Systems and Methods for Treating an Opioid-Induced Adverse Pharmacodynamic Response

Abstract

Disclosed in certain embodiments is a method of treating or preventing an opioid-induced adverse pharmacodynamic response comprising administering to a patient in need thereof an effective amount of buprenorphine.

We claim: 
     
         1 . A method of preventing or treating an opioid-induced adverse pharmacodynamic response comprising administering to a patient in need thereof an effective amount of buprenorphine to prevent or treat the adverse pharmacodynamic response induced by the administration of another opioid. 
     
     
         2 . The method of  claim 1 , wherein the other opioid is administered in an effective amount to provide an analgesic effect. 
     
     
         3 . The method of  claim 1 , wherein the patient is administered the buprenorphine concurrently with the other opioid. 
     
     
         4 . The method of  claim 3 , wherein the administration of the other opioid is initiated prior to administration of the buprenorphine. 
     
     
         5 . The method of  claim 4 , wherein the patient initiates administration of the other opioid on a chronic basis prior to administration of the buprenorphine. 
     
     
         6 . The method of  claim 5 , wherein the patient exhibits the opioid-induced adverse pharmacodynamic response prior to administration of the buprenorphine. 
     
     
         7 . The method of  claim 6 , wherein the administration of the buprenorphine treats the opioid-induced adverse pharmacodynamic response induced by the other opioid. 
     
     
         8 . The method of  claim 1 , wherein the administration of the other opioid is initiated concurrently with the administration of the buprenorphine. 
     
     
         9 . The method of  claim 8 , wherein the patient is opioid naive. 
     
     
         10 . The method of  claim 8 , wherein the patient is administered the other opioid on a chronic basis. 
     
     
         11 . The method of  claim 1 , wherein the administration of the buprenorphine is initiated prior to initiating the administration of the other opioid. 
     
     
         12 . The method of  claim 1 , wherein the other opioid has an E max  of greater than about 25%. 
     
     
         13 . The method of  claim 1 , wherein the buprenorphine is selected from the group consisting of buprenorphine base, pharmaceutically acceptable salt thereof, solvates thereof, polymorphs thereof, and mixtures thereof. 
     
     
         14 . The method of  claim 13 , wherein the buprenorphine is buprenorphine base. 
     
     
         15 . The method of  claim 1 , wherein the buprenorphine is administered transdermally. 
     
     
         16 . The method of  claim 15 , wherein the buprenorphine is administered transdermally with a dosing interval of about 24 hours. 
     
     
         17 . The method of  claim 15 , wherein the buprenorphine is administered transdermally with a dosing interval of about 3 days. 
     
     
         18 . The method of  claim 15 , wherein the buprenorphine is administered transdermally with a dosing interval of about 7 days. 
     
     
         19 . The method of  claim 15 , wherein the buprenorphine is administered transdermally at a rate of about 5 mcg/hour. 
     
     
         20 . The method of  claim 15 , wherein the buprenorphine is administered transdermally at a rate of less than 5 mcg/hour. 
     
     
         21 . The method of  claim 1 , wherein the buprenorphine is administered by the same route as the other opioid. 
     
     
         22 . The method of  claim 21 , wherein the other opioid and the buprenorphine are each administered by a route selected from the group consisting of oral, transdermal, sublingual, buccal, gingival, rectal, subcutaneous, intramuscular, intravenous and parenteral. 
     
     
         23 . The method of  claim 22 , wherein the other opioid and the buprenorphine are both administered orally. 
     
     
         24 . The method of  claim 23 , wherein the other opioid and the buprenorphine are administered orally in two separate dosage forms. 
     
     
         25 . The method of  claim 23 , wherein the other opioid and the buprenorphine are administered together orally in a single dosage form. 
     
     
         26 . The method of  claim 25 , wherein the single dosage form is a solid oral dosage form. 
     
     
         27 . The method of  claim 26 , wherein the solid oral dosage form is a tablet. 
     
     
         28 . The method of  claim 26 , wherein the solid oral dosage form is a capsule. 
     
