Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
RELISTOR vs ACEPHEN
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Peripherally acting mu-opioid receptor antagonist that blocks opioid-induced constipation without affecting central analgesia.
ACEPHEN (acetaminophen) is a para-aminophenol derivative with analgesic and antipyretic activity. Its mechanism involves inhibition of cyclooxygenase (COX) enzymes in the central nervous system, particularly COX-2, reducing prostaglandin synthesis. It has weak peripheral COX inhibition and minimal anti-inflammatory effect.
Treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain,Treatment of OIC in adult patients with advanced illness who are receiving palliative care
Mild to moderate pain,Fever
0.15 mg/kg subcutaneously once daily, maximum 16 mg per dose; for opioid-induced constipation, 8 mg subcutaneously once daily.
325-650 mg orally every 4-6 hours as needed; maximum 4 g/day.
Terminal elimination half-life is approximately 8-10 hours in patients with normal renal function. In patients with end-stage renal disease, half-life is prolonged (~14-18 hours).
Terminal elimination half-life: 1.0-1.5 hours in adults with normal renal function. Prolonged to 2-5 hours in hepatic impairment or elderly; requires dose adjustment in severe hepatic disease.
Primarily hepatic via CYP3A4 and CYP2D6 isoenzymes; also undergoes gut wall metabolism.
Acetaminophen is primarily metabolized in the liver via glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation (SULT1A1, SULT1A3). A minor fraction is oxidized by cytochrome P450 enzymes (CYP2E1, CYP1A2, CYP3A4) to a reactive toxic metabolite (NAPQI), which is normally detoxified by conjugation with glutathione.
Renal excretion of unchanged drug accounts for approximately 16% of the dose; biliary/fecal excretion is the major route (approximately 54% recovered in feces).
Renal: 90-95% as unchanged drug; tubular secretion and glomerular filtration. Biliary/fecal: <5%.
Approximately 11-15% bound to plasma proteins (primarily albumin).
Approximately 10-20% bound to serum albumin; extensive tissue binding.
Approximately 1.1 L/kg (central volume ~0.3 L/kg); indicates extensive extravascular distribution.
Apparent Vd: 0.5-0.7 L/kg (30-40 L in a 70 kg adult). Distributions into CSF and breast milk.
Subcutaneous: approximately 82-100% (mean ~97%); oral: approximately 6% (low due to first-pass metabolism).
Oral: 85-90% (first-pass metabolism minimal). Rectal: approximately 70-80% of oral bioavailability.
For creatinine clearance <30 m L/min: 0.075 mg/kg subcutaneously every other day, maximum 8 mg per dose; not recommended in patients with end-stage renal disease requiring dialysis.
GFR 10-50 m L/min: 650 mg every 6 hours; GFR <10 m L/min: 650 mg every 8 hours.
No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B); not studied in severe impairment (Child-Pugh C).
Child-Pugh Class A: no adjustment; Child-Pugh Class B: maximum 2 g/day; Child-Pugh Class C: maximum 1 g/day.
Safety and efficacy not established in pediatric patients.
10-15 mg/kg/dose orally every 4-6 hours; maximum 75 mg/kg/day or 4 g/day, whichever is less.
No specific dose adjustment recommended; use caution due to potential for renal impairment, monitor renal function.
Start at lowest effective dose (325 mg every 6 hours); avoid exceeding 3 g/day unless closely monitored.
Gastrointestinal perforation: Cases of gastrointestinal perforation have been reported in patients with conditions that may result in impaired structural integrity of the gastrointestinal tract.
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product.
Risk of gastrointestinal perforation,Opioid withdrawal symptoms including diarrhea, nausea, vomiting, abdominal pain,Disruption of analgesic effect if used with opioids crossing the blood-brain barrier (theoretical),Not recommended in patients with known or suspected mechanical gastrointestinal obstruction
Risk of severe liver injury with doses >4000 mg/day; use caution with hepatic impairment, chronic alcoholism, malnutrition, or concomitant hepatotoxic drugs; avoid exceeding recommended dose; limit use to 10 days for pain or 3 days for fever unless directed by physician; serious skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) have occurred.
Known or suspected mechanical gastrointestinal obstruction,Known hypersensitivity to methylnaltrexone or any component of the formulation
Hypersensitivity to acetaminophen or any component of the formulation; severe hepatic impairment or active liver disease.
No specific food interactions reported with methylnaltrexone. No dietary restrictions necessary. However, to optimize bowel function, patients should maintain adequate fluid intake and dietary fiber as tolerated, unless contraindicated due to underlying illness.
