Titration of pulmonary arterial hypertension therapeutics: Experience-based recommendations

Abstract

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.

Adherence to disease-specific drug treatment among patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension

“…In addition, previous experiences with pharmacological therapies might lead to a lack of motivation to adhere to a treatment [17]. Thus, it is important to address the patients concerns about a treatment, both at the time of first prescription as well as at subsequent meetings with the patient [18,19]. As shown in the present study, as well as in earlier studies, the longer time since diagnosis that has elapsed, the lower is the adherence to treatment [7,8].…”

“…All patients included in the present study have regular contact with the PAH/CTEPH-expert centres [24] which may have increased their understanding of the PAH-disease, improved involvement in treatment decision, and supported good medical literacy, factors that have been related to adherence [17,25]. Building trust between patients, caregivers and staff might affect the patient's health beliefs and attitudes concerning the effectiveness of the treatment [19,25,26]. However, this might also have an opposite effect as the health-care staff feels they know the patient, and thus, information about the disease and the importance of treatment is not repeated regularly, leading to declining adherence over time.…”

“…Chronic treatment (≥3 filled prescriptions/year) Angiotensin converting enzyme inhibitors 108 (19) 81 2127 (14) Angiotensin-receptor blockers 101 (18) 65 (17) 36 (19) Beta Asthmainhaler therapy 171 (30) 119 (31) 52 (28) Anti-diarrheal drugs 79 (14) 62 (16) 17 (9) Anti-emetics 61 (11) 52 (14) 9 (5) Anti-acid drugs 47 (8) 41 (11) 6 (3)…”

Transitions between infused and oral prostacyclin pathway agents in pulmonary arterial hypertension: key considerations

“…5 PPA doses must be carefully uptitrated and downtitrated, symptoms and hemodynamics must be monitored, and clinicians must manage side effects that could prevent effective dosing. 5–7…”

“…5 PPA doses must be carefully uptitrated and downtitrated, symptoms and hemodynamics must be monitored, and clinicians must manage side effects that could prevent effective dosing. [5][6][7] A few studies have examined transitions from one infused PPA to another or between infused and inhaled PPAs. 4 However, there exist only limited data on transitioning patients between infused and oral PPAs.…”