     
         29 . The method of  claim 26 , wherein the other opioid and the buprenorphine are both formulated for controlled release. 
     
     
         30 . The method of  claim 26 , wherein the other opioid and the buprenorphine are both formulated for immediate release. 
     
     
         31 . The method of  claim 26 , wherein the other opioid is formulated for controlled release and the buprenorphine is formulated for immediate release. 
     
     
         32 . The method of  claim 26 , wherein the other opioid is formulated for immediate release and the buprenorphine is formulated for controlled release. 
     
     
         33 . The method of  claim 2 , wherein the buprenorphine is administered by a different route than the other opioid. 
     
     
         34 . The method of  claim 33 , wherein the buprenorphine and the other opioid are administered by different routes independently selected from the group consisting of oral, transdermal, sublingual, buccal, gingival, rectal, subcutaneous, intramuscular, intravenous and parenteral. 
     
     
         35 . The method of  claim 34 , wherein the other opioid is administered orally. 
     
     
         36 . The method of  claim 35 , wherein the other opioid is formulated for controlled release. 
     
     
         37 . The method of  claim 35 , wherein the other opioid is formulated for immediate release. 
     
     
         38 . The method of  claim 35 , wherein the buprenorphine is administered transdermally. 
     
     
         39 . The method of  claim 35 , wherein the buprenorphine is administered by the oromucosal route. 
     
     
         40 . The method of  claim 1  or  2 , wherein the buprenorphine is administered in an amount to provide less than about 1 mg/kg. 
     
     
         41 . The method of  claim 1  or  2 , wherein the buprenorphine is administered in an amount to provide less than about 0.5 mg/kg. 
     
     
         42 . The method of  claim 1  or  2 , wherein the buprenorphine is administered in an amount to provide less than about 0.1 mg/kg. 
     
     
         43 . The method of  claim 1  or  2 , wherein the ratio of the daily dose of buprenorphine to the other opioid is less than about 1:5 (w/w). 
     
     
         44 . The method of  claim 1  or  2 , wherein the ratio of the daily dose of buprenorphine to the other opioid is less than about 1:10 (w/w). 
     
     
         45 . The method of  claim 1  or  2 , wherein the ratio of the daily dose of buprenorphine to the other opioid is less than about 1:50 (w/w). 
     
     
         46 . The method of  claim 1  or  2 , wherein the ratio of the daily dose of buprenorphine to the other opioid is less than about 1:100 (w/w). 
     
     
         47 . The method of  claim 1  or  2 , wherein the other opioid is selected from the group consisting of oxycodone, morphine, codeine, oxymorphone, fentanyl, hydrocodone, hydromorphone, tramadol and the pharmaceutically acceptable salts thereof. 
     
     
         48 . The method of  claim 1  or  claim 2 , wherein the other opioid is a peripherally restricted opioid. 
     
     
         49 . The method of  claim 48 , wherein the peripherally restricted opioid is selected from the group consisting of loperamide, frakefamide and the pharmaceutically acceptable salts thereof. 
     
     
         50 . The method of  claim 36 , wherein the other opioid is administered with a dosing interval of about 8 hours or about 12 hours or about 36 hours. 
     
     
         51 . The method of  claim 36 , wherein the other opioid is oxycodone free base or a pharmaceutically acceptable salt thereof. 
     
     
         52 . The method of  claim 51 , wherein the other opioid is oxycodone hydrochloride. 
     
     
         53 . The method of  claim 52 , wherein the controlled release dosage form comprises from about 10 mg to about 160 mg oxycodone hydrochloride. 
     
     
         54 . The method of  claim 26 , wherein the other opioid is oxycodone free base or a pharmaceutically acceptable salt thereof. 
     
     
         55 . The method of  claim 21  or  33 , wherein the other opioid is oxycodone hydrochloride. 
     
     
         56 . The method of  claim 55 , wherein the controlled release dosage form comprises from about 10 mg to about 160 mg oxycodone hydrochloride. 
     
     
         57 . The method of  claim 21  or  33 , wherein the other opioid is tramadol hydrochloride. 
     
