Background riociguat, a soluble guanylate cyclase stimulator, has been shown in a phase 2 trial to be beneficial in the treatment of pulmonary. The detailed clinical characteristics are also shown in the supplemental file see the supplemental file, table 1, in which we divided the new or addon group into two. Pdf selexipag for the treatment of pulmonary arterial hypertension. Riociguat pharmacokinetics absorption bioavailability. Highlights of prescribing information these highlights do not include all the information needed to use adempas safely and effectively.
Supplementary appendix the new england journal of medicine. Consequently, systemic exposure to riociguat and m1 in the ph population is 2. The majority of patients switched from a phosphodiesterase type 5 inhibitor pde5i to riociguat and the most common reason for switching was lack of efficacy. Here, we explore the efficacy and safety of riociguat in the subgroup of patients with. Riociguat for pulmonary arterial hypertension associated. Riociguat for patients with chronic thromboembolic. Impairment of nitric oxide synthesis and signaling through the nitric oxidesoluble guanylate cyclasecyclic guanosine monophosphate pathway is involved in the pathogenesis of pulmonary hypertension. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a pdf plugin installed and enabled in your browser.
Riociguat is a firstinclass guanylate cyclase stimulator approved for the treatment of pah and chronic thromboembolic pulmonary hypertension, at doses of up to 2. Riociguat constitutes the first drug of the class of sgc stimulators. Riociguat is the firstinclass sgc stimulator with a dual mode of action. Pdf adults with sickle cell disease can develop pulmonary hypertension from a multitude of etiologies. Riociguat for pulmonary arterial hypertension superseded docs if applicable contact details for further information document status this is a controlled document. Efficacy and safety of riociguat in patients with systemic sclerosis the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. See full prescribing information for complete boxed warning do not administer adempas to a pregnant female because it may cause fetal harm. Riociguat is an oral medication called a soluble guanylate cyclase stimulator approved for the treatment of pulmonary arterial hypertension pah in world health organization who group 1 patients. Efficacy and safety of riociguat in patients with systemic. Download acrobat pdf file 267kb supplementary appendix. Background riociguat, a member of a new class of compounds soluble guanylate cyclase stimulators, has been shown in previous clinical.
Given that switching patients from p de5i to riociguat is already taking place in clinical. Riociguat is the first drug to demonstrate improved hemodynamics and function in patients with chronic thromboembolic pulmonary hypertension. Acute hemodynamic effects of riociguat in patients with pulmonary hypertension associated with diastolic heart failure dilate1. This product information was approved at the time this auspar was published. Chronic thromboembolic pulmonary hypertension cteph.
The goal of this therapy for pah is to improve exercise ability, who functional class and delay clinical worsening. This is the only centre in denmark with a pea programme for patients with cteph. Four patients in the riociguat group and one patient in the placebo group had hypotension. Reallife experiences article pdf available in respiratory medicine case reports 22c june 2017 with 128. Riociguat, a soluble guanylate cyclase stimulator, has been shown in a phase 2 trial to be beneficial in the treatment of pulmonary arterial hypertension. Ghofrani ha1, galie n, grimminger f, grunig e, humbert m, jing zc, keogh. New pulmonary hypertension drug riociguat proves effective. In the treatment of inoperable cteph, riociguat is the only drug to consistently demonstrate clinical efficacy in. Four patients treated with riociguat and two treated with placebo had haemoptysis. Riociguat for the treatment of chronic thromboembolic pulmonary. Overview of randomized controlled trials in pulmonary. Chronic thromboembolic pulmonary hypertension cteph is an uncommon complication of pulmonary embolism, in which the pulmonary blood vessels become occluded by the bodys ongoing reaction to residual blood clots. It has been designated an orphan medicine by the european medicines agency and the us fda. Background riociguat, a soluble guanylate cyclase stimulator, has been shown in a phase 2 trial to be beneficial in the treatment of pulmonary arterial hypertension.
Riociguat for thromboembolic pulmonary hypertension. Switching from sildenafil to riociguat for the treatment of pah and inoperable cteph. Riociguat, a new pulmonary hypertension treatment pulmccm. Objectives riociguat is approved for pulmonary arterial hypertension and has antiproliferative, antiinflammatory and antifibrotic effects in animal models of tissue fibrosis. Adempas is indicated for the treatment of adult patients with who functional class fc ii to iii with. It is used to treat two forms of pulmonary hypertension ph. Article pdf available in new england journal of medicine. In the longterm extension, five patients treated with riociguat had adverse events of.
We evaluated the efficacy and safety of riociguat in patients with early diffuse cutaneous systemic sclerosis dcssc at high risk of skin fibrosis progression. Pdf riociguat in patients with chronic thromboembolic. Riociguat is a stimulator of guanylate cyclase which causes relaxation of vascular smooth muscle and is used to treat severe pulmonary arterial hypertension. Clearance of riociguat in subjects with ph is about half that in healthy subjects 1. Pulmonary arterial hypertension is a rare but lifethreatening illness affecting around 10,000 people in the u. Listing a study does not mean it has been evaluated by the u. Patent2 was an openlabel longterm extension to patent1.
