Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ACTIQ vs EVZIO
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Opioid agonist; binds to mu-opioid receptors in the CNS, altering pain perception and response.
Naloxone is an opioid antagonist that competitively binds to mu-opioid receptors, reversing opioid-induced respiratory depression and analgesia.
Management of breakthrough pain in cancer patients aged 16 and older who are already receiving and tolerant to opioid therapy for their underlying persistent cancer pain
Emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression.
200 mcg transmucosally, titrated upward as needed; initial dose for opioid-tolerant patients is 200 mcg, with additional doses possible after 15 minutes if needed. Maximum 4 doses per episode. At least 4 hours between episodes.
2 mg intramuscular (IM) or subcutaneous (SC) autoinjector into anterolateral thigh; repeat every 2-3 minutes as needed for opioid overdose.
Terminal half-life 0.83–2 hours (mean 1.3 h) in adults; note that context: transmucosal absorption leads to rapid onset but short duration; half-life is not correlated with clinical effect due to oral transmucosal route and rapid redistribution.
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 to inactive metabolites (norfentanyl, despropionylfentanyl, hydroxyfentanyl) and other metabolites; <7% excreted unchanged in urine.
Primarily hepatic glucuronidation, with N-allylnoroxymorphone as the major metabolite; CYP450 system not significantly involved.
Primarily renal as metabolites (about 75% as metabolites, <10% unchanged). Fecal excretion accounts for <9%. Biliary excretion is minor.
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.
Fentanyl is 80–85% bound to plasma proteins (primarily albumin and α1-acid glycoprotein).
Approximately 30-40% bound to plasma proteins, mainly albumin.
Approximately 4 L/kg (range 3–6 L/kg); large Vd indicates extensive tissue distribution and redistribution contributing to short duration.
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.
Oral transmucosal: 50% (range 47–54%) relative to IV; variable and enhanced by rapid absorption through buccal mucosa.
Intramuscular bioavailability is approximately 100% (assumed complete absorption). Oral bioavailability is <2% due to extensive first-pass metabolism; therefore, not used orally.
No specific GFR-based dose adjustment recommended; use with caution in severe renal impairment (Cr Cl < 30 m L/min) and consider dose reduction due to potential accumulation.
No dose adjustment required for renal impairment.
Child-Pugh Class A/B: No adjustment. Child-Pugh Class C: Reduce initial dose to 100 mcg and titrate slowly; monitor closely for prolonged effects.
No dose adjustment required for hepatic impairment.
Not approved for pediatric use; safety and efficacy not established in patients under 16 years.
Weight-based: <20 kg: 0.1 mg/kg IM/SC; ≥20 kg: 2 mg IM/SC; repeat every 2-3 minutes if needed.
Initiate at 100 mcg transmucosally; titrate slowly due to increased sensitivity and risk of respiratory depression. Monitor for adverse effects.
No specific dose adjustment; use standard adult dosing with monitoring for adverse effects due to potential comorbidities.
Risk of respiratory depression, addiction, abuse, and misuse; accidental ingestion can be fatal; concomitant use with benzodiazepines or CNS depressants may cause profound sedation, respiratory depression, coma, and death; not for use in opioid non-tolerant patients; risk of neonatal opioid withdrawal syndrome with prolonged use during pregnancy; serious, life-threatening, or fatal respiratory depression may occur even at recommended doses.
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 respiratory depression; addiction, abuse, and misuse; interactions with CNS depressants; serotonin syndrome; adrenal insufficiency; severe hypotension; seizures; withdrawal; use in patients with head injuries, increased intracranial pressure, biliary tract disease, pancreatitis; risk of choking with lozenge; oral mucosal irritation; dental caries; hypokalemia; hyponatremia; use in elderly, cachectic, or debilitated patients.
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.
Significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment; known or suspected paralytic ileus; hypersensitivity to fentanyl or any component; opioid non-tolerant patients; management of acute or postoperative pain including headache/migraine, dental pain, or emergency department use.
Hypersensitivity to naloxone or any component of the formulation.
No significant food interactions. Grapefruit juice may increase fentanyl levels, but specific studies with ACTIQ are lacking. Avoid alcohol, as it may increase sedation and respiratory depression risk.
None known; naloxone is not absorbed orally due to first-pass metabolism. No dietary restrictions.
FDA Pregnancy Category C. First trimester: limited human data; animal studies show increased resorptions and fetal growth restriction. Second/third trimester: chronic use may cause neonatal opioid withdrawal syndrome; avoid use during labor due to risk of neonatal respiratory depression.
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 breast milk; M/P ratio not established. Limited data suggest low levels, but risk of infant sedation and respiratory depression. Avoid use while breastfeeding unless potential benefit outweighs risk.
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.
Due to increased plasma volume and hepatic metabolism in pregnancy, dose requirements may increase; adjust based on clinical response and tolerance. Avoid use during labor and delivery due to risk of neonatal respiratory depression; short-term use preferred.
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.
ACTIQ is a transmucosal immediate-release fentanyl formulation indicated for breakthrough cancer pain in opioid-tolerant patients. Initiate with the lowest strength (200 mcg) and titrate upward. Avoid use in opioid-naive patients due to risk of fatal respiratory depression. Place the unit between cheek and lower gum, not sublingually. Instruct patient not to bite or suck the unit. Monitor for sedation and respiratory depression. Multiple units may be used per episode if needed, but wait at least 4 hours before next episode. Dispose of partially used units by flushing down toilet.
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.
Only use ACTIQ if you are already taking regular around-the-clock opioid pain medicine and are tolerant to opioids.,Do not use ACTIQ for short-term pain like after surgery, headache, or dental pain.,Place the unit in your cheek pouch, not under your tongue. Do not chew or suck it.,If you need more than 4 units per day, contact your doctor as your dose may need adjustment.,Store ACTIQ in a safe place away from children, as accidental ingestion can be fatal.,Dispose of unused or partially used units by flushing them down the toilet.
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 ACTIQ vs EVZIO, answered by our medical review team.
ACTIQ is a Opioid Analgesic that works by Opioid agonist; binds to mu-opioid receptors in the CNS, altering pain perception and response.. 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 ACTIQ 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 ACTIQ is: 200 mcg transmucosally, titrated upward as needed; initial dose for opioid-tolerant patients is 200 mcg, with additional doses possible after 15 minutes if needed. Maximum 4 doses per episode. At least 4 hours between episodes.. 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 ACTIQ 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. ACTIQ is classified as Category C. FDA Pregnancy Category C. First trimester: limited human data; animal studies show increased resorptions and fetal growth restriction. Second/third trimester: chronic use may cause. 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.