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. |
| Molecular Weight | 327.38 |
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 | Naloxone is generally considered safe during the first trimester. It is an opioid antagonist with minimal systemic absorption when given parenterally, and no teratogenicity has been reported in animal studies. Use only if clearly indicated for opioid reversal. |
| 2nd trimester | Naloxone can be used in the second trimester for opioid reversal. No fetal harm is expected due to its short half-life and absence of known teratogenic effects. Benefit outweighs risk in opioid overdose. |
| 3rd trimester | Naloxone is used in the third trimester for opioid reversal, including in pregnant patients to prevent neonatal opioid withdrawal. It may precipitate withdrawal in the mother and fetus; monitoring for preterm labor and fetal distress is recommended. |
Clinical note
No significant drug interactions Can precipitate acute withdrawal in patients dependent on opioids.
| Placental transfer | Naloxone crosses the placenta to a limited extent due to its low molecular weight and lipid solubility. Fetal levels are lower than maternal levels. Rapid metabolism limits fetal exposure. |
■ 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 or any component of the formulation
| Precautions | May precipitate acute withdrawal; monitor for recurrent respiratory depression due to short half-life; use caution in opioid-dependent patients and neonates. |
| Food/Dietary | None. Naloxone is not known to interact with food or beverages. |
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| Breastfeeding |
| Naloxone is not significantly absorbed orally and is poorly bioavailable when taken by the infant via breast milk. It is considered compatible with breastfeeding. However, maternal opioid withdrawal may affect lactation; caution with high-dose naloxone used for overdose management. |
| Lactation Rating | L2 (Probably Compatible or Safer Alternative) |
| 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. |
| 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. |
| Clinical Pearls | Naloxone has a short half-life (30-90 minutes) relative to many opioids, necessitating repeat doses or continuous infusion for long-acting opioid overdoses. In opioid-dependent patients, naloxone can precipitate acute withdrawal, which is distressing but not life-threatening. Use the smallest effective dose to reverse respiratory depression while minimizing withdrawal. Consider intranasal administration for ease of use in community settings; onset is slightly slower than IV but comparable efficacy. Monitor for recurrence of respiratory depression after initial reversal, especially with methadone, buprenorphine, or sustained-release formulations. In neonates, naloxone should be used cautiously due to risk of seizures; it is not recommended for routine resuscitation. |
| Patient Advice | Naloxone is a life-saving emergency medication used to reverse opioid overdose; it has no effect if no opioids are present. · Call 911 immediately after administering naloxone; it is a temporary measure and medical help is essential. · After giving naloxone, stay with the person and monitor their breathing; rescue breaths may be needed. · Naloxone may cause withdrawal symptoms like agitation, nausea, sweating, and rapid heart rate; these are signs it is working. · Store naloxone at room temperature, protect from light, and check expiration dates regularly. · If the person does not respond within 2-3 minutes, a second dose may be given if available. · Even if the person wakes up, do not leave them alone; the effects of some opioids can last longer than naloxone, causing breathing to stop again. |