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

• US 8,846,112 B2
• Filed: 11/21/2012
• Issued: 09/30/2014
• Est. Priority Date: 06/30/2009
• Status: Active Grant

• Current Assignee: Mallinckrodt Critical Care Finance Inc (Mallinckrodt plc), Mallinckrodt Pharma Ip Trading DAC (Mallinckrodt plc), Therakos, Inc (Mallinckrodt plc)
• Original Assignee: INO Therapeutics LLC (Mallinckrodt plc)
• Inventors: Baldassarre, James S.
• Primary Examiner(s): Arnold, Ernst V
• Application Number:
  US13/683,236
• Publication Number:
  US 20130068223A1
• Time in Patent Office: 678 Days
• Field of Search: 424/718, 128/200.24, 423/405
• US Class Current: 424/718
• CPC Class Codes: A61B 5/02007 Evaluating blood vessel condition, e.g. elasticity, compliance
• CPC Class Codes: A61B 5/0205 Simultaneously evaluating both cardiovascular conditions and different types of body conditions, e.g. heart and respiratory condition
• CPC Class Codes: A61B 5/08 Detecting, measuring or recording devices for evaluating the respiratory organs A61B5/0205 takes precedence
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/7275 Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
• CPC Class Codes: A61B 5/7278 Artificial waveform generation or derivation, e.g. synthesising signals from measured signals A61B5/327 takes precedence
• CPC Class Codes: A61B 8/0883 for diagnosis of the heart
• CPC Class Codes: A61B 8/48 Diagnostic techniques A61B8/13 takes precedence
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/04 Nitro compounds
• CPC Class Codes: A61K 31/21 Esters, e.g. nitroglycerine, selenocyanates
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61M 16/0057 Pumps therefor
• CPC Class Codes: A61M 16/104 specially adapted for anaesthetics A61M16/18 takes precedence
• CPC Class Codes: A61M 16/12 by mixing different gases
• CPC Class Codes: A61M 60/139 inside the aorta, e.g. intra-aortic balloon pumps
• CPC Class Codes: A61M 60/295 Balloon pumps for circulatory assistance
• CPC Class Codes: A61M 60/497 for balloon pumps for circulatory assistance
• CPC Class Codes: A61M 60/841 of balloon pumps for circulatory assistance
• CPC Class Codes: A61M 60/857 : Implantable blood tubes
• CPC Class Codes: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 : Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: F17C 2201/058 : portable (<30 l)
• CPC Class Codes: F17C 2203/0646 : Aluminium
• CPC Class Codes: F17C 2221/014 : Nitrogen
• CPC Class Codes: F17C 2221/03 : Mixtures
• CPC Class Codes: F17C 2223/0123 : gaseous, e.g. CNG, GNC
• CPC Class Codes: F17C 2223/036 : Very high pressure (>80 bar)
• CPC Class Codes: F17C 2270/025 : Breathing
• CPC Class Codes: G06Q 99/00 : Subject matter not provided for in other groups of this subclass
• CPC Class Codes: G16H 20/10 : relating to drugs or medications, e.g. for ensuring correct administration to patients

Abstract

Disclosed are methods of distributing a pharmaceutical product comprising nitric oxide gas. The methods include supplying a source of nitric oxide gas to a medical provider, informing the medical provider about a recommended dose of inhaled nitric oxide gas for treatment of neonates with hypoxic respiratory failure, and providing a warning about use of inhaled nitric oxide in patients with pre-existing left ventricular dysfunction.

Claims

1. A method of providing pharmaceutically acceptable nitric oxide gas, 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 neonates who have hypoxic respiratory failure, including some who do not have left ventricular dysfunction;

providing to the medical provider (i) information that a recommended dose of inhaled nitric oxide gas for treatment of neonates with hypoxic respiratory failure is 20 ppm nitric oxide

and (ii) information that, in patients with pre-existing left ventricular dysfunction, inhaled nitric oxide may increase pulmonary capillary wedge pressure (PCWP), leading to pulmonary edema, the information of (ii) being sufficient to cause a medical provider considering inhaled nitric oxide treatment for a plurality of neonatal patients who (a) are suffering from a condition for which inhaled nitric oxide is indicated, and (b) have pre-existing left ventricular dysfunction, to elect to avoid treating one or more of the plurality of patients with inhaled nitric oxide in order to avoid putting the one or more patients at risk of pulmonary edema.

2. The method of claim 1, wherein the information of (i) and the information of (ii) appear in prescribing information supplied to the medical provider with the cylinder containing compressed nitric oxide gas.

