Prenoxad: Uses, Dosage & Side Effects
An emergency opioid-antagonist pre-filled syringe containing naloxone hydrochloride 0.91 mg/ml, used to reverse life-threatening respiratory depression caused by known or suspected opioid overdose
Prenoxad is a pre-filled syringe containing naloxone hydrochloride 0.91 mg/ml (total 1.82 mg in 2 ml), designed as an emergency antidote for known or suspected opioid overdose. Naloxone is a competitive opioid-receptor antagonist that rapidly displaces opioids such as heroin, methadone, morphine, fentanyl or oxycodone from their receptors, restoring normal breathing within 2–5 minutes of intramuscular injection. Prenoxad is specifically designed for community use – by people who use opioids, their families, carers, outreach workers and first responders – while awaiting professional medical help. It is a prescription medicine in most jurisdictions but is widely distributed through take-home naloxone schemes. Because its effects last only 45–90 minutes (shorter than most opioids), emergency services must be called immediately and medical observation is always required.
Quick Facts: Prenoxad
Key Takeaways
- Prenoxad is an emergency, take-home naloxone product (0.91 mg/ml) that temporarily reverses the effects of opioids and restores breathing in someone who has overdosed on heroin, methadone, fentanyl, morphine, oxycodone or other opioid medicines.
- The standard technique is to remove the yellow cap, attach the needle, inject 0.4 ml (one graduation) intramuscularly into the outer thigh or upper outer arm, and repeat every 2–3 minutes until breathing returns or help arrives – up to the full 2 ml syringe.
- Naloxone acts within 2–5 minutes but only lasts 45–90 minutes, which is shorter than most opioids; the overdose can therefore return (re-sedation), so the person must always go to hospital even if they feel better.
- Prenoxad has no effect and does no harm if the person is not actually overdosed on opioids, but it will not reverse overdoses caused by alcohol, benzodiazepines, stimulants or other non-opioid drugs.
- Common side effects reflect sudden opioid withdrawal – nausea, vomiting, sweating, agitation, pain, tachycardia – and in rare cases seizures, cardiac arrhythmias or pulmonary oedema can occur; the life-saving benefit nearly always outweighs these risks.
What Is Prenoxad and What Is It Used For?
Prenoxad is a ready-to-use injectable formulation of naloxone hydrochloride, a pure opioid-receptor antagonist that has been the cornerstone of emergency opioid-overdose treatment for more than five decades. Unlike many other emergency medicines, Prenoxad is specifically engineered for community and take-home use: it is supplied in a graduated 2 ml pre-filled syringe that allows a non-medical user – a family member, friend, outreach worker, police officer or other first responder – to give small, incremental doses of 0.4 ml at a time while waiting for an ambulance. Each syringe contains 1.82 mg of naloxone hydrochloride, corresponding to five 0.4 ml doses.
Opioids – whether prescription painkillers such as morphine, oxycodone, codeine, tramadol and methadone, or illicit drugs such as heroin and illicitly manufactured fentanyl analogues – bind to specific receptors in the central nervous system. At therapeutic doses they produce pain relief, sedation and euphoria. At excessive doses they cause progressive sedation, loss of consciousness, slow and shallow breathing, and eventually complete respiratory arrest. Because the brain is exquisitely sensitive to oxygen, an opioid overdose typically kills by stopping breathing long before it stops the heart. Naloxone reverses all of these effects by displacing the opioid from the receptor.
Prenoxad’s primary indication is the emergency treatment of opioid overdose, whether the overdose is accidental (recreational drug use, medication error) or deliberate (self-poisoning). The World Health Organization (WHO) has, since 2014, recommended that “people likely to witness an opioid overdose should have access to naloxone and be instructed in its administration”. Public-health bodies in Europe, the United Kingdom, North America and Australia have developed community “take-home naloxone” programmes for precisely this reason, and Prenoxad is one of the best-established injectable products used in these schemes.
Typical situations in which Prenoxad is used include:
- Heroin overdose: Classic features include pin-point pupils, blue-grey lips, bluish fingertips, extreme drowsiness that cannot be roused, snoring or gurgling “agonal” breathing and, ultimately, complete apnoea. Naloxone rapidly reverses the respiratory depression.
