"Today, the U.S. Food and Drug Administration approved the XVIVO Perfusion System (XPS) with STEEN Solution, a device for preserving donated lungs that do not initially meet the standard criteria for lung transplantation but may be transplantable "...
The following serious adverse reactions are discussed elsewhere in the labeling:
- Embryo-Fetal Toxicity [see WARNINGS AND PRECAUTIONS]
- Hypotension [see WARNINGS AND PRECAUTIONS]
- Bleeding [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety data described below reflect exposure to Adempas in two, randomized, double blind, placebo-controlled trials in patients with inoperable or recurrent/persistent CTEPH (CHEST-1) and treatment naive or pre-treated PAH patients (PATENT-1). The population (Adempas: n = 490; Placebo: n = 214) was between the age of 18 and 80 years [See Clinical Studies].
The safety profile of Adempas in patients with inoperable or recurrent/persistent CTEPH (CHEST-1) and treatment naive or pre-treated PAH (PATENT-1) were similar. Therefore, adverse drug reactions (ADRs) identified from the 12 and 16 week placebo-controlled trials for PAH and CTEPH respectively were pooled, and those occurring more frequently on Adempas than placebo ( ≥ 3%) are displayed in Table 1 below. Most adverse reactions in Table 1 can be ascribed to the vasodilatory mechanism of action of Adempas.
The overall rates of discontinuation due to an adverse event in the pivotal placebo-controlled trials were 2.9% for Adempas and 5.1% for placebo (pooled data).
Table 1: Adverse Reactions Occurring More Frequently
( ≥ 3%) on Adempas than Placebo (Pooled from CHEST-1 and PATENT-1)
|Adverse Reactions||Adempas %
|Dyspepsia and Gastritis||21||8|
|Anemia (including laboratory parameters)||7||2|
|Gastroesophageal reflux disease||5||2|
Other events that were seen more frequently in Adempas compared to placebo and potentially related to treatment were: palpitations, nasal congestion, epistaxis, dysphagia, abdominal distension and peripheral edema. With longer observation in uncontrolled long-term extension studies the safety profile was similar to that observed in the placebo controlled phase 3 trials.
Read the Adempas (riociguat tablets) Side Effects Center for a complete guide to possible side effects
Pharmacodynamic Interactions With Adempas
Co-administration of Adempas with specific PDE-5 inhibitors (such as sildenafil, tadalafil, or vardenafil) and nonspecific PDE inhibitors (such as dipyridamole or theophylline), is contraindicated because of hypotension [see CONTRAINDICATIONS and CLINICAL PHARMACOLOGY]. Clinical experience with co-administration of Adempas and other phosphodiesterase inhibitors (for example, milrinone, cilostazole, roflumilast) is limited.
Pharmacokinetic Interactions With Adempas
Plasma concentrations in smokers are reduced by 50-60% compared to nonsmokers. Based on pharmacokinetic modeling, for patients who are smokers, doses higher than 2.5 mg three times a day may be considered in order to match exposure seen in nonsmoking patients. Safety and effectiveness of Adempas doses higher than 2.5 mg three times a day have not been established. A dose reduction should be considered in patients who stop smoking [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].
Strong CYP and P-gp/BCRP inhibitors
Concomitant use of riociguat with strong cytochrome CYP inhibitors and Pgp/BCRP inhibitors such as azole antimycotics (for example, ketoconazole, itraconazole) or HIV protease inhibitors (such as ritonavir) increase riociguat exposure and may result in hypotension. Consider a starting dose of 0.5 mg 3 times a day when initiating Adempas in patients receiving strong CYP and P-gp/BCRP inhibitors. Monitor for signs and symptoms of hypotension on initiation and on treatment with strong CYP and P-gp/BCRP inhibitors. A dose reduction should be considered in patients who may not tolerate the hypotensive effect of riociguat [see DOSAGE AND ADMINISTRATION, WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
Strong CYP3A inducers
Strong inducers of CYP3A (for example, rifampin, phenytoin, carbamazepine, phenobarbital or St. John's Wort) may significantly reduce riociguat exposure. Data are not available to guide dosing of riociguat when strong CYP3A inducers are co-administered [see CLINICAL PHARMACOLOGY].
Antacids such as aluminum hydroxide/magnesium hydroxide decrease riociguat absorption and should not be taken within 1 hour of taking Adempas [see CLINICAL PHARMACOLOGY].This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 5/27/2014
Additional Adempas Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.