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. |
| Molecular Weight | 363.84 |
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 | Naloxone hydrochloride is considered safe for use during the first trimester when administered for opioid overdose or reversal of opioid effects. It is a pregnancy category B drug with no evidence of teratogenicity in animal studies. However, use only if clearly needed as opioid withdrawal may pose risks. |
| 2nd trimester | Similar to first trimester; no known increased risk. Limited human data, but benefits of reversing opioid overdose outweigh potential risks. Avoid unnecessary use. |
| 3rd trimester | Use during third trimester is considered safe for acute opioid reversal. Prolonged use may precipitate withdrawal in the fetus or neonate, including symptoms like irritability, hypertonia, and seizures. Monitor for neonatal abstinence syndrome if mother is opioid-dependent. |
Clinical note
No significant drug interactions Can precipitate acute withdrawal in patients dependent on opioids.
| FDA category | Animal |
| Placental transfer |
■ 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 of the formulation
| 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). |
| Food/Dietary | No food interactions are known. Naloxone is administered parenterally or intranasally and is not affected by dietary factors. |
Loading safety data…
| Naloxone crosses the placenta readily based on its molecular weight and lipophilicity. Studies in animals have shown placental transfer, and human data indicate it reaches fetal circulation. However, due to rapid metabolism and short half-life, fetal exposure is limited unless high doses are administered. |
| Breastfeeding | Naloxone is poorly absorbed orally and has low bioavailability, making it unlikely to cause adverse effects in a breastfed infant. Administration via injection or nasal spray results in minimal excretion into breast milk. It is generally considered compatible with breastfeeding, but observe the infant for sedation, poor feeding, or respiratory depression if the mother is receiving high doses. |
| Lactation Rating | L1 (Safe) |
| Teratogenic Risk | 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. |
| Clinical Pearls | Naloxone has a shorter duration of action (20-90 min) than most opioids, necessitating repeat doses or continuous infusion. Onset is 1-2 min IV, 2-5 min IM/SC, 3-5 min intranasal. In opioid-dependent patients, titrate to effect to avoid acute withdrawal. Consider co-prescribing with high-dose opioids (≥50 MME/day) or in patients with respiratory compromise. |
| Patient Advice | Naloxone reverses opioid overdose but is not a treatment for opioid addiction. · Call emergency services immediately after administering a dose. · Repeat doses every 2-3 minutes if breathing does not improve. · May cause acute withdrawal symptoms such as agitation, nausea, and body aches. · Keep naloxone accessible and inform family members or caregivers of its location and use. |