6.1Clinical 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 the rates observed in practice. The adverse events described in this section were observed in clinical trials involving 3174 subjects (including 2896 adults and 278 pediatric subjects ages 0 to 17 years) exposed to ProHance.
Approximately 48% of the subjects were men and ethnic distribution was 78% Caucasian, 6% Black, 3% Hispanic, 6% Asian, and 2% other. In 5% of the subjects, race was not reported. Average age was 47 years (range from 1 day to 91 years) and the exposure ranged from 0.03 to 0.3 mmol/kg. Overall, approximately 5.8% of subjects reported one or more adverse reactions during a follow-up period that ranged from 24 hours to 7 days after ProHance administration.
Table 2 lists adverse reactions that occurred in ≥ 0.4% subjects who received ProHance. Table 2: More frequent adverse reactions in clinical trials Reaction Rate (%) N = 3174 Nausea 1.4% Dysgeusia 0.9% Headache 0.7% Dizziness 0.4% Urticaria 0.4% The following additional adverse events occurred in fewer than 0.4% of the subjects: General disorders and administration site conditions: Asthenia; chest discomfort, facial edema, feeling hot, injection site coldness, injection site erythema, injection site pain, injection site warmth, pain, pyrexia Cardiac: Angina pectoris, palpitations, atrio-ventricular block first degree Ear and labyrinth disorders: Ear discomfort, tinnitus Eye disorders: Eye pruritis, lacrimation increased Gastrointestinal disorders: Abdominal discomfort, abdominal pain, diarrhea, dry mouth, gingival pain, oral pruritis, swollen tongue, vomiting Infections and infestations: Gingivitis, rhinitis Investigations: Alanine aminotransferase increased, aspartate aminotransferase increased, blood chloride increased, blood pressure immeasurable, blood urea decreased, hemoglobin decreased, heart rate increased Metabolism and nutrition disorders: Decreased appetite, hypoglycemia Musculoskeletal and connective tissue disorders: Back pain, musculoskeletal stiffness Nervous system disorders: Formication, hypoesthesia, hypokinesia, lethargy, loss of consciousness, migraine, paresthesia, presyncope, seizure, syncope, taste disorder Psychiatric disorders: Anxiety, mental status changes Respiratory, thoracic and mediastinal disorders: Cough, dry throat, dyspnea, nasal discomfort, throat irritation Skin and subcutaneous tissue disorders: Hyperhidrosis, pruritis, rash, rash morbilliform Vascular disorders: Flushing, hypotension, peripheral coldness, vascular rupture, vasodilatation, vasospasm
6.2Postmarketing Experience
The following adverse reactions have been identified during post approval use of ProHance or other GBCAs that were not observed in the clinical trials. 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. * Cases of acute renal failure have been reported in patients with pre-existing severe renal impairment.
The following adverse drug reactions have also been reported: General Disorders and Administration Site Conditions: 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. Cardiac disorders: Cardiac arrest, bradycardia, hypertension Gastrointestinal disorders: Acute pancreatitis with onset within 48 hours after GBCA administration Immune system disorders: Hypersensitivity/anaphylactoid reactions including cardiac arrest, cyanosis, pharyngeal edema, laryngospasm, bronchospasm, angioedema, cough, sneezing, conjunctivitis, eyelid edema, hyperhidrosis, urticaria [see Warnings and Precautions ( 5.3 )] .
Nervous system disorders: Coma, loss of consciousness, vasovagal reaction, tremor Respiratory, thoracic and mediastinal disorders: Respiratory arrest, acute respiratory distress syndrome, pulmonary edema Renal and urinary system disorders: Acute renal failure *
