NEW YORK (Reuters Health) - Treatment with a calcium channel blocker may reduce the frequency of muscle cramps associated with vismodegib, a small study hints.
"When used at the regular antihypertensive dose of 10 mg daily, the effects on muscle cramps are usually noted within the first two weeks of treatment," Dr. Mina Ally from Stanford University in California told Reuters Health by email.
Genentech's vismodegib (Erivedge) is an oral hedgehog pathway inhibitor recently approved in the U.S. to treat locally advanced and metastatic basal cell carcinoma. Severe muscle cramps are a major side effect and may lead patients to stop the drug.
A recent study hints that vismodegib's effects on calcium channels may be behind the muscle cramps, suggesting that calcium channel blockade may help.
To investigate, Dr. Ally and colleagues studied nine patients with basal cell nevus syndrome taking vismodegib 150 mg daily. For eight weeks, the patients took amlodipine 10 mg daily. They also provided information on muscle cramps four weeks before baseline, at baseline and at two, four and eight weeks after amlodipine. One patient was excluded due to incomplete data on muscle cramps.
Over the eight weeks, amlodipine significantly reduced the frequency of muscle cramps (-5.81% per week, p=0.009), they report online July 22 in JAMA Dermatology.
However, there was no marked change in the severity or duration of muscle cramps or in the frequency of night awakenings due to cramps.
A control group of nine patients who did not take amlodipine but were taking vismodegib and answered questions on muscle cramps did not have a decrease in muscle cramps over eight weeks.
One patient on amlodipine reported mild intermittent dizziness and one reported grade 1 peripheral edema.
Dr. Ally told Reuters Health, "A larger controlled trial is warranted, but we do feel that it is worth attempting a 2-week trial of amlodipine 10 mg daily for appropriate patients, with continued use if successful. The most common side effects of amlodipine include low blood pressure (it is an anti-hypertensive), lower leg edema and constipation. It should not be used in patients with low blood pressure or those already taking multiple anti-hypertensive medications."
Reached for comment by email, Dr. Aleksandar Sekulic, Chair of the Cutaneous Oncology Disease Group at Mayo Clinic Arizona in Scottsdale said: "The results of this study are promising, but additional data will be needed to better assess the efficacy of calcium channel blockers and adequately balance their benefit and risks in management of muscle cramps induced by hedgehog pathway inhibitors."
He noted that a second drug in this class, sonidegib (Novartis), was recently approved in the U.S.
"Toxicity profile of the two drugs is similar, with muscle cramps being the most common and most bothersome toxicity. As both drugs bind to and inhibit 'smoothened' (SMO), the key molecule in the hedgehog signaling pathway, the shared toxicity profile is considered to be a drug class effect rather than a specific agent effect," said Dr. Sekulic, who wasn't involved in the study.
The decreased frequency of cramps with amlodipine in this study is "intriguing, however, given the small number of patients in the study, more work will be needed to a) validate these data and b) compare the efficacy of calcium channel blockers with other approaches aimed at preventing/reducing muscle cramps occurring in the setting of SMO inhibition," he noted.
"Although calcium channel blockers are one of the more commonly used chronic medications in general population, they are not without potential side effects (e.g., dizziness, lightheadedness, swelling of the ankles/feet)," Dr. Sekulic added.
The study was supported in part by Genentech. One author reports owning stock in Curis and Infinity. No other disclosures were reported. Dr. Sekulic led the clinical trial that resulted in approval of vismodegib.
SOURCE: http://bit.ly/1I816gD
JAMA Dermatol 2015.
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