Pharmaceutical compositions comprising meloxicam
View Patent ↗Disclosed herein are compositions comprising an NSAID such as meloxicam and/or rizatriptan in combination with a cyclodextrin and/or a carbonate or a bicarbonate. These compositions may be orally administered, for example, to improve the bioavailability or pharmacokinetics of the NSAID for the treatment of pain such as migraine, arthritis, and other conditions. Also disclosed herein are methods of treating pain, such as migraine, comprising administering meloxicam and rizatriptan to a human being suffering from pain, such as migraine. For migraine, these methods may be particularly useful when the meloxicam and rizatriptan are administered while the human being is suffering from an acute attack of migraine pain or migraine aura. In some embodiments, the combination of meloxicam and rizatriptan may be administered in a manner that results in a T max of meloxicam of 3 hours or less.
1. A method of more rapidly improving migraine pain relief associated with rizatriptan therapy, comprising: orally administering to a human being in need thereof, a combination of: 1) a complex of a meloxicam and a sulfobutylether-β-cyclodextrin, 2) a bicarbonate, and 3) a rizatriptan, wherein one hour after the combination is administered, the human being experiences a greater reduction in migraine pain than the human being would experience one hour after the same amount of the rizatriptan is administered alone.
2. The method of claim 1 , wherein 30 minutes after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience 30 minutes after the same amount of the rizatriptan is administered alone.
3. The method of claim 1 , wherein at 2 hours after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience 2 hours after the same amount of the rizatriptan is administered alone, and at 24 hours after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience 24 hours after the same amount of the rizatriptan is administered alone.
4. The method of claim 1 , wherein the human being has a history of inadequate response to prior migraine treatments.
5. The method of claim 1 , wherein the human being is selected for having a history of inadequate response to prior migraine treatments.
6. The method of claim 1 , wherein the human being has had an average of about 2 to about 8 moderate to severe migraine attacks per month.
7. The method of claim 1 , wherein the human being is selected for having an average of about 2 to about 8 moderate to severe migraine attacks per month.
8. The method of claim 1 , wherein 1) the complex of the meloxicam and the sulfobutylether-β-cyclodextrin, 2) the bicarbonate, and 3) the rizatriptan, are combined together in a monolayer tablet.
9. The method of claim 1 , wherein the combination contains: about 10 mg of rizatriptan in the free base form or a molar equivalent of a salt form; about 20 mg of the meloxicam in the free base form or a molar equivalent of a salt form; and about 400 mg to about 600 mg of the bicarbonate.
10. The method of claim 9 , wherein the bicarbonate is sodium bicarbonate.
11. The method of claim 9 , wherein 30 minutes after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience 30 minutes after the same amount of the rizatriptan is administered alone.
12. The method of claim 9 , wherein the human being has a history of inadequate response to prior migraine treatments.
13. The method of claim 9 , wherein the human being is selected for having a history of inadequate response to prior migraine treatments.
14. The method of claim 9 , wherein 1) the complex of the meloxicam and the sulfobutylether-β-cyclodextrin, 2) the bicarbonate, and 3) the rizatriptan, are combined together in a monolayer tablet.
15. The method of claim 9 , wherein at 2 hours after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience 2 hours after the same amount of the rizatriptan is administered alone, and at 24 hours after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience 24 hours after the same amount of the rizatriptan is administered alone.
16. The method of claim 1 , wherein the human being does not take any rescue medication for at least 24 hours after the combination is orally administered.
17. The method of claim 1 , wherein the human being achieves pain freedom at 2 hours after the combination is orally administered.
18. The method of claim 1 , wherein the human being achieves absence of at least one of the most bothersome symptoms of nausea, phonophobia, or photophobia at 2 hours after the combination is orally administered.
19. The method of claim 1 , wherein the complex of the meloxicam and the sulfobutylether-β-cyclodextrin are present in a dosage form with the bicarbonate, and the bicarbonate is present in an amount that is effective to increase the dissolution rate of the meloxicam.
20. The method of claim 1 , wherein at 2 hours after the combination is orally administered, the human being experiences a greater reduction in nausea than the human being would experience 2 hours after the same amount of the rizatriptan is administered alone.
21. The method of claim 1 , wherein the bicarbonate is sodium bicarbonate.
22. The method of claim 1 , wherein the meloxicam is in the free base form.
23. The method of claim 1 , wherein the rizatriptan is rizatriptan benzoate.
24. The method of claim 1 , wherein the complex of the meloxicam and the sulfobutylether-β-cyclodextrin, the bicarbonate, and the rizatriptan are present in a single dosage form.
25. The method of claim 1 , wherein the migraine pain is accompanied by disturbed vision.
26. The method of claim 25 , wherein the human being achieves absence of the disturbed vision at 2 hours after the combination is orally administered.