Pharmacokinetic Interaction Between Tadalafil and Bosentan in Healthy Male Subjects

Wrishko, Rebecca E.; Dingemanse, Jasper; Yu, Albert S.; Darstein, Christelle; Phillips, Donald A.; Mitchell, Malcolm I.

doi:10.1378/chest.130.4_meetingabstracts.254s-b

Cited by 32 publications

(60 citation statements)

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“…A July 2006 revision added language to the effect that in healthy subjects, coadministration of 125 mg of bosentan twice daily and 606 FRUMKIN 80 mg of sildenafil three times daily resulted in a 63% decrease in plasma concentration of sildenafil and a 50% increase in plasma concentration of bosentan . A similar pharmacokinetic phenomenon has been reported with the coadministration of tadalafil and bosentan to healthy male subjects (Wrishko et al, 2008). This raises the possibility that higher doses of sildenafil-and PDE-5 inhibitors in general-might be needed for patients receiving concomitant sildenafil and bosentan treatment.…”

Section: Label Expansion I Delay In Clinical Worseningsupporting

confidence: 73%

The Pharmacological Treatment of Pulmonary Arterial Hypertension

Frumkin

2012

Pharmacol Rev

106

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Section: Label Expansion I Delay In Clinical Worseningsupporting

confidence: 73%

The Pharmacological Treatment of Pulmonary Arterial Hypertension

Frumkin

2012

Pharmacol Rev

106

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“…In the PHIRST study [157,167], the combination of tadalafil and bosentan resulted in an improvement of exercise capacity of borderline statistical significance (subgroup analysis). For these two compounds a pharmacokinetic interaction has also been shown (table 20).…”

Section: Combination Therapymentioning

confidence: 97%

Guidelines for the diagnosis and treatment of pulmonary hypertension

Galiè¹,

Hoeper²,

Humbert³

et al. 2012

Revista Portuguesa de Cardiologia (English Edition)

419

738

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“…Therefore, combination therapy may be worth rechallenging if it is tolerated. The chronic use of bosentan is well known to decrease the plasma concentration of both tadalafil 9) and sildenafil, 10,11) but not ambrisentan. Thus, retreatment with tadalafil added on to ambrisentan would very likely reinduce more severe hypotension.…”

Section: Discussionmentioning

confidence: 99%

Medical Treatment for an Adult Patient With Eisenmenger Syndrome

Yao

2015

Int. Heart J.

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SummaryPrevious studies examining the use of pulmonary arterial hypertension (PAH) drugs in patients with Eisenmenger syndrome (ES) have shown that it may have beneficial effects in some patients with ES; however, experience with additional cases is necessary to confirm its efficacy and appropriate clinical use. We herein report our experience of an adult patient with ES who benefitted from treatment with PAH drugs. A 32-year-old Japanese man with severe ES induced by a ventricular septal defect associated with Down syndrome began treatment with bosentan at 62.5 mg. Eleven months later, he was admitted for tadalafil (40 mg) add-on therapy because his 6-minute walking distance and brain natriuretic peptide (BNP) level had not improved and his hepatic enzyme levels had increased. However, marked hypotension developed, and the tadalafil dose was decreased. His BNP level subsequently increased, so the bosentan dose was increased to 125 mg. The bosentan was then abruptly stopped because of a low platelet count and high liver enzyme levels. Ambrisentan was then administered for these side effects, but because severe dyspnea developed, the bosentan was started again at 62.5 mg. This resulted in immediate clinical improvement. The patient was finally switched to ambrisentan (5 mg), which was well tolerated. The findings in this particular case show that although it should be used with caution, bosentan may be beneficial in select patients with ES. In addition, ambrisentan may be considered as first-line treatment in some patients as long as liver enzymes and platelets are carefully monitored. (Int Heart J 2015; 56: S8-S11) Key words: Pulmonary arterial hypertension, Ventricular septal defect, Patent ductus arteriosus, Down syndrome, Bosentan, Ambrisentan, Tadalafil, 6-minute walking distance, Endothelin receptor antagonists U ntil bosentan was approved for clinical treatment of pulmonary arterial hypertension (PAH), no medical treatment had been recognized to be effective for patients with Eisenmenger syndrome (ES). The only effective treatment was lung and heart transplantation, which has been performed on a restricted number of patients.Several reports have described the effectiveness of PAH drugs for patients with ES. Fernandes, et al reported the usefulness of intravenous epoprostenol for patients with ES. 1) For the first time in a multicenter, randomized, double-blind, placebo-controlled study (BREATHE-5), Galiè, et al showed that medical monotherapy with bosentan not only significantly improved 6-minute walking distance, but also decreased pulmonary vascular resistance in patients with ES.2) At almost the same time, Singh, et al showed significantly beneficial effects of sildenafil on exercise tolerance and hemodynamic parameters in patients with ES.3) Mukhopadhyay, et al reported similar effects of tadalafil.4) Considering the results of these reports, it may be reasonable to routinely use PAH drugs for patients with ES. In fact, Dimopoulos, et al 5) reported that advanced therapy with PAH drugs improved the p...

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Pharmacokinetic Interaction Between Tadalafil and Bosentan in Healthy Male Subjects

Cited by 32 publications

References 0 publications

The Pharmacological Treatment of Pulmonary Arterial Hypertension

The Pharmacological Treatment of Pulmonary Arterial Hypertension

Guidelines for the diagnosis and treatment of pulmonary hypertension

Medical Treatment for an Adult Patient With Eisenmenger Syndrome

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