L-Carnitine Reduces Muscle Cramps in Patients taking Vismodegib

Main Article Content

Matthew S Dinehart
Stacy McMurray
Scott M Dinehart
Mark Lebwohl

Keywords

L-carnitine, levocarnitine, vismodegib, hedgehog inhibitor, muscle cramps

Abstract

Vismodegib is an oral, small-molecule hedgehog pathway inhibitor (HHI) approved for the treatment of locally advanced and metastatic basal cell carcinoma. While an effective treatment option for these conditions, HHI therapy is associated with muscle cramps in a significant number of patients. This adverse effect negatively impacts patient quality of life and patient adherence to the prescribed treatment regimen.

Levocarnitine (L-carnitine) is a trimethylated amino acid known to play a critical role in lipid metabolism. It has antioxidant properties, and several studies have illustrated its effectiveness in lessening the severity of muscle cramps in various disease processes.

We present three patients who developed muscle cramping associated with vismodegib treatment for basal cell carcinoma. Each was started on L-carnitine therapy, and all three reported a significant decrease in the severity of their muscle cramps to the point that they were able to continue HHI therapy without taking a drug holiday. These cases illustrate a promising treatment option for the most common side effect associated with HHI treatment. 

References

1. Sekulic A, Migden MR, Lewis K, et al. Pivotal ERIVANCE basal cell carcinoma (BCC) study: 12-month update of efficacy and safety of vismodegib in advanced BCC. J Am Acad Dermatol. 2015;72(6):1021-1026 e1028.

2. Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366(23):2171-2179.

3. Basset-Seguin N, Hauschild A, Grob JJ, et al. Vismodegib in patients with advanced basal cell carcinoma (STEVIE): a pre-planned interim analysis of an international, open-label trial. Lancet Oncol. 2015;16(6):729-736.

4. Lacouture ME, Dreno B, Ascierto PA, et al. Characterization and Management of Hedgehog Pathway Inhibitor-Related Adverse Events in Patients With Advanced Basal Cell Carcinoma. Oncologist. 2016;21(10):1218-1229.

5. Teperino R, Amann S, Bayer M, et al. Hedgehog partial agonism drives Warburg-like metabolism in muscle and brown fat. Cell. 2012;151(2):414-426.

6. Ally MS, Tang JY, Lindgren J, et al. Effect of Calcium Channel Blockade on Vismodegib-Induced Muscle Cramps. JAMA Dermatol. 2015;151(10):1132-1134.

7. Yuan JT, Tello TL, Hultman C, Barker CA, Arron ST, Yom SS. Medical marijuana for the treatment of vismodegib-related muscle spasm. JAAD Case Rep. 2017;3(5):438-440.

8. Garrison SR, Allan GM, Sekhon RK, Musini VM, Khan KM. Magnesium for skeletal muscle cramps. Cochrane Database Syst Rev. 2012(9):CD009402.

9. Yang YW, Macdonald JB, Nelson SA, Sekulic A. Treatment of vismodegib-associated muscle cramps with cyclobenzaprine: A retrospective review. J Am Acad Dermatol. 2017;77(6):1170-1172.

10. Fife K, Herd R, Lalondrelle S, et al. Managing adverse events associated with vismodegib in the treatment of basal cell carcinoma. Future Oncol. 2017;13(2):175-184.

11. Yang X, Dinehart SM. Intermittent Vismodegib Therapy in Basal Cell Nevus Syndrome. JAMA Dermatol. 2016;152(2):223-224.

12. Dreno B, Kunstfeld R, Hauschild A, et al. Two intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas (MIKIE): a randomised, regimen-controlled, double-blind, phase 2 trial. Lancet Oncol. 2017;18(3):404-412.

13. Mosterd K. Intermittent vismodegib dosing to treat multiple basal-cell carcinomas. Lancet Oncol. 2017;18(3):284-286.

14. CA. S. Carnitine deficiency disorders in children. . Ann NY Acad Sci 2004;1033:42-51.

15. Goral S. Levocarnitine and muscle metabolism in patients with end-stage renal disease. J Ren Nutr. 1998;8(3):118-121.

16. Nakanishi H, Kurosaki M, Tsuchiya K, et al. L-carnitine Reduces Muscle Cramps in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2015;13(8):1540-1543.

17. Longo N, Frigeni M, Pasquali M. Carnitine transport and fatty acid oxidation. Biochim Biophys Acta. 2016;1863(10):2422-2435.

18. Rubin MR, Volek JS, Gomez AL, et al. Safety measures of L-carnitine L-tartrate supplementation in healthy men. J Strength Cond Res. 2001;15(4):486-490.

19. Cruciani RA, Dvorkin E, Homel P, et al. Safety, tolerability and symptom outcomes associated with L-carnitine supplementation in patients with cancer, fatigue, and carnitine deficiency: a phase I/II study. J Pain Symptom Manage. 2006;32(6):551-559.

20. Hathcock JN, Shao A. Risk assessment for carnitine. Regul Toxicol Pharmacol. 2006;46(1):23-28.

Most read articles by the same author(s)

1 2 3 4 5 6 > >>