Methods of distributing a pharmaceutical product comprising nitric oxide gas for inhalation

Abstract

Disclosed are methods of distributing a pharmaceutical product comprising nitric oxide gas for inhalation. The methods include, for example, obtaining a cylinder containing nitric oxide gas and supplying the cylinder to a medical provider along with instructions regarding how to administer the gas safely to pediatric patients, the instructions including information that patients who have pre-existing left ventricular dysfunction and are administered inhaled nitric oxide may experience pulmonary edema.

1 - 30 . (canceled) 
     
     
         31 . A method of providing pharmaceutically acceptable nitric oxide gas to a medical provider, the method comprising:
 obtaining a cylinder containing compressed, pharmaceutically acceptable nitric oxide gas in the form of a gaseous blend of nitric oxide and nitrogen;   supplying the cylinder containing compressed nitric oxide gas to a medical provider responsible for treating pediatric patients who have pulmonary hypertension, including some who do not have left ventricular dysfunction;   providing to the medical provider instructions regarding how to administer the nitric oxide gas safely to pediatric patients, the instructions including information that patients who have pre-existing left ventricular dysfunction and are administered inhaled nitric oxide may experience pulmonary edema.   
     
     
         32 . The method of  claim 31 , wherein the instructions appear in prescribing information supplied to the medical provider with the cylinder containing compressed nitric oxide gas. 
     
     
         33 . The method of  claim 31 , wherein the instructions include instructions regarding how to administer nitric oxide gas to neonates. 
     
     
         34 . The method of  claim 33 , wherein the neonates include neonates with hypoxic respiratory failure. 
     
     
         35 . The method of  claim 31 , wherein the instructions include information that patients who have pre-existing left ventricular dysfunction and are administered inhaled nitric oxide gas may experience increased pulmonary capillary wedge pressure (PCWP), leading to pulmonary edema. 
     
     
         36 . The method of  claim 35 , wherein the instructions appear in prescribing information supplied to the medical provider with the cylinder containing compressed nitric oxide gas. 
     
     
         37 . The method of  claim 31 , wherein the instructions include information regarding possible adverse events that a patient who has pre-existing left ventricular dysfunction may experience upon administration of inhaled nitric oxide, the adverse events including increased PCWP, pulmonary edema, systemic hypotension, bradycardia, and cardiac arrest. 
     
     
         38 . The method of  claim 37 , wherein the instructions appear in prescribing information supplied to the medical provider with the cylinder containing compressed nitric oxide gas. 
     
     
         39 . The method of  claim 31 , wherein the information that, in patients with pre-existing left ventricular dysfunction, inhaling nitric oxide may cause pulmonary edema is sufficient to cause a medical provider considering inhaled nitric oxide administration for a plurality of pediatric patients who have pulmonary hypertension and pre-existing left ventricular dysfunction to elect to avoid administering inhaled nitric oxide to one or more of the plurality of patients, in order to avoid putting the one or more patients at increased risk of pulmonary edema. 
     
     
         40 . The method of  claim 31 , further comprising:
 performing at least one diagnostic process to identify a first pediatric patient who has pulmonary hypertension and is a candidate for inhaled nitric oxide administration;   determining that the first patient has pre-existing left ventricular dysfunction;   evaluating the potential benefit of administering inhaled nitric oxide to the first patient vs. the potential risk that inhaled nitric oxide can induce pulmonary edema in patients who have pre-existing left ventricular dysfunction, in order to arrive at a decision of whether or not to administer inhaled nitric oxide to the first patient;   identifying a second pediatric patient as having pulmonary hypertension and not having left ventricular dysfunction; and   administering inhaled nitric oxide from the cylinder to the second patient, in accordance with the instructions.   
     
     
         41 . The method of  claim 31 , further comprising:
 performing at least one diagnostic process to identify a plurality of pediatric patients who have pulmonary hypertension and so are candidates for inhaled nitric oxide administration;   determining prior to administration of inhaled nitric oxide whether or not each patient of the plurality has pre-existing left ventricular dysfunction;   determining that a first patient of the plurality does not have pre-existing left ventricular dysfunction;   administering inhaled nitric oxide from the cylinder to the first patient in accordance with the instructions;   determining that other patients of the plurality do have pre-existing left ventricular dysfunction;   for each patient of the plurality determined to have pre-existing left ventricular dysfunction, evaluating on a case-by-case basis the potential benefit of administering inhaled nitric oxide vs. the potential risk that inhaled nitric oxide could induce pulmonary edema;   for at least one patient of the plurality determined to have pre-existing left ventricular dysfunction, determining that the potential benefit of administering inhaled nitric oxide outweighs the potential risk of pulmonary edema;   administering inhaled nitric oxide to the at least one patient;   for a second patient of the plurality determined to have pre-existing left ventricular dysfunction, determining that the potential risk of pulmonary edema outweighs the potential benefit of administering inhaled nitric oxide; and   excluding the second patient from administration of inhaled nitric oxide.   
     
     
         42 . A method of providing pharmaceutically acceptable nitric oxide gas to a medical provider, the method comprising:
 obtaining a cylinder containing compressed nitric oxide gas in the form of a gaseous blend of nitric oxide and nitrogen;   supplying the cylinder containing compressed nitric oxide gas to a medical provider responsible for treating pediatric patients who have pulmonary hypertension, including some who do not have pre-existing left ventricular dysfunction; and   providing to the medical provider (i) instructions regarding how to administer the nitric oxide safely to pediatric patients, the instructions including information that patients who have pre-existing left ventricular dysfunction and are administered inhaled nitric oxide may experience pulmonary edema, and (ii) a recommendation that, if pulmonary edema occurs in a patient who has pre-existing left ventricular dysfunction and is administered inhaled nitric oxide, the inhaled nitric oxide administration should be discontinued.   
     
