Naloxone Accord: Uses, Dosage & Side Effects
Naloxone hydrochloride dihydrate — Opioid antagonist for emergency reversal of opioid overdose
Quick Facts About Naloxone Accord
Key Takeaways About Naloxone Accord
- Life-saving in opioid emergencies: Naloxone rapidly reverses respiratory depression caused by opioid overdose, restoring breathing within minutes
- Short duration of action: Effects last only 30-90 minutes, which is often shorter than the opioid being reversed — repeated dosing and monitoring are essential
- Withdrawal risk in dependent patients: Can precipitate severe withdrawal symptoms in opioid-dependent individuals, including hypertension and cardiac arrhythmias
- No effect without opioids present: Naloxone has virtually no pharmacological activity in the absence of opioids or opioid agonists
- Use with caution in cardiac patients: Patients with cardiovascular disease are at higher risk of serious adverse effects including ventricular tachycardia and fibrillation
What Is Naloxone Accord and What Is It Used For?
Naloxone Accord is an opioid antagonist containing naloxone hydrochloride dihydrate. It is used in emergency medicine to reverse the life-threatening effects of opioid overdose, including respiratory depression, CNS depression, and hypotension. It works by competitively blocking opioid receptors in the brain.
Naloxone belongs to a class of medicines known as opioid antagonists. It works by competing with opioid drugs — such as morphine, heroin, fentanyl, and methadone — for binding sites on opioid receptors (mu, kappa, and delta receptors) in the brain and throughout the body. When naloxone occupies these receptors, it displaces the opioid molecules and rapidly reverses their effects. This mechanism makes naloxone an essential tool in emergency medicine for the treatment of opioid overdose.
The primary indication for Naloxone Accord is the reversal of opioid-induced respiratory depression. Opioid overdose is a major cause of preventable death worldwide, with the World Health Organization (WHO) estimating that approximately 115,000 people die each year from opioid overdose globally. Naloxone has been on the WHO Model List of Essential Medicines since 1983, reflecting its critical importance in healthcare systems.
Naloxone Accord is specifically used in the following clinical situations:
- Emergency treatment of known or suspected opioid overdose: Rapid reversal of respiratory depression, sedation, and hypotension
- Reversal of postoperative opioid effects: After surgery, to counteract excessive respiratory depression from opioid analgesics used during anaesthesia
- Diagnostic tool: To confirm suspected opioid overdose or intoxication in unconscious patients
- Neonatal resuscitation: To reverse respiratory depression in newborns whose mothers received opioid analgesics during labour and delivery
Naloxone Accord is supplied as a clear, colourless solution in a 1 ml pre-filled glass syringe containing 0.4 mg naloxone hydrochloride (as dihydrate). The pre-filled syringe is equipped with a graduated scale (0.1 ml increments) and comes with a 23 G needle (30 mm), allowing for precise dose administration. It is intended for single use only and should be used immediately after opening.
Naloxone Accord pre-filled syringe should not be used in infants weighing less than 4 kg. In neonatal emergencies involving very small infants, alternative naloxone formulations with lower concentrations should be used to allow more precise dosing.
It is important to understand that naloxone has no pharmacological activity in the absence of opioids. If a patient has not been exposed to opioids, administering naloxone will have essentially no effect. This characteristic makes it a highly specific antidote. However, it also means that if a patient does not respond to naloxone, the clinician must consider alternative causes for the patient's condition, such as benzodiazepine overdose, head trauma, or metabolic disorders.
What Should You Know Before Receiving Naloxone Accord?
Naloxone Accord should not be used if you are allergic to naloxone hydrochloride or any of its excipients. Special caution is needed in opioid-dependent patients, as naloxone can trigger severe withdrawal symptoms, and in patients with cardiovascular conditions due to the risk of cardiac complications.
Contraindications
The only absolute contraindication to naloxone is a known hypersensitivity (allergic reaction) to naloxone hydrochloride or any of the other ingredients in the formulation. These excipients include sodium chloride, concentrated hydrochloric acid (for pH adjustment), and water for injections. True allergic reactions to naloxone are extremely rare.
