Fan Xue, Li Yuan, Lin Xiangchun
Department of Gastroenterology and Endoscopy Center, Peking University International Hospital, Beijing, China.
Front Pharmacol. 2025 Aug 6;16:1635792. doi: 10.3389/fphar.2025.1635792. eCollection 2025.
Linaclotide and plecanatide, as guanylate cyclase-C agonists, are effective treatments for irritable bowel syndrome with constipation and chronic idiopathic constipation. While their therapeutic benefits are well-established, the potential association between these drugs and the adverse reaction of muscle spasms remains understudied and controversial.
To evaluate the potential association between muscle spasms and linaclotide or plecanatide using real-world pharmacovigilance data.
Cases of muscle spasms linked to linaclotide or plecanatide as primary suspected drugs were extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS). Disproportionality analyses, including reporting odds ratio and information component, were employed to detect safety signals. Temporal patterns were assessed using Weibull distribution analysis.
A total of 231 muscle spasms cases were identified (linaclotide: 182; plecanatide: 49). Females accounted for 72.3% of the cases (n = 167), indicating a higher susceptibility. Disproportionality analysis revealed significant safety signals for both drugs, with plecanatide showing a stronger association (ROR = 6.12, 95% CI: 4.61-8.11) compared to linaclotide (ROR = 1.88, 95% CI: 1.63-2.18). Weibull analysis demonstrated an early failure-type curve (β < 1), suggesting a higher incidence shortly after treatment initiation.
This study identifies a significant association between linaclotide/plecanatide and muscle spasms. The findings highlight the need for vigilance in high-risk populations and call for further investigation into the underlying mechanisms.
利那洛肽和普卡那肽作为鸟苷酸环化酶-C激动剂，是治疗便秘型肠易激综合征和慢性特发性便秘的有效药物。虽然它们的治疗益处已得到充分证实，但这些药物与肌肉痉挛不良反应之间的潜在关联仍研究不足且存在争议。
利用真实世界的药物警戒数据评估肌肉痉挛与利那洛肽或普卡那肽之间的潜在关联。
从美国食品药品监督管理局不良事件报告系统（FAERS）中提取与利那洛肽或普卡那肽作为主要可疑药物相关的肌肉痉挛病例。采用不成比例分析，包括报告比值比和信息成分，来检测安全信号。使用威布尔分布分析评估时间模式。
共识别出231例肌肉痉挛病例（利那洛肽：182例；普卡那肽：49例）。女性占病例的72.3%（n = 167），表明易感性更高。不成比例分析显示两种药物均有显著的安全信号，与利那洛肽（报告比值比 = 1.88，95%置信区间：1.63 - 2.18）相比，普卡那肽显示出更强的关联（报告比值比 = 6.12，95%置信区间：4.61 - 8.11）。威布尔分析显示为早期失效型曲线（β < 1），表明在治疗开始后不久发病率较高。
本研究确定了利那洛肽/普卡那肽与肌肉痉挛之间存在显著关联。研究结果强调了对高危人群保持警惕的必要性，并呼吁对潜在机制进行进一步研究。
