Department of Palliative Medicine, Tokyo Medical University, Tokyo, Japan.
Ann Palliat Med. 2024 Mar;13(2):428-432. doi: 10.21037/apm-23-581.
Many of the drugs used for the treatment and alleviation of symptoms in cancer patients are known to inhibit or induce cytochrome P450 (CYP). Therefore, it is important to pay attention to the drug interactions of opioid analgesics that are metabolized by CYPs, because for example when using oxycodone metabolized by CYP3A4, it is possible that the effect will be attenuated or enhanced by the concomitant use of drugs that induce or inhibit CYP3A4. Aprepitant, an antiemetic drug used in many patients receiving anticancer drugs, is known as a moderate competitive inhibitor of CYP3A4. We experienced a case of respiratory depression caused by opioids, which was suspected to be caused by a drug interaction with antiemetics especially aprepitant.
The patient was a 72-year-old man. He had been treated with continuous oxycodone infusion for perianal pain associated with the rectal invasion of prostate cancer. No comorbidities other than renal dysfunction were observed. Oxycodone treatment was started at 48 mg/day, and was increased to 108 mg/day, and then the pain decreased. Once the pain was controlled, chemotherapy was planned. Antiemetics (dexamethasone, palonosetron, and aprepitant) were administered before anticancer drug administration. Approximately 3 hours after antiemetics administration and before the administration of the anticancer drugs, a ward nurse noticed that oversedation and respiratory depression had occurred. When the patient was called, he immediately woke up and was able to talk normally, so the anticancer drugs were administered as scheduled. About 2 hours after the nurse noticed oversedation, the attending physician reduced the dose of oxycodone infusion to 48 mg/day. After that, his drowsiness persisted, but his respiratory condition improved. Despite reducing the dose of oxycodone to less than half, the pain remained stable at numeric rating scale (NRS) 0-1, without the use of a rescue dose. The patient was discharged from the hospital 36 days after the administration of anticancer drugs, without any problems.
The cause of respiratory depression in this case was thought to be a combination of factors, including drug interactions between oxycodone and antiemetics, and oxycodone accumulation due to renal dysfunction.
许多用于治疗和缓解癌症患者症状的药物已知可抑制或诱导细胞色素 P450（CYP）。因此，需要注意通过 CYP 代谢的阿片类镇痛药的药物相互作用，因为例如在使用由 CYP3A4 代谢的羟考酮时，同时使用诱导或抑制 CYP3A4 的药物可能会减弱或增强其效果。阿瑞匹坦是一种在许多接受抗癌药物治疗的患者中使用的止吐药，已知是 CYP3A4 的中度竞争性抑制剂。我们遇到了一例由阿片类药物引起的呼吸抑制病例，该病例疑似由止吐药特别是阿瑞匹坦的药物相互作用引起。
患者为 72 岁男性，因前列腺癌直肠侵犯所致肛周疼痛，持续接受羟考酮输注治疗。除肾功能不全外，无其他合并症。开始给予羟考酮治疗，剂量为 48mg/天，逐渐增加至 108mg/天，随后疼痛减轻。疼痛得到控制后，计划进行化疗。在给予抗癌药物之前给予止吐药（地塞米松、帕洛诺司琼和阿瑞匹坦）。给予止吐药后约 3 小时，在给予抗癌药物之前，病房护士注意到患者出现镇静过度和呼吸抑制。当呼叫患者时，他立即醒来并能够正常交谈，因此按计划给予了抗癌药物。在护士注意到镇静过度约 2 小时后，主治医生将羟考酮输注剂量减少至 48mg/天。此后，他的嗜睡持续存在，但呼吸状况改善。尽管将羟考酮的剂量减少至不到一半，但疼痛仍保持在数字评定量表（NRS）0-1，无需使用解救剂量。在给予抗癌药物 36 天后，患者出院，无任何问题。
认为该例呼吸抑制的原因是多种因素的综合作用，包括羟考酮和止吐药之间的药物相互作用，以及肾功能不全导致羟考酮蓄积。
