EVZIO (AUTOINJECTOR)
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EVZIO (AUTOINJECTOR) (EVZIO (AUTOINJECTOR)).
Competitive antagonist at mu-opioid receptors, reversing opioid-induced respiratory depression and other central nervous system depressant effects.
| Metabolism | Primarily hepatic via glucuronidation; minor pathways include N-dealkylation. CYP450 involvement is minimal. |
| Excretion | 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%). |
| Half-life | 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). |
| Protein binding | Approximately 45% bound to plasma proteins, primarily albumin. |
| Volume of 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). |
| Bioavailability | 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. |
| Onset of Action | Intramuscular (IM) or subcutaneous (SC) injection via autoinjector: onset within 2–5 minutes. If no response, repeat doses every 2–3 minutes as needed. Intravenous (IV) administration (not typical for autoinjector) yields onset within 0.5–2 minutes. |
| Duration of Action | 20–90 minutes, depending on dose and route. The clinical duration of action may be shorter than the half-life due to reversal of opioid effect; duration is dose-dependent. In opioid overdose, the effect may last 30–60 minutes, often requiring repeat dosing or continuous infusion if the opioid has a longer half-life. |
Adults: 2 mg intramuscularly or subcutaneously into the anterolateral thigh, repeat every 2-3 minutes as needed until emergency medical assistance arrives.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No dose adjustment required for hepatic impairment. |
| Pediatric use | 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. |
| Geriatric use | No specific dose adjustment needed; use caution due to potential comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EVZIO (AUTOINJECTOR) (EVZIO (AUTOINJECTOR)).
| Breastfeeding | Naloxone is excreted in breast milk in trace amounts; no adverse effects reported in nursing infants. M/P ratio not available. |
| Teratogenic Risk | 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. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to naloxone or any component of the autoinjector."]
| Precautions | ["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."] |
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| Monitor maternal vital signs (heart rate, blood pressure, respiratory rate) and fetal heart rate tracing for signs of distress during opioid reversal; assess for recurrence of respiratory depression due to naloxone's shorter half-life than many opioids. |
| Fertility Effects | No significant effects on fertility reported in animal studies at therapeutic doses. |