     
         43 . The method of  claim 42 , wherein the instructions and the recommendation appear in prescribing information supplied to the medical provider with the cylinder containing compressed nitric oxide gas. 
     
     
         44 . The method of  claim 42 , wherein the instructions include instructions regarding administration of inhaled nitric oxide to neonates. 
     
     
         45 . The method of  claim 44 , wherein the neonates include neonates with hypoxic respiratory failure. 
     
     
         46 . The method of  claim 42 , wherein the instructions include information that patients who have pre-existing left ventricular dysfunction and are administered inhaled nitric oxide may experience increased PCWP, leading to pulmonary edema. 
     
     
         47 . The method of  claim 42 , wherein the instructions include information regarding of possible adverse events that a patient who has pre-existing left ventricular dysfunction may experience upon administration of inhaled nitric oxide, the adverse events including increased PCWP, pulmonary edema, systemic hypotension, bradycardia, and cardiac arrest. 
     
     
         48 . The method of  claim 42 , wherein the recommendation is sufficient to cause a medical provider to discontinue administration of inhaled nitric oxide to a pediatric patient who has pre-existing left ventricular dysfunction and develops pulmonary edema upon administration of inhaled nitric oxide. 
     
     
         49 . A method comprising:
 obtaining a source of nitric oxide gas comprising (a) a cylinder of compressed gas and/or (b) a device that delivers nitric oxide gas into an inspiratory limb of a breathing circuit, for inhalation by a patient;   supplying the source of nitric oxide gas to a medical provider responsible for treating pediatric patients who have pulmonary hypertension, including some who do not have left ventricular dysfunction; and   providing to the medical provider instructions regarding how to administer the nitric oxide gas safely to pediatric patients, the instructions including information that patients who have pre-existing left ventricular dysfunction and are administered inhaled nitric oxide may experience pulmonary edema.   
     
     
         50 . The method of  claim 49 , wherein the instructions appear in prescribing information supplied to the medical provider with the source of nitric oxide gas. 
     
     
         51 . The method of  claim 49 , wherein the instructions include instructions regarding how to administer the nitric oxide gas to neonates. 
     
     
         52 . The method of  claim 49 , wherein the instructions include information that patients who have pre-existing left ventricular dysfunction and are administered inhaled nitric oxide may experience increased PCWP, leading to pulmonary edema. 
     
     
         53 . The method of  claim 49 , wherein the instructions include information regarding possible adverse events that a patient who has pre-existing left ventricular dysfunction may experience upon administration of inhaled nitric oxide, the adverse events including increased PCWP, pulmonary edema, systemic hypotension, bradycardia, and cardiac arrest. 
     
     
         54 . The method of  claim 49 , wherein the information that, in patients with pre-existing left ventricular dysfunction, inhaled nitric oxide may cause pulmonary edema is sufficient to cause a medical provider considering inhaled nitric oxide administration for a plurality of pediatric patients who have pulmonary hypertension and pre-existing left ventricular dysfunction to elect to avoid administering inhaled nitric oxide to one or more of the plurality of patients in order to avoid putting the one or more patients at risk of pulmonary edema. 
     
     
         55 . A method comprising:
 obtaining a device that delivers nitric oxide gas into an inspiratory limb of a breathing circuit, for inhalation by a patient;   supplying the device to a medical provider responsible for treating pediatric patients who have pulmonary hypertension, including some who do not have pre-existing left ventricular dysfunction;   providing to the medical provider instructions regarding how to administer the nitric oxide gas safely to pediatric patients, the instructions including information that patients who have pre-existing left ventricular dysfunction and are administered inhaled nitric oxide may experience pulmonary edema.   
     
     
         56 . The method of  claim 55 , wherein the instructions appear in prescribing information supplied to the medical provider with the device. 
     
     
         57 . The method of  claim 55 , wherein the instructions include instructions regarding how to administer nitric oxide gas safely to neonates. 
     
     
         58 . The method of  claim 55 , wherein the instructions include information that patients who have pre-existing left ventricular dysfunction and are administered inhaled nitric oxide may experience increased PCWP, leading to pulmonary edema. 
     
     
         59 . The method of  claim 55 , wherein the instructions include information regarding possible adverse events that a patient who has pre-existing left ventricular dysfunction may experience upon administration of inhaled nitric oxide, the adverse events including increased PCWP, pulmonary edema, systemic hypotension, bradycardia, and cardiac arrest. 
     
     
         60 . The method of  claim 55 , further comprising:
 identifying a first pediatric patient who has pulmonary hypertension and is a candidate for inhaled nitric oxide administration;   determining that the first patient has pre-existing left ventricular dysfunction;   based on the information that patients who have pre-existing left ventricular dysfunction and are administered inhaled nitric oxide may experience pulmonary edema, evaluating the potential benefit of administering inhaled nitric oxide to the first patient vs. the potential risk of pulmonary edema described in the information;   using the device to administer inhaled nitric oxide to the first patient while monitoring the first patient for increased PCWP and/or pulmonary edema;   identifying a second pediatric patient as having pulmonary hypertension and not having pre-existing left ventricular dysfunction; and   using the device to administer inhaled nitric oxide to the second patient.