FDA label cab17e4b-44a0-40cc-b6ed-677bb12535a3

NOT FOR INTRATHECAL USE

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 ensure that this drug product is not administered intrathecally. Ionic iodinated contrast media inhibit blood coagulation, in vitro , more than nonionic contrast media. Nonetheless, it is prudent to avoid prolonged contact of blood with syringes containing ionic contrast media. 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. 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 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 medium reaction. Serious neurologic sequelae, including permanent paralysis, have been reported following injections of concentrated contrast media into arteries supplying the spinal cord. The injection of a contrast medium should never be made following the administration of vasopressors, since they strongly potentiate neurologic effects ( see PRECAUTIONS pertaining to Aortography). In patients with subarachnoid hemorrhage, a rare association between contrast administration and clinical deterioration, including convulsions and death, has been reported. Therefore, administration of intravascular iodinated ionic contrast media in these patients should be undertaken with caution. A definite risk exists in the use of intravascular contrast agents in patients who are known to have multiple myeloma. In such instances, there has been anuria resulting in progressive uremia, renal failure and eventually death. Although neither the contrast agent nor dehydration has separately proved to be the cause of anuria in myeloma, it has been speculated that the combination of both may be the causative factor. The risk in myelomatous patients is not a contraindication to the procedures; however, partial dehydration in the preparation of these patients for the examination is not recommended, since this may predispose to the precipitation of myeloma protein in the renal tubules. No form of therapy, including dialysis, has been successful in reversing this effect. Myeloma, which occurs most commonly in persons over age 40, should be considered before intravascular administration of a contrast agent. Administration of radiopaque materials to patients known or suspected to have 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 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. Contrast media have been shown to promote the phenomenon of sickling in individuals who are homozygous for sickle cell disease when the material is injected intravenously or intra-arterially. In patients with advanced renal disease, iodinated contrast media should be used with caution, and only when the need for the examination dictates, since excretion of the medium may be impaired. Patients with combined renal and hepatic disease, those with severe hypertension or congestive heart failure, and recent renal transplant recipients may present an additional risk. Renal failure has been reported in patients with liver dysfunction who were given an oral cholecystographic agent followed by an intravascular iodinated radiopaque agent, and also in patients with occult renal disease, notably diabetics and hypertensives. In these classes of patients, there should be no fluid restriction and every attempt should be made to maintain normal hydration, prior to contrast medium administration, since dehydration is the single most important factor influencing further renal impairment. Acute renal failure has been reported in diabetic patients with diabetic nephropathy and in susceptible nondiabetic patients (often elderly with pre-existing renal disease) following the administration of iodinated contrast agents. Therefore, careful consideration of the potential risks should be given before performing this radiographic procedure in these patients. Caution should be exercised in performing contrast medium studies in patients with endotoxemia and/or those with elevated body temperatures. Reports of thyroid storm occurring 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 this drug. Serious 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 MD-76R to patients with a history of a severe cutaneous adverse reaction to MD-76R. Avoid accidental introduction of this preparation into the subarachnoid space, since even small amounts may produce convulsions and possible fatal reactions. Convulsions have occurred in patients with primary or metastatic cerebral lesions following administration of contrast media for contrast enhancement of CT brain images.

ADVERSE REACTIONS Adverse reactions to injectable contrast media fall into two categories: chemotoxic reactions and idiosyncratic reactions. Chemotoxic reactions result from the physio-chemical properties of the contrast media, the dose, and speed of injection. All hemodynamic disturbances and injuries to organs or vessels perfused by the contrast medium are included in this category. Idiosyncratic reactions include all other reactions. They occur more frequently in patients 20 to 40 years old. Idiosyncratic reactions may or may not be dependent on the amount of dose injected, the speed of injection, the mode of injection and the radiographic procedure. Idiosyncratic reactions are subdivided into minor, intermediate and severe. The minor reactions are self-limited and of short duration; the severe reactions are life-threatening and treatment is urgent and mandatory. Fatalities have been reported following the administration of iodine-containing contrast agents. Based upon clinical literature, the incidence of death is reported to range from one in 10,000 (0.01 percent) to less than one in 100,000 (0.001 percent). Nausea, vomiting, flushing, or a generalized feeling of warmth are the reactions seen most frequently with intravascular injection. Symptoms which may occur include chills, fever, sweating, headache, dizziness, pallor, weakness, severe retching and choking, wheezing, a rise or fall in blood pressure, facial or conjunctival petechiae, urticaria, pruritus, rash and other eruptions, edema, cramps, tremors, itching, sneezing and lacrimation. Antihistaminic agents may be of benefit; rarely, such reactions may be severe enough to require discontinuation of dosage. Although venous tolerance is usually good, there have been reports of a burning or stinging sensation or numbness, venospasm or venous pain, and partial collapse of the injected vein. Neutropenia or thrombophlebitis may occur. Tissue necrosis has occurred with extravasation. Severe reactions which may require emergency measures may take the form of a cardiovascular reaction characterized by peripheral vasodilatation with resultant hypotension and reflex tachycardia, dyspnea, agitation, confusion, convulsions, and cyanosis progressing to unconsciousness. Or, the histamine-liberating effect of these compounds may induce an allergic-like reaction, which may range in severity from rhinitis or angioneurotic edema to laryngeal or bronchial spasm or anaphylactoid shock. Extremely rare cases of disseminated intravascular coagulation resulting in death have been reported. Temporary renal shutdown or other nephropathy may occur. Thyroid function tests indicative of hypothyroidism or transient thyroid suppression have been uncommonly reported following iodinated contrast media administration to adult and pediatric patients, including infants. Some patients were treated for hypothyroidism. Skin and Subcutaneous Tissue Disorders: Reactions range from mild (e.g. rash, erythema, pruritus, urticaria and skin discoloration) to severe: [e.g. Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS)]. In addition to the adverse reactions described above, adverse reactions may sometimes occur as a consequence of the procedure for which the contrast agent is used. Adverse reactions in excretion urography have included cardiac arrest, ventricular fibrillation, anaphylaxis with severe asthmatic reaction, and flushing due to generalized vasodilation. In aortography , the risks of procedures include injury to the aorta and neighboring organs, pleural puncture, renal damage including infarction and acute tubular necrosis with oliguria and anuria, accidental selective filling of the right renal artery during the translumbar procedure in the presence of pre-existent renal disease, retroperitoneal hemorrhage from the translumbar approach, spinal cord injury and pathology associated with the syndrome of transverse myelitis, generalized petechiae, and death following hypotension, arrhythmia, and anaphylactoid reactions. Adverse reactions in pediatric angiocardiography have included arrhythmia and death. During peripheral arteriography , complications have occurred including hemorrhage from the puncture site, thrombosis of the vessel, and brachial plexus palsy following axillary artery injections. During selective coronary arteriography with or without left ventriculography, most patients will have transient ECG changes. Transient arrhythmias may occur infrequently. Ventricular fibrillation may result from manipulation of the catheter during the procedure or administration of the medium. Other reactions may include hypotension, chest pain, and myocardial infarction. Fatalities have been reported. Complications due to the procedure include hemorrhage, thrombosis, pseudoaneurysms at the puncture site, and dislodgment of arteriosclerotic plaques. Dissection of the coronary vessels and transient sinus arrest have occurred rarely. Adverse reactions in selective renal arteriography include nausea, vomiting, hypotension and hypertension.