- Methadone or buprenorphine overdose: Often seen in patients starting or re-titrating opioid substitution therapy, in children who have accidentally ingested a parent’s dose, or in mixed overdoses.
- Prescription-opioid overdose: Morphine, oxycodone, hydromorphone, codeine, dihydrocodeine, tramadol and transdermal fentanyl can all cause life-threatening respiratory depression, particularly in opioid-naive patients, elderly patients or those who combine opioids with other central nervous system depressants.
- Synthetic-opioid overdose: Illicit fentanyl and its analogues (such as carfentanil) are extremely potent and increasingly found in the illicit drug supply. Overdoses involving these substances may need multiple doses of naloxone because of their potency and, in some cases, their prolonged duration of action.
- Mixed-drug overdose: When an opioid has been taken together with alcohol, benzodiazepines, pregabalin, gabapentin, ketamine or stimulants, naloxone is still given because reversing the opioid component can be sufficient to restore adequate breathing.
Prenoxad is not a substitute for emergency medical care. It is a first-aid medicine whose purpose is to keep the person alive and breathing for the 5–20 minutes typically required for an ambulance to arrive. Because naloxone’s duration of action (45–90 minutes) is shorter than most opioids (heroin 4–6 hours, methadone 24–48 hours, sustained-release oxycodone up to 12 hours), re-sedation is a real risk and medical observation is mandatory.
If you suspect an opioid overdose, the first action is to call emergency services immediately: 112 in the European Union, 999 in the United Kingdom, 911 in North America, 000 in Australia, or your local emergency number. Give Prenoxad as soon as possible, start rescue breathing if you are trained, and stay with the person until the ambulance arrives. Naloxone saves lives but is not a replacement for professional medical treatment.
What Should You Know Before Using Prenoxad?
Contraindications
In the context of a life-threatening opioid overdose, naloxone has no absolute contraindications: withholding it is far more dangerous than giving it. However, there are important clinical considerations a prescriber and user should be aware of.
- Hypersensitivity: Prenoxad should not be used in a person with a documented severe hypersensitivity reaction (such as anaphylaxis) to naloxone hydrochloride or to any of the excipients (sodium chloride, hydrochloric acid, sodium hydroxide, water for injections). True naloxone allergy is extremely rare.
- Non-emergency, non-opioid situations: Prenoxad is intended only for emergency treatment of known or suspected opioid overdose. It has no effect on overdoses that do not involve opioids (for example, benzodiazepines, alcohol, stimulants, tricyclic antidepressants, paracetamol or beta-blockers).
Warnings and Precautions
In people who are physically dependent on opioids – through regular use of heroin, methadone, buprenorphine, prescribed morphine or other opioids – naloxone may precipitate a sudden, severe and distressing withdrawal syndrome. Symptoms include body aches, restlessness, agitation, sweating, shivering, yawning, runny nose and eyes, abdominal cramps, nausea, vomiting and diarrhoea, piloerection, tachycardia and hypertension. Although uncomfortable and sometimes frightening, precipitated withdrawal is rarely life-threatening and is far preferable to the consequences of continued respiratory depression.
Several clinical situations deserve special caution when naloxone is used. These do not prevent the use of Prenoxad in an emergency, but they should be communicated to the medical team on arrival.
- Opioid dependence and long-term opioid therapy: People who take opioids daily for pain, addiction or other reasons may develop intense withdrawal when given naloxone. Whenever possible, the smallest effective dose is given first – 0.4 ml of Prenoxad is designed exactly for this purpose, so that the dose can be titrated to restore breathing without unnecessarily precipitating full withdrawal.
- Cardiovascular disease: Abrupt opioid reversal can cause tachycardia, hypertension, cardiac arrhythmias, pulmonary oedema and, very rarely, cardiac arrest or ventricular fibrillation, particularly in patients with pre-existing cardiovascular disease or after high-dose opioid use in the perioperative period.
- Seizure disorders: Seizures have been reported during opioid reversal, although a direct causal role of naloxone is difficult to establish because hypoxia itself can provoke seizures.
- Recent opioid replacement with partial agonists: In people taking buprenorphine-based medicines, higher or repeated doses of naloxone may be needed because of the tight receptor binding of buprenorphine. The reversal may also be incomplete.
