Ultravist Injection

ULTRAVIST® Injection is an iodinated contrast agent indicated for:

Intra-Arterial Procedures*

• 150 mg Iodine per mL for intra-arterial digital subtraction angiography (IA-DSA) • 300 mg Iodine per mL for cerebral arteriography and peripheral arteriography • 370 mg Iodine per mL for coronary arteriography and left ventriculography, visceral angiography, and aortography

Intravenous Procedures*

• 240 mg Iodine per mL for peripheral venography • 300 mg Iodine per mL for excretory urography • 300 mg Iodine per mL and 370 mg Iodine per mL for contrast Computed Tomography (CT) of the head and body (intrathoracic, intra-abdominal and retroperitoneal regions) for the evaluation of neoplastic and non-neoplastic lesions. The usefulness of contrast enhancement for the investigation of the retrobulbar space and of low grade or infiltrative glioma has not been demonstrated.

*For information on the concentrations and doses for the Pediatric Population [see Dosage and Administration (2.3) and Use in Specific Populations (8.4)].

• Do not administer Ultravist Injection intrathecally. Inadvertent intrathecal administration may cause death, convulsions, cerebral hemorrhage, coma, paralysis, arachnoiditis, acute renal failure, cardiac arrest, seizures, rhabdomyolysis, hyperthermia, and brain edema. • Preparatory dehydration (for example, prolonged fasting and the administration of a laxative) before Ultravist Injection is contraindicated in pediatric patients because of risk of acute renal failure.

The most important adverse drug reactions in patients receiving ULTRAVIST are anaphylactoid shock, contrast induced acute kidney injury, coma, cerebral infarction, stroke, brain edema, convulsion, arrhythmia, cardiac arrest, myocardial ischemia, myocardial infarction, cardiac failure, bradycardia, cyanosis, hypotension, shock, dyspnea, pulmonary edema, respiratory insufficiency and aspiration.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect or predict the rates observed in practice.

The following table of incidence of reactions is based upon controlled clinical trials in which Ultravist Injection was administered to 1142 patients. This listing includes all reported adverse reactions regardless of attribution.

Adverse reactions are listed by System Organ Class and in decreasing order of occurrence for rates greater than 1% in the ULTRAVIST group: see Table 3.

Table 3: ADVERSE REACTIONS REPORTED IN > 1% OF PATIENTS WHO RECEIVED Ultravist Injection IN CLINICAL TRIALS
System Organ Class	Adverse Reaction	Ultravist Injection
		N=1142 (%)
Nervous system disorders	Headache	46 (4)
	Dysgeusia	15 (1.3)
Eye disorders	Abnormal Vision	12 (1.1)
Cardiac disorders	Chest pain	18 (1.6)
Vascular disorders	Vasodilatation	30 (2.6)
Gastrointestinal disorders	Nausea	42 (3.7)
	Vomiting	22 (1.9)
Musculoskeletal and connective tissue disorders	Back pain	22 (1.9)
Renal and urinary disorders	Urinary urgency	21 (1.8)
General disorders and administration site conditions	Injection site and infusion site reactions (hemorrhage, hematoma, pain, edema, erythema, rash)	41 (3.7)
	Pain	13 (1.4)

One or more adverse reactions were recorded in 273 of 1142 (24%) patients during the clinical trials, coincident with the administration of Ultravist Injection or within the defined duration of the study follow-up period (24–72 hours). Ultravist Injection is often associated with sensations of warmth and/or pain.

Serious, life-threatening and fatal reactions have been associated with the administration of iodine-containing contrast media, including Ultravist Injection. In clinical trials 7/1142 patients given Ultravist Injection died 5 days or later after drug administration. Also, 10/1142 patients given Ultravist Injection had serious adverse events.

The following adverse reactions were observed in ≤  1% of the subjects receiving Ultravist Injection:

Cardiac disorders: atrioventricular block (complete), bradycardia, ventricular extrasystole

Gastrointestinal disorders: abdominal discomfort, abdominal pain, abdominal pain upper, constipation, diarrhea, dry mouth, dyspepsia, gastrointestinal disorder, gastrointestinal pain, salivation increased, stomach discomfort, rectal tenesmus

General disorders and administration site conditions: asthenia, chest discomfort, chills, excessive thirst, extravasation, feeling hot, hyperhidrosis, malaise, edema peripheral, pyrexia

Immune system disorders: asthma, face edema

Investigations: blood lactate dehydrogenase increased, blood urea increased, hemoglobin increased, white blood cell count increased