     
         58 . The method of  claim 57 , wherein the tramadol hydrochloride is present in an amount from about 100 mg to about 300 mg. 
     
     
         59 . The method of  claim 21  or  33 , wherein the other opioid is oxymorphone hydrochloride. 
     
     
         60 . The method of  claim 59 , wherein the oxymorphone hydrochloride is present in an amount from about 5 mg to about 40 mg oxymorphone hydrochloride. 
     
     
         61 . The method of  claim 21  or  33 , wherein the other opioid is hydrocodone bitratrate. 
     
     
         62 . The method of  claim 61 , wherein the hydrocodone bitratrate is present in an amount from about 2 mg to about 200 mg. 
     
     
         63 . The method of  claim 21  or  33 , wherein the other opioid is hydromorphone hydrochloride. 
     
     
         64 . The method of  claim 63 , wherein the hydromorphone hydrochloride is present in an amount from about 2 mg to about 200 mg hydromorphone hydrochloride. 
     
     
         65 . The method of  claim 12 , wherein the other opioid has an E max  of greater than about 40%. 
     
     
         66 . The method of  claim 12 , wherein the buprenorphine is administered in an amount that does not cause or exacerbate an opioid-induced adverse pharmacodynamic response. 
     
     
         67 . The method of  claim 2 , wherein the buprenorphine is administered in an amount that does not cause a decrease in the analgesic effectiveness of the other opioid. 
     
     
         68 . The method of  claim 2 , wherein the buprenorphine is administered in an amount that does not cause a substantial decrease in the analgesic effectiveness of the other opioid. 
     
     
         69 . The method of  claim 2 , wherein the buprenorphine is administered in an amount that provides an increase in analgesia over the analgesia provided by the other opioid alone. 
     
     
         70 . The method of  claim 1  or  2 , wherein the opioid-induced adverse pharmacodynamic response is selected from the group consisting of bowel dysfunction, nausea, vomiting, somnolence, dizziness, respiratory depression, headache, dry mouth, sedation, sweats, asthenia, hypotension, dysphoria, delirium, miosis, pruritis, urticaria, urinary retention, hyperalgesia, allodynia, physical dependence and tolerance. 
     
     
         71 . The method of  claim 70 , wherein the opioid-induced adverse pharmacodynamic response is bowel dysfunction. 
     
     
         72 . The method of  claim 71 , wherein the opioid-induced bowel dysfunction is constipation. 
     
     
         73 . The method of  claim 71 , wherein the opioid-induced bowel dysfunction is decreased gastric emptying. 
     
     
         74 . The method of  claim 71 , wherein the opioid-induced bowel dysfunction is abdominal cramping. 
     
     
         75 . The method of  claim 71 , wherein the opioid-induced bowel dysfunction is spasm. 
     
     
         76 . The method of  claim 71 , wherein the opioid-induced bowel dysfunction is bloating. 
     
     
         77 . The method of  claim 71 , wherein the opioid-induced bowel dysfunction is delayed gastro-intestinal transit. 
     
     
         78 . The method of  claim 71 , wherein the opioid-induced bowel dysfunction is the formation of hard dry stools. 
     
     
         79 . The method of  claim 1 , wherein the other opioid is administered in an effective amount to treat diarrhea, cough or anxiety. 
     
     
         80 . The method of  claim 1  or  2 , wherein the buprenorphine is administered transdermally at a rate from about 0.001 mcg/hour to about 5 mcg/hour. 
     
     
         81 . The method of  claim 1  or  2 , wherein the buprenorphine is administered to a mucosal membrane. 
     
     
         82 . The method of  claim 1 , wherein the buprenorphine is administered transdermally in an amount of about 5 mcg/hr or less, and concurrently with oral controlled release oxycodone hydrochloride in a unit dose of about 10 mg to about 160 mg. 
     
     
         83 . The method of  claim 79 , wherein the buprenorphine dosing interval is about 3 days or about 7 days, and the oxycodone dosing interval is about 12 hours. 
     