3. The method of claim 1, further comprising:

performing at least one diagnostic process to identify a first neonatal patient who has hypoxic respiratory failure and is a candidate for 20 ppm inhaled nitric oxide treatment;

determining that the first neonatal patient has pre-existing left ventricular dysfunction;

evaluating the potential benefit of treating the first neonatal patient with 20 ppm inhaled nitric oxide vs. the potential risk that inhaled nitric oxide could cause an increase in PCWP leading to pulmonary edema in patients who have pre-existing left ventricular dysfunction, in order to arrive at a decision of whether or not to treat the first neonatal patient with inhaled nitric oxide;

identifying a second neonatal patient as having hypoxic respiratory failure and not having left ventricular dysfunction; and

treating the second neonatal patient with 20 ppm inhaled nitric oxide.

4. The method of claim 1, further comprising:

performing at least one diagnostic process to identify a plurality of neonatal patients who have hypoxic respiratory failure and are candidates for inhaled nitric oxide treatment;

determining prior to treatment with 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;

treating the first patient with 20 ppm inhaled nitric oxide;

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 treating the patient with 20 ppm inhaled nitric oxide vs. the potential risk that inhaled nitric oxide could cause an increase in PCWP, leading to pulmonary edema;

for at least one patient of the plurality determined to have pre-existing left ventricular dysfunction, determining that the potential benefit of the treatment outweighs the potential risk described in the second warning; and

treating the at least one patient with 20 ppm inhaled nitric oxide.

5. The method of claim 3, wherein the information of (i) and the information of (ii) appear in prescribing information supplied to the medical provider with the cylinder containing compressed nitric oxide gas.

6. The method of claim 4, wherein the information of (i) and the information of (ii) appear in prescribing information supplied to the medical provider with the cylinder containing compressed nitric oxide gas.

10. The method of claim 4, wherein the at least one patient is monitored for evidence of increased PCWP and/or for evidence of pulmonary edema during treatment with 20 ppm inhaled nitric oxide.

7. A method of providing pharmaceutically acceptable nitric oxide gas, 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 neonates who have hypoxic respiratory failure, including some who do not have pre-existing left ventricular dysfunction; and

providing to the medical provider (i) information that a recommended dose of inhaled nitric oxide gas for treatment of neonates with hypoxic respiratory failure is 20 ppm nitric oxide,

(ii) information that patients who have pre-existing left ventricular dysfunction and are treated with inhaled nitric oxide may experience pulmonary edema, and (iii) a recommendation that, if pulmonary edema occurs in a patient who has pre-existing left ventricular dysfunction and is treated with inhaled nitric oxide, the treatment with inhaled nitric oxide should be discontinued.

8. The method of claim 7, wherein the information of (i) and (ii) and the recommendation of (iii) appear in prescribing information supplied to the medical provider with the cylinder containing compressed nitric oxide gas.

9. The method of claim 7, further comprising:

performing at least one diagnostic process to identify a neonatal patient who has hypoxic respiratory failure and is a candidate for inhaled nitric oxide treatment;

determining prior to treatment with inhaled nitric oxide that the neonatal patient has pre-existing left ventricular dysfunction;

treating the neonatal patient with 20 ppm inhaled nitric oxide, whereupon the neonatal patient experiences pulmonary edema; and

in accordance with the recommendation of (iii), discontinuing the treatment with inhaled nitric oxide due to the neonatal patient'"'"'s pulmonary edema.

11. The method of claim 9, wherein the neonatal patient is monitored for evidence of increased PCWP and/or for evidence of pulmonary edema during treatment with 20 ppm inhaled nitric oxide.

12. A method comprising:

obtaining a source of nitric oxide gas comprising a cylinder of compressed gas and/or 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 neonates who have hypoxic respiratory failure, including some who do not have left ventricular dysfunction; and

providing to the medical provider (i) information that a recommended dose of inhaled nitric oxide gas for treatment of neonates with hypoxic respiratory failure is 20 ppm nitric oxide

and (ii) information that, in patients with pre-existing left ventricular dysfunction, inhaled nitric oxide may increase PCWP, leading to pulmonary edema, the information of (ii) being sufficient to cause a medical provider considering inhaled nitric oxide treatment for a plurality of neonatal patients who (a) are suffering from a condition for which inhaled nitric oxide is indicated, and (b) have pre-existing left ventricular dysfunction, to elect to avoid treating one or more of the plurality of patients with inhaled nitric oxide in order to avoid putting the one or more patients at risk of pulmonary edema.

13. The method of claim 12, wherein the information of (i) and the information of (ii) appear in prescribing information supplied to the medical provider with the source of nitric oxide gas.

