QCan L-carnitine help to relieve muscle cramps in patients taking hedgehog pathway inhibitors?

Medically reviewed by Nick Brownstone, MD

Oral hedgehog inhibitors (HHI) like vismodegib and sonidegib are approved by the Food and Drug Administration (FDA) for the treatment of locally advanced basal cell carcinoma in cases where surgery and radiation are inappropriate.¹ Significant therapeutic response can be achieved using these molecules, however many clinicians are hesitant to deploy them due to their vast side effect profiles.^1,2

Muscle cramps are the most frequently reported side effect, affecting approximately 60–70% of patients. These cramps can significantly impact quality of life, lead to treatment interruptions or discontinuation, and negatively affect both patient adherence and therapeutic outcomes..² For this reason, it is imperative that practitioners counsel patients adequately on the potential adverse events (AE) prior to initiating therapy and reassure patients that measures can be taken to alleviate some of these burdensome side effects.^1,2

In addition to several off label dosing regimens or drug holidays, clinicians can initiate supplementation with levocarnitine (L carnitine) concomitant with HHI therapy to reduce the severity of muscle cramps. L-carnitine is a naturally occurring amino acid derivative that plays an essential role in energy production. By enhancing energy supply to muscles, these cells can more readily pump out the calcium that has flooded the cell due to HHI use.^2,3 Exogenous supplementation has been demonstrated to substantially decrease muscle cramps, thereby enhancing patient quality of life, treatment compliance, and overall clinical outcomes.

Optimal dosage for HHI related cramps has yet to be established, however many authorities on the subject matter recommend dosing anywhere from 1000-2000 mg daily.² Dr. Scott Dinehart, a board-certified dermatologist and fellowship-trained Mohs surgeon recommends initiating patients on 1500 mg once daily two weeks prior to starting HHI therapy and continues this for the duration of treatment. Dr. Dinehart recommends patients procure L-carnitine 3000 mg liquid shots on Amazon and instructs patients to take one half teaspoon daily.

Precautions with this supplement include avoiding use in patients with significant renal impairment unless under the direction of a nephrologist, as it is primarily excreted by the kidneys. Mild to moderate drug interactions have been reported with warfarin and thyroid medications, the latter potentially reducing the efficacy of thyroid hormone replacement therapy. Caution is also advised in individuals with a history of seizures.²

Muscle cramps often develop early in the course of HHI therapy and may worsen with ongoing treatment.² This AE can disrupt patients’ quality of life and can result in both the interruption and discontinuation of therapy. L-carnitine supplementation can help to make muscle spasms palatable for patients and can improve patient outcomes.

References:

1. Dummer R, Ascierto PA, Basset‐Seguin N, et al. Sonidegib and vismodegib in the treatment of patients with locally advanced basal cell carcinoma: a joint expert opinion. Acad Dermatol Venereol. 2020;34(9):1944-1956. doi:10.1111/jdv.16230
2. Dinehart MS, McMurray S, Dinehart SM, Lebwohl M. L-Carnitine Reduces Muscle Cramps in Patients taking Vismodegib. J of Skin. 2018;2(2):90-95. doi:10.25251/skin.2.2.1
3. Sivandzadeh GR, Shahsavari A, Meftah E, Niknam R, Safarpour AR. Effect of L-carnitine supplementation on muscle cramps in liver cirrhosis: results from a retrospective cohort study. BMC Gastroenterol. 2025;25(1):150. doi:10.1186/s12876-025-03730-4