Additionally, Naloxone Accord pre-filled syringe should not be used in infants weighing less than 4 kg, as the graduated syringe does not allow sufficiently precise dosing for very small patients. In these cases, an alternative naloxone preparation that permits smaller volume dosing must be used.
It is critical to understand that in a genuine opioid overdose emergency with life-threatening respiratory depression, there are no other absolute contraindications. The life-saving benefit of reversing respiratory arrest far outweighs any potential risk from the drug itself. Hypersensitivity to naloxone is the only situation where it should truly be withheld.
Warnings and Precautions
Several important warnings and precautions must be considered when using Naloxone Accord:
Physical opioid dependence: This is the most significant clinical concern. In patients who are physically dependent on opioids — whether from therapeutic use (e.g., chronic pain management with morphine or fentanyl patches) or substance use disorder (e.g., heroin or illicit fentanyl use) — administering naloxone can precipitate an acute withdrawal syndrome. This occurs because naloxone abruptly displaces opioids from their receptors. Withdrawal symptoms may include:
- Severe hypertension (dangerously high blood pressure)
- Tachycardia (rapid heart rate) and palpitations
- Severe respiratory distress, including pulmonary oedema
- Cardiac arrest in extreme cases
- Agitation, tremor, sweating, nausea, vomiting, and diarrhoea
- Seizures
To minimise the risk and severity of withdrawal, healthcare providers should titrate the dose carefully, administering the smallest effective dose to restore adequate breathing without completely reversing all opioid effects. The goal is to reverse respiratory depression while avoiding full withdrawal.
Cardiovascular disease: Patients with pre-existing heart or circulatory problems face an increased risk of adverse cardiovascular events when receiving naloxone. Serious complications including ventricular tachycardia, ventricular fibrillation, hypertension, hypotension, and pulmonary oedema have been reported. These risks are particularly elevated in patients who have also been exposed to cardiotoxic substances such as cocaine, methamphetamine, tricyclic antidepressants, calcium channel blockers, beta-blockers, or digoxin.
Naloxone has a shorter duration of action (30-90 minutes) than most opioids. After the naloxone wears off, opioid effects — including life-threatening respiratory depression — can return. All patients must be closely monitored for at least 2 hours after the last naloxone dose, and additional doses may be required every 1-2 hours.
Pregnancy and Breastfeeding
There is limited clinical data on the use of naloxone during pregnancy. In a genuine opioid overdose emergency, the life-saving benefit to the mother generally outweighs the potential risks to the foetus. However, naloxone can cross the placenta and may trigger withdrawal syndrome in the newborn if the mother is opioid-dependent. The healthcare provider will carefully weigh the benefits and risks in each individual case.
It is not known whether naloxone is excreted in breast milk. As a precautionary measure, breastfeeding should be avoided for up to 24 hours after naloxone administration. Given the emergency nature of most naloxone use, this is generally a manageable precaution.
Driving and Operating Machinery
After receiving naloxone to reverse opioid effects, patients must not drive, operate machinery, or engage in physically or mentally demanding activities for at least 24 hours. The effects of the opioid may return as naloxone wears off, potentially causing sudden drowsiness, impaired judgement, or loss of consciousness. Patients should be informed of this risk before discharge.
Sodium Content
Naloxone Accord contains less than 1 mmol (23 mg) sodium per 1 ml dose, making it essentially sodium-free. This is relevant for patients on sodium-restricted diets.
How Does Naloxone Accord Interact with Other Drugs?
Naloxone interacts primarily with opioid analgesics, reversing both their therapeutic and adverse effects. Its action may be delayed in patients taking sedatives or who have consumed alcohol. Caution is required with cardiovascular medications, and the interaction with buprenorphine is clinically significant due to buprenorphine's high receptor affinity.
