center"/> </colgroup> <tbody> <tr styleCode="Botrule First Toprule"> <td styleCode="Lrule Rrule" align="left">Body System</td> <td styleCode="Lrule Rrule" align="center">Adverse Event</td> <td styleCode="Lrule Rrule" align="center">Ioxilan (n = 531)</td> <td styleCode="Lrule Rrule" align="center">Comparator (n = 542)</td> </tr> <tr styleCode="Botrule Toprule"> <td styleCode="Lrule Rrule" rowspan="4" align="left">Body as a Whole</td> <td styleCode="Lrule Rrule" align="center">Headache</td> <td styleCode="Lrule Rrule" align="center">19 (3.6%)</td> <td styleCode="Lrule Rrule" align="center">15 (2.8%)</td> </tr> <tr styleCode="Botrule Toprule"> <td styleCode="Lrule Rrule" align="center">Fever</td> <td styleCode="Lrule Rrule" align="center">9 (1.7%)</td> <td styleCode="Lrule Rrule" align="center">11 (2.0%)</td> </tr> <tr styleCode="Botrule Toprule"> <td styleCode="Lrule Rrule" align="center">Hematoma at Injection Site</td> <td styleCode="Lrule Rrule" align="center">4 (0.8%)</td> <td styleCode="Lrule Rrule" align="center">0 (0%)</td> </tr> <tr styleCode="Botrule Toprule"> <td styleCode="Lrule Rrule" align="center">Chills</td> <td styleCode="Lrule Rrule" align="center">3 (0.6%)</td> <td styleCode="Lrule Rrule" align="center">0 (0%)</td> </tr> <tr styleCode="Botrule Toprule"> <td styleCode="Lrule Rrule" rowspan="4" align="left">Cardiovascular</td> <td styleCode="Lrule Rrule" align="center">Angina Pectoris</td> <td styleCode="Lrule Rrule" align="center">7 (1.3%)</td> <td styleCode="Lrule Rrule" align="center">11 (2.0%)</td> </tr> <tr styleCode="Botrule Toprule"> <td styleCode="Lrule Rrule" align="center">Hypertension</td> <td styleCode="Lrule Rrule" align="center">6 (1.1%)</td> <td styleCode="Lrule Rrule" align="center">3 (0.6%)</td> </tr> <tr styleCode="Botrule Toprule"> <td styleCode="Lrule Rrule" align="center">Bradycardia</td> <td styleCode="Lrule Rrule" align="center">4 (0.8%)</td> <td styleCode="Lrule Rrule" align="center">0 (0%)</td> </tr> <tr styleCode="Botrule Toprule"> <td styleCode="Lrule Rrule" align="center">Hypotension</td> <td styleCode="Lrule Rrule" align="center">5 (0.9%)</td> <td styleCode="Lrule Rrule" align="center">3 (0.6%)</td> </tr> <tr styleCode="Botrule Toprule"> <td styleCode="Lrule Rrule" rowspan="4" align="left">Digestive</td> <td styleCode="Lrule Rrule" align="center">Nausea</td> <td styleCode="Lrule Rrule" align="center">8 (1.5%)</td> <td styleCode="Lrule Rrule" align="center">7 (1.3%)</td> </tr> <tr styleCode="Botrule Toprule"> <td styleCode="Lrule Rrule" align="center">Diarrhea</td> <td styleCode="Lrule Rrule" align="center">5 (0.9%)</td> <td styleCode="Lrule Rrule" align="center">4 (0.7%)</td> </tr> <tr styleCode="Botrule Toprule"> <td styleCode="Lrule Rrule" align="center">Nausea with Vomiting</td> <td styleCode="Lrule Rrule" align="center">5 (0.9%)</td> <td styleCode="Lrule Rrule" align="center">5 (0.9%)</td> </tr> <tr styleCode="Botrule Toprule"> <td styleCode="Lrule Rrule" align="center">Vomiting</td> <td styleCode="Lrule Rrule" align="center">3 (0.6%)</td> <td styleCode="Lrule Rrule" align="center">4 (0.7%)</td> </tr> <tr styleCode="Botrule Toprule"> <td styleCode="Lrule Rrule" align="left">Nervous</td> <td styleCode="Lrule Rrule" align="center">Dizziness</td> <td styleCode="Lrule Rrule" align="center">4 (0.8%)</td> <td styleCode="Lrule Rrule" align="center">1 (0.2%)</td> </tr> <tr styleCode="Botrule Toprule"> <td styleCode="Lrule Rrule" rowspan="2" align="left">Skin</td> <td styleCode="Lrule Rrule" align="center">Urticaria</td> <td styleCode="Lrule Rrule" align="center">4 (0.8%)</td> <td styleCode="Lrule Rrule" align="center">4 (0.7%)</td> </tr> <tr styleCode="Botrule Last Toprule"> <td styleCode="Lrule Rrule" align="center">Rash</td> <td styleCode="Lrule Rrule" align="center">3 (0.6%)</td> <td styleCode="Lrule Rrule" align="center">4 (0.7%)</td> </tr> </tbody> </table>