16. The method of claim 12, further comprising:

identifying a first neonatal patient who has hypoxic respiratory failure and is a candidate for 20 ppm inhaled nitric oxide treatment;

determining that the first neonatal patient has pre-existing left ventricular dysfunction;

evaluating the potential benefit of treating the first neonatal patient with 20 ppm inhaled nitric oxide vs. the potential risk described in the information of (ii) that inhaled nitric oxide could cause an increase in PCWP leading to pulmonary edema in patients who have pre-existing left ventricular dysfunction, in order to arrive at a decision of whether or not to treat the first neonatal patient with inhaled nitric oxide;

identifying a second neonatal patient as having hypoxic respiratory failure and not having left ventricular dysfunction; and

using the source of nitric oxide gas to treat the second neonatal patient with 20 ppm inhaled nitric oxide.

17. The method of claim 12, further comprising:

identifying a plurality of neonatal hypoxic respiratory failure patients who are candidates for inhaled nitric oxide treatment;

determining prior to treatment with inhaled nitric oxide whether or not each patient of the plurality has pre-existing left ventricular dysfunction, thereby determining that a first patient of the plurality does not have pre-existing left ventricular dysfunction;

using the source of nitric oxide gas to treat the first patient with 20 ppm inhaled nitric oxide;

determining that other patients of the plurality do have pre-existing left ventricular dysfunction;

for each patient of the plurality who is determined to have pre-existing left ventricular dysfunction, evaluating on a case-by-case basis the potential benefit of treating the patient with 20 ppm inhaled nitric oxide vs. the potential risk described in the information of (ii) that inhaled nitric oxide could cause an increase in PCWP, leading to pulmonary edema;

for at least one of the evaluated patients, determining that the potential benefit of the treatment outweighs the potential risk; and

using the source of nitric oxide gas to treat the at least one patient with 20 ppm inhaled nitric oxide.

14. 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 neonates who have hypoxic respiratory failure, including some who do not have pre-existing left ventricular dysfunction;

providing to the medical provider (i) information that a recommended dose of inhaled nitric oxide gas for treatment of neonates with hypoxic respiratory failure is 20 ppm nitric oxide

and (ii) information that, in patients with pre-existing left ventricular dysfunction, inhaled nitric oxide may increase PCWP, leading to pulmonary edema, the information of (ii) being sufficient to cause a medical provider considering inhaled nitric oxide treatment for multiple neonatal patients who (a) are suffering from hypoxic respiratory failure, and (b) have pre-existing left ventricular dysfunction, to elect to avoid treating one or more of the multiple patients with inhaled nitric oxide in order to avoid putting the one or more patients at risk of pulmonary edema.

15. The method of claim 14, wherein the information of (i) and the information of (ii) appear in prescribing information supplied to the medical provider with the device.

18. The method of claim 14, further comprising:

identifying a first neonatal patient who has hypoxic respiratory failure and is a candidate for 20 ppm inhaled nitric oxide treatment;

determining that the first neonatal patient has pre-existing left ventricular dysfunction;

evaluating the potential benefit of treating the first neonatal patient with 20 ppm inhaled nitric oxide vs. the potential risk described in the information of (ii) that inhaled nitric oxide could cause an increase in PCWP leading to pulmonary edema in patients who have pre-existing left ventricular dysfunction, in order to arrive at a decision of whether or not to treat the first neonatal patient with inhaled nitric oxide;

identifying a second neonatal patient as having hypoxic respiratory failure and not having left ventricular dysfunction; and

using the device to treat the second neonatal patient with 20 ppm inhaled nitric oxide.

19. The method of claim 14, further comprising:

identifying a plurality of neonatal hypoxic respiratory failure patients who are candidates for inhaled nitric oxide treatment;

determining, prior to treatment with inhaled nitric oxide, whether or not each patient of the plurality has pre-existing left ventricular dysfunction, thereby determining that a first patient of the plurality does not have pre-existing left ventricular dysfunction;

using the device to treat the first patient with 20 ppm inhaled nitric oxide;

determining that other patients of the plurality do have pre-existing left ventricular dysfunction;

for each patient of the plurality who is determined to have pre-existing left ventricular dysfunction, evaluating on a case-by-case basis the potential benefit of treating the patient with 20 ppm inhaled nitric oxide vs. the potential risk described in the information of (ii) that inhaled nitric oxide could cause an increase in PCWP, leading to pulmonary edema;

for at least one of the evaluated patients, determining that the potential benefit of the treatment outweighs the potential risk; and

using the device to treat the at least one patient with 20 ppm inhaled nitric oxide.