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.