XENOVIEW

5 WARNINGS AND PRECAUTIONS Risk of Decreased Image Quality from Supplemental Oxygen : Supplemental oxygen administered simultaneously with XENOVIEW inhalation can cause degradation of image quality. For patients on supplemental oxygen, withhold oxygen inhalation for two breaths prior to XENOVIEW inhalation, and resume oxygen inhalation immediately following the imaging breath hold. ( 5.1 ) Risk of Transient Hypoxia : Inhalation of an anoxic gas such as XENOVIEW may cause transient hypoxemia in susceptible patients. Monitor all patients for oxygen saturation and symptoms of hypoxemia, and treat as clinically indicated. ( 5.2 ) 5.1 Risk of Decreased Image Quality from Supplemental Oxygen Supplemental oxygen administered simultaneously with XENOVIEW inhalation can cause degradation of image quality due to depolarization of XENOVIEW. For patients on supplemental oxygen, withhold oxygen inhalation for two breaths prior to XENOVIEW inhalation, and resume oxygen inhalation immediately following the imaging breath hold [see Dosage and Administration ( 2.2 )] . 5.2 Risk of Transient Hypoxia Inhalation of an anoxic gas such as XENOVIEW may cause transient hypoxemia in susceptible patients [see Adverse Reactions ( 6.1 )] . Monitor all patients for oxygen desaturation and symptoms of hypoxemia, and treat as clinically indicated.

6 ADVERSE REACTIONS The adverse reactions (> one patient) in efficacy trials in adults were oropharyngeal pain, headache, and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Polarean, Inc. at 1‑844-936-6843 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 the rates observed in practice. Adverse Reactions in Adult Patients The safety of XENOVIEW was evaluated in two prospective efficacy trials that enrolled a total of 83 adult patients with various lung disorders who were being evaluated for possible lung surgery [see Clinical Studies ( 14 ) ] . Mean age of these patients was 62 years, 88% were White and 69% were male. In these two trials, mean xenon gas volume per XENOVIEW dose was 330.2 mL and 81 of 83 patients (98%) received a single administration of XENOVIEW. For safety assessment, the volume of administered xenon gas in the XENOVIEW dose is noted rather than the DE, because isotopic enrichment and hyperpolarization are not known to affect the safety profile of xenon gas. Adverse reactions were reported in 12 (14%) of the 83 patients. Adverse reactions reported by more than one patient were oropharyngeal pain (n = 4 patients), headache (n = 2 patients), and dizziness (n = 2 patients). A hypersensitivity reaction that included transient pruritus and erythema occurred in one patient with a history of allergic reactions to several drugs, foods, and other substances. In pooled data of 123 adult patients from published studies, most of whom had lung disorders such as COPD, idiopathic pulmonary fibrosis, and asthma, who received 1 dose to 2 doses of hyperpolarized xenon Xe 129 with xenon volumes of approximately 500 mL to 1,000 mL of xenon gas per dose, the following transient adverse reactions were reported: numbness, tingling, euphoria, and dizziness. Overall frequency of these adverse reactions could not be determined from the published information. Adverse Reactions in Pediatric Patients In pooled data of 120 pediatric patients aged 6 to 18 years from published studies, most of whom had either asthma or cystic fibrosis, who received 1 dose to 2 doses of hyperpolarized xenon Xe 129 with xenon volumes based on predicted TLC, the following transient adverse reactions were reported: blood oxygen desaturation, heart rate elevation, numbness, tingling, dizziness, and euphoria. Overall frequency of these adverse reactions could not be determined from the published information. In one of the published studies of 23 pediatric patients aged 6 to 18 years, 11 of whom had cystic fibrosis and 12 of whom were healthy, the mean difference of SpO 2 % from baseline was -6% following hyperpolarized xenon Xe 129 administration with xenon volumes based on predicted total lung capacity. In the same study, the mean change in heart rate from baseline was +6.6 beats per minute following hyperpolarized xenon Xe 129 administration. Both reported oxygen desaturation and heart rate elevation resolved by 2 minutes post-dose without intervention.