- Long-acting opioid overdoses: When the overdose involves methadone, sustained-release oxycodone, modified-release morphine, transdermal fentanyl patches or some fentanyl analogues, the overdose often outlasts the effect of a single dose of naloxone. Repeat dosing or a continuous naloxone infusion in hospital is often required.
- Neonates exposed in utero: Naloxone administered to a mother in late pregnancy or to a newborn whose mother has used opioids may precipitate acute neonatal opioid withdrawal, including seizures. In practice, Prenoxad should still be given to a mother with an opioid overdose – her life takes precedence – but the neonatal team must be informed immediately.
- Re-sedation: Because naloxone’s duration of action is shorter than that of most opioids, the person must be observed closely. They must always be transported to hospital, even if they appear fully recovered after the first dose, so that they can be monitored for re-sedation.
- Mechanical suffocation or injury: If the person has fallen, choked on vomit, or injured their airway, Prenoxad alone is not enough. Standard first aid (airway management, recovery position, rescue breathing or CPR if trained) must also be performed.
Pregnancy and Breastfeeding
Naloxone crosses the placenta. Its safety profile in pregnancy has not been established in large clinical trials, and there is a theoretical risk of precipitating acute withdrawal in an opioid-dependent mother and her fetus, which may cause fetal distress, premature labour and, in the newborn, convulsions. Nevertheless, an untreated maternal opioid overdose is very likely to be fatal for both mother and fetus. International guidelines therefore recommend that Prenoxad should be given without delay whenever a pregnant person is in opioid overdose, with the smallest effective dose used first and careful obstetric and neonatal follow-up in hospital.
Naloxone is minimally absorbed orally and is not expected to produce significant pharmacological effects in a breastfed infant if the mother receives it for overdose reversal. However, breastfeeding should be temporarily paused until the mother is clinically stable, particularly if the mother remains confused or is receiving further sedating medications.
Driving and Operating Machinery
After receiving naloxone, people may experience dizziness, agitation, drowsiness (as the opioid re-emerges when naloxone wears off), vomiting or confusion. They must not drive, operate machinery or make important decisions until fully recovered and assessed by a doctor.
Important Information About Ingredients
Prenoxad solution contains sodium chloride, hydrochloric acid and sodium hydroxide for pH adjustment, and water for injections. The sodium content of a 2 ml syringe is less than 1 mmol, which is considered “essentially sodium-free”. The product contains no preservatives and is designed for single use only; any unused solution must be discarded.
How Does Prenoxad Interact with Other Drugs?
Because naloxone is essentially a chemical lock-pick for the opioid receptor, almost all its pharmacological interactions are with opioid medicines – and this is precisely the desired effect in overdose. Naloxone has negligible pharmacokinetic interactions: it does not meaningfully inhibit or induce cytochrome P450 enzymes and is not protein-bound to an extent that would displace other drugs. The interactions that matter in practice are pharmacodynamic – how naloxone interacts with the patient’s other medicines and substances at the receptor level.
Major Interactions
| Interacting Drug / Class | Effect | Clinical Significance |
|---|---|---|
| Full opioid agonists (heroin, morphine, methadone, oxycodone, fentanyl, codeine, tramadol, pethidine) | Complete reversal of analgesia, sedation, respiratory depression; precipitation of acute withdrawal in dependent users | Therapeutic goal in overdose; use smallest dose that restores adequate breathing |
| Buprenorphine (partial mu-opioid agonist) | Reversal is partial and may require higher or repeated naloxone doses because of buprenorphine’s high receptor affinity | Expect multiple doses of Prenoxad; hospital observation essential |
| Long-acting opioids (methadone, sustained-release oxycodone, transdermal fentanyl patches) | Overdose outlasts naloxone; re-sedation after 45–90 minutes is very likely | Continuous observation and often naloxone infusion needed in hospital |
| Highly potent synthetic opioids (illicit fentanyl, carfentanil) | Multiple sequential doses of naloxone often required | Give full Prenoxad syringe in 0.4 ml increments every 2–3 minutes; a second syringe may be needed |
Minor Interactions
| Interacting Drug / Class | Effect | Clinical Significance |
|---|---|---|
| Benzodiazepines (diazepam, alprazolam, nitrazepam) | Not reversed by naloxone; continued sedation and respiratory depression possible even after opioid reversal | Airway protection and observation remain essential; flumazenil is not routinely used |
| Alcohol and other CNS depressants | Not reversed by naloxone; additive depression persists | Maintain airway; do not assume full recovery after opioid reversal |
| Clonidine, tizanidine, other alpha-2 agonists | Sedation and bradycardia not reversed by naloxone | Consider alternative antidotes (e.g., supportive care, atropine for bradycardia) |
| Stimulants (cocaine, amphetamines, methamphetamine) | Unmasked sympathetic effects (tachycardia, agitation) as opioids are reversed | Monitor cardiovascular status; sedation or cooling may be needed |
| Opioid antagonists (naltrexone, nalmefene) | No additional benefit; can worsen precipitated withdrawal | Rarely used concurrently; ensure clear medication history |
In an emergency setting, detailed drug interactions are rarely known in advance. The principles are simple: give Prenoxad if opioid overdose is even possible, be prepared to use more than one dose, and understand that other drugs the person has taken may still cause sedation after the opioid component has been reversed. All clinical decisions about subsequent treatment – including the need for further naloxone, intubation, other antidotes, or intensive care – should be made by a qualified medical team.
