Methods for alleviating statin myopathy
View Patent ↗Disclosed herein are methods and compositions for alleviating side effects of statin administration, such as myopathic or myalgic side effects, short-term memory loss, abnormal liver function, glucose intolerance, hyperglycemia, increased risk for diabetes, or cumulative trauma disorder, comprising administration of β-hydroxy β-methylbutyrate (HMB) to an individual taking a statin. Also disclosed are methods and compositions for alleviating acute rhabdomyolysis comprising administration of HMB. The disclosure further provides uses of HMB in combination with a statin to alleviate side effects of statin administration.
1. A pharmaceutical formulation comprising a statin side effect-alleviating amount of β-hydroxy β-methylbutyrate (HMB), or a pharmaceutically acceptable salt thereof, in combination with a statin or a pharmaceutically acceptable salt thereof; wherein HMB is formulated for extended release, or wherein HMB is an HMB prodrug or derivative.
2. The pharmaceutical formulation of claim 1 , wherein the statin is atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin, or a pharmaceutically acceptable salt thereof.
3. The pharmaceutical formulation of claim 2 , which comprises:
(a) 10 to 80 mg atorvastatin;
(b) 5 to 40 mg rosuvastatin;
(c) 10 to 80 mg pravastatin;
(d) 5 to 80 mg simvastatin;
(e) 10 to 80 mg lovastatin;
(f) 1 to 4 mg pitavastatin; or
(g) 20 to 80 mg fluvastatin;
or a pharmaceutically acceptable salt thereof.
4. The pharmaceutical formulation of claim 2 , which comprises:
(a) 10 mg, 20 mg, 40 mg, or 80 mg atorvastatin;
(b) 5 mg, 10 mg, 20 mg, or 40 mg rosuvastatin;
(c) 10 mg, 20 mg, 40 mg, or 80 mg pravastatin;
(d) 10 mg, 20 mg, 40 mg, or 80 mg simvastatin;
(e) 10 mg, 20 mg, 40 mg, or 80 mg lovastatin;
(f) 1 mg, 2 mg, or 4 mg pitavastatin; or
(g) 20 mg, 40 mg, or 80 mg fluvastatin;
or a pharmaceutically acceptable salt thereof.
5. The pharmaceutical formulation of claim 1 , wherein the statin-side effect-alleviating amount of HMB or a pharmaceutically acceptable salt thereof is 4 to 6 grams.
6. The pharmaceutical formulation of claim 5 , wherein the statin-side effect-alleviating amount of HMB or a pharmaceutically acceptable salt thereof is 4 grams or 6 grams.
7. The pharmaceutical formulation of claim 1 , wherein the formulation comprises a statin-to-HMB ratio of approximately 0.001 to 0.1 by weight.
8. The pharmaceutical formulation of claim 1 , wherein HMB is an HMB prodrug modified at the carboxylic acid moiety or hydroxy moiety.
9. The pharmaceutical formulation of claim 1 , wherein HMB is bound to a slow release carrier.
10. The pharmaceutical formulation of claim 1 , wherein the slow release carrier is succinate.
11. The pharmaceutical formulation of claim 1 , wherein HMB is formulated for release of HMB over a period of from about 12 hours to about 48 hours.
12. The pharmaceutical formulation of claim 11 , wherein HMB is formulated for release of HMB over a period of about 24 hours.
13. The pharmaceutical formulation of claim 1 , wherein HMB is calcium HMB monohydrate or HMB free acid.
14. A pharmaceutical formulation comprising a statin and a statin side effect-alleviating amount of β-hydroxy β-methylbutyrate (HMB), or a pharmaceutically acceptable salt thereof, wherein HMB is formulated for extended release, or wherein HMB is an HMB prodrug or derivative.
15. The pharmaceutical formulation of claim 14 , comprising 1 to 12 grams HMB.
16. The pharmaceutical formulation of claim 15 , comprising 3, 4, 6, or 12 grams HMB.
17. The pharmaceutical formulation of claim 14 , wherein HMB is an HMB prodrug modified at the carboxylic acid moiety or hydroxy moiety.
18. The pharmaceutical formulation of claim 14 , wherein HMB is bound to a slow release carrier.
19. The pharmaceutical formulation of claim 18 , wherein the slow release carrier is succinate.
20. The pharmaceutical formulation of claim 14 , wherein HMB is formulated for release of HMB over a period of from about 12 hours to about 48 hours.
21. The pharmaceutical formulation of claim 20 , wherein HMB is formulated for release of HMB over a period of about 24 hours.
22. The pharmaceutical formulation of claim 14 , wherein HMB is calcium HMB monohydrate or HMB free acid.
23. A method for alleviating one or more side effects of statin administration, the method comprising supplementing statin administration with administration of a therapeutically effective amount of the pharmaceutical formulation of claim 14 .
24. The method of claim 23 , wherein the one or more side effects of statin administration are myopathic or myalgic side effects, short-term memory loss, elevated alanine transaminase (ALT) or aspartate transaminase (AST) levels, glucose intolerance, hyperglycemia, increased risk for diabetes, or cumulative trauma disorder.
25. A method for treating acute rhabdomyolysis in a patient, the method comprising administering a therapeutically effective amount of the pharmaceutical formulation of claim 14 to the patient.
26. The method of claim 25 , wherein the pharmaceutical formulation is administered for at least three days.
27. A method for treating cumulative trauma disorder with myalgia/myositis, repetitive use disorder with micro-traumatic myalgia/myositis, acute or chronic rhabdomyolysis, statin-induced glucose intolerance, or statin-induced short-term memory loss, the method comprising administering to a subject a therapeutically effective amount of the pharmaceutical formulation of claim 14 .