Methods and compositions for reducing the risk associated with the administration of opioid analgesics in patients with diagnosed or undiagnosed respiratory illness

Abstract

The present invention relates to methods for reducing the risk associated with the administration of opioid analgesics in patients diagnosed or undiagnosed with respiratory illness by administering an analgesic composition comprising a sub-analgesic dosage of a μ-opioid agonist selected from the group consisting of morphine, fentanyl, sufentanil, alfentanil, oxymorphone and hydromorphone, or a pharmaceutically acceptable salt thereof, and a sub-analgesic dosage of oxycodone which is a κ 2 -opioid agonist or a pharmaceutically acceptable salt thereof.

1 . A method for reducing the risk associated with the administration of opioid analgesics in patients with diagnosed or undiagnosed respiratory illness, or at risk for same, by administering an analgesic composition comprising a sub-analgesic dosage of a μ-opioid agonist selected from the group consisting of morphine, fentanyl, sufentanil, alfentanil, oxymorphone and hydromorphone, or a pharmaceutically acceptable salt thereof, and a sub-analgesic dosage of oxycodone, a κ 2 -opioid agonist, or a pharmaceutically acceptable salt thereof, wherein the method achieves an analgesic effect in the patient to which the composition is administered.  
     
     
         2 . The method of  claim 1 , wherein the μ-opioid agonist is in the form of a pharmaceutically acceptable salt.  
     
     
         3 . The method of  claim 1 , wherein the μ-opioid agonist is morphine.  
     
     
         4 . The method of  claim 1 , wherein the μ-opioid agonist is fentanyl.  
     
     
         5 . The method of  claim 1 , wherein the μ-opioid agonist is hydromorphone.  
     
     
         6 . The method of  claim 1 , wherein the μ-opioid agonist is oxymorphone.  
     
     
         7 . The method of  claim 1  wherein the oxycodone is in the form of a pharmaceutically acceptable salt.  
     
     
         8 . The method of  claim 3 , wherein the combined mass of morphine and oxycodone is about 50% of the mass of morphine alone required to achieve the same analgesic effect in the patient to which the composition is administered.  
     
     
         9 . The method of  claim 3 , wherein the combined mass of morphine and oxycodone is about 75% of the mass of oxycodone alone required to achieve the same analgesic effect in the patient to which the composition is administered.  
     
     
         10 . The method of  claim 1 , wherein the composition is administered in an immediate release oral dosage form.  
     
     
         11 . The method of  claim 1 , wherein the composition is administered in a sustained release oral dosage form.  
     
     
         12 . The method of  claim 1 , wherein the composition is administered through a subcutaneous, intravenous, intramuscular, epidural, transdermal, inhalation, buccal or sublingual route.  
     
     
         13 . The method of  claim 1 , wherein the respiratory illness is selected from the group consisting of asthma, bronchiectasis, pulmonary tuberculosis, chronic obstructive pulmonary disease, bronchitis, bronchopneumonia, chronic laryngitis, chronic sinusitis, emphysema, fibrosing alveolitis, idiopathic pulmonary fibrosis and sarcoidosis.  
     
     
         14 . The method of  claim 1 , wherein the respiratory illness is cancer.  
     
     
         15 . The method of  claim 14 , wherein the cancer is lung cancer.  
     
     
         16 . The method of  claim 14 , wherein the cancer is selected from the group consisting of non-small cell lung cancer, adenocarcinoma, squamous cell carcinoma, large cell carcinoma, undifferentiated carcinoma, small cell lung cancer, oat cell cancer and mesothelioma.  
     
     
         17 . The method of  claim 1 , wherein the respiratory illness is a respiratory sleep disorder.  
     
     
         18 . The method of  claim 17 , wherein the respiratory sleep disorder is sleep apnea.  
     
     
         19 . The method of  claim 18 , wherein the sleep apnea is selected from the group consisting of central sleep apnea, obstructive sleep apnea and mixed sleep apnea.  
     
     
         20 . A method of minimizing the risk of developing sleep apnea in susceptible patients treated for the alleviation or prevention of pain, wherein the method comprises the step of administering an analgesic composition comprising a sub-analgesic dosage of a μ-opioid agonist selected from the group consisting of morphine, fentanyl, sufentanil, alfentanil, oxymorphone and hydromorphone, or a pharmaceutically acceptable salt thereof, and a sub-analgesic dosage of oxycodone, a κ 2 -opioid agonist, or a pharmaceutically acceptable salt thereof.  
     
     
         21 . The method of  claim 20 , wherein the sleep apnea is selected from the group consisting of central sleep apnea, obstructive sleep apnea and mixed sleep apnea.  
     
     
         22 . An analgesic composition comprising a sub-analgesic dosage of morphine, a μ-opioid agonist, and a sub-analgesic dosage of oxycodone, a κ 2 -opioid agonist, or pharmaceutically acceptable salts thereof, wherein the composition, upon administration to a patient, achieves an analgesic effect in that patient, equivalent to the analgesic effect that would result from the administration of an analgesic composition consisting of about twice the mass of morphine alone.  
     
     
         23 . An analgesic composition comprising a sub-analgesic dosage of morphine, a μ-opioid agonist, and a sub-analgesic dosage of oxycodone, a κ 2 -opioid agonist, or pharmaceutically acceptable salts thereof, wherein the composition, upon administration to a patient, achieves an analgesic effect in that patient equivalent to the analgesic effect that would result from the administration of an analgesic composition consisting of about 1.5 times the mass of oxycodone alone.