Consumer medicine information

Naloxone SXP

Naloxone hydrochloride

BRAND INFORMATION

Brand name

Naloxone SXP

Active ingredient

Naloxone hydrochloride

Schedule

S3 | S4

SUMMARY CMI

NALOXONE SXP

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I being given NALOXONE SXP?

NALOXONE SXP contains the active ingredient naloxone hydrochloride dihydrate. NALOXONE SXP is used to reverses the effect of opium-like substances such as morphine, heroin and codeine.

For more information, see Section 1. Why am I being given NALOXONE SXP? in the full CMI.

2. What should I know before I am given NALOXONE SXP?

You should not be given NALOXONE SXP if you have ever had an allergic reaction to this medicine or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I am given NALOXONE SXP? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with NALOXONE SXP and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How am I given NALOXONE SXP?

NALOXONE SXP Injection is given as an injection into a muscle, under the skin or as a slow injection into a vein.
NALOXONE SXP Injection should only be given by a doctor or nurse. Your doctor will decide on the dose.
In emergency situations, NALOXONE SXP may be given by paramedical staff, such as an ambulance attendant.
More instructions can be found in Section 4. How am I given NALOXONE SXP? in the full CMI.

5. What should I know while being given NALOXONE SXP?

Things you should do	Remind any doctor, dentist or pharmacist that you visit that you have been given NALOXONE SXP. Tell your doctor if you are pregnant, intending to become pregnant or are breastfeeding. Tell your doctor if you have heart disease, lung disease, drug addiction, kidney disease or liver disease. If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly after being given NALOXONE SXP.
Driving or using machines	Be careful driving or operating machinery until you know how NALOXONE SXP Injection affects you. NALOXONE SXP may cause dizziness or light-headedness in some people and therefore driving or operating machinery may be dangerous.
Drinking alcohol	Be careful when drinking alcohol while you are being given this medicine, as it may cause light-headedness or dizziness in some people.
Looking after your medicine	NALOXONE SXP Injection will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place, protected from light, where the temperature stays below 25°C.

For more information, see Section 5. What should I know while being given NALOXONE SXP? in the full CMI.

6. Are there any side effects?

Common side effects include nausea or vomiting, headache, light-headedness or dizziness, high or low blood pressure.

Signs of drug withdrawal are serious and may include sweating, increased heart rate, tremor, rapid breathing, paranoia, self-harm, seizures, violent behaviour, delirium, nervousness, restlessness, irritability, excitement, agitation and tingling in the hands or feet. Other serious side effects are flaking skin or fluid in the lungs.

Symptoms of an allergic reaction may be serious and they include shortness of breath, wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body, and rash, itching or hives on the skin.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

NALOXONE SXP

Active ingredient: naloxone hydrochloride dihydrate

Consumer Medicine Information (CMI)

This leaflet provides important information about using NALOXONE SXP. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about being given NALOXONE SXP.

Where to find information in this leaflet:

1. Why am I being given NALOXONE SXP?
2. What should I know before I am given NALOXONE SXP?
3. What if I am taking other medicines?
4. How am I given NALOXONE SXP?
5. What should I know while being given NALOXONE SXP?
6. Are there any side effects?
7. Product details

1. Why am I being given NALOXONE SXP?

NALOXONE SXP contains the active ingredient naloxone hydrochloride dihydrate. NALOXONE SXP is a medicine which, when injected, reverses the effect of opium-like substances such as morphine, heroin and codeine.

NALOXONE SXP is used after surgical operations when powerful pain killers which have been given during an operation and are no longer required.

As NALOXONE SXP acts very quickly, within one or two minutes when injected into a vein, it can also be used as a lifesaving measure in those people who have received an overdose of an opioid-like drug.

2. What should I know before I am given NALOXONE SXP?

Warnings

You must not be given NALOXONE SXP if:

you are allergic to naloxone, or any of the ingredients listed at the end of this leaflet.
Always check the ingredients to make sure you can be given this medicine.
Symptoms of an allergic reaction to naloxone may include: shortness of breath, wheezing ordifficulty breathing, swelling of the face, lips, tongue or other parts of the body, rash, itching or hives on the skin.

