University of California San Diego, 9444 Medical Center Drive, Suite 2-042, La Jolla, CA, 92037, USA.
University of Texas Southwestern Medical Center at Dallas, 5939 Harry Hines Blvd., Suite 600, Dallas, TX, 75390, USA.
Respir Med. 2018 Oct;143:139-146. doi: 10.1016/j.rmed.2018.09.002. Epub 2018 Sep 5.
The availability of new medications has improved exercise capacity, enhanced quality of life, and extended time to clinical worsening in patients with pulmonary arterial hypertension (PAH). For many of these medications, careful individualized dose titration is required to maximize therapeutic effectiveness while minimizing side effects. In addition, specific routes of administration, including intravenous (IV), subcutaneous (SC), and inhaled administration may present additional challenges for patients and healthcare providers. These challenges include the possibility of catheter-related infections (IV), infusion site pain (SC), and adherence to frequent dosing schedules (inhaled). Temporary discontinuations may require re-titration and, in some cases, may even be life threatening. Here, based on our clinical experience, we provide our recommendations for dose titration schemes for PAH medications that require individualized dosing in adult patients, including agents acting on the endothelin-1 pathway (bosentan and ambrisentan), the prostacyclin pathway (epoprostenol, treprostinil, and selexipag), and the nitric oxide pathway (tadalafil and the soluble guanylate cyclase stimulator riociguat). A case study that illustrates the application of best practices for PAH medication dose titration in a real-world setting is presented. Good two-way communication between specialty pharmacies and other healthcare providers promotes optimal medication usage and patient health. Experience has shown that slow, cautious up-titration is generally associated with better long-term outcomes. In all cases, patient education, frequent monitoring and careful management of side effects, and treatment adherence are critical.
新型药物的出现改善了肺动脉高压（PAH）患者的运动能力、生活质量，并延长了临床恶化时间。对于许多这些药物，需要仔细个体化剂量滴定以最大化治疗效果，同时最小化副作用。此外，包括静脉内（IV）、皮下（SC）和吸入途径在内的特定给药途径可能会给患者和医疗保健提供者带来额外的挑战。这些挑战包括导管相关感染（IV）、输注部位疼痛（SC）以及频繁给药方案的依从性（吸入）的可能性。临时停药可能需要重新滴定，在某些情况下，甚至可能危及生命。在这里，根据我们的临床经验，我们为需要个体化剂量的成人 PAH 药物的剂量滴定方案提供建议，包括作用于内皮素-1 途径的药物（波生坦和安立生坦）、前列环素途径的药物（依前列醇、曲前列尼尔和塞立生坦）和一氧化氮途径的药物（他达拉非和可溶性鸟苷酸环化酶刺激剂利奥西呱）。呈现了一个说明在真实环境中应用 PAH 药物剂量滴定最佳实践的案例研究。专业药房和其他医疗保健提供者之间的良好双向沟通促进了最佳药物使用和患者健康。经验表明，缓慢、谨慎的剂量递增通常与更好的长期结果相关。在所有情况下，患者教育、频繁监测和仔细管理副作用以及治疗依从性至关重要。