What Is the Correct Dosage of Prenoxad?
Prenoxad is designed for immediate emergency use, not scheduled dosing. Each pre-filled syringe contains 2 ml of naloxone hydrochloride 0.91 mg/ml solution, providing 1.82 mg of naloxone in total. The barrel is marked in 0.4 ml graduations to allow precise incremental dosing by non-medical users. The standard technique, consistent with the World Health Organization’s 2014 community opioid-overdose guidelines and with national harm-reduction protocols in the UK, EU, US, Canada and Australia, is to give small repeated doses titrated to respiratory response.
Adults
Standard Emergency Dose
Initial dose: 0.4 ml intramuscularly (= 0.36 mg naloxone hydrochloride).
If no response within 2–3 minutes: Give another 0.4 ml.
Continue: Repeat every 2–3 minutes, up to the full 2 ml syringe (total 1.82 mg), until the person starts breathing adequately or an ambulance arrives.
Injection site: Outer thigh (vastus lateralis) or upper outer arm (deltoid); the injection may be given through clothing if necessary.
Needle choice: Use the intramuscular needle supplied (or equivalent), typically a 23G 25 mm (1 inch) orange-hub needle for adults. A longer needle may be required for very muscular or larger adults.
Opioid-Dependent Patients
In people who are physically dependent on opioids (for example, people with heroin addiction or patients on opioid replacement therapy), the aim is to restore adequate breathing without fully reversing all opioid effects, in order to minimise precipitated withdrawal.
The standard 0.4 ml incremental approach is still used. If the person begins to breathe at 10–12 breaths per minute with improved colour, further doses are not needed unless breathing deteriorates again.
Post-Operative Opioid Reversal (Hospital Setting Only)
For iatrogenic opioid-induced respiratory depression in a monitored setting, naloxone is usually given intravenously in 40–100 microgram increments every 2 minutes, titrated to response. Prenoxad (0.91 mg/ml) is intended for emergency community use; in hospitals, lower-concentration naloxone products are generally preferred for fine IV titration.
Children and Neonates
Prenoxad is designed primarily for adults and older adolescents, and it is recognised that in a community emergency it may be given to younger children if no alternative is available. Weight-based dosing in a medical setting is as follows.
Children (0.91 mg/ml solution)
Initial dose: 10 micrograms/kg intramuscularly or intravenously. If no adequate response, a subsequent dose of 100 micrograms/kg may be given.
Maximum single dose: Commonly 2 mg, though higher doses may be required in potent-synthetic-opioid overdose.
Emergency community use: If only Prenoxad is available, 0.1–0.2 ml doses titrated to response are used while awaiting the ambulance. In children, the preferred intramuscular site is usually the anterolateral thigh.
Neonates (exposed in utero or with opioid-induced respiratory depression)
Initial dose: 10 micrograms/kg intramuscularly or intravenously, repeated every 2–3 minutes if respiration remains inadequate.
Neonates born to opioid-dependent mothers should generally receive supportive care (ventilation, oxygen) rather than naloxone, because naloxone can precipitate severe neonatal withdrawal including seizures. The decision is always made by a neonatologist or paediatric team.
