You’re using a public version of DrugPatentWatch with 5 free searches available | Register to unlock more free searches. CREATE FREE ACCOUNT

Last Updated: March 19, 2024

Details for Patent: 7,749,542


✉ Email this page to a colleague

« Back to Dashboard


Title:Opioid agonist/antagonist combinations
Abstract: The invention is directed in part to oral dosage forms comprising a combination of an orally analgesically effective amount of an opioid agonist and an orally active opioid antagonist, the opioid antagonist being included in a ratio to the opioid agonist to provide a combination product which is analgesically effective when the combination is administered orally, but which is aversive in a physically dependent subject. Preferably, the amount of opioid antagonist included in the combination product provides at least a mildly negative, "aversive" experience in physically dependent addicts (e.g., precipitated abstinence syndrome).
Inventor(s): Kaiko; Robert F. (Weston, CT), Colucci; Robert D. (Newtown, CT)
Assignee: Purdue Pharma LP (Stamford, CT)
Filing Date:Jul 28, 2008
Application Number:12/220,760
Claims:1. An oral dosage form, comprising an orally therapeutically effective dose of an opioid agonist, and an amount of an opioid antagonist selected from the group consisting of naltrexone, naloxone, nalmephene, cyclazocine, levallorphan, pharmaceutically acceptable salts and mixtures thereof, wherein part or all of said amount is in a sustained release form; the dosage form having a ratio of opioid antagonist to opioid agonist that provides a combination product which is analgesically effective when the combination is administered orally, but which (i) is aversive in physically dependent human subjects when administered at the same dose or at a higher dose than said therapeutically effective dose; and (ii) maintains an analgesic effect but does not increase analgesic efficacy of the opioid agonist relative to the same therapeutic dose of opioid agonist when administered to human patients without said opioid antagonist; wherein the ratio of the opioid antagonist to the opioid agonist is selected from the group consisting of from about 0.03:1 to about 0.27:1, based on the opioid antagonist being naltrexone or a pharmaceutically acceptable salt thereof and the opioid agonist being hydrocodone or a pharmaceutically acceptable salt thereof; from about 0.037:1 to about 0.296:1, based on the opioid antagonist being naltrexone or a pharmaceutically acceptable salt thereof and the opioid agonist being oxycodone or a pharmaceutically acceptable salt thereof; from about 0.148:1 to about 1.185:1, based on the opioid antagonist being naltrexone or a pharmaceutically acceptable salt thereof and the opioid agonist being hydromorphone or a pharmaceutically acceptable salt thereof; from about 0.278:1 to about 2.222:1, based on the opioid antagonist being naltrexone or a pharmaceutically acceptable salt thereof and the opioid agonist being levorphanol or a pharmaceutically acceptable salt thereof; from about 0.056:1 to about 0.444:1, based on the opioid antagonist being naltrexone or a pharmaceutically acceptable salt thereof and the opioid agonist being methadone or a pharmaceutically acceptable salt thereof; and from about 0.018:1 to about 0.148:1, based on the opioid antagonist being naltrexone or a pharmaceutically acceptable salt thereof and the opioid agonist being morphine or a pharmaceutically acceptable salt thereof.

2. The oral dosage form of claim 1, wherein the amount of the antagonist included in the oral dosage form causes an aversive experience in a physically dependent addict taking about 2-3 times said therapeutically effective dose.

3. The oral dosage form of claim 1, wherein the opioid agonist is hydrocodone or a pharmaceutically acceptable salt thereof and the antagonist is naltrexone or a pharmaceutically acceptable salt thereof.

4. The oral dosage form of claim 3, wherein the ratio of naltrexone or a pharmaceutically acceptable salt thereof to hydrocodone or a pharmaceutically acceptable salt thereof is from about 0.03:1 to about 0.27:1.

5. The oral dosage form of claim 3, wherein the ratio of naltrexone or a pharmaceutically acceptable salt thereof to hydrocodone or a pharmaceutically acceptable salt thereof is from about 0.05:1 to about 0.20:1.

6. The oral dosage form of claim 1, wherein the opioid agonist is selected from the group consisting of morphine, hydromorphone, hydrocodone, oxycodone, codeine, levorphanol, meperidine, methadone, pharmaceutically acceptable salts thereof and mixtures thereof.

7. The oral dosage form of claim 1, further comprising an additional non-opioid drug selected from the group consisting of an NSAID, a COX-2 inhibitor, acetaminophen, aspirin, an NMDA receptor antagonist, a drug that blocks a major intracellular consequence of NMDA-receptor activation, an antitussive, an expectorant, a decongestant, an antihistamine and mixtures thereof.

8. The oral dosage form of claim 1, further comprising one or more pharmaceutically acceptable inert excipients.

9. The oral dosage form of claim 6, wherein said opioid antagonist is naltrexone or a pharmaceutically acceptable salt thereof.

10. The oral dosage form of claim 1, further comprising a sustained release carrier which imparts sustained release properties to said opioid agonist.

11. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone or a pharmaceutically acceptable salt thereof and said opioid agonist is oxycodone or a pharmaceutically acceptable salt thereof, in a ratio of from about 0.037:1 to about 0.296:1.

12. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone or a pharmaceutically acceptable salt thereof and said opioid agonist is hydromorphone or a pharmaceutically acceptable salt thereof, in a ratio of from about 0.148:1 to about 1.185:1.

13. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone or a pharmaceutically acceptable salt thereof and said opioid agonist is levorphanol or a pharmaceutically acceptable salt thereof, in a ratio of from about 0.278:1 to about 2.222:1.

14. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone or a pharmaceutically acceptable salt thereof and said opioid agonist is methadone or a pharmaceutically acceptable salt thereof, in a ratio of from about 0.056:1 to about 0.444:1.

15. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone or a pharmaceutically acceptable salt thereof and said opioid agonist is morphine or a pharmaceutically acceptable salt thereof, in a ratio from about 0.018:1 to about 0.148:1.

16. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone or a pharmaceutically acceptable salt thereof and said opioid agonist is oxycodone or a pharmaceutically acceptable salt thereof, in a ratio of from about 0.056:1 to about 0.222:1.

17. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone or a pharmaceutically acceptable salt thereof and said opioid agonist is codeine or a pharmaceutically acceptable salt thereof, in a ratio of from about 0.0083:1 to about 0.033:1.

18. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone or a pharmaceutically acceptable salt thereof and said opioid agonist is hydromorphone or a pharmaceutically acceptable salt thereof, in a ratio of from about 0.222:1 to about 0.889:1.

19. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone or a pharmaceutically acceptable salt thereof and said opioid agonist is levorphanol or a pharmaceutically acceptable salt thereof, in a ratio of from about 0.417:1 to about 1.667:1.

20. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone or a pharmaceutically acceptable salt thereof and said opioid agonist is methadone or a pharmaceutically acceptable salt thereof, in a ratio of from about 0.083:1 to about 0.333:1.

21. The oral dosage form of claim 1, wherein said opioid antagonist is naltrexone or a pharmaceutically acceptable salt thereof and said opioid agonist is morphine or a pharmaceutically acceptable salt thereof, in a ratio of from about 0.028:1 to about 0.111:1.

22. An oral dosage form, comprising an orally therapeutically effective dose of an opioid agonist, and an opioid antagonist selected from the group consisting of naltrexone, naloxone, nalmephene, cyclazocine, levallorphan, pharmaceutically acceptable salts and mixtures thereof, part or all of said opioid antagonist is in sustained release form, the dosage form having a ratio of opioid antagonist to opioid agonist that provides a combination product which is analgesically effective when the combination is administered orally, but which (i) is aversive in physically dependent human subjects when administered at the same dose or at a higher dose than said therapeutically effective dose; and (ii) maintains or decreases analgesic efficacy of the opioid agonist relative to the same therapeutic dose of opioid agonist when administered to human patients without said opioid antagonist; wherein the ratio of the opioid antagonist to the opioid agonist is selected from the group consisting of from about 0.03:1 to about 0.27:1, based on the opioid antagonist being naltrexone or a pharmaceutically acceptable salt thereof and the opioid agonist being hydrocodone or a pharmaceutically acceptable salt thereof; from about 0.037:1 to about 0.296:1, based on the opioid antagonist being naltrexone or a pharmaceutically acceptable salt thereof and the opioid agonist being oxycodone or a pharmaceutically acceptable salt thereof; from about 0.148:1 to about 1.185:1, based on the opioid antagonist being naltrexone or a pharmaceutically acceptable salt thereof and the opioid agonist being hydromorphone or a pharmaceutically acceptable salt thereof; from about 0.278:1 to about 2.222:1, based on the opioid antagonist being naltrexone or a pharmaceutically acceptable salt thereof and the opioid agonist being levorphanol or a pharmaceutically acceptable salt thereof; from about 0.056:1 to about 0.444:1, based on the opioid antagonist being naltrexone or a pharmaceutically acceptable salt thereof and the opioid agonist being methadone or a pharmaceutically acceptable salt thereof; and from about 0.018:1 to about 0.148:1, based on the opioid antagonist being naltrexone or a pharmaceutically acceptable salt thereof and the opioid agonist being morphine or a pharmaceutically acceptable salt thereof.

23. The oral dosage form of claim 1, wherein the opioid antagonist in the sustained release form is incorporated as separate pellets within a gelatin capsule or as part of a melt-extruded multiparticulate comprising the opioid agonist.

24. The oral dosage form of claim 22, wherein the opioid antagonist in the sustained release form is incorporated as separate pellets within a gelatin capsule or as part of a melt-extruded multiparticulate comprising the opioid agonist.

25. The oral dosage form of claim 22, wherein the opioid antagonist is naltrexone or a pharmaceutically acceptable salt thereof, and the opioid agonist is morphine or a pharmaceutically acceptable salt thereof.

Make Better Decisions: Try a trial or see plans & pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.