Understanding drug interactions with naloxone is essential for safe and effective use. While naloxone is highly specific for opioid receptors, several clinically important interactions can affect its efficacy and safety profile.
| Interacting Drug | Effect | Clinical Significance | Management |
|---|---|---|---|
| Opioid analgesics (morphine, fentanyl, heroin, methadone) | Complete reversal of opioid effects including analgesia | High — Pain may return abruptly | Titrate dose to restore breathing without fully reversing analgesia |
| Buprenorphine | Analgesic effect may paradoxically increase; respiratory depression reversal is limited | High — Higher doses of naloxone may be needed | May require higher or repeated doses; consider mechanical ventilation |
| Sedatives (benzodiazepines, barbiturates) | Onset of naloxone action may be delayed | Moderate — Mixed overdose complicates management | Consider flumazenil for benzodiazepine component; supportive care |
| Alcohol | Delayed onset of naloxone action in mixed intoxication | Moderate | Allow more time for response; provide supportive care |
| Cardiovascular drugs (clonidine, beta-blockers, digoxin) | Increased risk of cardiovascular adverse events | High — Risk of arrhythmias | Cardiac monitoring; titrate naloxone slowly; have resuscitation equipment ready |
| Cocaine / methamphetamine | Additive cardiovascular stress; risk of ventricular tachycardia/fibrillation | High — Potentially life-threatening | Cardiac monitoring mandatory; use lowest effective dose; have antiarrhythmics available |
Buprenorphine Interaction
The interaction between naloxone and buprenorphine deserves special attention. Buprenorphine is a partial opioid agonist with very high affinity for opioid receptors. This means that naloxone has limited ability to displace buprenorphine from the receptors. In cases of buprenorphine-induced respiratory depression, substantially higher doses of naloxone may be required, and even then, reversal may be incomplete. In such situations, mechanical ventilation and intensive supportive care may be necessary as adjunctive therapy.
Mixed Overdose Considerations
In clinical practice, many overdose cases involve multiple substances simultaneously (polypharmacy). When opioids are combined with sedatives such as benzodiazepines, alcohol, or other CNS depressants, the clinical picture is more complex. Naloxone will only reverse the opioid component of the intoxication. The patient may remain sedated and at risk of respiratory depression from the non-opioid substances even after adequate naloxone dosing. Comprehensive supportive care and monitoring remain essential in all mixed overdose scenarios.
What Is the Correct Dosage of Naloxone Accord?
Dosage varies by indication and patient population. For opioid overdose in adults, the initial dose is 0.4-2 mg IV, repeatable every 2-3 minutes up to a maximum of 10 mg. For reversal of postoperative opioid effects, the dose is 0.1-0.2 mg IV. Children receive weight-based dosing at 0.01-0.02 mg/kg. Naloxone is always administered by a qualified healthcare professional.
Naloxone Accord is always administered by an anaesthetist or other experienced physician. The route of administration is intravenous (IV) or intramuscular (IM) injection, or intravenous infusion after dilution. The intravenous route is preferred when rapid onset is critical, as it provides the fastest response (1-2 minutes). The intramuscular route is an alternative when IV access is not immediately available, though onset is slightly slower (2-5 minutes).
Adults
Reversal of Postoperative Opioid Effects
Initial dose: 0.1-0.2 mg IV. Additional 0.1 mg increments as needed. This lower dose aims to reverse respiratory depression while preserving some analgesic effect.
Treatment of Opioid Overdose or Poisoning
Initial dose: 0.4-2 mg IV. May repeat every 2-3 minutes. Maximum total dose: 10 mg. If no response after 10 mg, reconsider the diagnosis — the condition may not be opioid-related.
Children
Reversal of Opioid Effects in Children
Initial dose: 0.01-0.02 mg/kg body weight IV or IM. Additional doses of the same amount may be given if necessary.
Treatment of Opioid Overdose in Children
Initial dose: 0.01 mg/kg body weight. If a further dose is needed, increase to 0.1 mg/kg at the next injection.
Neonates
Reversal of Neonatal Respiratory Depression
Dose: 0.01 mg/kg body weight IV or IM. Additional injections may be given if necessary. Do not use the pre-filled syringe in infants weighing less than 4 kg.