Elderly and Medically Vulnerable Adults
No specific dose reduction is recommended for older adults in the context of emergency overdose reversal. However, elderly patients are more likely to have cardiovascular disease and multiple co-morbidities that make the hemodynamic effects of abrupt opioid reversal (tachycardia, hypertension, arrhythmias, pulmonary oedema) more dangerous. The stepwise 0.4 ml approach is therefore particularly appropriate in this group.
How to Use Prenoxad: Step-by-Step
- Recognise overdose: Check for unresponsiveness, slow or absent breathing, pin-point pupils, blue or grey lips, grey or pale skin, limp body. Try to rouse the person by shouting their name and rubbing their sternum hard with your knuckles.
- Call emergency services immediately: 112 (EU), 999 (UK), 911 (North America), 000 (Australia), or your local emergency number. Say clearly: “Suspected opioid overdose, unconscious, not breathing normally.”
- Prepare Prenoxad: Open the plastic case. Remove the yellow plastic cap covering the syringe tip. Screw the needle onto the syringe tip until secure. Pull off the needle cap.
- Inject 0.4 ml (one graduation on the barrel): Into the outer thigh or upper outer arm, through clothing if necessary. Push the needle straight in at 90° and press the plunger until the next graduation mark is reached.
- Place in the recovery position: Turn the person on their side with their head tilted back and mouth open, to prevent choking if they vomit. If trained, perform rescue breathing if they are not breathing.
If there is no response after 2–3 minutes, repeat the 0.4 ml dose. Continue every 2–3 minutes up to the full 2 ml. Stay with the person and monitor their breathing until the ambulance arrives. When help arrives, hand over the used syringe and tell the paramedics exactly what was given and when.
Missed Dose
Because Prenoxad is an emergency-use product rather than a scheduled medicine, the concept of a “missed dose” does not apply. Prenoxad should be used only when an opioid overdose is known or suspected.
Overdose of Naloxone
Large doses of naloxone in opioid-naive individuals are generally well tolerated and do not cause significant toxicity. In people physically dependent on opioids, however, excessive naloxone can provoke severe acute withdrawal with vomiting, agitation, hypertension, tachycardia and, rarely, pulmonary oedema, cardiac arrhythmias or seizures. Management is supportive: maintain the airway, monitor cardiovascular status, and allow the withdrawal to resolve as naloxone is cleared. Any concern about naloxone overdose should be managed by emergency medical services.
Even if the person is fully awake and says they feel fine after Prenoxad, they must still go to hospital. Opioids often outlast naloxone, and re-sedation with life-threatening respiratory depression is possible 30–90 minutes after the last dose. In opioid-dependent people, the person may refuse transport because they are in acute withdrawal and want to use more opioids to relieve the symptoms. This is extremely dangerous: taking more opioids immediately after naloxone can cause a second, fatal overdose as naloxone wears off.
What Are the Side Effects of Prenoxad?
Like all medicines, Prenoxad can cause side effects, although they do not occur in everyone and the vast majority reflect the predictable pharmacological consequences of reversing opioid effects. Naloxone itself has an excellent safety profile – in people who have not taken opioids, even very large doses produce minimal effects. The adverse events observed in clinical practice are almost entirely due to (a) abrupt reversal of opioid-induced analgesia, sedation and respiratory depression, and (b) precipitated acute withdrawal in physically dependent individuals.
