NALOXONE HYDROCHLORIDE (AUTOINJECTOR)
Clinical safety rating: safe
No significant drug interactions Can precipitate acute withdrawal in patients dependent on opioids.
Competitive antagonist at mu, kappa, and delta opioid receptors, reversing opioid-induced respiratory depression and analgesia.
| Metabolism | Primarily hepatic glucuronidation via UGT1A1 and UGT2B7 to inactive metabolites (naloxone-3-glucuronide); minor CYP450 involvement. |
| Excretion | Primarily hepatic metabolism (glucuronidation) followed by renal excretion of metabolites. Less than 1% excreted unchanged in urine. Fecal excretion minimal (<5%). |
| Half-life | Terminal elimination half-life approximately 1 to 1.5 hours in adults. In neonates, half-life is prolonged (about 3 hours). Clinical context: due to short half-life, repeated doses or continuous infusion may be needed for opioid overdose with long-acting opioids. |
| Protein binding | Approximately 50% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 2 to 3 L/kg in adults, indicating extensive distribution into tissues. |
| Bioavailability | Intravenous: 100%. Intramuscular: ~100% (rapid absorption). Subcutaneous: ~100% (rapid absorption). Intranasal: ~40-50% compared to IV, but effective for opioid reversal. Oral: <2% due to extensive first-pass metabolism. |
| Onset of Action | Intravenous: within 1-2 minutes. Intramuscular: within 2-5 minutes. Subcutaneous: within 2-5 minutes. Intranasal: within 2-5 minutes. |
| Duration of Action | Duration is dose-dependent and shorter than most opioids. Typically 30 to 90 minutes for reversal of opioid effects. Clinical note: may need repeat doses or infusion if opioid half-life exceeds naloxone duration. |
| Molecular Weight | 363.84 |
Initial: 0.4 mg or 2 mg intramuscularly (IM) or subcutaneously (SC); may repeat every 2-3 minutes as needed. For autoinjector: 2 mg single dose, administer IM or SC into anterolateral thigh; may repeat every 2-3 minutes with a new device if no response. Max total dose: 10 mg.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for any degree of renal impairment. |
| Liver impairment | No dose adjustment required for any Child-Pugh class (A, B, or C). |
| Pediatric use | 0.01 mg/kg IV, IM, or SC; may repeat every 2-3 minutes. If weight unknown: 0.1 mg/kg for infants <20 kg; alternative: 0.4 mg (1 mg/mL solution) for children 20-40 kg and 2 mg for children >40 kg. Autoinjector (2 mg) approved for weight ≥20 kg, administer IM or SC into anterolateral thigh. Max total dose: 10 mg. |
| Geriatric use | No specific dose adjustment. Administer standard adult dosing with monitoring for adverse effects such as hypertension, arrhythmia, and acute withdrawal symptoms. |
| 1st trimester | No teratogenic effects in animal studies; limited human data, but considered safe for acute use. |
| 2nd trimester | No known fetal harm; use only if clearly needed (e.g., opioid overdose). |
| 3rd trimester | May precipitate withdrawal in opioid-dependent fetus, but maternal survival takes priority. |
Clinical note
No significant drug interactions Can precipitate acute withdrawal in patients dependent on opioids.
| FDA category | Animal |
| Placental transfer | Readily crosses placenta; peak fetal concentrations approach maternal levels within minutes. |
| Breastfeeding | Minimal excretion into breast milk; oral bioavailability is poor, so risk to infant is low. However, monitor for irritability or withdrawal if mother is opioid-dependent. |
■ FDA Black Box Warning
Risk of acute opioid withdrawal in opioid-dependent patients; may precipitate life-threatening withdrawal symptoms (e.g., hypertension, seizures) in neonates if used during pregnancy.
| Common Effects | Precipitated withdrawal |
| Serious Effects |
Known hypersensitivity to naloxone
| Precautions | May precipitate acute withdrawal syndrome; monitor for recurrent respiratory depression due to shorter duration of action than many opioids; caution in opioid-dependent patients and neonates; ensure emergency medical services are contacted; multiple doses may be needed. |
| Food/Dietary | No known food interactions. Naloxone is not absorbed orally; only injectable route is relevant. Avoid alcohol unless directed by physician, but no direct food restriction. |
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| Lactation Rating | L1 (Safest) |
| Teratogenic Risk | Animal studies show no teratogenic effects; limited human data. Naloxone hydrochloride is not associated with increased risk of major birth defects in any trimester. Use during pregnancy only if clearly needed, as opioid withdrawal may precipitate fetal distress. |
| Fetal Monitoring | Monitor for signs of opioid withdrawal in mother and fetus (tachycardia, hypertension, fetal heart rate changes) following administration. In neonates, observe for irritability and excessive crying if naloxone is administered near delivery. |
| Fertility Effects | No known adverse effects on fertility. Animal studies show no impairment of fertility at therapeutic doses. |
| Clinical Pearls | Autoinjector delivers 2 mg naloxone hydrochloride intramuscularly or subcutaneously; use outer thigh, can inject through clothing. Onset 2-5 min, duration 30-90 min; repeat every 2-3 min if no response. Higher doses may be needed for synthetic opioids (e.g., fentanyl). Monitor for opioid withdrawal (agitation, hypertension, vomiting). Ensure patient is transported to hospital after use. May cause acute withdrawal in physically dependent patients. |
| Patient Advice | Autoinjector is for emergency use only; recognize signs of opioid overdose (unconsciousness, slow/stopped breathing, pinprick pupils). · Call 911 immediately before or after administering naloxone. · Place patient on back, inject into outer thigh through clothing if necessary. · Administer one dose; if no response in 2-3 minutes, give another dose. · Stay with patient until emergency help arrives; may need rescue breathing or CPR. · Side effects: sudden withdrawal symptoms (body aches, diarrhea, rapid heartbeat, fever). · Store at room temperature, protect from light; check expiration date. · Train family members and caregivers on how to use the device. |