Elderly and Patients with Cardiovascular Disease
In elderly patients and those with cardiovascular conditions or who have taken cardiotoxic substances (cocaine, methamphetamine, tricyclic antidepressants, calcium channel blockers, beta-blockers, digoxin), naloxone must be used with particular caution. Serious adverse events including ventricular tachycardia and ventricular fibrillation have been reported. The dose should be titrated slowly and cardiac monitoring should be in place.
| Patient Group | Indication | Initial Dose | Repeat Dose | Max Dose |
|---|---|---|---|---|
| Adults | Postoperative reversal | 0.1-0.2 mg IV | 0.1 mg increments | Titrate to effect |
| Adults | Opioid overdose | 0.4-2 mg IV | Every 2-3 min | 10 mg |
| Children | Reversal of opioid effects | 0.01-0.02 mg/kg | Same dose as needed | Titrate to effect |
| Children | Opioid overdose | 0.01 mg/kg | 0.1 mg/kg at next injection | Titrate to effect |
| Neonates | Neonatal respiratory depression | 0.01 mg/kg | As needed | Titrate to effect |
Intravenous Infusion
For continuous administration, Naloxone Accord can be diluted with 0.9% sodium chloride solution or 5% glucose solution. A typical preparation is 5 pre-filled syringes (2 mg total naloxone) in 500 ml of diluent, yielding a concentration of 4 micrograms/ml. The infusion rate is adjusted based on the patient's clinical response. Naloxone infusions should not be mixed with solutions containing bisulphite, metabisulphite, high molecular weight long-chain anions, or alkaline pH solutions.
Monitoring After Administration
All patients who receive naloxone must be closely monitored to ensure the desired effect is achieved and maintained. Because naloxone's duration of action (30-90 minutes) is frequently shorter than that of the opioid being reversed, additional doses may be needed every 1-2 hours. Monitoring should continue for a minimum of 2 hours after the last dose, and longer when long-acting opioids (such as methadone or sustained-release formulations) are involved.
What Are the Side Effects of Naloxone Accord?
The most common side effect of naloxone is nausea. Distinguishing between side effects of naloxone and withdrawal symptoms from opioid reversal can be difficult. Serious but rare adverse events include cardiac arrhythmias, pulmonary oedema, seizures, and anaphylaxis. Most side effects are transient and related to the abrupt reversal of opioid effects.
Like all medicines, Naloxone Accord can cause side effects, although not everyone experiences them. It can be difficult to distinguish the direct side effects of naloxone from the symptoms caused by opioid withdrawal, since naloxone is almost always given after other substances have been used. The following side effects have been reported:
Very Common
- Nausea
Common
- Dizziness
- Headache
- Elevated or reduced blood pressure
- Tachycardia (rapid heart rate)
- Vomiting
- Post-surgical pain (when excessive doses reverse analgesia)
Uncommon
- Cardiac arrhythmias (changes in heart rhythm)
- Bradycardia (slow heart rate)
- Tremor (involuntary shaking)
- Sweating
- Diarrhoea
- Dry mouth
- Hyperventilation (increased breathing rate)
- Vascular wall irritation (IV site) or local inflammation (IM site)
Rare
- Seizures
- Tension / agitation
Very Rare
- Allergic reactions (urticaria, rhinitis, dyspnoea, angioedema)
- Anaphylactic shock
- Ventricular fibrillation
- Cardiac arrest
- Pulmonary oedema (fluid in the lungs)
- Erythema multiforme (skin discolouration and damage)
The cardiovascular side effects deserve particular attention. When naloxone abruptly reverses opioid effects in dependent patients, the sudden release of catecholamines (stress hormones) can place enormous strain on the heart. This is why careful dose titration is so important, especially in patients with underlying cardiovascular disease. Post-cardiac surgery patients and those with known arrhythmias require particularly careful monitoring.