Check with your doctor if you:

have any other medical conditions
take any medicines for any other condition
you allergies to any other medicines, or other substances, such as foods, preservatives or dyes.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant. Your doctor will discuss the possible risks and benefits of being given NALOXONE SXP Injection during pregnancy.

Talk to your doctor if you are breastfeeding or intend to breastfeed. Your doctor will discuss the possible risks and benefits of being given NALOXONE SXP Injection during breast-feeding. It is not known whether passes into breast milk.

Tell your doctor or pharmacist if you have or have had any medical conditions, especially the following:

heart disease
lung disease
drug addiction
kidney disease
liver disease.

If you have not told your doctor or pharmacist about any of the above, tell them before you are given NALOXONE SXP Injection.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with NALOXONE SXP and affect how it works.

These include:

pain killers
cough and cold remedies
heart or blood pressure medication

These medicines may be affected by naloxone or may affect how well it works. You may need different amounts of your medicine or you may need to take or use different medicines. Your doctor or pharmacist will advise you.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect NALOXONE SXP.

4. How am I given NALOXONE SXP?

How much is given

Your doctor will decide what dose you will receive.
Your dose will depend on your condition and other factors.
NALOXONE SXP Injection is usually given as a single dose but may be repeated if necessary.

How it is given

NALOXONE SXP Injection is given either:

as an injection into a muscle (intramuscular),
just under the skin (subcutaneous) or
as a slow injection into a vein (intravenous).

Injection into a vein is the most common site of administration in an emergency situation.

NALOXONE SXP Injection should only be given by a doctor or nurse. In emergency situations it may be given by paramedical staff, such as an ambulance attendant.

If you are given too much NALOXONE SXP

If you think that you have been given too much NALOXONE SXP, you may need urgent medical attention.

You should immediately:

phone the Poisons Information Centre
(by calling 13 11 26), or
contact your doctor, or
go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

NALOXONE SXP Injection is known to be safe in very large doses in animals.

However, severe withdrawal symptoms can be produced in drug addicts if too much naloxone is used.

As NALOXONE SXP Injection is given by a medical professional, they will monitor for symptoms of overdose.

5. What should I know while being given NALOXONE SXP?

Things you should do

Remind any doctor, dentist or pharmacist you visit that you have been given NALOXONE SXP Injection.

Tell your doctor if you are pregnant, intending to become pregnant or are breastfeeding.

Tell your doctor if you have heart disease, lung disease, drug addiction, kidney disease or liver disease.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly.

Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how NALOXONE SXP Injection affects you.

NALOXONE SXP may cause dizziness in some people.

Drinking alcohol

Be careful when drinking alcohol while you are taking this medicine.

This medicine may cause light-headedness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Looking after your medicine

NALOXONE SXP Injection will be stored in the pharmacy or on the ward. The injection is kept in a cool dry place, protected from light, where the temperature stays below 25°C.

Getting rid of any unwanted medicine

NALOXONE SXP Injection will be disposed of by a health care professional.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Abrupt reversal of the effects of opium-like substances may result in withdrawal symptoms.

Less serious side effects

Less serious side effects	What to do
nausea vomiting light-headedness dizziness headache high or low blood pressure	Speak to your doctor if you have any of these side effects and they worry you.

These are the more common side effects of naloxone. Mostly these are mild and short-lived.

You should tell your doctor if these symptoms worry, you as they may be signs of drug withdrawal.

Serious side effects

Serious side effects

What to do

fluid in the lungs
flaking skin

Symptoms of drug withdrawal include:

paranoia
self-harm
seizures
delirium
violent behaviour or agitation
irritability or excitement.
tingling in the hands or feet
nervousness or restlessness
sweating
increased heart rate
tremor
rapid breathing

Symptoms of an allergic reaction include:

shortness of breath
wheezing or difficulty breathing
swelling of the face, lips, tongue or other parts of the body
rash, itching or hives on the skin.

Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Do not be alarmed by the following list of side effects. You may not experience any of them.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What NALOXONE SXP contains

Active ingredient (main ingredient)	naloxone hydrochloride (as dihydrate)
Other ingredients (inactive ingredients)	hydrochloric acid sodium chloride water for Injections sodium edetate

Do not take this medicine if you are allergic to any of these ingredients.

NALOXONE SXP Injection does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

NALOXONE SXP Injection is not addictive.

What NALOXONE SXP looks like

NALOXONE SXP Injection is a clear colourless solution.

It should not be given if there are any crystals or particles visible in the solution.

NALOXONE SXP Injection is available in the following strengths and packs:

400 microgram/mL,
5 x 2 mL ampoules
10 x 2 mL ampoules
(AUST R 315388)

Who distributes NALOXONE SXP

Southern XP Pty Ltd
Unit 5/118 Church Street
Hawthorn VIC 3122

Sponsor:

Southern XP IP Pty Ltd
Unit 5/118 Church Street
Hawthorn, 3122, Victoria
Australia

This leaflet was prepared in June 2022.

Published by MIMS August 2022

BRAND INFORMATION

Brand name

Naloxone SXP

Active ingredient

Naloxone hydrochloride

Schedule

S3 | S4

Notes

Distributed by Southern XP Pty Ltd

1 Name of Medicine

Naloxone hydrochloride dihydrate.

2 Qualitative and Quantitative Composition

Each ampoule contains naloxone hydrochloride (as dihydrate) 400 microgram in 1 mL. The preparation has a pH of approximately 3.5.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Naloxone Hydrochloride Injection is a sterile, clear, colourless solution, free from visible particulates.
Naloxone is a semi-synthetic opioid antagonist which differs structurally from oxymorphone only in that the methyl group on the nitrogen atom of oxymorphone is replaced by an allyl group.
Naloxone hydrochloride dihydrate is 17-allyl-4,5 α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride.
Naloxone hydrochloride dihydrate occurs as a white to slightly off-white powder and is soluble in water, dilute acids and strong alkalis and is slightly soluble in alcohol. It is practically insoluble in ether or chloroform.

4 Clinical Particulars

4.1 Therapeutic Indications

Naloxone is indicated for the complete or partial reversal of opioid depression, including respiratory depression, induced by natural and synthetic opioids including propoxyphene, methadone, codeine, morphine and heroin, and the mixed opioid agonist-antagonist analgesics such as pentazocine. Naloxone is also indicated for the diagnosis of suspected acute opioid overdosage.

4.2 Dose and Method of Administration

Dosage.

Use in adults.

Opioid overdosage - known or suspected.

An initial dose of 400 microgram (0.4 milligram) to 2 milligram of naloxone hydrochloride may be administered intravenously. This dose may be repeated at 2 to 3 minute intervals, if necessary. If no response is seen after a total of 10 milligram has been administered, the diagnosis of opioid-induced or partial opioid-induced toxicity should be questioned. If the intravenous route is not available, the medicine may be administered by intramuscular or subcutaneous injection.

Post-operative opioid depression.

For the partial reversal of opioid-induced depression following the use of opioids during surgery, smaller doses of naloxone are usually sufficient. The dose should be titrated according to the patient's response. The usual initial dosage is 100 to 200 microgram (0.1 to 0.2 milligram) administered intravenously at 2 to 3 minute intervals until the desired degree of reversal is achieved, i.e. adequate ventilation and alertness without significant pain or discomfort. Doses of naloxone larger than necessary may result in significant reversal of analgesia and increase in blood pressure. Too rapid reversal may induce nausea, vomiting, sweating or circulatory stress.
Repeat doses of naloxone may be required within one or two hours, depending on the type and amount of opioid administered and the time interval since the last dose. Supplemental intramuscular doses have been shown to produce a longer lasting effect.
Use in children.

Opioid overdose - known or suspected.

