1 INDICATIONS AND USAGE Gadoterate Meglumine Injection is a gadolinium-based contrast agent indicated for intravenous use with magnetic resonance imaging (MRI) in brain (intracranial), spine and associated tissues in adult and pediatric patients (including term neonates) to detect and visualize areas with disruption of the blood brain barrier (BBB) and/or abnormal vascularity.

Gadoterate Meglumine Injection is a gadolinium-based contrast agent indicated: for intravenous use with magnetic resonance imaging (MRI) in brain (intracranial), spine and associated tissues in adult and pediatric patients (including term neonates) to detect and visualize areas with disruption of the blood brain barrier (BBB) and/or abnormal vascularity.

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6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Nephrogenic systemic fibrosis [see Warnings and Precautions ( 5.2 )] .

Hypersensitivity reactions [see Warnings and Precautions ( 5.3 )].

Gadolinium Retention [see Warnings and Precautions ( 5.4 )] .

The most frequent (≥ 0.2%) adverse reactions in clinical studies were nausea, headache, injection site pain, injection site coldness, and rash.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Slate Run Pharmaceuticals, LLC at 1-888-341-9214 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Studies 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 the rates observed in clinical practice.

The data described below reflect Gadoterate Meglumine Injection exposure in 2867 patients, representing 2682 adults and 185 pediatric patients.

Overall, 55% of the patients were men.

In clinical trials where ethnicity was recorded, the ethnic distribution was 81% Caucasian, 11% Asian, 4% Black, and 4% others.

The average age was 53 years (range from < 1 week to 97 years).

Overall, 4% of patients reported at least one adverse reaction, primarily occurring immediately or within 24 hours following Gadoterate Meglumine Injection administration.

Most adverse reactions were mild or moderate in severity and transient in nature.

Table 2 lists adverse reactions that occurred in ≥ 0.2% patients who received Gadoterate Meglumine Injection.

Table 2: Adverse Reactions in Clinical Trials Reaction Rate (%) n=2867 Nausea 0.6% Headache 0.4% Injection Site Pain 0.4% Injection Site Coldness 0.2% Rash 0.2% Adverse reactions that occurred with a frequency < 0.2% in patients who received Gadoterate Meglumine Injection include: feeling cold, feeling hot, burning sensation, somnolence, pain, dizziness, dysgeusia, blood creatinine increased, hypotension, hypertension, asthenia, fatigue, injection site reactions (inflammation, extravasation, pruritus, swelling, warmth), paresthesia, pruritus, laryngeal discomfort, pain in extremity, vomiting, anxiety and palpitations.

Adverse Reactions in Pediatric Patients During clinical trials, 185 pediatric patients (52 aged < 24 months, 33 aged 2 - 5 years, 57 aged 6 – 11 years and 43 aged 12 - 17 years) received Gadoterate Meglumine Injection.

Overall, 7 pediatric patients (3.8%) reported at least one adverse reaction following Gadoterate Meglumine Injection administration.

The most frequently reported adverse reaction was headache (1.1%).

Most adverse events were mild in intensity and transient in nature.

6.2 Post-Marketing Experience The following additional adverse reactions have been identified during postmarketing use of Gadoterate Meglumine 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.

Table 3: Adverse Reactions in the Postmarketing Experience System Organ Class Adverse Reaction Cardiac Disorders bradycardia, tachycardia, arrhythmia Immune System Disorders hypersensitivity/anaphylactoid reactions including cardiac arrest, respiratory arrest, cyanosis, pharyngeal edema, laryngospasm, bronchospasm, angioedema, conjunctivitis, ocular hyperemia, eyelid edema, lacrimation increased, hyperhidrosis, urticaria Nervous System Disorders coma, convulsion, syncope, presyncope, parosmia, tremor Musculoskeletal and Connective Tissue Disorders muscle contracture, muscle weakness Gastrointestinal Disorders diarrhea, salivary hypersecretion, acute pancreatitis with onset within 48 hours after GBCA administration General Disorders and Administration Site Conditions malaise, fever Adverse events with variable onset and duration have been reported after GBCA administration [see Warnings and Precautions ( 5.4 )] .

These include fatigue, asthenia, pain syndromes, and heterogeneous clusters of symptoms in the neurological, cutaneous, and musculoskeletal systems.

Respiratory, Thoracic and Mediastinal Disorders Acute respiratory distress syndrome, pulmonary edema Skin and Subcutaneous Tissue Disorders NSF, in patients whose reports were confounded by the receipt of other GBCAs or in situations where receipt of other GBCAs could not be ruled out.

No unconfounded cases of NSF have been reported with Gadoterate Meglumine Injection.

Gadolinium-associated plaques Vascular Disorders superficial phlebitis