Method for noribogaine treatment in patients on methadone

Patent metadata

Field	Value
Publication number	US-9744174-B2
Application number	US-201414295273-A
Country	US
Kind code	B2
Filing date	Jun 3, 2014
Priority date	Mar 15, 2013
Publication date	Aug 29, 2017
Grant date	Aug 29, 2017

Abstract

A short treatment with noribogaine shows promise for treating drug dependency. Many opioid addicts are treated with methadone. Giving noribogaine to mammal concurrently being administered methadone surprisingly exacerbates methadone's negative side-effects, and increases the risk of death. Therefore, prior to noribogaine treatment, a patient on methadone therapy undergoes a period of methadone abstinence to wash out the methadone. Surprisingly, noribogaine does not react negatively to morphine. According to the invention, methadone regimen is replaced with morphine prior to noribogaine treatment.

First claim

What is claimed is:

1. A method for treating addiction in a patient in need thereof being administered methadone, the method comprising:
(a) replacing methadone administration with another opioid for a period of time of at least one day such that the serum level of methadone is reduced; and thereafter
(b) administering noribogaine, an ester thereof, or a pharmaceutically acceptable salt or solvate of each thereof to the patient at an amount of from about 60 mg to about 180 mg per day, wherein the patient's QT interval is maintained at less than about 500 ms.

2. The method of claim 1 , wherein step (b) comprises:
i) administering an initial dose of noribogaine, the ester thereof, or the pharmaceutically acceptable salt or solvate thereof, wherein the initial dose provides an average serum noribogaine concentration of 50 ng/mL to 180 ng/mL; and
ii) administering at least one additional dose of noribogaine, the ester thereof, or the pharmaceutically acceptable salt or solvate thereof, such that the at least one additional dose maintains the average serum noribogaine concentration of 50 ng/mL to 180 ng/mL.

3. The method of claim 2 , wherein the initial dose is from 50 mg to 120 mg.

4. The method of claim 2 , wherein the at least one additional dose is from 5 mg to 50 mg.

5. The method of claim 2 , wherein the at least one additional dose is administered from 6 hours to 24 hours after the initial dose.

6. The method of claim 2 , wherein at least two additional doses are administered, and further wherein each additional dose is administered from 6 hours to 24 hours after the previous dose.

7. The method of claim 1 , further comprising selecting an addicted patient who is prescreened to evaluate tolerance for prolongation of QT interval.

8. The method of claim 1 , wherein the serum level of methadone is from about 3 μg/L to about 56 μg/L.

9. The method of claim 1 , further comprising measuring the level of methadone or methadone metabolites in a bodily fluid from the patient.

10. The method of claim 1 , wherein the opioid is morphine.

11. The method of claim 10 , wherein the morphine is an extended-release morphine.

12. The method of claim 1 , wherein the cessation of methadone administration occurs through a gradual reduction in the dose or frequency of administration of methadone.

13. The method of claim 1 , wherein the period of time is at least 200 hours.

14. The method of claim 1 , wherein the period of time is at least a week.

15. The method of claim 1 , wherein all or substantially all of the drug is removed from the patient prior to step b).

16. The method of claim 1 , wherein step (b) comprises:
i) administering an initial dose of noribogaine, the ester thereof, or the pharmaceutically acceptable salt or solvate thereof, wherein the initial dose is from 50 mg to 120 mg; and
ii) administering at least one additional dose of noribogaine, the ester thereof, or the pharmaceutically acceptable salt or solvate thereof, wherein the at least one additional dose is from 5 mg to 75 mg.

17. A method for treating addiction in a patient in need thereof, comprising: (a) determining the presence of a drug that interacts negatively with noribogaine in the patient, wherein the drug is methadone, a mu agonist, a drug which prolongs QT interval, or a drug that causes respiratory depression; (b) in a patient positive for the presence of the drug, replacing administration of the drug with another opioid for a period of time until all or substantially all of the drug is removed; and (c) to a patient negative for the drug, or from whom all or substantially all of the drug is removed, administering noribogaine, an ester thereof, or a pharmaceutically acceptable salt or solvate of each thereof at an amount of from about 60 mg to about 180 mg per day to treat said patient's addiction, wherein the patient's QT interval is maintained at less than about 500 ms during said treatment.

18. The method of claim 17 , wherein the drug that interacts negatively with noribogaine is methadone.

19. The method of claim 17 , wherein, prior to administration of noribogaine, the ester thereof, or the pharmaceutically acceptable salt or solvate thereof, the patient is placed in a controlled environment until the level of the drug in the patient is substantially zero.

20. The method claim 17 , wherein the opioid is morphine.

21. A method of treating addiction in a patient in need thereof, comprising:
(a) administering a unit dose of noribogaine, an ester thereof, or a pharmaceutically acceptable salt or solvate of each thereof to the patient, wherein the unit dose provides an average serum concentration of 50 ng/mL to 180 ng/mL, said concentration being sufficient to treat said addiction while maintaining a QT interval of less than about 500 ms during said treatment;
(b) monitoring the presence of noribogaine in the patient; and
(c) preventing exposure to methadone until all or substantially all of the noribogaine in the patient is removed.

22. A method of treating post-acute withdrawal in a patient in need thereof, comprising:
(a) administering a unit dose of noribogaine, an ester thereof, or a pharmaceutically acceptable salt or solvate of each thereof to the patient, wherein the unit dose provides an average serum concentration of 50 ng/mL to 180 ng/mL, said concentration being sufficient to treat post-acute withdrawal while maintaining a QT interval of less than about 500 ms during said treatment;
(b) monitoring the presence of noribogaine in the patient; and
(c) preventing exposure to methadone during the administration, wherein the unit dose is from 5% to 50% of a dose for treating the acute phase of addiction withdrawal.

23. The method of claim 22 , wherein the unit dose is between about 3.5 mg and about 105 mg per day.

Assignees

• Demerx Inc

Inventors

• Friedhoff Lawrence

Classifications

• A61P25/36

  Opioid-abuse · CPC title

• A61P25/32

  Alcohol-abuse · CPC title

• A61P25/30

  for treating abuse or dependence · CPC title

• A61K31/485

  Morphinan derivatives, e.g. morphine, codeine · CPC title

• A61K31/137

  Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone} · CPC title