Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
RELISTOR vs EVZIO (AUTOINJECTOR)
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.
Competitive antagonist at mu-opioid receptors, reversing opioid-induced respiratory depression and other central nervous system depressant effects.
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
Emergency treatment of known or suspected opioid overdose, manifested by respiratory and/or central nervous system depression
0.15 mg/kg subcutaneously once daily, maximum 16 mg per dose; for opioid-induced constipation, 8 mg subcutaneously once daily.
Adults: 2 mg intramuscularly or subcutaneously into the anterolateral thigh, repeat every 2-3 minutes as needed until emergency medical assistance arrives.
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 of naloxone is approximately 1–2 hours in adults. The short half-life results in a duration of action that may be shorter than that of the opioid (e.g., fentanyl, methadone), necessitating repeated doses or continuous infusion. In neonates, half-life is prolonged (3–4 hours).
Primarily hepatic via CYP3A4 and CYP2D6 isoenzymes; also undergoes gut wall metabolism.
Primarily hepatic via glucuronidation; minor pathways include N-dealkylation. CYP450 involvement is minimal.
Renal excretion of unchanged drug accounts for approximately 16% of the dose; biliary/fecal excretion is the major route (approximately 54% recovered in feces).
Naloxone is primarily metabolized in the liver via glucuronidation, with minor contributions from N-dealkylation. The metabolites (naloxone-3-glucuronide) and parent drug are excreted renally. Approximately 50% of a dose is excreted in urine as naloxone-3-glucuronide, 25% as unchanged naloxone (after IV), and <5% in feces. Biliary excretion is minimal (<1%).
Approximately 11-15% bound to plasma proteins (primarily albumin).
Approximately 45% bound to plasma proteins, primarily albumin.
Approximately 1.1 L/kg (central volume ~0.3 L/kg); indicates extensive extravascular distribution.
2–3 L/kg in adults. The large Vd indicates extensive tissue distribution, including crossing the blood-brain barrier rapidly to reverse central opioid effects. In neonates, Vd is higher (3–5 L/kg).
Subcutaneous: approximately 82-100% (mean ~97%); oral: approximately 6% (low due to first-pass metabolism).
Intramuscular or subcutaneous: approximately 60–80% relative to IV (with the autoinjector delivering 0.4 mg or 2 mg doses). Oral bioavailability is <2% due to extensive first-pass metabolism, making oral administration ineffective for opioid reversal; thus, the autoinjector is for IM/SC use only.
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.
No dose adjustment required for renal impairment.
No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B); not studied in severe impairment (Child-Pugh C).
No dose adjustment required for hepatic impairment.
Safety and efficacy not established in pediatric patients.
Weight-based dosing: For children weighing <20 kg, 0.1 mg/kg intramuscularly or subcutaneously; for ≥20 kg, 2 mg intramuscularly or subcutaneously. Repeat every 2-3 minutes as needed.
No specific dose adjustment recommended; use caution due to potential for renal impairment, monitor renal function.
No specific dose adjustment needed; use caution due to potential comorbidities.
Gastrointestinal perforation: Cases of gastrointestinal perforation have been reported in patients with conditions that may result in impaired structural integrity of the gastrointestinal tract.
None.
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 acute withdrawal syndrome in opioid-dependent patients.,May precipitate severe withdrawal in neonates if used during pregnancy.,Limited efficacy against buprenorphine or partial agonists; higher or repeat doses may be needed.,Monitor for recurrence of respiratory depression due to short duration of action relative to some opioids.,Not a substitute for emergency medical care.
Known or suspected mechanical gastrointestinal obstruction,Known hypersensitivity to methylnaltrexone or any component of the formulation
Hypersensitivity to naloxone or any component of the autoinjector.
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.
No known food interactions with naloxone. No dietary restrictions required.
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.
Naloxone crosses the placenta. First trimester: No evidence of teratogenicity in animal studies at doses up to 100 mg/kg/day (SC). Second/third trimester: No known risk of fetal malformations; may precipitate withdrawal in opioid-dependent fetuses, potentially causing fetal distress or preterm labor.
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.
Naloxone is excreted in breast milk in trace amounts; no adverse effects reported in nursing infants. M/P ratio not available.
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 pharmacokinetic data indicate dose adjustments; use same dose as non-pregnant adults. Reversal of opioid effects may precipitate withdrawal; monitor closely.
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.
EVZIO is a naloxone auto-injector for emergency treatment of opioid overdose. Administer intramuscularly or subcutaneously into anterolateral thigh (through clothing if necessary). Each device delivers a single 2 mg dose. After use, seek immediate medical attention due to short half-life (30-81 min) relative to opioids; repeated doses may be needed. Monitor for opioid withdrawal syndrome, especially in physically dependent patients. Store at 20-25°C (68-77°F), excursions permitted to 15-30°C (59-86°F). Do not remove the auto-injector from its case until ready to use.
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.
Inject EVZIO into the outer thigh, through clothing if needed, as soon as overdose is suspected.,After injecting, call 911 or seek emergency medical help immediately.,The effect of EVZIO lasts only 30-90 minutes; opioids may last longer, so repeated doses might be necessary.,Family and caregivers should receive training on recognizing overdose signs (unconsciousness, slow breathing, pinpoint pupils) and using EVZIO.,Store EVZIO in its case at room temperature, away from light and moisture; do not refrigerate or freeze.,Check expiration date regularly and replace before expiry; training devices are for practice only.,An overdose may cause withdrawal symptoms such as nausea, vomiting, sweating, rapid heart rate, or agitation.
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 EVZIO (AUTOINJECTOR), 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.. EVZIO (AUTOINJECTOR) is a Opioid Antagonist that works by Competitive antagonist at mu-opioid receptors, reversing opioid-induced respiratory depression and other central nervous system depressant effects.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between RELISTOR and EVZIO (AUTOINJECTOR) 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 EVZIO (AUTOINJECTOR) is: Adults: 2 mg intramuscularly or subcutaneously into the anterolateral thigh, repeat every 2-3 minutes as needed until emergency medical assistance arrives.. 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 EVZIO (AUTOINJECTOR) 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. EVZIO (AUTOINJECTOR) is classified as Category C. Naloxone crosses the placenta. First trimester: No evidence of teratogenicity in animal studies at doses up to 100 mg/kg/day (SC). Second/third trimester: No known risk of fetal ma. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.