HYPERPOLARIZED xe-129-(Dec 2022)

Indn- To evaluate pulmonary function and imaging  

Comp-  XENOVIEW is a clear, colorless, odorless gas contained in a 1,000 mL  Dose Delivery Bag. e bag contains at least 75 mL DE of hyperpolarized xenon Xe 129 in a volume of 250 mL to 750 mL total xenon.

The recommended target dose of for adult and pediatric patients aged 12 years and older is 75 mL to 100 mL Dose Equivalent (DE) of hyperpolarized xenon Xe 129 by oral inhalation of the entire contents of one  Dose Delivery Bag.

ADR- The adverse reactions (> one patient) in efficacy trials were oropharyngeal pain, headache, and dizziness.

CI-  None. 

WARNINGS -

 Risk of Decreased Image Quality from Supplemental Oxygen: Supplemental oxygen administered simultaneously with  inhalation can cause degradation of image quality. For patients on supplemental oxygen, withhold oxygen inhalation for two breaths prior to  inhalation, and resume oxygen inhalation immediately following the imaging breath hold..

Pat Inform-

Dose Delivery Bags are supplied in a carton of 50 with attachable mouthpieces and affixable dose labels. 

Storage and Handling-                                                                                              Store at 20° to 25°C (68° to 77°F) for no more than 5 minutes after final DE measurement. Do not use and discard  60 minutes after filling of Dose Delivery Bag.

Store  Gas Blend at 20° to 25°C (68° to 77°F), with excursions permitted to 15°C to 30°C (59°F to 86°F).

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U.S.  APPROVED DRUGS DURING 2022                                        

Serial No 35

Name-        XENOVIEW

Acive  Ingredient -  Hyperpolarized Xe -129

Pharmacological clssificiation-  To evaluate pulmonary function and imaging                                                                                                                                      

  Date of  Approval-         23/12/2022      

HIGHLIGHTS OF PRESCRIBING INFORMATION-

 These highlights do not include all the information needed to use                             XENOVIEW safely and effectively.                                                                                    See full prescribing information for XENOVIEW. XENOVIEW (xenon Xe 129 hyperpolarized), for oral inhalation

Initial U.S. Approval: 2022

INDICATIONS AND USAGE-

 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 12 years and older.

Limitations of Use-                                                                                                    XENOVIEW has not been evaluated for use with lung perfusion imaging.

ADVERSE REACTIONS-

 The adverse reactions (> one patient) in efficacy trials were oropharyngeal pain, headache, and dizziness. 

CONTRAINDICATIONS--

 None. 

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.

 • 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.

DOSAGE AND ADMINISTRATION-

 • The recommended target dose of XENOVIEW for adult and pediatric patients aged 12 years and older is 75 mL to 100 mL Dose Equivalent (DE) of hyperpolarized xenon Xe 129 by oral inhalation of the entire contents of one XENOVIEW Dose Delivery Bag.

• Each bag contains at least 75 mL DE of hyperpolarized xenon Xe 129 with a recommended target DE range of 75 mL to 100 mL measured within 5 minutes of administration, in a volume of 250 mL to 750 mL total xenon with additional nitrogen, NF (99.999% purity) added to reach a total volume of 1,000 mL.

• Administer dose within 5 minutes of DE measurement. (2.2) • Initiate imaging immediately after inhalation.

DOSAGE FORMS AND STRENGTHS-

 • XENOVIEW is a clear, colorless, odorless gas contained in a 1,000 mL 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 strength is DE per 1,000 mL administered. The minimum DE for a dose of XENOVIEW is 75 mL with a recommended DE target range of 75 to 100 mL. DE of greater than 100 mL is acceptable. 

 HOW SUPPLIED/STORAGE AND HANDLING-                                                               How Supplied XENOVIEW (xenon Xe 129 hyperpolarized) is provided in a 1,000 mL XENOVIEW

Dose Delivery Bag (NDC 80534-1000-1). XENOVIEW -                                           Dose Delivery Bags are supplied in a carton of 50 with attachable mouthpieces and affixable dose labels. Xenon Xe 129 Gas Blend for preparation of XENOVIEW is supplied as a compressed gas under high pressure (2,105 pounds per square inch gauge [psig]) in size 302 aluminum cylinders (NDC 80534-6350- 1) with a volume of 6,350 liters.

Storage and Handling-                                                                                               Store XENOVIEW at 20° to 25°C (68° to 77°F) for no more than 5 minutes after final DE measurement. Do not use and discard XENOVIEW 60 minutes after filling of Dose Delivery Bag. Store Xenon Xe 129 Gas Blend at 20° to 25°C (68° to 77°F), with excursions permitted to 15°C to 30°C (59°F to 86°F).

Man- for: Polarean, Inc. 2500 Meridian Parkway, Suite 175 Durham, NC 27713 Tel: 1-844-936-6843 XENOVIEWTM is a trademark of Polarean, Inc. Doc #: 34660B

 CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                                   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. 12.2 Pharmacodynamics The MRI signal of hyperpolarized xenon Xe 129 is dependent on the volume of gas inhaled, degree of xenon Xe 129 isotopic enrichment, and degree of hyperpolarization..

3. Pharmacokinetics-                                                                                                   The pharmacokinetics of hyperpolarized xenon Xe 129 are similar to those of non-polarized xenon.

Distribution-                                                                                                              Xenon is a readily diffusible gas. Inhalation of xenon results in dispersion in the ventilated areas of the lung with uptake of a small amount of xenon into the pulmonary vessels followed by distribution to more distal organs.

The solubility of xenon is higher in fatty tissues than in aqueous tissues and body compartments such as plasma.

Elimination-                                                                                                                 Following a single breath hold, xenon is eliminated through exhalation with an elimination half-life of 14.5 seconds for a 75% Xe/25% N2 gas mixture and 14.3 seconds for a 25% Xe/75% N2 gas mixture.

USE IN SPECIFIC POPULATIONS

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 

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.

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.

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.

 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.

3. Pediatric Use-                                                                                                           The safety and effectiveness of XENOVIEW have been established in pediatric patients aged 12 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 literature. .

Although supportive safety data are available for pediatric patients 6 years to less than 12 years of age, use of XENOVIEW is not approved in this age group because the ageappropriate dose of XENOVIEW cannot be accurately administered.

Safety and effectiveness of XENOVIEW have not been established in pediatric patients less than 6 years of age.

4.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.