Riociguat improves chronic thromboembolic pulmonary. Riociguat can cause serious birth defects if taken during pregnancy. Riociguat for the treatment of chronic thromboembolic. The aim of this article is to share reallife practical clinical experience of switching from sildenafil to riociguat based on three selected case studies from the department of cardiology at aarhus university hospital. Weir1,2, anna conrey1, denise lewis2 and alem mehari3 1cardiovascular and pulmonary branch and hematology branch, national heart, lung and blood institute, national institutes of health, bethesda, usa. Riociguat is a member of a new class of therapeutic agents called soluble guanylate cyclase stimulators. Riociguat in patients with chronic thromboembolic pulmonary hypertension. Riociguat for the treatment of pulmonary arterial hypertension nejm. Identification of the substancemixture and of the companyundertaking product name. Females must not be pregnant when starting riociguat or become pregnant during treatment. See full prescribing information for complete boxed warning. Riociguat improves chronic thromboembolic pulmonary hypertension cteph.
Product information for auspar adempas riociguat bayer australia ltd pm 200307 final 12 june 2014. Riociguat is the first drug approved by the us food and drug administration for the treatment of both pah and inoperable or persistentrecurrent cteph 17, 22, 23. Riociguat is a firstinclass drug of the soluble guanylate cyclase. Following positive results from the phase iii chest1 study in patients with inoperable or persistentrecurrent chronic thromboembolic pulmonary hypertension cteph, the phase iiib cteph early access study eas was designed to assess the safety and tolerability of riociguat in realworld clinical practice, as well as to provide patients with early access to riociguat before launch. Riociguat use in sickle cell related chronic thromboembolic pulmonary hypertension. Riociguat for the treatment of pulmonary arterial hypertension. Persons with disabilities having problems accessing the pdf files below may call 301 7963634 for assistance. The new england journal of medicine n engl j med 369. During the main study, 11 patients reported adverse events of special interest. Any printed copies of this document are not controlled. Pah and inoperable or persistentrecurrent chronic thromboembolic ph. Riociguat in patients with operable cteph prior to.
Pdf switching from sildenafil to riociguat for the. Riociguat dose was unmasked at the end of the 8week doseadjustment phase. Riociguat treatment for portopulmonary hypertension. Objective the pulmonary arterial hypertension sgcstimulator trial1 patent1 was a randomised, doubleblind, placebocontrolled phase iii trial evaluating riociguat in patients with pulmonary arterial hypertension pah. Riociguat for idiopathic interstitial pneumoniaassociated.
Predictors of longterm outcomes in patients treated with. Results from an early access study article pdf available in bmc pulmonary medicine 171 december 2017 with 115 reads. Riociguat is readily absorbed, with an absolute oral bioavailability of approximately 94% that is not affected by food. Physicians were already using the recommended treatmentfree period when switching patients to riociguat from sildenafil, but a slightly longer period than recommended for tadalafil. Riociguat in patients with operable cteph prior to pulmonary endarterectomy pea bridging study the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Nejm career center valuable tools for building a rewarding career in health care. Riociguat for pulmonary hypertension a glass half full. Our content is curated, written and edited by practicing health professionals who have clinical and scientific expertise in their field of reporting.
Riociguat is the firstinclass soluble guanylate cyclase sgc stimulator 4 and is approved in two separate ph indications. Adempas is a prescription medicine used to treat adults with. Riociguat was well tolerated in longterm studies of pah and cteph. Riociguat has not been linked to significant serum enzyme elevations during therapy or to instances of clinically apparent acute liver injury. Background the 12week, phase iii pulmonary arterial hypertension sgcstimulator trial patent1 study investigated riociguat in patients with pulmonary arterial hypertension pah. Riociguat trade name adempas is a drug by bayer that is a stimulator of soluble guanylate cyclase sgc. Pdf riociguat versus sildenafil on hypoxic pulmonary. Here, we present a prospectively planned analysis of the safety and efficacy of riociguat in the subgroup of patients with pah associated with connective tissue disease pahctd. Switching from sildenafil to riociguat for the treatment. Downloaded from at assistance publique hopitaux paris on. Nejm journal watch concise summaries and expert physician commentary that busy clinicians need to enhance patient care. It has subsequently been approved in the usa for the treatment of patients with cteph and also received its first global approval in. Nejm resident 360 information, resources, and support needed to approach rotations and life as a resident.
Pharmacology pharmacodynamic properties riociguat is a stimulator of soluble guanylate cyclase sgc, an enzyme found in most. Whilst this document may be printed, the electronic version posted on the intranet is the controlled copy. Macitentan and riociguat are new drugs that received health canada. The primary outcome was the safety and tolerability of longterm riociguat therapy up to cutoff in march, 2014, assessed with recording of adverse events, serious adverse events, discontinuations, and deaths. Riociguat in patients with early diffuse cutaneous. Riociguat is the worlds first approved pharmacotherapy for cteph, with its first global approval in this indication occurring in canada. The result is slowly worsening shortness of breath, pulmonary hypertension, and eventually right. For this reason, females who can become pregnant must have regular testing to insure they are not pregnant, or become pregnant during therapy or within one month of stopping riociguat.