EVZIO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EVZIO (EVZIO).
Naloxone is an opioid antagonist that competitively binds to mu-opioid receptors, reversing opioid-induced respiratory depression and analgesia.
| Metabolism | Primarily hepatic glucuronidation, with N-allylnoroxymorphone as the major metabolite; CYP450 system not significantly involved. |
| Excretion | 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. |
| Half-life | 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. |
| Protein binding | Approximately 30-40% bound to plasma proteins, mainly albumin. |
| Volume of 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. |
| Bioavailability | Intramuscular bioavailability is approximately 100% (assumed complete absorption). Oral bioavailability is <2% due to extensive first-pass metabolism; therefore, not used orally. |
| Onset of Action | Intramuscular administration: 2-5 minutes. Clinical effect: Reversal of opioid-induced respiratory depression. |
| Duration of Action | Duration of action is dose-dependent but typically 30-120 minutes. Clinical note: May be shorter than the duration of effect of the opioid, requiring repeat doses or continuous monitoring for recurrence of respiratory depression. |
2 mg intramuscular (IM) or subcutaneous (SC) autoinjector into anterolateral thigh; repeat every 2-3 minutes as needed for opioid overdose.
| 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: <20 kg: 0.1 mg/kg IM/SC; ≥20 kg: 2 mg IM/SC; repeat every 2-3 minutes if needed. |
| Geriatric use | No specific dose adjustment; use standard adult dosing with monitoring for adverse effects 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 (EVZIO).
| Breastfeeding | 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. |
| Teratogenic Risk | 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. |
■ FDA Black Box Warning
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.
| Serious Effects |
Hypersensitivity to naloxone or any component of the formulation.
| Precautions | 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. |
| Food/Dietary | None known; naloxone is not absorbed orally due to first-pass metabolism. No dietary restrictions. |
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| Fetal Monitoring | Monitor fetal heart rate and uterine activity if administered near term. Assess for signs of opioid withdrawal in neonate (e.g., irritability, poor feeding). Maternal monitoring: respiratory rate, oxygen saturation, level of consciousness, blood pressure. |
| Fertility Effects | No known direct effects on fertility from naloxone. Opioid reversal may restore normal hypothalamic-pituitary-gonadal axis function, potentially improving fertility in opioid-dependent individuals. |
| Clinical Pearls | 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. |
| Patient Advice | 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. |