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The opioid crisis continues to be a major public health issue, with overdose rates still rising in many areas, particularly due to the increasing prevalence of synthetic opioids like fentanyl. This edition of our Guidelines+ Monograph series will be dedicated to International Overdose Awareness Day, a day on August 31st of each year dedicated to spread awareness that drug overdose is preventable. This article explores naloxone hydrochloride, focusing on Narcan, a nasal spray by Emergent BioSolutions designed to quickly reverse opioid overdoses. With its approval as the first over-the-counter naloxone nasal spray in 2023, access to Narcan has expanded significantly, supported by widespread distribution programs. Despite this progress, there is an ongoing need for comprehensive public education on its use and targeted efforts to ensure it reaches those most at risk.

This monograph provides a detailed overview of Narcan, covering its indications, dosing, administration, and potential side effects. The information is accurate as of August 2024. For the latest updates and further details on the guidelines presented in this monograph, please refer to Guideline Central’s guidelines library and medication search toolkit.

Medication Overview: 

• Generic Name: naloxone hydrochloride
• Brand Name: Narcan
• Pharmaceutical Manufacturer: Emergent BioSolutions
• FDA Approvals:
  • In 1971, the medication received initial FDA approval as a prescription drug.
  • In 2023, the FDA approved Narcan as the first over-the-counter naloxone nasal spray.

Indications and FDA Approval Details

Dosage Forms and Strengths

Dosage Form	Strength
Narcan (naloxone hydrochloride) nasal spray in 0.1 mL	4 mg

Dosage by Indication and Patient Population

Indication and Details	Initial Dosage	Additional Dosage
Adult patients	Narcan (naloxone hydrochloride) 4 mg intranasal administration	Administer additional doses every 2 to 3 minutes using a new Narcan nasal spray each time and alternating nostrils until desired response is obtained and/or emergency medical assistance arrives.
Pediatric patients	Narcan (naloxone hydrochloride) 4 mg intranasal administration	Administer additional doses every 2 to 3 minutes using a new Narcan nasal spray each time and alternating nostrils until desired response is obtained and/or emergency medical assistance arrives.

Additional Dosing Considerations:

• Administer Narcan nasal spray immediately to prevent prolonged respiratory depression, which can cause brain damage or death. 
• Each Narcan nasal spray is single-use; do not reuse.
• Position the patient on their back, insert the nozzle into a nostril, support their neck, and press the plunger to deliver the dose.
• After use, remove the nozzle and turn the patient onto their side.

Contraindications:

• Narcan nasal spray should not be used in patients who are known to have hypersensitivity to naloxone hydrochloride or any of its other components.
• There are otherwise no absolute contraindications to using naloxone emergently.

Warnings and Precautions

Key Warnings and Precautions:

• Recurrent Respiratory and CNS Depression: Opioid effects may outlast Narcan nasal spray, risking recurrent respiratory or CNS depression. Immediately seek emergency medical care post-administration and monitor the patient continuously, administering additional doses as needed.
• Limited Efficacy with Partial Agonists/Mixed Agonist-Antagonists: Reversal may be incomplete with agents like buprenorphine or pentazocine due to their prolonged action. Larger or repeat naloxone doses may be required.
• Precipitation of Severe Opioid Withdrawal: Narcan nasal spray can precipitate acute withdrawal symptoms in opioid-dependent patients, including tachycardia, nausea and vomiting, irritability, and hypertension. In neonates, withdrawal can be life-threatening. Monitor closely and consider alternative naloxone formulations for titration, especially in postpartum cases with opioid exposure. Abrupt reversal may also induce severe cardiovascular events in patients with pre-existing conditions.

Adverse Reactions

Some of the side effects patients could experience are:

• Hypotension
• Hypertension 
• Ventricular tachycardia and fibrillation
• Dyspnea
• Pulmonary edema
• Cardiac arrest
• Musculoskeletal pain
• Headache
• Diarrhea
• Fever
• Nasal dryness
• Nasal edema
• Nasal congestion
• Nasal inflammation
• Shivering or trembling
• Sweating
• Nausea or vomiting
• Feeling angry
• Nervousness
• Restlessness or irritability
• Stomach cramping
• Weakness

*These are only some of the possible adverse reactions someone may have after administering Narcan nasal spray. 

Specific Inclusions of Naloxone in Clinical Guidelines:

