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

Webster, Lynn R.; Chey, William D.; Tack, Jan; Lappalainen, Jaakko; Diva, Ulysses; Sostek, Mark

doi:10.1111/apt.12899

Cited by 109 publications

(154 citation statements)

References 14 publications

Supporting

Mentioning

141

Contrasting

Unclassified

Order By: Relevance

“…Serious adverse events did not occur in any of the randomized controlled trials Webster et al 2014]. QT/QTc interval prolongation was not observed when 150 mg of naloxegol was given to healthy men [Gottfridsson et al 2013].…”

Section: Naloxegolmentioning

confidence: 86%

Opioid-induced constipation: advances and clinical guidance

Nelson

Camilleri

2016

Therapeutic Advances in Chronic Disease

View full text Add to dashboard Cite

Currently opioids are the most frequently used medications for chronic noncancer pain. Opioid-induced constipation is the most common adverse effect associated with prolonged use of opioids, having a major impact on quality of life. There is an increasing need to treat opioid-induced constipation. With the recent approval of medications for the treatment of opioid-induced constipation, there are several therapeutic approaches. This review addresses the clinical presentation and diagnosis of opioid-induced constipation, barriers to its diagnosis, effects of opioids in the gastrointestinal tract, differential tolerance to opiates in different gastrointestinal organs, medications approved and in development for the treatment of opioid-induced constipation, and a proposed clinical management algorithm for treating opioid-induced constipation in patients with noncancer pain.

show abstract

Section: Naloxegolmentioning

confidence: 86%

Opioid-induced constipation: advances and clinical guidance

Nelson

Camilleri

2016

Therapeutic Advances in Chronic Disease

View full text Add to dashboard Cite

show abstract

“…Vrlo uporno neželjeno dejstvo opioidne terapije, uprkos dobrom kupiranju bola, značajno remeti kvalitet života pacijenata. Ovo je navelo farmaceutske kuće da razmišljaju o uvođe-nju leka koji bi kupirao gastrointestinalna neželje-na dejstva opioida 41 . Biohemijskom modifikacijom α-naloxola došlo se do oralne formulacije leka veće molekulske mase, koji ostvaruje lokalni efekat na μ2-opioidnim receptorima.…”

Section: α-Naloxolunclassified

Old drugs are new again (drugs)

Jovičić¹,

Gvozdić²,

Volaš³

et al. 2017

Serb J Anes Inten Therap

View full text Add to dashboard Cite

Sažetak UvodS obzirom na to da je akutni bol praiskonski zaštit-ni simptom, a da je hronični bol označen kao bolest savremenog čoveka, zbrinjavanje obe vrste bola, prema Montrealskoj deklaraciji, predstavlja osnovno pravo svakog čoveka i etički imperativ 1 . U eri dobro razvijene farmaceutske industrije, postoji ogroman pritisak društva za proizvodnju novih grupa farmakoloških sredstava u cilju tretiranja bolnih stanja.Osnovna mana novih grupa lekova je nedovoljno poznati spektar neželjenih dejstava, koji se otkriva nakon dovoljno duge upotrebe u praksi. Kako navodi Pharmacy Times iz 2011. godine 2 , za dobijanje odobrenja od Federal drug administration (FDA) za plasiranje novog leka na tržište, potrebno je ogromno finansijsko ulaganje i prelazak dugog puta u sprovođenju pretkliničkih i kliničkih istraživanja. Na primer, 1996. godine, 53% podnetih zahteva za sprovođenje kliničkog istraživanja bilo je odobreno od strane FDA, za razliku od 19% zahteva koliko je bilo podržano 2009. godine 3 . Taj trend se i dalje održava. Ono što je preporuka ovih autora je da se stari, već dobro poznati farmakološki profil lekova proširi novim indikacionim područjem (eng. prepurposing) i da se poznate farmakokinetske i farmakodinamske osobine iskoriste za unapređenje formulacije leka (eng. preformulation). Kroz navedena dva procesa, prolaze neki od najmoćnih medikamenata iz palete multimodalnog pristupa terapiji bola.Kako navode Wu i saradnici, multimodalni pristup lečenju akutnog postoperativnog bola, koji obuhvata i upotrebu modulatora bola, terapijski je pristup koji bi poboljšao kontrolu bola i smanjio potrebu za primenom opioida 4 . Međutim, problematika koju ističu ovi autori se odnosi na širok dijapazon primenjenih doza istog leka, kombinaciju različitih tehnika u različitoj vrsti hirurgije, a sve to ne stvara podlogu za formiranje jednog konzistentnog zaključka. Nasuprot ovom podatku, u tertmanu hroničnog nemalignog bola, primena multimodalnog pristupa i modulatora bola je neophodan terapijski pristup s obzirom na komplek-

show abstract

“…The authors concluded that treatment with naloxegol, as compared with placebo, resulted in a significantly higher rate of treatment response, without reducing opioidmediated analgesia [35 && ]. The long-term safety of naloxegol was addressed in a 52-week, multicenter, open-label, randomized, parallel-group phase 3 study [47] in patients with noncancer pain and OIC. Patients were randomized 2 : 1 to receive oral naloxegol 25 mg/day or usual care (usual care; investigator-chosen laxative regimen) treatment for OIC.…”

Section: Key Pointsmentioning

confidence: 99%

“…Treatment-emergent adverse events occurring more frequently for naloxegol versus usual care were abdominal pain (17.8 versus 3.3%), diarrhea (12.9 versus 5.9%), nausea (9.4 versus 4.1%), headache (9.0 versus 4.8%), flatulence (6.9 versus 1.1%) and upper abdominal pain (5.1 versus 1.1%). Most naloxegol-emergent gastrointestinal adverse events occurred early, resolving during or after naloxegol discontinuation and were mild or moderate in severity [47].…”

Section: Key Pointsmentioning

confidence: 99%