Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
RELISTOR vs EVZIO
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.
Naloxone is an opioid antagonist that competitively binds to mu-opioid receptors, reversing opioid-induced respiratory depression and analgesia.
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, as 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.
2 mg intramuscular (IM) or subcutaneous (SC) autoinjector into anterolateral thigh; repeat every 2-3 minutes as needed for opioid overdose.
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).
The terminal elimination half-life of naloxone in adults is approximately 1-2 hours. In neonates, half-life may be prolonged to 3-4 hours. Clinical context: Short half-life necessitates repeated dosing or continuous infusion for sustained opioid reversal, especially with long-acting opioids.
Primarily hepatic via CYP3A4 and CYP2D6 isoenzymes; also undergoes gut wall metabolism.
Primarily hepatic glucuronidation, with N-allylnoroxymorphone as the major metabolite; CYP450 system not significantly involved.
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 undergoes extensive hepatic metabolism primarily via glucuronidation, with approximately 70% excreted in urine as naloxone-3-glucuronide. About 25% is excreted in feces via biliary elimination. Less than 1% is excreted unchanged in urine.
Approximately 11-15% bound to plasma proteins (primarily albumin).
Approximately 30-40% bound to plasma proteins, mainly albumin.
Approximately 1.1 L/kg (central volume ~0.3 L/kg); indicates extensive extravascular distribution.
Volume of distribution is approximately 2-3 L/kg, indicating extensive distribution into tissues beyond plasma volume. Clinical meaning: High Vd suggests rapid distribution and short half-life.
Subcutaneous: approximately 82-100% (mean ~97%); oral: approximately 6% (low due to first-pass metabolism).
Intramuscular bioavailability is approximately 100% (assumed complete absorption). Oral bioavailability is <2% due to extensive first-pass metabolism; therefore, not used orally.
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: <20 kg: 0.1 mg/kg IM/SC; ≥20 kg: 2 mg IM/SC; repeat every 2-3 minutes if needed.
No specific dose adjustment recommended; use caution due to potential for renal impairment, monitor renal function.
No specific dose adjustment; use standard adult dosing with monitoring for adverse effects 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.
Risk of recurrent respiratory depression: The duration of action of naloxone is shorter than that of most opioids, so repeat doses may be necessary. Patients should be monitored until respiratory function is fully recovered.
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
May precipitate acute opioid withdrawal in opioid-dependent patients; risk of incomplete response or need for repeat doses due to short half-life; not effective for non-opioid overdoses; avoid in known hypersensitivity; use caution in patients with cardiovascular disease or those taking cardiotoxic drugs.
Known or suspected mechanical gastrointestinal obstruction,Known hypersensitivity to methylnaltrexone or any component of the formulation
Hypersensitivity to naloxone or any component of the formulation.
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.
None known; naloxone is not absorbed orally due to first-pass metabolism. No dietary restrictions.
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.
EVZIO (naloxone) is not associated with major congenital malformations; limited data in pregnancy. Immediate reversal of opioid effects may precipitate withdrawal in the fetus, potentially causing adverse outcomes such as preterm labor or fetal distress. Third trimester use may cause neonatal opioid withdrawal syndrome (NOWS) in opioid-dependent mothers if naloxone is administered.
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 unlikely to be excreted in breast milk in significant amounts due to low bioavailability. M/P ratio not established. Preterm infusion studies show minimal transfer. Consider benefits of breastfeeding against risk of maternal opioid overdose reversal.
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 studies in pregnancy demonstrate need for dose adjustment. Standard dosing (0.4 mg or 2 mg intranasal/IM) is used. Pregnant patients may require higher doses due to increased volume of distribution and metabolic changes, but evidence insufficient to recommend routine dose adjustment.
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 outer thigh; can be given through clothing. Repeat every 2-3 minutes if no response. Onset of action within 2-5 minutes. Duration shorter than most opioids; monitor for recurrence of respiratory depression. Not for non-opioid overdoses.
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.
Always call 911 immediately after giving EVZIO.,Place the device against the outer thigh and press firmly; it will automatically inject.,A short, clicking sound indicates the injection has started.,Stay with the person after injection; they may become agitated due to opioid withdrawal.,Store at room temperature; check expiration date regularly.,Tell family and friends where you keep EVZIO.
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, 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 is a Opioid Antagonist that works by Naloxone is an opioid antagonist that competitively binds to mu-opioid receptors, reversing opioid-induced respiratory depression and analgesia.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between RELISTOR and EVZIO 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 is: 2 mg intramuscular (IM) or subcutaneous (SC) autoinjector into anterolateral thigh; repeat every 2-3 minutes as needed for opioid overdose.. 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 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 is classified as Category C. EVZIO (naloxone) is not associated with major congenital malformations; limited data in pregnancy. Immediate reversal of opioid effects may precipitate withdrawal in the fetus, pot. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.