The usual initial dose in children is 10 microgram (0.01 milligram) per kg body weight given intravenously. If the desired degree of clinical improvement is not seen, a subsequent dose of 100 microgram (0.1 milligram) per kg may be administered. If the intravenous route is not available, naloxone may be administered by intramuscular or subcutaneous injection in divided doses. If necessary, naloxone can be diluted with sterile water for injections.

Post-operative opioid depression.

Follow the recommendations and cautions under "Adult post-operative opioid depression". In children, the initial dose of naloxone hydrochloride for reversal of respiratory depression should be in increments of 5 to 10 microgram (0.005 to 0.01 milligram) administered intravenously at 2 to 3 minute intervals until the desired degree of reversal is achieved.
Use in neonates.

Opioid-induced depression.

The usual initial dose is 10 microgram (0.01 milligram) per kg body weight administered by intravenous, intramuscular or subcutaneous injection. This dose may be repeated in accordance with the adult administration guidelines for post-operative opioid depression.

Method of administration.

Naloxone Hydrochloride Injection may be administered by the intravenous, intramuscular or subcutaneous route. Intravenous administration is recommended in emergency situations, as this route of administration provides the most rapid onset of action.
The duration of action of naloxone may be shorter than that of some opioids. Therefore, the patient should be kept under continued surveillance and repeated doses of naloxone should be administered as necessary.
Continuous intravenous infusion of Naloxone Hydrochloride Injection may be the most appropriate method of administration for patients who require higher doses, or who continue to experience respiratory or central nervous system (CNS) depression after effective therapy with repeated doses, and/or in whom the effects of long acting opioids are being antagonised. For continuous intravenous infusion, 2 milligram of naloxone hydrochloride may be diluted in 500 mL of sodium chloride 0.9% or glucose 5% injection to produce a solution containing 4 microgram/mL.
Naloxone Hydrochloride Injection should not be mixed with preparations containing bisulfite, metabisulfite, long-chain or high molecular weight anions or any solution having an alkaline pH. No medicine or chemical agent should be added to naloxone unless its effect on the chemical and physical stability has first been established. Prior to administration, intravenous solutions of Naloxone Hydrochloride Injection should be visually inspected for the presence of particles or discolouration. To reduce microbiological hazard, use as soon as practicable after reconstitution/preparation. If storage is necessary, hold at 2-8°C for not more than 24 hours. Product is for single use in one patient only. Discard any residue.

4.3 Contraindications

Naloxone hydrochloride dihydrate is contraindicated in patients with known hypersensitivity to naloxone or to any of the excipients.

4.4 Special Warnings and Precautions for Use

Naloxone should be administered with caution to patients who have received large doses of opioids, or who are known or suspected to be physically dependent on opioids (including neonates born to women who are opioid dependent), because the drug may precipitate severe withdrawal symptoms.
The signs and symptoms of opioid withdrawal in a patient physically dependent on opioids may include, but are not limited to, the following: body aches, diarrhoea, tachycardia, fever, runny nose, sneezing, pilo-erection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure.
In the neonate, opioid withdrawal may also include: convulsions, excessive crying, and hyperactive reflexes.
Patients who have satisfactorily responded to naloxone should be carefully monitored since the duration of action of some opioids may exceed that of naloxone. Repeated doses of naloxone should be administered when necessary.
Naloxone is not effective against respiratory depression caused by non-opioid drugs.
Reversal of respiratory depression by partial agonists or mixed agonist/antagonists, such as buprenorphine and pentazocine, may be incomplete or require higher doses of naloxone (also see Section 4.2 Dose and Method of Administration). If an incomplete response occurs, respirations should be mechanically assisted as clinically indicated.
When naloxone is used in the management of acute opioid overdosage, other resuscitative measures such as maintenance of a free airway, artificial ventilation, cardiac massage and vasopressor agents should be readily available and used when necessary.
Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, pulmonary oedema, and cardiac arrest have been reported in post-operative patients following naloxone administration. Death, coma, and encephalopathy have been reported as sequelae of these events. Although a direct cause and effect relationship has not been established, naloxone should be used with caution in patients with pre-existing cardiac disease or patients who have received medications with potentially cardiotoxic drugs, since serious cardiovascular effects, such as hypotension, hypertension, ventricular tachycardia or fibrillation, pulmonary oedema and cardiac arrest have occurred. It has been suggested that the pathogenesis of pulmonary oedema associated with the use of naloxone is similar to neurogenic pulmonary oedema i.e. a centrally mediated massive catecholamine response leading to a dramatic shift of blood volume into the pulmonary vascular bed resulting in increased hydrostatic pressures.
Naloxone should also be used with caution in patients with pre-existing pulmonary disease, since sudden exacerbation of underlying pulmonary disease may occur. Abrupt post-operative reversal of opioid depression may result in nausea, vomiting, sweating, tremulousness, hyperventilation, tachycardia, increased blood pressure, seizures, ventricular tachycardia and fibrillation, pulmonary oedema, and cardiac arrest which may result in death.

