Vasodilator

Ulspira

Approved 27 Jul 2023InhalationGas

Indications

ULSPIRA™ is indicated to improve oxygenation and reduce the need for extracorporeal membrane oxygenation in term and near-term (>34 weeks gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension in conjunction with ventilatory support and other appropriate agents. ULSPIRA is a vasodilator indicated to improve oxygenation and reduce the need for extracorporeal membrane oxygenation in term and near- term (>34 weeks gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension in conjunction with ventilatory support and other appropriate agents.

Contraindications

ULSPIRA is contraindicated in neonates dependent on right-to-left shunting of blood. Neonates dependent on right-to-left shunting of blood (4).

Warnings and precautions

5.1Rebound Pulmonary Hypertension

Syndrome following Abrupt Discontinuation Wean from ULSPIRA [see Dosage and Administration (2.2)]. Abrupt discontinuation of ULSPIRA may lead to worsening oxygenation and increasing pulmonary artery pressure, i.e., Rebound Pulmonary Hypertension Syndrome. Signs and symptoms of Rebound Pulmonary Hypertension Syndrome include hypoxemia, systemic hypotension, bradycardia, and decreased cardiac output. If Rebound Pulmonary Hypertension occurs, reinstate ULSPIRA therapy immediately.

5.2Hypoxemia from Methemoglobinemia

Nitric oxide combines with hemoglobin to form methemoglobin, which does not transport oxygen. Methemoglobin levels increase with the dose of ULSPIRA; it can take 8 hours or more before steady-state methemoglobin levels are attained. Monitor methemoglobin and adjust the dose of ULSPIRA to optimize oxygenation. If methemoglobin levels do not resolve with decrease in dose or discontinuation of ULSPIRA, additional therapy may be warranted to treat methemoglobinemia [see Overdosage (10)].

5.3Airway Injury from Nitrogen Dioxide

Nitrogen dioxide (NO2) forms in gas mixtures containing NO and O2. Nitrogen dioxide may cause airway inflammation and damage to lung tissues. If there is an unexpected change in NO2 concentration, or if the NO2 concentration reaches 3 ppm when measured in the breathing circuit, then the delivery system should be assessed in accordance with the Nitric Oxide Delivery System O&M Manual troubleshooting section, and the NO2 analyzer should be recalibrated.

At a glance

Brand name: Ulspira
Active substance: nitric oxide
Pharmacologic class: Vasodilator
Route: Inhalation
Dosage form: Gas
Applicant: Airgas Therap
Status: Prescription
FDA approval: 27 Jul 2023
Application: ANDA203144-001

Indications

Warnings and precautions

5.1Rebound Pulmonary Hypertension

5.2Hypoxemia from Methemoglobinemia

5.3Airway Injury from Nitrogen Dioxide

Adverse reactions

The following adverse reactions are discussed elsewhere in the label; Hypoxemia [see Warnings and Precautions (5.2)] Worsening Heart Failure [see Warnings and Precautions (5.4)]

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 reaction information from the clinical studies does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Controlled studies have included 325 patients on nitric oxide doses of 5 to 80 ppm and 251 patients on placebo. Total mortality in the pooled trials was 11% on placebo and 9% on nitric oxide, a result adequate to exclude nitric oxide mortality being more than 40% worse than placebo. In both the NINOS and CINRGI studies, the duration of hospitalization was similar in nitric oxide and placebo-treated groups. From all controlled studies, at least 6 months of follow-up is available for 278 patients who received nitric oxide and 212 patients who received placebo.

Among these patients, there was no evidence of an adverse effect of treatment on the need for rehospitalization, special medical services, pulmonary disease, or neurological sequelae. In the NINOS study, treatment groups were similar with respect to the incidence and severity of intracranial hemorrhage, Grade IV hemorrhage, periventricular leukomalacia, cerebral infarction, seizures requiring anticonvulsant therapy, pulmonary hemorrhage, or gastrointestinal hemorrhage.

In CINRGI, the only adverse reaction (>2% higher incidence on nitric oxide than on placebo) was hypotension (14% vs. 11%).

6.2Post-Marketing Experience

Post marketing reports of accidental exposure to nitric oxide for inhalation in hospital staff has been associated with chest discomfort, dizziness, dry throat, dyspnea, and headache. The most common adverse reaction is hypotension. (6). To report SUSPECTED ADVERSE REACTIONS, contact Airgas Therapeutics at 1-833-ULSPIRA (857-7472) and http://www.ulspira.com/ or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Ulspira

Indications

Contraindications

Warnings and precautions

5.1Rebound Pulmonary Hypertension

5.2Hypoxemia from Methemoglobinemia

5.3Airway Injury from Nitrogen Dioxide

At a glance

Two medicines in one question?

Ulspira

Indications

Contraindications

Warnings and precautions

5.1Rebound Pulmonary Hypertension

5.2Hypoxemia from Methemoglobinemia

5.3Airway Injury from Nitrogen Dioxide

At a glance

Two medicines in one question?

5.4Worsening Heart Failure Patients

Interactions

7.1Nitric Oxide Donor Agents

Adverse reactions

6.1Clinical Trials Experience

6.2Post-Marketing Experience

Composition

Official product information