Alcohol: increased risk of hepatotoxicity. Avoid concurrent use. Food: no significant interaction, but taking with food may reduce minor gastrointestinal irritation.
Animal studies show no teratogenic effects at doses up to 300 mg/kg/day in rats and rabbits. No adequate human data; risk cannot be excluded in first trimester. Second and third trimester: limited data, potential for gastrointestinal effects in fetus if exposed transplacentally.
Pregnancy Category C. First trimester: potential risk of neural tube defects and orofacial clefts (limited human data, animal studies show embryotoxicity). Second and third trimesters: NSAID exposure associated with oligohydramnios, premature ductus arteriosus constriction, and fetal renal impairment. Avoid in third trimester.
Excreted in human milk at low concentrations; M/P ratio approximately 0.6. No reported adverse effects in breastfeeding infants. Caution advised due to potential for gastrointestinal effects.
Excreted into breast milk in low concentrations (M/P ratio approximately 0.10). Considered compatible with breastfeeding; however, use lowest effective dose for shortest duration given potential for neonatal adverse effects (e.g., thrombocytopenia, renal dysfunction).
No pharmacokinetic studies in pregnancy; dose adjustments not recommended based on available data. Use only if clearly needed for severe opioid-induced constipation unresponsive to standard therapy.
No standard dose adjustments recommended; however, due to increased plasma volume and metabolism in pregnancy, higher doses may be required to achieve therapeutic effect. Avoid near term.
Relistor (methylnaltrexone) is a peripherally acting mu-opioid receptor antagonist (PAMORA) used for opioid-induced constipation (OIC) in patients with advanced illness or chronic pain. It does not cross the blood-brain barrier, thus does not reverse central opioid analgesia. Administer subcutaneously; onset typically within 1-4 hours. Contraindicated in patients with known or suspected mechanical gastrointestinal obstruction. Use with caution in renal impairment (Cr Cl <30 m L/min) as dose reduction recommended. Monitor for gastrointestinal perforation, especially in patients with underlying GI pathology. Coadministration with other opioid antagonists may precipitate opioid withdrawal.
ACEPHEN (acetaminophen) is commonly used for mild to moderate pain and fever. Avoid exceeding 4 g/day in adults to prevent hepatotoxicity. In patients with hepatic impairment, reduce maximum daily dose to 2 g. Consider acetylcysteine for overdose. Onset of action is 15-30 minutes orally.
Relistor is used to treat constipation caused by opioid pain medications without affecting pain relief.,Inject the medication exactly as prescribed; do not use more often than every other day.,You should have a bowel movement within a few hours of receiving the injection; if not, contact your doctor.,Common side effects include abdominal pain, nausea, diarrhea, and flatulence.,Stop Relistor and seek immediate medical attention if you experience severe abdominal pain, vomiting, or signs of intestinal obstruction (e.g., inability to pass gas).,Tell your doctor if you have kidney problems, as the dose may need adjustment.,Do not take other medicines for constipation without your doctor's approval.
Do not exceed 4000 mg (4 grams) in 24 hours.,Avoid drinking alcohol while taking this medication.,Do not combine with other products containing acetaminophen.,Take with food if stomach upset occurs.,Seek immediate medical help if you experience symptoms of liver damage: yellowing of skin/eyes, dark urine, severe abdominal pain.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about RELISTOR vs ACEPHEN, answered by our medical review team.
RELISTOR is a Peripheral Opioid Antagonist that works by Peripherally acting mu-opioid receptor antagonist that blocks opioid-induced constipation without affecting central analgesia.. ACEPHEN is a Non-Opioid Analgesic that works by ACEPHEN (acetaminophen) is a para-aminophenol derivative with analgesic and antipyretic activity. Its mechanism involves inhibition of cyclooxygenase (COX) enzymes in the central nervous system, particularly COX-2, reducing prostaglandin synthesis. It has weak peripheral COX inhibition and minimal anti-inflammatory effect.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between RELISTOR and ACEPHEN depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of RELISTOR is: 0.15 mg/kg subcutaneously once daily, maximum 16 mg per dose; for opioid-induced constipation, 8 mg subcutaneously once daily.. The standard adult dose of ACEPHEN is: 325-650 mg orally every 4-6 hours as needed; maximum 4 g/day.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between RELISTOR and ACEPHEN in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. RELISTOR is classified as Category C. Animal studies show no teratogenic effects at doses up to 300 mg/kg/day in rats and rabbits. No adequate human data; risk cannot be excluded in first trimester. Second and third tr. ACEPHEN is classified as Category C. Pregnancy Category C. First trimester: potential risk of neural tube defects and orofacial clefts (limited human data, animal studies show embryotoxicity). Second and third trimest. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.