Pharmaceutical compositions comprising meloxicam
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 treating migraine, 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 the combination is orally administered when the human being is suffering from moderate to severe migraine pain of an acute migraine, and wherein the human being experiences improvement in the Patient Global Impression of Change (PGI-C) at twenty-four hours after the combination is orally administered.
2. The method of claim 1 , wherein two hours after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience two hours after the same amount of the rizatriptan is orally administered alone.
3. The method of claim 1 , wherein two hours after the combination is orally administered, the human being experiences a greater reduction in the human being's most bothersome symptom than the human being would experience two hours after the same amount of the rizatriptan is orally administered alone, and wherein the most bothersome symptom is nausea, phonophobia, or photophobia.
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 meloxicam in the free acid 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 thirty minutes after the combination is orally administered, the human being experiences a greater reduction in migraine pain than the human being would experience thirty minutes after the same amount of the rizatriptan is orally administered alone.
12. The method of claim 11 , wherein the human being has a history of inadequate response to prior migraine treatments.
13. The method of claim 11 , wherein the human being is selected for having a history of inadequate response to prior migraine treatments.
14. The method of claim 11 , 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 1 , wherein the human being does not take any rescue medication for at least twenty-four hours after the combination is orally administered.
16. The method of claim 1 , wherein the human being achieves absence of the most bothersome symptom to the human being two hours after the combination is orally administered, and wherein the most bothersome symptom is nausea, phonophobia, or photophobia.
17. 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 meloxicam.
18. The method of claim 1 , wherein the human being has migraine pain that is accompanied with nausea.
19. The method of claim 18 , wherein two hours after the combination is orally administered, the human being experiences a greater reduction in nausea than the human being would experience two hours after the same amount of the rizatriptan is orally administered alone.
20. The method of claim 1 , wherein the bicarbonate is sodium bicarbonate.
21. The method of claim 1 , wherein the meloxicam is in the free acid form.
22. The method of claim 1 , wherein the rizatriptan is rizatriptan benzoate.
23. 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.
24. The method of claim 1 , wherein migraine pain is accompanied by disturbed vision.
25. The method of claim 24 , wherein the human being achieves absence of the disturbed vision two hours after the combination is orally administered.
26. The method of claim 1 , wherein the human being is more likely to experience improvement in the PGI-C at two hours after the combination is orally administered as compared to orally taking a placebo.
27. The method of claim 1 , wherein the human being experiences more improvement in the PGI-C at two hours after the combination is orally administered than the human being would have experienced after administering the rizatriptan alone.
28. The method of claim 1 , wherein the human being is more likely to return to normal functioning at twenty-four hours after the combination is orally administered as compared to orally taking a placebo.
29. The method of claim 1 , wherein the human being is more likely to return to normal functioning at twenty-four hours after the combination is orally administered as compared to orally taking the same amount of the rizatriptan alone.