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. |
| Molecular Weight | 327.37 |
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 | Naloxone crosses the placenta. Use only if clearly needed for maternal opioid overdose. Limited data, but no known teratogenicity in animal studies. |
| 2nd trimester | Same as T1. Use for life-threatening opioid overdose. Monitor fetal heart rate if possible. |
| 3rd trimester | Use for maternal opioid overdose. May precipitate withdrawal in fetus/newborn, requiring neonatal resuscitation. |
Clinical note
Comprehensive clinical and safety monograph for EVZIO (AUTOINJECTOR) (EVZIO (AUTOINJECTOR)).
| Placental transfer | Naloxone crosses the placenta by passive diffusion. Studies show measurable fetal concentrations after maternal administration, with fetal/maternal ratio approximately 0.5-1.0. |
| Breastfeeding | Naloxone is excreted in breast milk in low concentrations. After maternal administration, amounts are unlikely to affect the infant. However, if used during labor, observe infant for respiratory depression, hypotonia, and poor feeding. |
■ 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. |
| Food/Dietary | No known food interactions with naloxone. No dietary restrictions required. |
| Clinical Pearls |
Loading safety data…
| Lactation Rating | L2 (Safer) |
| 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 | 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. |
| 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. |
| Patient Advice | 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. |