Pulmonary oedema, while very rare, is one of the most serious potential complications. It typically occurs in the context of opioid overdose reversal and may be related to the sudden increase in sympathetic nervous system activity. When it does occur, it requires immediate medical intervention including supplemental oxygen and, in severe cases, mechanical ventilation.
It is important to report suspected adverse reactions after the medicine has been authorised. This allows continuous monitoring of the benefit-risk balance. Healthcare professionals and patients can report suspected adverse reactions to their national pharmacovigilance authority (e.g., the EMA in Europe, the FDA in the United States, or the MHRA in the United Kingdom).
How Should You Store Naloxone Accord?
Store Naloxone Accord out of the sight and reach of children, in its outer carton to protect from light. No special temperature requirements. Use immediately after opening. After dilution, the solution is stable for up to 36 hours at 2-8°C or at 25°C, though it should ideally be used immediately.
Proper storage is essential to ensure that Naloxone Accord remains effective when needed in an emergency situation. The following storage requirements apply:
- Keep out of the sight and reach of children
- No special temperature storage requirements — store at room temperature
- Store the syringe in its outer carton to protect from light (the solution is light-sensitive)
- Do not use after the expiry date printed on the carton and syringe label (marked EXP). The expiry date refers to the last day of that month
- Do not use if you notice discolouration of the solution or visible particles — only use clear, colourless solutions that are practically free from visible particles
Stability After Opening and Dilution
The pre-filled syringe is designed for single use only and the contents should be used immediately after first opening. Any unused solution must be discarded.
When diluted for intravenous infusion, chemical and physical stability has been demonstrated for 36 hours at 2-8°C and at 25°C. From a microbiological perspective, diluted solutions should be used immediately. If not used immediately, storage should normally not exceed 24 hours at 2-8°C, unless dilution was performed under controlled and validated aseptic conditions.
Medicines should not be disposed of via wastewater or household waste. Consult your pharmacist about how to dispose of medicines no longer in use. These measures help to protect the environment.
What Does Naloxone Accord Contain?
Each 1 ml pre-filled syringe contains 0.4 mg naloxone hydrochloride (as dihydrate) as the active substance. Excipients are sodium chloride, concentrated hydrochloric acid for pH adjustment, and water for injections. The solution is clear, colourless, and practically free from visible particles.
Active Substance
The active ingredient is naloxone hydrochloride dihydrate. Each pre-filled syringe contains 1 ml of solution with 0.4 mg of naloxone hydrochloride (as dihydrate). Naloxone hydrochloride is the salt form of naloxone, which improves its water solubility and stability in aqueous solution, making it suitable for injection.
Excipients (Inactive Ingredients)
- Sodium chloride — used to make the solution isotonic (compatible with body fluids)
- Concentrated hydrochloric acid — used for pH adjustment to ensure the solution is at an appropriate pH for injection
- Water for injections — the solvent/vehicle for the solution
Packaging
Naloxone Accord is supplied in a 1 ml pre-filled syringe made of clear glass, fitted with a tip cap, a plunger stopper (grey bromobutyl rubber), and a plunger rod (polypropylene). The syringe barrel has graduation marks at every 0.1 ml. Each pack contains one pre-filled syringe and one needle (23 G; 30 mm), packed in an outer carton.
The marketing authorisation holder is Accord Healthcare B.V. (Winthontlaan 200, 3526KV Utrecht, The Netherlands). The medicine is manufactured by Accord Healthcare Polska Sp.z o.o. (Pabianice, Poland) or Laboratori Fundacio Dau (Barcelona, Spain).
Frequently Asked Questions About Naloxone Accord
Naloxone is an opioid antagonist — a medicine that blocks the effects of opioid drugs. It works by competitively binding to opioid receptors (mu, kappa, and delta) in the brain, displacing opioid molecules such as morphine, heroin, or fentanyl. This rapidly reverses the dangerous effects of opioid overdose, including respiratory depression (slowed or stopped breathing), excessive sedation, and low blood pressure. When given intravenously, naloxone begins working within 1-2 minutes. Importantly, naloxone has no pharmacological effect in the absence of opioids.