Side Effects by Frequency
Very Common
May affect more than 1 in 10 people
- Acute opioid withdrawal syndrome in opioid-dependent individuals (restlessness, muscle aches, bone pain, body aches)
- Nausea and vomiting
- Sweating and shivering
- Rapid heartbeat (tachycardia)
- Raised blood pressure (hypertension)
- Yawning, lacrimation (watering eyes), runny nose
- Agitation, irritability, restlessness
- Tremor
- Headache
Common
May affect up to 1 in 10 people
- Dizziness, light-headedness
- Abdominal cramps, diarrhoea
- Goose flesh (piloerection)
- Anxiety, confusion, disorientation
- Pain at the injection site
- Hyperventilation
- Weakness (asthenia)
- Flushing
Uncommon
May affect up to 1 in 100 people
- Cardiac arrhythmias (atrial fibrillation, ventricular ectopic beats)
- Loss of consciousness or fainting (often when sitting or standing up too quickly)
- Seizures (particularly in patients with existing seizure disorders or concurrent hypoxia)
- Severe hypertension or hypotension
- Tremor
Rare
May affect up to 1 in 1000 people
- Pulmonary oedema (fluid in the lungs) – particularly after opioid reversal in surgical or cardiac-compromised patients
- Ventricular tachycardia or ventricular fibrillation
- Cardiac arrest, especially in those with underlying cardiac disease
- Encephalopathy
- Coma (from return of opioid effect after naloxone wears off)
Not Known / Very Rare
Frequency cannot be estimated from available data
- Hypersensitivity reactions including urticaria, angioedema and anaphylaxis
- Erythema multiforme
- Neonatal withdrawal syndrome (when given to a mother or neonate in the perinatal period)
- Cerebral oedema, intracranial hemorrhage (very rare, in the context of severe acute hypertension)
Side Effects That Reflect Opioid Withdrawal
The cluster of very common side effects listed above – sweating, piloerection, tremor, yawning, watery eyes, abdominal cramps, muscle aches, tachycardia, raised blood pressure and restlessness – together form the classic picture of acute opioid withdrawal. In a physically dependent person who has just been reversed, this syndrome is often distressing and can last for 30–120 minutes after each naloxone dose. It is essential that the person receiving Prenoxad is told what to expect, and that by-standers understand the withdrawal is a consequence of the life-saving treatment rather than a new medical problem.
Serious but Rare Complications
The most serious reported adverse events after naloxone administration are cardiovascular: acute pulmonary oedema, ventricular arrhythmias, severe hypertension, and – in very rare cases – cardiac arrest. These events have been documented most often in patients with pre-existing cardiovascular disease, post-cardiac surgery, or after high-dose opioid anaesthesia. The incremental 0.4 ml dosing of Prenoxad is designed to minimise this risk by providing the smallest effective reversal. Seizures have been reported in rare cases, usually in patients with pre-existing seizure disorders, severe hypoxia from prolonged apnoea, or concomitant use of seizure-lowering drugs such as tramadol.
Allergic reactions to naloxone itself are extremely rare. If a person develops rash, swelling of the face, lips or throat, or sudden difficulty breathing after Prenoxad that is different from expected withdrawal symptoms, an anaphylactic reaction should be considered and standard anaphylaxis treatment (intramuscular adrenaline) given immediately.
If you experience any side effects after using Prenoxad, tell a doctor, nurse or pharmacist as soon as possible. You can also report suspected side effects directly to your national pharmacovigilance authority (for example, the MHRA Yellow Card Scheme in the UK, the EMA EudraVigilance system in the EU, or the FDA MedWatch programme in the US). Reporting adverse events helps ensure the ongoing safety monitoring of naloxone products.
How Should Prenoxad Be Stored?
Prenoxad is designed to be kept ready for immediate use in the home, a bag, a harm-reduction “naloxone kit”, a first-aid cabinet or a vehicle. Correct storage preserves its potency and safety for the full duration of its shelf life, which is typically 24 months from manufacture. The specifics are as follows:
- Temperature: Store below 25°C (77°F). Naloxone solution is stable at room temperature but may degrade if exposed to prolonged high temperatures, for example in a car glove-box during summer or on a warm radiator. If Prenoxad has been stored in unsuitable conditions, discuss replacement with your pharmacist or harm-reduction service.
- Light: Keep the pre-filled syringe in its original carton to protect it from light until it is needed.
- Freezing: Do not freeze. Freezing can damage the syringe and alter the solution.
- Physical protection: Store in the protective plastic case provided. Avoid dropping or crushing the carton. Do not store with sharp objects that could puncture the packaging.
- Children and pets: Keep out of the sight and reach of children. Although accidental injection is very rare, the needle is a sharps hazard.
- Expiry date: Do not use after the expiry date printed on the carton and syringe label (EXP MM/YYYY). The expiry date refers to the last day of that month. Check the date periodically and replace expired syringes promptly.
- Inspection before use: Before injection, inspect the solution through the clear syringe barrel. It should be a clear, colourless liquid free from particles or discoloration. Do not use if the solution is cloudy, discoloured, or contains visible particles, or if the syringe is damaged.
