NALOXONE
Clinical safety rating: safe
Animal studies have demonstrated safety
Competitive antagonist at mu, kappa, and delta opioid receptors, reversing opioid effects.
| Metabolism | Primarily hepatic via glucuronidation (UGT2B7) to naloxone-3-glucuronide; minor CYP450 involvement. |
| Excretion | Renal: ~70% as metabolites (naloxone-3-glucuronide, naloxone-3-sulfate) and <2% unchanged; biliary/fecal: ~25% primarily as conjugated metabolites. |
| Half-life | 60-90 minutes in adults; shorter in neonates (3 hours); prolonged in hepatic impairment (up to 2-3 hours). |
| Protein binding | ~50-60% primarily to albumin; less bound than opioids. |
| Volume of Distribution | 2.0-3.0 L/kg; high due to lipophilicity, distributing rapidly into tissues including brain. |
| Bioavailability | Oral: <2% (extensive first-pass metabolism); Intranasal: ~50%; IM/SC: near 100% with rapid absorption. |
| Onset of Action | IV: 1-2 minutes; IM/SC: 2-5 minutes; Intranasal: 3-5 minutes; Endotracheal: 2-5 minutes. |
| Duration of Action | 30-90 minutes; shorter than most opioids, requiring repeated doses or continuous infusion for sustained reversal. |
0.4-2 mg IV/IM/SC, may repeat every 2-3 minutes; if no response after 10 mg, reconsider diagnosis.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required; naloxone is not significantly renally eliminated. |
| Liver impairment | No dose adjustment required; naloxone undergoes extensive hepatic metabolism, but no guidelines exist for Child-Pugh adjustments. |
| Pediatric use | 0.01-0.1 mg/kg IV/IM/SC, maximum 2 mg per dose; may repeat every 2-3 minutes as needed. |
| Geriatric use | Use lower initial doses (0.4 mg) and titrate cautiously due to increased sensitivity and risk of withdrawal. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
No significant drug interactions Can precipitate acute withdrawal in patients dependent on opioids.
| Breastfeeding | Naloxone is excreted into breast milk in small amounts. M/P ratio is unknown. Milk levels are low and unlikely to affect nursing infant. Oral bioavailability of naloxone is poor (<2%), so infant exposure via breast milk is minimal. Considered compatible with breastfeeding; use when clinically indicated. |
| Teratogenic Risk | FDA Pregnancy Category B. Animal reproduction studies have not shown fetal risk; no adequate human studies in pregnant women. Naloxone crosses the placenta but has low bioavailability. Risk in first trimester is unknown; theoretical benefit in opioid reversal outweighs potential risk. Second and third trimesters: no known teratogenicity; may cause withdrawal in opioid-dependent fetus if maternal use reversed. |
■ FDA Black Box Warning
Risk of precipitating severe opioid withdrawal in physically dependent patients; caution in neonates.
| Common Effects | Precipitated withdrawal |
| Serious Effects |
Hypersensitivity to naloxone; acute opioid withdrawal syndrome.
| Precautions | May precipitate acute withdrawal; monitor for recurrent respiratory depression due to short half-life; use caution in opioid-dependent patients and neonates. |
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| Fetal Monitoring | Monitor maternal respiratory rate, oxygen saturation, blood pressure, heart rate, and level of consciousness. Fetal monitoring (heart rate, uterine activity) for signs of withdrawal or distress, especially in opioid-dependent parturient. Electrocardiogram if arrhythmia suspected. |
| Fertility Effects | No known direct effects on fertility. Naloxone may reverse opioid-induced hyperprolactinemia, potentially affecting lactation but not fertility. No data on impairment of male or female fertility in animal studies. |