Table 7. Treatment adverse events of PAMORAs.

PAMORAS: peripherally acting μ-opioid receptor antagonists, CVA: cerebrovascular accident, MI: myocardial infarction.

Drug/route/dose	Withdrawal effect	Increase in pain	Increased opioid requirements	TAEs	References
Almivopan oral: 0.5-1 mg	Not commented	No	No	Most common: headache, GI system disturbance	[35]
Methylnaltrexone SC: 0.1-0.3 mg/kg or 1-20 mg; IV: 0.2 mg/kg; oral: 150-450 mg	No or mild, e.g., hyperidrosis. In subjects on methadone no withdrawal symptoms [35].	No or minimal change	No or negligible	Most common: abdominal pain, flatulence or diarrhea at a higher dose. Very rare: extrasystoles [41], syncope [37] and non-cardiac chest pain, cardiac arrest, MI, CVA, sudden death (in patients with underlying CV risk factors).	[36-38,41,42, 44-49]
Naloxegol oral: 5-50 mg once daily	None [34] or hyperidrosis more frequent at increased doses [29]	No [33]	No [33]	No difference [33]. Yes - most common: abdominal pain, flatulence or diarrhea, more common at increasing dose [32].	[31-34]
Naldemedine oral: 0.1-0.4 mg	More than placebo, especially over the age of 65 [54]	No [56]	No [56]	Most common: abdominal pain, flatulence or diarrhea at increasing dose. Most commonly reported, nasopharyngitis and diarrhea [61]. Very rare: CVA (not connected to the used medicine) [58].	[50-56]