Disposal
After use, place the used syringe and needle in a sharps container or rigid puncture-proof container if one is available. Do not attempt to recap the needle. Take used or expired syringes to a pharmacy, needle-exchange service, harm-reduction programme, hospital or community drug service for safe disposal with other clinical waste. Never dispose of medicines in household waste or via wastewater (such as toilets or sinks). Responsible disposal helps protect the environment and prevents accidental needle-stick injuries.
What Does Prenoxad Contain?
Active Substance
The active substance is naloxone hydrochloride dihydrate, expressed as naloxone hydrochloride. Each 1 ml of solution contains 0.91 mg of naloxone hydrochloride. Each 2 ml pre-filled syringe therefore delivers a total of 1.82 mg of naloxone hydrochloride, divided into five 0.4 ml doses (each 0.4 ml dose contains approximately 0.36 mg of naloxone hydrochloride).
Naloxone hydrochloride is a semi-synthetic derivative of oxymorphone. Structurally, it is a morphinan derivative with N-allyl substitution that converts the molecule from an agonist into a pure competitive antagonist at the mu-, kappa- and delta-opioid receptors. Its affinity is highest for the mu-receptor, which is responsible for most clinically important effects of opioid analgesics, including analgesia, euphoria, sedation and respiratory depression.
Inactive Ingredients (Excipients)
- Sodium chloride – to make the solution isotonic with blood plasma
- Hydrochloric acid – for pH adjustment
- Sodium hydroxide – for pH adjustment
- Water for injections – as the solvent
Prenoxad contains no preservatives, no parabens and no sulfites. The product is supplied sterile and is intended for single use only.
Appearance and Packaging
Prenoxad is supplied as a clear, colourless, sterile aqueous solution in a glass pre-filled syringe with a Luer-lock tip and a plunger with graduations at 0.4 ml intervals. Each syringe is packaged in a protective plastic case together with a set of hypodermic needles (typically two or three 23G 25 mm needles with an orange hub suitable for intramuscular use). The carton also contains patient information leaflets and, in many public-health distributions, a basic pictorial instruction card.
Pack sizes vary by distributor but the most common presentation is a single-unit kit containing one pre-filled 2 ml syringe and two to three needles. Harm-reduction services may distribute multi-pack kits with additional needles or alcohol swabs.
Marketing and Manufacture
Prenoxad Injection is marketed by Martindale Pharma, an Ethypharm company, and is distributed in the United Kingdom and a number of European and international markets under national take-home naloxone programmes. The marketing authorisation holder and detailed batch information are printed on the carton. Prenoxad is classified as a prescription-only medicine (POM / Rx), but in many jurisdictions regulations allow it to be supplied without a standard prescription by qualified professionals under specific arrangements (Patient Group Directions, standing orders, or harm-reduction statutes) to enable widespread community access.
Frequently Asked Questions About Prenoxad
Prenoxad (naloxone hydrochloride 0.91 mg/ml) is an emergency medicine used to reverse the effects of a known or suspected opioid overdose. It temporarily blocks opioids such as heroin, morphine, methadone, fentanyl, oxycodone and codeine at their receptors, restoring normal breathing in a person whose respiration has slowed or stopped. Prenoxad is supplied as a pre-filled syringe so that a family member, carer or first responder can give it by intramuscular injection while waiting for an ambulance.
Call emergency services first (112 in Europe, 911 in the US, 999 in the UK, 000 in Australia). Remove the yellow needle cap, attach a needle (usually the orange hub is for intramuscular use), and inject 0.4 ml (one marked division) into the outer thigh or upper outer arm – you can inject through clothing if needed. If there is no response within 2–3 minutes, give another 0.4 ml. Repeat every 2–3 minutes up to the full 2 ml if breathing does not return. Put the person in the recovery position and stay with them until the ambulance arrives.
Side effects usually relate to the abrupt reversal of opioid effects and the appearance of acute opioid withdrawal. Common reactions include nausea, vomiting, sweating, shivering, tremor, headache, rapid heartbeat and raised blood pressure. In opioid-dependent people, withdrawal symptoms such as agitation, abdominal pain, muscle aches and runny nose are very common. Rare but serious side effects include seizures, cardiac arrhythmias, pulmonary oedema and, very rarely, severe allergic reactions. The benefits of using naloxone in a life-threatening overdose greatly outweigh these risks.
