Modi Sujal, Kahwash Rami, Kissling Kevin
Cardiovascular Medicine, The Ross Heart Hospital at The Ohio State University Wexner Medical Center, 473 W. 12th Avenue, Columbus, OH 43210, USA.
Eur Heart J Case Rep. 2023 Apr 22;7(5):ytad193. doi: 10.1093/ehjcr/ytad193. eCollection 2023 May.
Tacrolimus toxicity in patient's status post-orthotropic heart transplantation is not commonly reported. Given its narrow therapeutic window and drug-drug interactions, it must be closely monitored by providers who are experienced in transplant management. There are no case series of patients with tacrolimus toxicity in the setting of treatment for Sars-2-CoV-19 (COVID 19) for heart-transplant recipients. We present a case of tacrolimus toxicity in the setting of concurrent ritonavir-nirmatrelvir (Paxlovid) use.
The patient was a 74-year-old male with a prior significant history of heart transplantation and on maintenance immunosuppression with tacrolimus. He contracted COVID-19 and was prescribed antiviral therapy with Paxlovid by an outside provider prior to admission. The patient complained of severe headaches, dehydration, and tremors. After eliminating acute intracranial processes with imaging, laboratory investigation revealed a severely elevated tacrolimus level with acute renal injury. The patient was taken off tacrolimus and treated conservatively with intravenous hydration. The symptoms improved, particularly the headaches. He was discharged with instructions to resume his home dosing of tacrolimus and return to clinic in 1 week with a repeat trough level. The subsequent trough level was no longer supra-therapeutic.
Tacrolimus has a potent drug-drug interaction with Paxlovid (ritonavir-nirmatrelvir) and can be supra-therapeutic. Toxicity is associated with multiple adverse effects, including but not limited to, acute renal injury, neurotoxicity, and infections due to over-immunosuppression. As Paxlovid is effective in treating Sars-2-CoV-19 in heart-transplant recipients, knowledge and understanding of drug-drug interactions is crucial in preventing and mitigating toxicity.
原位心脏移植术后患者发生他克莫司毒性反应的情况并不常见。鉴于其治疗窗狭窄以及存在药物相互作用，必须由有移植管理经验的医护人员密切监测。目前尚无关于心脏移植受者在治疗Sars-2-CoV-19（新冠病毒）时发生他克莫司毒性反应的病例系列报道。我们报告一例在同时使用利托那韦-奈玛特韦（帕罗韦德）时出现他克莫司毒性反应的病例。
该患者为一名74岁男性，既往有心脏移植史，一直在接受他克莫司维持免疫抑制治疗。他感染了新冠病毒，入院前由外部医疗机构给予帕罗韦德抗病毒治疗。患者主诉严重头痛、脱水和震颤。经影像学检查排除急性颅内病变后，实验室检查发现他克莫司水平严重升高并伴有急性肾损伤。患者停用他克莫司，通过静脉补液进行保守治疗。症状有所改善，尤其是头痛症状。患者出院时医嘱恢复在家服用他克莫司，并在1周后返回诊所复查血药谷浓度。随后的血药谷浓度不再高于治疗水平。
他克莫司与帕罗韦德（利托那韦-奈玛特韦）存在强效药物相互作用，可能导致血药浓度高于治疗水平。毒性反应与多种不良反应相关，包括但不限于急性肾损伤、神经毒性以及因免疫抑制过度导致的感染。由于帕罗韦德对心脏移植受者的新冠病毒治疗有效，了解药物相互作用对于预防和减轻毒性反应至关重要。
