Safety, Tolerability, and Efficacy of Overnight Switching From Sildenafil to Tadalafil in Patients With Pulmonary Arterial Hypertension

Abstract

SUMMARYAims: Tadalafil, a once-daily phosphodiesterase type 5 inhibitor (PDE-5I), offers clinicians an alternative to sildenafil, a 3-times-daily (t.i.d.) PDE-5I for treatment of pulmonary arterial hypertension (PAH). However, there are limited data describing the risks and benefits or recommended methodology of switching patients from sildenafil to tadalafil. Methods: Chart reviews were conducted on all World Health Organization group 1 patients on sildenafil for ≥3 months who transitioned to tadalafil with documented clinic visits and 6-min walk tests on both drugs. Most patients were transitioned by discontinuing sildenafil after the evening dose and initiating tadalafil 40 mg/day the next day. Data collected included demographics, PAH etiology, diagnostic hemodynamics, 6-min walk distance (6MWD), PDE-5I side effects, and concomitant medications. Data on B-type natriuretic peptide (BNP) levels were available for most patients also receiving endothelin receptor antagonists (ERAs). Results: Medical records from 98 patients were evaluated. Most patients (92%) were on sildenafil for >1 year, and 78% were receiving sildenafil 80-100 mg t.i.d. Ninetyseven percent of patients (95/98) were successfully transitioned and maintained on 40 mg/ day. With a mean duration on tadalafil therapy of 243 AE 127 days at the time of analysis, 6MWD was unchanged. Patient-reported adverse events included headache (4%) and heartburn (2%). There was minimal change in BNP levels in the subset of patients receiving an ERA concomitantly. Conclusions: Transition from sildenafil to tadalafil 40 mg/day appears feasible without clinical deterioration or intolerable side effects. This study provides guidance to physicians considering transition from sildenafil to tadalafil for selecting patients.

Tadalafil Treatment Improves Inflammation, Cognitive Function, And Mismatch Negativity Of Patients With Low Urinary Tract Symptoms And Erectile Dysfunction

“…Increasing the NO/cGMP pathway activity by inhibiting PDE5 with inhibitors, such as tadalafil, is used in daily clinical practice for treatment of benign prostatic hyperplasia and erectile dysfunction 4 . Tadalafil is currently being used to treat pulmonary arterial hypertension, benign prostatic hyperplasia and erectile dysfunction 4,5 . PDE5 inhibitors have also recently emerged as a potential therapeutic strategy for neuroinflammatory, neurodegenerative, and memory loss diseases 6,7 .…”

Switching to riociguat: a potential treatment strategy for the management of CTEPH and PAH

“…32 Other studies have also supported these findings demonstrating tolerance and reduced deterioration. 31,33…”

“…29 Reasons for switching from a PCA to an ERA included having met specific disease stability criteria while receiving a PCA, 28 and for those patients who switched to a PDE5i, concerns over the availability of PCA therapy in the study region. 29 Switching within other drug classes such as ERAs 30 and PDE5i [31][32][33] has also been evaluated and, although data are limited, exercise capacity and World Health Organization functional class (WHO FC) were sustained. The patients who switched from sitaxsentan 30 Patients in studies of switching between PDE5i did so due to drug-related AEs, 31 the desire for greater adherence and convenience, 32,33 as well as potentially lower costs and higher quality of life.…”

“…29 Switching within other drug classes such as ERAs 30 and PDE5i [31][32][33] has also been evaluated and, although data are limited, exercise capacity and World Health Organization functional class (WHO FC) were sustained. The patients who switched from sitaxsentan 30 Patients in studies of switching between PDE5i did so due to drug-related AEs, 31 the desire for greater adherence and convenience, 32,33 as well as potentially lower costs and higher quality of life. 33 The SITAR study assessed safety and patient satisfaction after switching from sildenafil to tadalafil, and demonstrated that tadalafil was well tolerated with improved convenience for patients.…”

Oral Tadalafil in Children with Pulmonary Arterial Hypertension

“…Medical records from 98 patients were evaluated. Patient-reported adverse events included headache (4 %) and heartburn (2 %) and transition from sildenafil to tadalafil 40 mg/day appeared feasible without clinical deterioration or intolerable side effects [22]. Also Takatsuki et al study showed that the side effect profiles of tadalafil initial therapy were similar for the patients who had transitioned from sildenafil to tadalafil including headache, nausea, myalgia, nasal congestion, flushing, and allergic reaction; 2 patients discontinued tadalafil due to migraine or allergic reaction and one patient receiving sildenafil had no breakthrough syncope after transition to tadalafil [20].…”