Use in hepatic impairment.

The safety and effectiveness of naloxone in patients with hepatic disease have not been established in well controlled clinical trials. In one small study in patients with hepatic cirrhosis, plasma naloxone concentrations were approximately six times higher than in patients without hepatic disease. Caution should be exercised when naloxone is administered to patients with hepatic disease.

Use in renal impairment.

The safety and effectiveness of naloxone in patients with renal insufficiency/failure have not been established in well controlled clinical trials. Caution should be exercised when naloxone is administered to this patient population.

Use in the elderly.

No data available.

Paediatric use.

Naloxone should be given with caution to patients who are known or suspected to be physically dependent on opioids (including neonates born to women who are opioid dependent), because the drug may precipitate the onset of severe withdrawal symptoms.

Effects on laboratory tests.

None known.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Naloxone reverses the analgesic and other effects of opioid agonist-antagonists such as pentazocine, so may precipitate withdrawal symptoms if used concurrently with these medicines in physically dependent patients.
High doses of naloxone may be required to antagonize buprenorphine since the latter has a long duration of action due to its slow rate of binding and subsequent slow dissociation from the opioid receptor. Buprenorphine antagonism is characterized by a gradual onset of the reversal effects and a decreased duration of action of the normally prolonged respiratory depression.
Naloxone reverses the analgesic and other effects of opioid agonist analgesics, and may precipitate withdrawal symptoms if used concurrently with these medicines in physically dependent patients, including patients receiving methadone to treat opioid dependence.
When naloxone is used post-operatively to reverse the central depressive effects of opioid agonists used as anaesthesia adjuncts, the dose of naloxone must be carefully titrated to achieve the desired effect without interfering with control of post-operative pain, or causing other adverse effects.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No evidence for impaired fertility was observed in a reproductive study in male or female rats given naloxone at doses 8 times the highest recommended human dose (based on body surface area).
(Category B1)
Category B1: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus being observed. Studies in animals have not shown evidence of an increased occurrence of foetal damage.
There are no adequate and controlled studies of naloxone in pregnant women. Naloxone should be administered to a pregnant woman only when, in the judgement of the physician, the potential benefits outweigh the possible hazards. Caution should be used when administering naloxone to a pregnant woman who is known to be opioid dependent, since maternal dependence may often be accompanied by foetal dependence. Naloxone crosses the placenta and may precipitate withdrawal in the foetus as well as in the mother.
Reproduction studies in mice and rats at doses of 4 to 8 times the highest recommended human dose (based on body surface area) revealed no evidence of harm to the foetus.
It is not known whether naloxone is excreted in human milk. Therefore, naloxone should be used with caution in breastfeeding women.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration. The effect of naloxone on the ability to drive or use machines has not been systematically evaluated.

4.8 Adverse Effects (Undesirable Effects)

The adverse effects are listed within each system organ class (SOC). See Table 1.

Post-operative.

The following adverse events have been associated with the use of naloxone in post-operative patients: hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnoea, pulmonary oedema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. Excessive doses of naloxone in postoperative patients may result in significant reversal of analgesia and may cause agitation (see Section 4.4 Special Warnings and Precautions for Use; Section 4.2 Dose and Method of Administration).

Opioid depression.

