Xenon Xe 129 Hyperpolarized

XENOVIEW ® , prepared from the Xenon Xe 129 Gas Blend, is indicated for use with magnetic resonance imaging (MRI) for evaluation of lung ventilation in adults and pediatric patients aged 6 years and older. Limitations of Use XENOVIEW has not been evaluated for use with lung perfusion imaging. XENOVIEW, prepared from the Xenon Xe 129 Gas Blend, is a hyperpolarized contrast agent indicated for use with magnetic resonance imaging (MRI) for evaluation of lung ventilation in adults and pediatric patients aged 6 years and older. Limitations of Use XENOVIEW has not been evaluated for use with lung perfusion imaging. ( 1 )

XENOVIEW, prepared from the Xenon Xe 129 Gas Blend by the HPX Hyperpolarizer, is a clear, colorless, odorless gas contained in a 300 mL, 500 mL, 750 mL or 1,000 mL XENOVIEW Dose Delivery Bag. Each bag contains at least 75 mL Dose Equivalent (DE) of hyperpolarized xenon Xe 129 in a volume of 250 mL to 750 mL total xenon and a total volume administered of 300 mL, 500 mL, 750 mL, or 1,000 mL. The strength is DE per volume administered (see Table 2). The minimum DE for a dose of XENOVIEW ® is 75 mL with a recommended DE target range of 75 mL to 100 mL. DE of greater than 100 mL is acceptable. Table 2. Minimum Dosage Strength for Each Dose Delivery Bag Dose Delivery Bag (mL) Minimum Dose Equivalent (mL) Total Volume Administered (mL) Minimum Dosage Strength * 300 75 300 75 mL DE per 300 mL total volume 500 75 500 75 mL DE per 500 mL total volume 750 75 750 75 mL DE per 750 mL total volume 1,000 75 1,000 75 mL DE per 1,000 mL total volume * Minimum Dosage Strength = mL Minimum Dose Equivalent per mL Total Volume Administered XENOVIEW is a clear, colorless, odorless gas contained in a XENOVIEW Dose Delivery Bag. The bag contains at least 75 mL DE of hyperpolarized xenon Xe 129 in a volume of 250 mL to 750 mL total xenon. The bag total volume administered is 300 mL, 500 mL, 750 mL, or 1,000 mL. The dosage strength is DE per volume administered. The minimum DE for a dose of XENOVIEW is 75 mL with a recommended DE target range of 75 mL to 100 mL. DE of greater than 100 mL is acceptable. ( 3 )

None. None. ( 4 )

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.

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.

8.1 Pregnancy Risk Summary XENOVIEW is minimally absorbed systemically following the inhalation route of administration, and maternal use is not expected to result in fetal exposure to the drug [see Clinical Pharmacology ( 12.3 )]. Adequately designed animal reproduction studies have not been conducted with hyperpolarized xenon Xe 129. Although not adequately designed to evaluate reproductive and developmental toxicity, there are animal reproduction data available in the literature. Animal reproduction studies were conducted in rats by administering an 80% Xe/20% O 2 gas mixture for 2 hours twice a week for 2 and 10 weeks, with no observed effects on fertility or pregnancy. Gas mixtures containing 70% to 75% Xe gas and 25% to 30% O 2 gas were found to be non-teratogenic in rats when administered for 24 hours. In a separate study, rats were administered an 80%/20% Xe/O 2 gas mixture for 2 hours twice a week from the first to nineteenth day of pregnancy with no observed effects on embryo-fetal development or signs of teratogenicity. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively.

8.2 Lactation Risk Summary XENOVIEW ® is minimally absorbed systemically following the inhalation route of administration, and breastfeeding is not expected to result in exposure of the infant to the drug [see Clinical Pharmacology ( 12.3 )]. There is no information on the presence of hyperpolarized xenon Xe 129 in human milk, the effect on the breastfed infant, or the effect on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for XENOVIEW ® and any potential adverse effects on the breastfed child from XENOVIEW or from the underlying maternal condition.

8.4 Pediatric Use The safety and effectiveness of XENOVIEW have been established in pediatric patients aged 6 years and older for use with MRI to evaluate lung ventilation. Use of XENOVIEW in this age group is supported by evidence from adequate and well-controlled studies in adults with additional safety data from published studies [see Adverse Reactions ( 6.1 ) and Clinical Studies ( 14 )] . Safety and effectiveness of XENOVIEW have not been established in pediatric patients less than 6 years of age.

8.5 Geriatric Use Of the total number of patients in clinical studies of XENOVIEW, 36 (43%) were 65 years of age and older, while 6 (7%) were 75 years of age and older. No overall differences in safety or effectiveness have been observed between patients 65 years of age and older and younger adult patients although the number of patients in the trials was not large enough to allow definitive comparison.

When hyperpolarized xenon Xe 129 gas is inhaled, a multi-nuclear capable MRI scanner can be used to image the hyperpolarized xenon Xe 129 distribution throughout the ventilated lung. Hyperpolarized xenon Xe 129 nuclei are directly detected by a Xe 129 MRI coil.