Naloxone - Drug Monograph

Introduction

Naloxone is a life-saving opioid antagonist medication used to rapidly reverse opioid overdose. First approved by the FDA in 1971, it has become an essential tool in addressing the ongoing opioid crisis. Available in various formulations including injectable solutions and nasal sprays, naloxone is now widely distributed to first responders, community organizations, and at-risk individuals to prevent fatal opioid overdoses.

Mechanism of Action

Naloxone competitively binds to mu, kappa, and delta opioid receptors with higher affinity than most opioid agonists. It displaces opioid molecules from these receptors without activating them, effectively reversing central nervous system and respiratory depression caused by opioid overdose. Its action is rapid but temporary, typically lasting 30-90 minutes, which is shorter than many opioid agonists it antagonizes.

Indications

• Emergency treatment of known or suspected opioid overdose
• Complete or partial reversal of opioid depression
• Diagnosis of suspected acute opioid overdose
• Postoperative opioid reversal (in hospital settings)

Dosage and Administration

• Initial dose: 0.4-2 mg IV/IM/SC
• May repeat every 2-3 minutes as needed
• Maximum dose: 10 mg

• Administer one spray into one nostril
• May repeat every 2-3 minutes if no response
• Alternate nostrils if multiple doses required

• Pediatric: 0.01 mg/kg IV initial dose
• Hepatic impairment: No dosage adjustment required
• Renal impairment: No dosage adjustment required

Pharmacokinetics

Contraindications

• Hypersensitivity to naloxone or any component of formulation
• No absolute contraindications in life-threatening opioid overdose situations

Warnings and Precautions

• May precipitate acute opioid withdrawal syndrome
• Reversal effect may be temporary; monitor for resedation
• Not effective for respiratory depression due to non-opioid drugs
• Use with caution in patients with cardiovascular disease
• May cause pulmonary edema and cardiovascular instability
• Repeated dosing may be necessary for long-acting opioids

Drug Interactions

• Opioid agonists: Reverses effects
• Opioid partial agonists: May precipitate withdrawal
• Clonidine: May reduce antihypertensive effects
• No significant pharmacokinetic interactions with CYP450 enzymes

Adverse Effects

• Acute opioid withdrawal symptoms
• Nausea and vomiting
• Sweating
• Tachycardia
• Hypertension
• Tremors

• Pulmonary edema
• Cardiac arrhythmias
• Seizures (rare)
• Hypertension crisis
• Ventricular fibrillation

Monitoring Parameters

• Respiratory rate and oxygen saturation
• Level of consciousness
• Vital signs (blood pressure, heart rate)
• Signs of opioid withdrawal
• Recurrence of respiratory depression
• Cardiac rhythm in patients with heart disease

Patient Education

• Seek emergency medical help immediately after administration
• Effects may wear off before opioids; do not leave patient alone
• Recognize signs of opioid overdose (slow breathing, unresponsiveness)
• Proper storage and expiration date checking
• How to administer specific formulation provided
• Importance of calling 911 even if patient revives
• Availability of addiction treatment resources

References

1. FDA. (2021). Naloxone Hydrochloride Injection prescribing information 2. World Health Organization. (2014). Guidelines for the management of opioid overdose 3. American Heart Association. (2020). ACLS guidelines for opioid-associated emergencies 4. Boyer EW. (2012). Management of opioid analgesic overdose. New England Journal of Medicine 5. Substance Abuse and Mental Health Services Administration. (2018). Opioid Overdose Prevention Toolkit 6. Centers for Disease Control and Prevention. (2022). Evidence-based strategies for preventing opioid overdose 7. Clinical Pharmacokinetics. (2019). Naloxone pharmacokinetic properties review 8. Journal of Medical Toxicology. (2021). Consensus guidelines for naloxone administration