Overdose Reversal Uses, Warnings, Side Effects, Dosage

What is naloxone, and what is it used for?

Naloxone is a life-saving medication used to rapidly reverse the effects of overdose of opioids such as heroin and morphine or for post-surgical reversal when opioids are used for pain relief (analgesia).

Naloxone injection is the immediate treatment for opioid overdose, usually given by emergency medical technicians, police officers and military personnel trained to administer the injection. In some states in the U.S., friends and family members may be trained to administer naloxone, if they are caregivers to a patient at high risk for opioid overdose.

Opioids are medically used for pain relief and are also widely abused for the euphoria they produce, which can lead to dependence, tolerance, addiction and overdose. Opioid overdose can cause severe depression of the central nervous system that can result in death if not promptly treated. Naloxone works within two minutes to reverse opioid effects including sedation, low blood pressure (hypotension), and respiratory depression.

Opioids exert their effects by binding to protein molecules known as opioid receptors on nerve cells. Naloxone is an opioid antagonist that competes for the same receptor sites and prevents opioids from exerting their action. Long-acting opioids may require repeated doses of naloxone because its effects last only up to a maximum of two hours depending on the dose and route of administration.

Reversal of opioids can cause withdrawal symptoms which should be treated appropriately. All symptoms will not resolve with naloxone if other drugs are involved. Naloxone reverses the effects of only opioid drugs and cannot reverse the effects of non-opioid drugs such as benzodiazepines or stimulant drugs such as cocaine and methamphetamines.

The uses of naloxone include:

• Opioid overdose
• Postoperative opioid depression
• Reversal of respiratory depression with therapeutic opioid doses
• Temporary prophylaxis of respiratory and/or central nervous system depression in military personnel and chemical incident responders entering an area contaminated with high-potency opioids such as fentanyl analogues

What are the side effects of naloxone?

Naloxone can precipitate severe opioid withdrawal symptoms. Side effects may include:

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

What are the dosages of naloxone?

Injectable Solution

Injectable Solution, High-Dose

• 5 mg/0.5 mL prefilled syringe (Zimhi)

Adult:

Opioid Overdose

• Indicated for the complete or partial reversal of opioid depression (including respiratory depression) induced by natural and synthetic opioids
• 0.4-2 mg intravenous/intramuscular/subcutaneous (IV/IM/SC); repeat every 2-3 minutes as needed; not to exceed 10 mg (0.01 mg/kg)  
• Consider other causes of respiratory depression if desired response not achieved after administering 10 mg cumulative total
• Endotracheal (this is the least desirable route of administration and supported only by anecdotal evidence): 2-2.5 times (0.8-5 mg) initial IV dose
• For chronic opioid abuse, use smallest doses (0.1-0.2 mg) to avoid acute withdrawal; titrate to reversal of respiratory depression
• Following reversal, additional dose(s) may need to be administered at later interval (i.e., 20 to 60 minutes) depending on type and duration of opioid

Continuous IV infusion (Off-label)

• For use in patients exposed to long acting opioids (e.g., methadone), sustained release products
• Calculate dose/hour based on effective intermittent dose used and duration of adequate response seen
• Alternatively, use two-thirds of initial effective naloxone bolus on an hourly basis (0.25-6.25 mg/hour); administer one-half of initial bolus dose 15 minutes after initiating continuous IV infusion to prevent drop in naloxone levels

Zimhi High-Dose

• Indicated for immediate administration as emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression
• 5 mg IM/SC into anterolateral aspect of the thigh (through clothing if necessary); if the child is under 1 year, pinch the thigh muscle while administering the dose
• Seek emergency medical care immediately after use
• Additional doses may be administered every 2-3 minutes until EMS arrives

Reversal of Respiratory Depression with Therapeutic Opioid Doses

• 0.04-0.4 mg IV/IM/SC initially; may repeat until desired response achieved; if desired response not observed after 0.8 mg total, consider other causes of respiratory depression
• Postoperative Opioid Depression
• 0.1-0.2 mg IV every 2-3 minutes to desired degree of reversal (e.g., adequate ventilation and alertness without significant pain)
• May repeat within 1-2 hour intervals depending on amount, type (e.g., short or long acting), and timing of last dose administered; supplemental IM doses have produced longer-lasting effects

Pediatric:

Opioid Reversal

Postanesthesia (acute) opioid reversal

• Neonates: 0.01 mg/kg IV into umbilical vein/IM/SC; give subsequent dose of 0.1 mg/kg if needed  
• Children: 0.01 mg/kg IV once; may repeat with 0.1 mg/kg

Reversal of respiratory depression with therapeutic opioid dosing

• Manufacturer dosing: 0.005-0.01 mg; repeat every 2-3 minutes as needed based on response
• American Academy of Pediatrics (AAP) dosing: 0.001-0.015 mg/kg/dose IV; titrate to effect  

Acute opioid overdose

• 20 kg and less or under 5 years: 0.1 mg/kg/dose IV/IM/SC/endotracheal (ET); if needed, repeat every 2-3 minutes as needed; not to exceed 2 mg/dose  
• More than 20 kg or 5 years and above: 2 mg IV/IM/SC/ET; if needed, repeat every 2-3 minutes as needed
• Consider endotracheal administration when IV/intraosseous route not available; optimal endotracheal dose unknown; 2-3 times the IV dose recommended

Zimhi High-Dose

• Indicated for immediate administration as emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression
• 5 mg IM/SC into anterolateral aspect of the thigh (through clothing if necessary); if the child is under 1 year, pinch the thigh muscle while administering the dose
• Seek emergency medical care immediately after use
• Additional doses may be administered every 2-3 minutes until EMS arrives

Overdose

• Naloxone is administered primarily by trained health professionals, police officers and military personnel to reverse opioid effects and overdose is unlikely. Naloxone effects last for a duration of one to two hours. Naloxone does not have any significant effect on individuals who have not taken opioids.
• Abrupt reversal of opioids because of naloxone administration may cause severe withdrawal symptoms.
• Although no causal relationship has been established, after postoperative administration of naloxone, there have been reports of severe cardiopulmonary effects such as blood pressure rise or drop, rapid and irregular ventricular beats, shortness of breath, fluid in the lungs and cardiac arrest, leading to death.
• Naloxone overdose treatment may be discontinuation of the drug and supportive and symptomatic care.

What drugs interact with naloxone?

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Naloxone has no known severe interactions with other drugs.
• Serious interactions of naloxone include:
• Naloxone has no known moderate interactions with other drugs.
• Mild interactions of naloxone include:

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

Pregnancy and breastfeeding

• Naloxone is a life-saving therapy for opioid overdose and should not be withheld from pregnant women. Opioid overdose is a medical emergency that can be fatal to both the mother and the fetus.
• It is not known if naloxone is present in breast milk, and no data are available on its effects on milk production or its effect on the breastfed infant. Naloxone’s oral availability is minimal and is unlikely to affect the breastfed infant.

What else should I know about naloxone?

• If you are a family member or friend of a patient at risk for opioid overdose and trained to administer naloxone:
  • Administer naloxone exactly as directed immediately if you know or suspect opioid overdose.
  • Call 911 immediately after and get emergency medical attention.
• Naloxone effects last only for 1 to 2 hours. If the overdose is from long-acting opioid, the patient may need additional doses of naloxone.
• Patient may also need life-saving measures in the hospital.
• Naloxone reverses only opioids, it cannot reverse effects of other drugs such as cocaine, methamphetamine, and benzodiazepines.