From the FDA Drug Label
In two controlled trials of 6 to 8 weeks duration where the ability of patients to discontinue medication was measured, 71%-93% of patients treated with alprazolam tapered completely off therapy compared to 89%-96% of placebo-treated patients ... Other symptoms, such as anxiety and insomnia, were frequently seen during discontinuation, but it could not be determined if they were due to return of illness, rebound, or withdrawal ... the following were identified as symptoms of withdrawal: ... muscle cramps, muscle twitch
- Xanax (alprazolam) can cause muscle cramps as a symptom of withdrawal.
- There is no information about Lyrica (pregabalin), Fetzima (levomilnacipran), or Zanaflex (tizanidine) causing calf cramping in the provided drug label.
- The FDA drug label for the other medications is not provided, therefore, no conclusion can be drawn about Lyrica (pregabalin), Fetzima (levomilnacipran), or Zanaflex (tizanidine). 1
From the Research
Yes, all four medications—Lyrica (pregabalin), Xanax (alprazolam), Fetzima (levomilnacipran), and Zanaflex (tizanidine)—can potentially cause calf cramping as a side effect, though with varying frequencies. Muscle cramps or pain are listed side effects for Lyrica, particularly when starting treatment or increasing dosage 2. Xanax may cause muscle cramps less commonly, but they can occur as part of its effect on the central nervous system. Fetzima, an antidepressant, can cause muscle tension and pain in some patients. Zanaflex, a muscle relaxant, paradoxically may cause muscle cramping in some individuals, particularly as the medication wears off. Some key points to consider:
- The exact mechanism of muscle cramps is often unknown, but they can be caused by muscle fatigue and nerve dysfunction rather than electrolyte or other abnormalities 3.
- Medications that are strongly associated with leg cramps include intravenous iron sucrose, conjugated estrogens, raloxifene, naproxen, and teriparatide 3.
- Tizanidine (Zanaflex) has been shown to prolong the QT interval by blocking IKr, which may increase the risk of cardiac proarrhythmia during impaired drug elimination 4. If you experience persistent or severe calf cramping while taking any of these medications, you should contact your healthcare provider rather than discontinuing them abruptly. Proper hydration, gentle stretching, and maintaining electrolyte balance may help reduce cramping. Your doctor might consider adjusting your dosage, switching medications, or adding supplements if the cramping significantly affects your quality of life.