Naloxone starts to work within 2–5 minutes of intramuscular injection and lasts approximately 45–90 minutes. Many opioids – particularly methadone, long-acting morphine, sustained-release oxycodone and some fentanyl analogues – last longer than naloxone. This means the overdose can return (re-sedation) once the naloxone wears off. The person must be taken to hospital for observation even if they appear fully recovered, because further doses of naloxone or a continuous infusion may be required.
Yes, naloxone reverses fentanyl and most fentanyl analogues, but higher or repeated doses may be needed compared with a heroin overdose. International guidelines recommend giving the first dose, calling an ambulance, and repeating the dose every 2–3 minutes until breathing returns or professional help arrives. Because of the rising prevalence of highly potent synthetic opioids, current WHO and public-health guidance supports wide community access to take-home naloxone products such as Prenoxad, and in some regions two or more kits are distributed to each high-risk individual.
No. Prenoxad only reverses opioid effects. It has no effect on overdoses caused by alcohol, benzodiazepines, cocaine, amphetamines, gabapentinoids or other non-opioid drugs. However, if opioids are suspected to be part of a mixed overdose, naloxone should still be given because reversing the opioid component can restore breathing even if other substances are involved. Always call emergency services, describe what has been taken if known, and continue basic resuscitation (airway management, recovery position, rescue breathing if trained).
Yes. Prenoxad is designed specifically as a take-home naloxone product for people at risk of opioid overdose, their family, friends and carers. The pre-filled syringe is stable at room temperature (below 25°C) for the duration of its shelf life, and it has no addictive or harmful effect on someone who has not taken opioids. Training from a pharmacist, harm-reduction service or drug service is recommended so that users feel confident with the technique before they need to use it in an emergency. In many countries, brief training is integrated into community naloxone distribution.
Yes. If you have reasonable suspicion of an opioid overdose – because you know the person uses opioids, because you find drug paraphernalia nearby, or because the typical signs (unresponsiveness, slow or absent breathing, blue lips, tiny pupils) are present – give Prenoxad without delay. Naloxone has essentially no effect in a person who has not taken opioids, so the risk of giving it unnecessarily is very low compared with the life-saving benefit if an opioid really is involved. Legal protections for bystanders who administer naloxone in good faith exist in many jurisdictions.
References
- World Health Organization. Community Management of Opioid Overdose. Geneva: WHO; 2014. Available from: WHO Guidelines.
- Medicines and Healthcare products Regulatory Agency (MHRA). Prenoxad Injection 910 micrograms/ml Solution for Injection – Summary of Product Characteristics. Revised 2024.
- European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Take-home naloxone: Perspectives on Drugs. Lisbon: EMCDDA; 2022. Available from: EMCDDA.
- National Institute for Health and Care Excellence (NICE). Clinical Knowledge Summary: Opioid dependence. Last revised 2024.
- British National Formulary (BNF). Naloxone hydrochloride. London: BMJ Group and Royal Pharmaceutical Society; 2025.
- Strang J, McDonald R, Campbell G, et al. Take-Home Naloxone for the Emergency Interim Management of Opioid Overdose: The Public Health Application of an Emergency Medicine. Drugs. 2019;79(13):1395–1418. doi:10.1007/s40265-019-01154-5.
- McDonald R, Strang J. Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria. Addiction. 2016;111(7):1177–1187. doi:10.1111/add.13326.
- Clarke SFJ, Dargan PI, Jones AL. Naloxone in opioid poisoning: walking the tightrope. Emerg Med J. 2005;22(9):612–616. doi:10.1136/emj.2003.009613.
- U.S. Food and Drug Administration (FDA). Naloxone Hydrochloride Injection – Prescribing Information. Revised 2024.
- Substance Abuse and Mental Health Services Administration (SAMHSA). SAMHSA Opioid Overdose Prevention Toolkit. Rockville, MD: SAMHSA; 2023.
- Boyer EW. Management of opioid analgesic overdose. N Engl J Med. 2012;367(2):146–155. doi:10.1056/NEJMra1202561.
- European Resuscitation Council. ERC Guidelines 2021: Special Circumstances – Poisoning. Resuscitation. 2021;161:152–219.
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