Randomised clinical trial: the long-term safety and tolerability of naloxegol in patients with pain and opioid-induced constipation

Autor:	Lynn R. Webster, Jan Tack, Ulysses Diva, William D. Chey, Mark Sostek, Jaakko Lappalainen
Rok vydání:	2014
Předmět:	Adult Male medicine.medical_specialty Abdominal pain Constipation Nausea Narcotic Antagonists Pain Polyethylene Glycols Naloxegol chemistry.chemical_compound Naldemedine Internal medicine Humans Medicine Pharmacology (medical) Adverse effect Aged Morphine Hepatology business.industry Gastroenterology Middle Aged Analgesics Opioid Morphinans chemistry Opioid Tolerability Laxatives Anesthesia Female medicine.symptom business medicine.drug
Zdroj:	Alimentary Pharmacology & Therapeutics. 40:771-779
ISSN:	0269-2813
Popis:	SummaryBackground Opioid-induced constipation (OIC) is a common adverse effect of opioid therapy. Aim To evaluate the long-term safety and tolerability of naloxegol, an oral, peripherally acting μ-opioid receptor antagonist (PAMORA), in patients with noncancer pain and OIC. Methods A 52-week, multicenter, open-label, randomised, parallel-group phase 3 study was conducted in out-patients taking 30–1000 morphine-equivalent units per day for ≥4 weeks. Patients were randomised 2:1 to receive naloxegol 25 mg/day or usual-care (UC; investigator-chosen laxative regimen) treatment for OIC. Results The safety set comprised 804 patients (naloxegol, n = 534; UC, n = 270). Mean exposure duration was 268 days with naloxegol and 297 days with UC. Frequency of adverse events (AEs) was 81.8% with naloxegol and 72.2% with UC. Treatment-emergent AEs occurring more frequently for naloxegol vs. UC were abdominal pain (17.8% vs. 3.3%), diarrhoea (12.9% vs. 5.9%), nausea (9.4% vs. 4.1%), headache (9.0% vs. 4.8%), flatulence (6.9% vs. 1.1%) and upper abdominal pain (5.1% vs. 1.1%). Most naloxegol-emergent gastrointestinal AEs occurred early, resolving during or after naloxegol discontinuation and were mild or moderate in severity; 11 patients discontinued due to diarrhoea and nine patients owing to abdominal pain. Pain scores and mean daily opioid doses remained stable throughout the study; no attributable opioid withdrawal AEs were observed. Two patients in each group had an adjudicated major adverse cardiovascular event unrelated to study drug; no AEs were reported nor adjudicated as bowel perforations. Conclusion In patients with noncancer pain and opioid-induced constipation, naloxegol 25 mg/day up to 52 weeks was generally safe and well tolerated.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dfc803e8dc475fdd4f1b4a9f307c8634 https://doi.org/10.1111/apt.12899 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.