NALOXONE HYDROCHLORIDE
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 via glucuronidation (UGT2B7 and UGT1A8); minor CYP450 metabolism (CYP3A4). |
| Excretion | Primarily hepatic metabolism (glucuronidation) with renal excretion of metabolites. ~70% as naloxone-3-glucuronide in urine, <5% unchanged. Minor fecal elimination (<10%). |
| Half-life | Terminal elimination half-life is 1–1.5 hours in adults; shorter in neonates (approx. 3 hours due to immature clearance). Clinically, rapid decline limits duration of antagonism. |
| Protein binding | Approximately 45% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 2–3 L/kg in adults; neonates: 3.5–4 L/kg. High Vd indicates extensive tissue distribution and rapid redistribution from CNS. |
| Bioavailability | Oral: ~2% (high first-pass metabolism). Intranasal: about 40–50% relative to IV. IM/SC: approximately 50–100% (presumed high due to similar exposure). |
| Onset of Action | IV: 1–2 minutes; IM: 2–5 minutes; SC: 2–5 minutes; Intranasal: 2–5 minutes. Onset may be delayed in opioid-dependent patients with tolerance. |
| Duration of Action | 30–90 minutes, but often shorter than most opioids (e.g., morphine half-life 2–4 hours). May require repeated doses or continuous infusion for long-acting opioids (e.g., methadone, buprenorphine). |
0.4 mg to 2 mg intravenous, intramuscular, or subcutaneous every 2 to 3 minutes as needed for opioid reversal; may repeat until response achieved. For continuous infusion, 0.25-6.25 mg/hour IV.
| Dosage form | INJECTABLE |
| Renal impairment | No specific GFR-based dose adjustment required; naloxone is extensively hepatically metabolized with minimal renal excretion. |
| Liver impairment | No specific Child-Pugh based dose adjustment recommended; however, in severe hepatic impairment, dose reduction may be considered due to decreased clearance, though data insufficient for formal guidelines. |
| Pediatric use | Weight-based dose: 0.01 mg/kg (up to 0.1 mg/kg) intravenous, intramuscular, or subcutaneous every 2-3 minutes as needed. For continuous IV infusion: starting at 0.01 mg/kg/hour, titrated to effect. Maximum single dose 2 mg. |
| Geriatric use | No specific dose adjustment; use caution due to potential cardiovascular stress from acute opioid reversal. Start at lower end of dosing range and titrate slowly. |
| 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.
| FDA category | Animal |
| Breastfeeding | Naloxone is minimally excreted into breast milk. M/P ratio unknown. Due to poor oral bioavailability, infant exposure via milk is negligible. It is considered compatible with breastfeeding, though caution is advised if the infant is opioid-exposed. |
| Teratogenic Risk | Naloxone hydrochloride is not associated with increased risk of major congenital malformations. Pregnancy exposure data are limited but do not indicate teratogenicity. In opioid-dependent pregnant women, naloxone may precipitate withdrawal, posing risks to the fetus including placental abruption, preterm labor, and fetal distress. Use only for opioid overdose reversal. |
■ FDA Black Box Warning
Risk of recurrent respiratory depression; duration of action may be shorter than that of the opioid, requiring repeated administration.
| Common Effects | Precipitated withdrawal |
| Serious Effects |
Known hypersensitivity to naloxone hydrochloride or any component of the formulation.
| Precautions | May precipitate acute opioid withdrawal. Use caution in patients with cardiovascular disease (potential for hypertension, tachycardia, ventricular arrhythmias, and pulmonary edema). Monitor respiratory rate and oxygen saturation. |
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| Fetal Monitoring | Monitor maternal vital signs (heart rate, blood pressure, respiratory rate, oxygen saturation) and fetal heart rate during and after administration. Observe for signs of opioid withdrawal in both mother and fetus. In pregnant patients, prolonged monitoring for recurrence of respiratory depression due to short naloxone half-life. |
| Fertility Effects | No known adverse effects on fertility. Animal studies have not shown reproductive impairment. However, chronic opioid use itself may affect fertility; reversal with naloxone does not have independent negative impact. |