BUPRENORPHINE TO TREAT RESPIRATORY DEPRESSION
The disclosure provides methods for treating, preventing, and reducing the incidence of opioid-induced respiratory depression, opioid-induced apnea, and opioid overdose in patients by administering buprenorphine or a pharmaceutically acceptable salt thereof.
1 . A method of treating or preventing fentanyl-induced respiratory depression in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising buprenorphine free base, a poly(lactide-co-glycolide) copolymer, and N-methyl-2-pyrrolidone, to treat or prevent fentanyl-induced respiratory depression.
2 . The method of claim 1 , further comprising: (a) administering the pharmaceutical composition to the patient once per month by subcutaneous injection; (b) administering the pharmaceutical composition prior to occurrence of fentanyl-induced respiratory depression; and/or (c) treating the patient for opioid use disorder.
3 . The method of claim 1 , wherein the pharmaceutical composition comprises: (a) about 18 wt % buprenorphine free base, about 32 wt % of a 50:50 poly(DL-lactide-co-glycolide) copolymer, and about 50 wt % of N-methyl-2-pyrrolidone; and/or (b) about 100 mg of buprenorphine free base or about 300 mg of buprenorphine free base.
4 - 6 . (canceled)
7 . A method of treating or preventing opioid-induced respiratory depression or reducing the incidence of opioid-induced respiratory depression in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising buprenorphine or a pharmaceutically acceptable salt thereof.
8 . The method of claim 7 , for: (a) treating or preventing opioid-induced respiratory depression; and/or (b) reducing the incidence of opioid-induced respiratory depression.
9 . (canceled)
10 . The method of claim 7 , wherein the opioid is: (a) fentanyl, a fentanyl analogue, carfentanil, a carfentanil analogue, heroin, butorphanol, oxycodone, hydrocodone, hydromorphone, levorphanol, oxymorphone, opium, meperidine, morphine, codeine, dihydrocodeine, methadone, pentazocine, tapentadol, tramadol, heroin, or a combination of two or more thereof; (b) acetylfentanyl, butyrfentanyl, para-tolylfentanyl, 3-methylfentanyl, α-methylfentanyl, mefentanyl, phenaridine, ohmefentanyl, or mirfentanil; (c) sufentanil, remifentanil, alfentanil, lofentanil, brifentanil, or trefentanil; (d) fentanyl; and/or (e) carfentanil.
11 - 14 . (canceled)
15 . The method of claim 7 , comprising: (a) administering the pharmaceutical composition to the patient once per week by subcutaneous injection; (b) administering the pharmaceutical composition to the patient twice per month by subcutaneous injection; (c) administering the pharmaceutical composition to the patient once per month by subcutaneous injection; (d) administering the pharmaceutical composition to the patient once every two months by subcutaneous injection; and/or (e) parenterally administering the pharmaceutical composition to the patient.
16 - 19 . (canceled)
20 . The method of claim 7 , wherein: (a) the pharmaceutical composition is a long-acting pharmaceutical composition; (b) the pharmaceutical composition comprises buprenorphine, a poly(lactide-co-glycolide) copolymer, and N-methyl-2-pyrrolidone; (c) the pharmaceutical composition comprises about 18 wt % buprenorphine free base, about 32 wt % of a 50:50 poly(DL-lactide-co-glycolide) copolymer, and about 50 wt % of N-methyl-2-pyrrolidone; (d) the pharmaceutical composition comprises (i) buprenorphine, (ii) phosphatidylcholine, (iii) glycerol dioleate, and (iv) ethanol, N-methyl-2-pyrrlidone, or a combination thereof; and/or (e) the pharmaceutical composition comprises buprenorphine, dextrose, and water.
21 - 24 . (canceled)
25 . The method of claim 7 , wherein: (a) the therapeutically effective amount of buprenorphine provides a sustained buprenorphine plasma concentration of about 2 ng/mL or more; (b) the pharmaceutical composition is administered to the patient prior to occurrence of opioid-induced respiratory depression; and/or (c) the method further comprises treating the patient for opioid use disorder.
26 - 27 . (canceled)
28 . A method of treating or preventing opioid-induced apnea, reducing the incidence of opioid-induced apnea, treating or preventing an opioid overdose, or reducing the incidence of opioid overdose in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising buprenorphine or a pharmaceutically acceptable salt thereof.