• CDC Guidelines for Prescribing Opioids for Pain – United States 2022
  • Authoring Society: Centers for Disease Control and Prevention (CDC)
  • Publication Date: November 4, 2022
  • Recommendation(s):
    • Discuss risks to household members and other persons if opioids are intentionally or unintentionally shared with others for whom they are not prescribed, including the possibility that others might experience overdose at the same or lower dosage than prescribed for the patient and that young children and pets are susceptible to unintentional ingestion. Discuss storage of opioids in a secure and preferably locked location, options for safe disposal of unused opioids, and the value of having naloxone available.
    • Discuss expectations for clinician and patient responsibilities to mitigate risks of opioid therapy and planned use of precautions to reduce risks, including naloxone for overdose reversal and clinician use of PDMP information and toxicology screening.
    • Clinicians should advise patients of an increased risk for overdose on abrupt return to a previously prescribed higher dose because of loss of opioid tolerance, provide opioid overdose education, and offer naloxone.
    • Clinicians should closely monitor patients who are unable to taper and who continue on high-dose or otherwise high-risk opioid regimens (e.g., opioids prescribed concurrently with benzodiazepines) and should work with patients to mitigate overdose risk (e.g., by providing overdose education and naloxone).
    • Before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk for opioid-related harms and discuss risk with patients. Clinicians should work with patients to incorporate into the management plan strategies to mitigate risk, including offering naloxone.
    • If clinicians consider opioid therapy for chronic pain for patients with substance use disorder, they should discuss increased risks for opioid use disorder and overdose with patients, carefully consider whether benefits of opioids outweigh increased risks, and incorporate strategies to mitigate risk into the management plan (e.g., offering naloxone and increasing frequency of monitoring).
    • If clinicians continue opioid therapy in patients with previous opioid overdose, they should discuss increased risks for overdose with patients, carefully consider whether benefits of opioids outweigh substantial risks, and incorporate strategies to mitigate risk into the management plan (e.g., offering naloxone and increasing frequency of monitoring).
    • Clinicians should not dismiss patients from their practice on the basis of PDMP information. Doing so can adversely affect patient safety and could result in missed opportunities to provide potentially lifesaving information (e.g., about risks of prescription opioids and about overdose prevention) and interventions (e.g., safer prescriptions, nonopioid pain treatment, naloxone, and effective treatment for substance use disorders).
    • Discuss safety concerns, including increased risk for respiratory depression and overdose, with patients found to be receiving overlapping prescription opioids from multiple clinicians who are not coordinating the patient’s care or patients who are receiving medications that increase risk when combined with opioids (e.g., benzodiazepines), and offer naloxone.
    • Consider the total MME/day for concurrent opioid prescriptions to help assess the patient’s overdose risk. Buprenorphine should not be counted in the total MME/day in calculations because of its partial agonist properties at opioid receptors that confer a ceiling effect on respiratory depression. If a patient is found to be receiving total daily dosages of opioids that put them at risk for overdose, discuss safety concerns with the patient, consider in collaboration with the patient whether or not benefits of tapering outweigh risks of tapering, and offer naloxone.
    • Clinicians should use unexpected results to improve patient safety (e.g., optimize pain management strategy, carefully weigh benefits and risks of reducing or continuing opioid dosage, reevaluate more frequently, offer naloxone, and offer treatment or refer the patient for treatment with medications for opioid use disorder, all as appropriate).

• Management of Stimulant Use Disorder
  • Authoring Society: American Society of Addiction Medicine
  • Publication Date: November 8, 2023
  • Recommendation(s):
    • For patients who use stimulants from non-medical sources or are socially engaged with others who do, clinicians should prescribe or distribute overdose reversal medications (eg, naloxone) or refer patients to locations where they can obtain these medications in the community.

• Treatment of Opioid Use Disorder
  • Authoring Society: American Society of Addiction Medicine (ASAM)
  • Publication Date: March 20, 2020
  • Recommendation(s):
    • Naloxone, for the reversal of opioid overdose, should be provided to patients being treated for, or with a history of, opioid use disorder. Patients and family members/significant others should be trained in the use of naloxone in overdose.
    • There is no recommended time limit for pharmacological treatment with methadone. Patients who discontinue methadone treatment should be made aware of the risks associated with opioid overdose, and especially the increased risk of overdose death if they return to illicit opioid use. Treatment alternatives including buprenorphine and naltrexone, as well as opioid overdose prevention with naloxone, should be discussed with any patient choosing to discontinue treatment.
    • There is no recommended time limit for pharmacological treatment with buprenorphine. Patients who discontinue buprenorphine treatment should be made aware of the risks associated with opioid overdose, and especially the increased risk of death if they return to illicit opioid use. Treatment alternatives including methadone (see Part 4) and naltrexone (see Part 6), as well as opioid overdose prevention with naloxone (see part 13) should be discussed with any patient choosing to discontinue treatment.
    • Patients who discontinue naltrexone treatment should be made aware of the increased risks associated with opioid overdose, and especially the increased risk of overdose death, if they return to illicit opioid use. Treatment alternatives including methadone (see Part 4) and buprenorphine (see Part 5), as well as overdose prevention with naloxone (see part 13) should be discussed with any patient choosing to discontinue treatment.
    • Naloxone kits should be available within correctional facilities. Individuals with opioid use disorder should receive a naloxone kit prior to release, and individuals and families should be educated in how to administer naloxone.
    • Naloxone may be administered to pregnant women in cases of overdose to save the mother’s life.
    •  The Guideline Committee, based on consensus opinion, recommends that first responders such as emergency medical services personnel, police officers, and firefighters be trained in and authorized to carry and administer naloxone.

• Pain Management in the Post-Acute and Long-Term Care Setting
  • Authoring Society: American Medical Directors Association/Society for Post Acute and Long-term Care (PALTC)
  • Publication Date: November 1, 2012
  • Recommendation(s):
    • Acute sedation, manifested by difficulty arousing the patient to full consciousness, always precedes respiratory depression. To reduce risk of respiratory depression, nurses should be instructed to assess the patient 30-60 minutes after a dose of an oral opioid and to notify the practitioner and hold the opioid dose if the patient:
      • Is unarousable (i.e., following verbal stimulation or light touch, patient is not able to give an appropriate verbal response or take nutrients safely), 
      • Has a respiratory rate <10/minute associated with excessive sedation, or develops hypoxia.
    • Some practitioners also monitor pulse oximetry during titration or initiation of an oral opioid and specify notification parameters. Naloxone hydrochloride (Narcan) should be available in the facility’s emergency kit.

The information provided here on Narcan (naloxone hydrochloride) nasal spray highlights its role in the ongoing management of epithelial ovarian cancer. As with any medication, it’s crucial to be aware of its indications, dosing, potential side effects, and contraindications to ensure safe and effective use. Sign up for alerts and stay updated with the latest clinical guidelines and evidence-based practices.

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