Vasodilator

Inomax

Approved 23 Dec 1999InhalationGas

The FDA lists this product in 3 strengths and forms.

Indications

INOmax ® 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. INOmax 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

INOmax 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

Rebound: Abrupt discontinuation of INOmax may lead to worsening oxygenation and increasing pulmonary artery pressure ( 5.1 ). Methemoglobinemia: Methemoglobin increases with the dose of nitric oxide; following discontinuation or reduction of nitric oxide, methemoglobin levels return to baseline over a period of hours ( 5.2 ). Elevated NO 2 Levels: Monitor NO 2 levels ( 5.3 ). Heart Failure: In patients with pre-existing left ventricular dysfunction, INOmax may increase pulmonary capillary wedge pressure leading to pulmonary edema ( 5.4 ).

5.1Rebound Pulmonary Hypertension

Syndrome following Abrupt Discontinuation Wean from INOmax [see Dosage and Administration (2.2) ]. Abrupt discontinuation of INOmax 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 INOmax 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 INOmax; it can take 8 hours or more before steady-state methemoglobin levels are attained. Monitor methemoglobin and adjust the dose of INOmax to optimize oxygenation. If methemoglobin levels do not resolve with decrease in dose or discontinuation of INOmax, additional therapy may be warranted to treat methemoglobinemia [see Overdosage (10) ].

At a glance

Brand name: Inomax
Active substance: nitric oxide
Pharmacologic class: Vasodilator
Route: Inhalation
Dosage form: Gas
Applicant: Mallinckrodt Ireland
Status: Discontinued
FDA approval: 23 Dec 1999
Application: NDA020845-002

Indications

Warnings and precautions

5.1Rebound Pulmonary Hypertension

5.2Hypoxemia from Methemoglobinemia

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) ] The most common adverse reaction is hypotension. ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact INO Therapeutics at 1-877-566-9466 and http://www.inomax.com/ or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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

Inomax

Indications

Contraindications

Warnings and precautions

5.1Rebound Pulmonary Hypertension

5.2Hypoxemia from Methemoglobinemia

At a glance

Two medicines in one question?

Inomax

Indications

Contraindications

Warnings and precautions

5.1Rebound Pulmonary Hypertension

5.2Hypoxemia from Methemoglobinemia

At a glance

Two medicines in one question?

5.3Airway Injury from Nitrogen Dioxide

5.4Worsening Heart Failure Patients

Interactions

7.1Nitric Oxide Donor Agents

Adverse reactions

6.1Clinical Trials Experience

6.2Post-Marketing Experience

Composition

Strengths and forms

Official product information