29 . The method of claim 28 , for: (a) treating or preventing opioid-induced apnea; (b) reducing the incidence of opioid-induced apnea; (c) treating or preventing an opioid overdose; and/or (d) reducing the incidence of opioid overdose.
30 - 32 . (canceled)
33 . The method of claim 28 , wherein the opioid is: (a) heroin, butorphanol, oxycodone, hydrocodone, hydromorphone, levorphanol, oxymorphone, opium, meperidine, morphine, codeine, dihydrocodeine, methadone, pentazocine, tapentadol, tramadol, or a combination of two or more thereof; (b) fentanyl, acetylfentanyl, butyrfentanyl, para-tolylfentanyl, 3-methylfentanyl, α-methylfentanyl, mefentanyl, phenaridine, ohmefentanyl, or mirfentanil; (c) fentanyl; (d) sufentanil, remifentanil, alfentanil, lofentanil, brifentanil, or trefentanil; and/or (e) carfentanil.
34 - 37 . (canceled)
38 . The method of claim 28 , comprising: (a) administering the pharmaceutical composition to the patient once per week by subcutaneous injection; (b) The method of claim 28 , comprising administering the pharmaceutical composition to the patient once per month by subcutaneous injection; (c) The method of claim 28 , comprising administering the pharmaceutical composition to the patient once every two months by subcutaneous injection; (d) The method of claim 28 , comprising parenterally administering the pharmaceutical composition to the patient.
39 - 41 . (canceled)
42 . The method of claim 28 , wherein the pharmaceutical composition: (a) is a long-acting pharmaceutical composition; (b) The method of claim 28 , wherein the pharmaceutical composition comprises buprenorphine, a poly(lactide-co-glycolide) copolymer, and N-methyl-2-pyrrolidone; (c) The method of claim 43 , wherein the pharmaceutical composition comprises about 18 wt % buprenorphine free base, about 32 wt % of a 50:50 poly(DL-lactide-co-glycolide) copolymer, and about 50 wt % of N-methyl-2-pyrrolidone; (d) The method of claim 28 , wherein the pharmaceutical composition comprises (i) buprenorphine, (ii) phosphatidylcholine, (iii) glycerol dioleate, and (iv) ethanol, N-methyl-2-pyrrlidone, or a combination thereof; (e) The method of claim 28 , wherein the pharmaceutical composition comprises buprenorphine, dextrose, and water; and/or (f) The method of claim 28 , wherein the pharmaceutical composition comprises buprenorphine, dextrose, and water.
43 - 46 . (canceled)
47 . The method of claim 28 , wherein: (a) the pharmaceutical composition is administered prior to occurrence of opioid-induced apnea or opioid overdose; (b) the method further comprises treating the patient for opioid use disorder; (c) the therapeutically effective amount of buprenorphine provides a sustained buprenorphine plasma concentration of about 2 ng/mL or more; (d) the therapeutically effective amount of buprenorphine provides a sustained buprenorphine plasma concentration from about 2 ng/mL to about 20 ng/mL; and/or (e) the therapeutically effective amount of buprenorphine or the pharmaceutically acceptable salt thereof achieves sustained μ-opioid receptor occupancy of at least 70%.
48 - 51 . (canceled)
52 . A method of treating or preventing fentanyl-induced respiratory depression in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising buprenorphine, a phospholipid, a neutral diacyl lipid, and an organic solvent, to treat or prevent fentanyl-induced respiratory depression.
53 . The method of claim 52 , wherein: (a) (i) the phospholipid is phosphatidylcholine, (ii) the neutral diacyl lipid is glycerol dioleate, and (iii) the organic solvent is ethanol, N-methyl-2-pyrrolidone, or a combination thereof; and/or (b) the therapeutically effective amount of buprenorphine is 8 mg, 16 mg, 24 mg, 32 mg, 64 mg, 96 mg, or 128 mg.
54 . (canceled)
55 . The method of claim 52 , comprising: (a) administering the pharmaceutical composition to the patient once per week, twice per month, or once per month by subcutaneous injection; (b) administering the pharmaceutical composition prior to occurrence of fentanyl-induced respiratory depression; and/or (c) treating the patient for opioid use disorder.
56 - 57 . (canceled)