NALOXONE HCL
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 to naloxone-3-glucuronide; minor CYP450 involvement (CYP2C19, CYP3A4). |
| Excretion | Primarily hepatic metabolism (glucuronidation). Renal excretion accounts for approximately 50% of total clearance, with biliary/fecal elimination contributing 20-30%. Unchanged naloxone in urine is <5%. |
| Half-life | Terminal elimination half-life is 1.0-1.5 hours in adults. In neonates, half-life is prolonged (3-4 hours) due to immature hepatic function. Clinically, the short half-life necessitates repeated or continuous dosing to reverse opioid effects lasting longer than naloxone's duration. |
| Protein binding | Approximately 45-50% bound primarily to albumin, with minimal binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | Distribution volume is 1.5-2.0 L/kg, indicating extensive tissue distribution. Higher Vd in neonates (3-4 L/kg). Large Vd reflects rapid distribution out of plasma into tissues. |
| Bioavailability | Oral: <2% (extensive first-pass metabolism). Sublingual: approximately 20-30%. Intranasal: around 30-50% (absolute bioavailability ~45% with approved nasal spray). IM: 100% (systemic). |
| Onset of Action | IV: 1-2 minutes; IM: 2-5 minutes; Subcutaneous: within 15 minutes; Intranasal: 8-13 minutes; Endotracheal: 2-5 minutes. |
| Duration of Action | Duration is dose-dependent but generally 20-60 minutes for IV bolus, 45-120 minutes for IM, and may be extended with higher doses. Duration is shorter than most opioids, requiring repeat doses or infusion for sustained reversal. |
0.4 mg to 2 mg IV, IM, or subcutaneously, may repeat every 2-3 minutes as needed. For continuous infusion, IV infusion rate of 0.25-6.25 mg/hour.
| Dosage form | Injectable |
| Renal impairment | No dosage adjustment required for renal impairment. |
| Liver impairment | No specific dosage adjustment recommended; use with caution in hepatic impairment due to altered metabolism. |
| Pediatric use | Initial dose: 0.1 mg/kg IV, IM, or subcutaneously; may repeat every 2-3 minutes. If no response after total of 10 mg, reconsider diagnosis. Continuous IV infusion: 0.04-0.16 mg/kg/hour. |
| Geriatric use | No specific dosage adjustment required; use lowest effective dose due to increased sensitivity and potential for adverse effects. |
| 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 excreted into breast milk in minimal amounts; M/P ratio not established. Oral bioavailability in infants is low, so systemic effects are unlikely. However, use with caution in breastfeeding mothers, as theoretical risk exists if infant has opioid dependency. The World Health Organization considers naloxone compatible with breastfeeding. |
| Teratogenic Risk |
■ FDA Black Box Warning
Risk of precipitating severe opioid withdrawal, especially in opioid-dependent patients; may cause acute withdrawal syndrome including uncontrolled pain, agitation, hypertension, tachycardia, and cardiac arrest.
| Common Effects | Precipitated withdrawal |
| Serious Effects |
Hypersensitivity to naloxone or any component; do not use in neonates of opioid-dependent mothers (risk of severe withdrawal).
| Precautions | May precipitate withdrawal in opioid-dependent patients; duration of effect may be shorter than duration of opioid, requiring repeated doses; monitor for recurrent respiratory depression; use with caution in patients with cardiovascular disease (risk of hypertension, arrhythmias). |
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| Naloxone is not associated with teratogenic effects in humans. Animal studies show no malformations. However, risk during pregnancy is low due to limited systemic absorption. First trimester: No increased risk of major birth defects. Second and third trimesters: No known fetal adverse effects. Naloxone can cross the placenta, but its short half-life minimizes exposure. Use is considered low risk if administered for opioid overdose. |
| Fetal Monitoring | Monitor maternal vital signs (heart rate, blood pressure, respiratory rate) and oxygen saturation during administration. Fetal heart rate monitoring is recommended if fetus is viable, as naloxone can precipitate withdrawal stress in opioid-dependent fetuses, potentially leading to nonreassuring fetal status. Assess uterine activity if preterm labor risk. |
| Fertility Effects | No known effects on fertility. Naloxone is an opioid antagonist and does not alter reproductive hormone levels. Animal studies show no impairment of fertility. |