Understanding Relistor:

Relistor is the first FDA-approved peripherally acting mu-opioid receptor antagonist (PAMORA). Its quaternary structure prevents it from crossing the blood-brain barrier — selectively blocking opioid effects on the GI tract while preserving central analgesic effects. Available as both subcutaneous injection and oral tablet formulations to suit different patient situations.

How it works:

Opioids cause constipation by activating mu-opioid receptors in the GI tract — reducing intestinal motility, increasing fluid absorption, and increasing anal sphincter tone. Standard laxatives often inadequately address this mechanism in patients on chronic opioids.

Methylnaltrexone selectively antagonizes mu-opioid receptors in the GI tract — restoring normal motility and reducing constipation. Its quaternary ammonium structure prevents blood-brain barrier penetration, so central analgesic effects are preserved. Subcutaneous injection has rapid onset (within hours); oral tablet for chronic non-cancer pain OIC management.

Form and use:

Relistor subcutaneous injection (8 mg or 12 mg single-use vials, prefilled syringes) for advanced illness OIC — weight-based dosing every other day or as needed. Oral tablets (450 mg) for chronic non-cancer pain OIC — once daily on empty stomach (1 hour before food). Discontinue stool softeners and stimulant laxatives when starting Relistor (no benefit, may add side effects). Discontinue Relistor if opioid use stops.

Generic availability:

No generic Relistor. Other PAMORAs: naloxegol (Movantik — generic now available, oral once daily), naldemedine (Symproic — brand only, oral once daily). Other OIC therapies (mostly generic): lubiprostone (Amitiza generic — chloride channel activator), linaclotide (Linzess — GC-C agonist, also for IBS-C and chronic idiopathic constipation), prucalopride (Motegrity — 5-HT4 agonist for chronic idiopathic constipation). OTC standard laxative regimens (very cheap first-line): osmotic laxatives (polyethylene glycol/PEG/Miralax, lactulose generic), stimulant laxatives (senna, bisacodyl), stool softeners (docusate — limited evidence). Lifestyle interventions: hydration, dietary fiber, physical activity. Address opioid use: opioid rotation (different opioid may have less constipation), dose minimization, opioid sparing (NSAIDs where safe, acetaminophen, adjuvants like gabapentinoids, antidepressants, regional anesthesia, interventional procedures, multimodal pain management). For palliative care patients, methylnaltrexone has the longest history; for chronic non-cancer pain, naloxegol generic is often first-line PAMORA due to cost.

Warnings:

**GI perforation (rare but serious — caution in patients with known or suspected GI tract impairments such as diverticular disease, GI malignancy with peritoneal involvement, infiltrative GI tract malignancies, history of recent GI surgery, peptic ulcer disease, severe constipation with impaction; discontinue immediately if severe or persistent abdominal pain develops).** Opioid withdrawal symptoms (rare with proper peripheral selectivity — caution in patients with possible disruption of the blood-brain barrier such as advanced multiple sclerosis, recent neurosurgery, uncontrolled seizures, brain tumors, or other CNS pathology). Common: abdominal pain, nausea, diarrhea, flatulence, hyperhidrosis. Drug interactions minimal (not metabolized through CYP enzymes significantly). Use during pregnancy: limited human data — methylnaltrexone may precipitate withdrawal in the neonate exposed to maternal opioids. Lactation: limited data.