     
         84 . The method of  claim 2 , wherein the buprenorphine is administered transdermally in an amount of about 5 mcg/hr or less, and concurrently with oral controlled release oxymorphone hydrochloride in a unit dose of about 5 mg to about 40 mg. 
     
     
         85 . The method of  claim 84 , wherein the buprenorphine dosing interval is about 3 days or about 7 days, and the oxymorphone dosing interval is about 12 hours. 
     
     
         86 . The method of  claim 2 , wherein the buprenorphine is administered transdermally in an amount of about 5 mcg/hr or less, and concurrently with transdermally administered fentanyl in an amount of about 12.5 mcg/hr to about 100 mcg/hr. 
     
     
         87 . The method of  claim 86 , wherein the buprenorphine dosing interval is about 3 days or about 7 days, and the fentanyl dosing interval is about 3 or 7 days. 
     
     
         88 . The method of  claim 2 , wherein the concentration of buprenorphine that affects the analgesic effectiveness of the concurrently administered opioid is about 90 times, about 80 times, about 70 times, about 60 times, about 50 times, about 40 times, about 30 times, about 20 times, about 10 times, about 5 times, or about 2 times the concentration of buprenorphine that prevents or treats an opioid induced adverse pharmacodynamic response. 
     
     
         89 . A pharmaceutical unit dosage form comprising an effective amount of buprenorphine to prevent or treat an adverse pharmacodynamic response induced by another opioid, and a therapeutically effective amount of the other opioid. 
     
     
         90 . The pharmaceutical unit dose of  claim 89 , which is a solid dosage form adapted for oral administration. 
     
     
         91 . The pharmaceutical unit dose of  claim 90 , which is a tablet or capsule. 
     
     
         92 . The pharmaceutical unit dose of  claim 89 , wherein the other opioid is selected from the group consisting of oxycodone, morphine, codeine, oxymorphone, fentanyl, hydrocodone, hydromorphone, tramadol and the pharmaceutically acceptable salts thereof. 
     
     
         93 . A kit comprising (i) a unit dose of an effective amount of buprenorphine to prevent or treat an opioid-induced adverse pharmacodynamic response induced by another opioid and (ii) a unit dose of the other opioid in an effective amount to treat pain, diarrhea, cough or anxiety. 
     
     
         94 . The kit of  claim 93 , further comprising a label or printed instructions regarding the use of the buprenorphine to prevent or treat an opioid-induced adverse pharmacodynamic response. 
     
     
         95 . The kit of  claim 93  comprising a transdermal patch of buprenorphine and a controlled release oral solid dosage form of oxycodone hydrochloride. 
     
     
         96 . The kit of  claim 95 , wherein the buprenorphine and oxycodone are in an amount to provide treatment for about 3 or 7 days. 
     
     
         97 . The kit of  claim 93  comprising a transdermal patch of buprenorphine and a controlled release oral solid dosage form of oxymorphone hydrochloride. 
     
     
         98 . The kit of  claim 97 , wherein the buprenorphine and oxymorphone are in an amount to provide treatment for about 3 or 7 days. 
     
     
         99 . The kit of  claim 93  comprising a transdermal patch of buprenorphine and a controlled release oral solid dosage form of hydrocodone bitratrate. 
     
     
         100 . The kit of  claim 97 , wherein the buprenorphine and hydrocodone are in an amount to provide treatment for about 3 or 7 days. 
     
     
         101 . The kit of  claim 93  comprising a transdermal patch of buprenorphine and a controlled release oral solid dosage form of hydromorphone hydrochloride. 
     
     
         102 . The kit of  claim 97 , wherein the buprenorphine and hydromorphone are in an amount to provide treatment for about 3 or 7 days. 
     
     
         103 . The kit of  claim 93  comprising an oral solid dosage form of buprenorphine and an oral solid dosage form of another opioid selected from the group consisting of oxycodone, morphine, codeine, oxymorphone, fentanyl, hydrocodone, hydromorphone, tramadol and the pharmaceutically acceptable salts thereof.