Musculoskeletal and connective tissue disorders: arthralgia, musculoskeletal pain, myasthenia, neck pain, pain in extremity

Nervous system disorders: agitation, confusion, convulsion, dizziness, hypertonia, hypesthesia, incoordination, neuropathy, somnolence, speech disorder, tremor, paresthesia, visual field defect

Psychiatric disorders: anxiety

Renal and urinary disorders: dysuria, renal pain, urinary retention

Respiratory, thoracic and mediastinal disorders: apnea, cough increased, dyspnea, hypoxia, pharyngeal edema, pharyngitis, pleural effusion, pulmonary hypertension, respiratory disorder, sore throat

Skin and subcutaneous tissue disorders: erythema, pruritus, rash, urticaria

Vascular disorders: coronary artery thrombosis, flushing, hypertension, hypotension, peripheral vascular disorder, syncope, vascular anomaly

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Ultravist Injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions reported in foreign postmarketing surveillance and other trials with the use of Ultravist Injection include:

Cardiac disorders: cardiac arrest, ventricular fibrillation, atrial fibrillation, tachycardia, palpitations, congestive heart failure, myocardial infarction, angina pectoris

Ear and labyrinth disorders: vertigo, tinnitus

Endocrine disorders: hyperthyroidism, thyrotoxic crisis, hypothyroidism; Thyroid function tests indicative of hypothyroidism or transient thyroid suppression have been uncommonly reported following iodinated contrast administration to adult and pediatric patients, including infants. Some patients were treated for hypothyroidism.

Eye disorders: mydriasis, lacrimation disorder

Gastrointestinal disorders: dysphagia, swelling of salivary glands

Immune system disorders: anaphylactoid reaction (including fatal cases), respiratory arrest, anaphylactoid shock, angioedema, laryngeal edema, laryngospasm, bronchospasm, hypersensitivity

Musculoskeletal and connective tissue disorders: compartment syndrome in case of extravasation

Nervous system disorders: cerebral ischemia/infarction, paralysis, paresis, transient cortical blindness, aphasia, coma, unconsciousness, amnesia, hypotonia, aggravation of myasthenia gravis symptoms

Renal and urinary disorders: renal failure, hematuria

Respiratory, thoracic and mediastinal disorders: pulmonary edema, acute respiratory distress syndrome, asthma

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)].

Vascular disorders: vasospasm

Pediatrics

The overall character, quality, and severity of adverse reactions in pediatric patients are generally similar to those reported in adult patients. Additional adverse reactions reported in pediatric patients from foreign marketing surveillance or other information are: epistaxis, angioedema, migraine, joint disorder (effusion), muscle cramps, mucous membrane disorder (mucosal swelling), conjunctivitis, hypoxia, fixed eruptions, vertigo, diabetes insipidus, and brain edema[see Use in Specific Populations (8.4)].

The adverse effects of overdosage are life-threatening and affect mainly the pulmonary and cardiovascular systems. Treatment of an overdosage is directed toward the support of all vital functions, and prompt institution of symptomatic therapy.

Ultravist Injection binds negligibly to plasma or serum protein and can, therefore, be dialyzed.

Instruct patients receiving Ultravist Injection to inform their physician or healthcare provider of the following:

• If they are pregnant [see Use in Specific Populations (8.1)] • If they are diabetic or if they have multiple myeloma, pheochromocytoma, sickle cell disease or thyroid disorder [see Warnings and Precautions (5.2, 5.5)] • If they are allergic to any drugs or food, or if they have immune, autoimmune or immune deficiency disorders. Also, if they have had any reaction to previous injections of dyes used for x-ray procedures [see Warnings and Precautions (5.1)] • All medications they are currently taking, including non-prescription (over-the-counter) drugs • Advise patients to inform their physician if they develop a rash after receiving ULTRAVIST [see Warnings and Precautions (5.9)]   Manufactured for:   Bayer HealthCare Pharmaceuticals Inc.
Whippany, NJ 07981   Manufactured in Germany

©2017, Bayer HealthCare Pharmaceuticals Inc. All rights reserved.

The following are representative examples of Ultravist labeling. See the "How Supplied" section for a complete listing of all components.

Consult your pharmacist.

How to use Ultravist Vial

Consult your pharmacist.

Consult your pharmacist.

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

Notes

No monograph available at this time.

Missed Dose

Consult your pharmacist.

Storage

Consult your pharmacist.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2016. Copyright(c) 2016 First Databank, Inc.