Abrupt reversal of opioid depression may result in nausea, vomiting, sweating, tachycardia, increased blood pressure, hyperventilation, tremulousness, seizures, ventricular tachycardia and fibrillation, pulmonary oedema, and cardiac arrest which may result in death (see Section 4.4 Special Warnings and Precautions for Use).

Opioid dependence.

(See Section 4.4 Special Warnings and Precautions for Use).
Naloxone may precipitate severe withdrawal symptoms in patients known or suspected to be physically dependent on opioids (including neonates born to women who are opioid dependent) (see Section 4.4 Special Warnings and Precautions for Use). Agitation and paraesthesias have been infrequently reported with the use of naloxone. Seizures have occurred rarely following administration of naloxone, however, a causal relationship has not been established. Violent behaviour, nervousness, restlessness, excitement and irritability may also occur.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

Symptoms of overdosage would be expected to be similar to the effects seen with therapeutic use (see Section 4.8 Adverse Effects (Undesirable Effects)).

Treatment.

Treatment of overdosage is symptomatic and supportive.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Naloxone is essentially a pure opioid antagonist, it has little or no agonistic activity. Naloxone is thought to act as a competitive antagonist at mu, kappa, and sigma opioid receptors in the central nervous system (CNS), although the precise mechanism of action has not been fully determined. Naloxone prevents or reverses the effects of opioids, including respiratory depression, sedation and hypotension. Naloxone can also reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine, but higher doses are required. One milligram of naloxone intravenously completely blocks the effects of 25 milligram of diacetylmorphine (heroin).
When administered in usual doses to patients who have not recently received opioids, naloxone exerts little or no pharmacological effect. Even extremely high doses (10 times the usual therapeutic dose) produce insignificant analgesia, only slight drowsiness, and no respiratory depression, psychotomimetic effects, circulatory changes or miosis. Naloxone does not produce tolerance or physical or psychological dependence. Parenteral administration of naloxone will produce withdrawal symptoms in patients physically dependent on opioids or pentazocine.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Naloxone has an onset of action within 1 to 2 minutes following intravenous administration and within 2 to 5 minutes following subcutaneous or intramuscular administration. The duration of action depends on the dose and route of administration and is more prolonged following intramuscular administration than after intravenous administration. The duration of action is reported to be up to several hours but the practical duration is probably 1 hour or less. Repeat doses of naloxone may be required depending on the amount, type and route of administration of the opioid being antagonised, as well as the duration of action of naloxone.

Distribution.

Following parenteral administration, naloxone is rapidly distributed into body tissues and fluids.

Metabolism.

Naloxone is rapidly metabolised in the liver, principally by conjugation with glucuronic acid.

Excretion.

Naloxone is 50% protein-bound and is excreted in the urine. The mean plasma half-life of naloxone has been reported to be about 60 minutes in adults with a range of from about 30 to 80 minutes, and about 3 hours in neonates.

5.3 Preclinical Safety Data

Genotoxicity.

In assays for gene mutations, naloxone was positive in the Ames test but negative in the mouse lymphoma assay. Naloxone was also positive in an assay for chromosomal damage (human lymphocytes in vitro).

Carcinogenicity.

Studies in animals to assess the carcinogenic potential of naloxone have not been conducted.

6 Pharmaceutical Particulars

6.1 List of Excipients

Hydrochloric acid; sodium chloride; water for injections; sodium edetate.
See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

Naloxone hydrochloride solution for injection should not be mixed with preparations containing bisulfites, metabisulfites, long chain or high molecular weight anions, or those with an alkaline pH.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Protect from light. Store below 25°C.

6.5 Nature and Contents of Container

Naloxone Hydrochloride Injection is available in clear glass ampoules: 400 microgram naloxone hydrochloride/1 mL.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

The chemical formula for anhydrous naloxone hydrochloride is C₁₉H₂₁NO₄.HCl. Its molecular weight is 363.84.

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Consumer medicine information

Naloxone SXP

Naloxone hydrochloride

Keep track of your medicines

BRAND INFORMATION