Naloxone acts very rapidly. When administered intravenously, effects are seen within 1-2 minutes. Intramuscular injection produces effects within 2-5 minutes. However, the duration of action is relatively short at 30-90 minutes. This is often shorter than the duration of effect of the opioid being reversed, which is why patients must be closely monitored after receiving naloxone. The opioid effects can return once naloxone wears off, potentially causing recurrent respiratory depression. Additional doses may be needed every 1-2 hours.
Yes, in patients who are physically dependent on opioids, naloxone can precipitate acute withdrawal syndrome. This happens because naloxone abruptly displaces opioids from their receptor sites. Symptoms may include severe hypertension, tachycardia, sweating, tremor, agitation, nausea, vomiting, diarrhoea, and in extreme cases, seizures or cardiac arrest. To minimise this risk, healthcare providers carefully titrate the dose, using the smallest amount necessary to restore adequate breathing without triggering full withdrawal.
There is limited data on naloxone use during pregnancy. In a life-threatening opioid overdose emergency, the benefit of saving the mother's life generally outweighs the potential risks to the foetus. However, naloxone can cross the placenta and may trigger withdrawal syndrome in both the mother and the newborn if the mother is opioid-dependent. The healthcare provider will carefully evaluate the risks and benefits in each individual situation. Breastfeeding should be avoided for 24 hours after naloxone administration.
For the treatment of known or suspected opioid overdose in adults, individual doses of 0.4-2 mg can be given intravenously and repeated every 2-3 minutes. The maximum total dose is 10 mg. If a patient does not respond after receiving 10 mg of naloxone, the diagnosis of opioid overdose should be questioned, as the condition may be caused by a non-opioid substance or another medical condition. For postoperative reversal and paediatric use, the doses are lower and based on individual titration.
Naloxone has a shorter duration of action (30-90 minutes) than most opioids. This means that after naloxone wears off, the opioid that was reversed can regain its effect, potentially causing dangerous respiratory depression to return. This is particularly concerning with long-acting opioids such as methadone, sustained-release morphine or oxycodone formulations, and fentanyl patches. Patients must be monitored for at least 2 hours after the last dose, and additional naloxone doses may be required every 1-2 hours to maintain adequate breathing.
References
- World Health Organization (WHO). WHO Model List of Essential Medicines — 23rd list, 2023. Geneva: WHO; 2023. Naloxone listed as an essential medicine for treatment of opioid overdose.
- European Medicines Agency (EMA). Naloxone — Summary of Product Characteristics. EMA; 2025. Regulatory-approved prescribing information for the European Union.
- U.S. Food and Drug Administration (FDA). Naloxone Hydrochloride Injection — Prescribing Information. FDA; 2024. Complete prescribing information including pharmacokinetics and dosing.
- British National Formulary (BNF). Naloxone hydrochloride. NICE; 2025. UK prescribing guidance including dose recommendations and interactions.
- Boyer EW. Management of opioid analgesic overdose. New England Journal of Medicine. 2012;367(2):146-155. doi:10.1056/NEJMra1202561
- Schiller EY, Goyal A, Mechanic OJ. Opioid Overdose. StatPearls Publishing; 2024. Comprehensive review of opioid overdose management including naloxone use.
- World Health Organization (WHO). Community management of opioid overdose. Geneva: WHO; 2014. WHO guidelines on naloxone distribution for community overdose prevention.
- Rzasa Lynn R, Galinkin JL. Naloxone dosage for opioid reversal: current evidence and clinical implications. Ther Adv Drug Saf. 2018;9(1):63-88. doi:10.1177/2042098617744161
Editorial Team
This article has been written and medically reviewed by the iMedic Medical Editorial Team, consisting of licensed physicians with specialist qualifications in emergency medicine, clinical pharmacology, and addiction medicine.
All medical content is reviewed according to international guidelines (WHO, EMA, FDA, BNF) and the GRADE evidence framework. Evidence Level 1A.
iMedic has no commercial funding. All content is editorially independent with no pharmaceutical industry influence.