Nyxoid

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Nyxoid 1.8 mg nasal spray, solution in a single-dose container 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each nasal spray container delivers 1.8 mg of naloxone (as hydrochloride dihydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Nasal spray, solution in a single-dose container (nasal spray) 
 
Clear, colourless to pale yellow solution 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Nyxoid is intended for immediate administration as emergency therapy for known or suspected opioid 
overdose as manifested by respiratory and/or central nervous system depression in both non-medical 
and healthcare settings. 
 
Nyxoid is indicated in adults and adolescents aged 14 years and over. 
 
Nyxoid is not a substitute for emergency medical care. 
 
4.2 Posology and method of administration 
 
Posology 
 
Adults and adolescents aged 14 years and over 
 
The recommended dose is 1.8 mg administered into one nostril (one nasal spray).   
 
In some cases, further doses may be necessary.  The appropriate maximum dose of Nyxoid is situation 
specific.  If the patient does not respond, the second dose should be administered after 2-3 minutes.  If 
the patient responds to the first administration but then relapses again into respiratory depression, the 
second dose should be administered immediately.  Further doses (if available) should be administered 
in alternate nostrils and the patient should be monitored whilst awaiting arrival of the emergency 
services.  Emergency services may administer further doses according to local guidelines. 
 
Paediatric population 
 
The safety and efficacy of Nyxoid in children below 14 years has not been established.  No data are 
available. 
 
Method of administration 
 
Nasal use.   
 
Nyxoid should be administered as soon as possible to avoid damage to the central nervous system or 
death.  



3 

 
Nyxoid contains only one dose and therefore it must not be primed or tested prior to administration. 
 
Detailed instructions on how to use Nyxoid are provided in the Package Leaflet and a Quick Start 
Guide is printed on the back of each blister.  In addition, training is provided via a video and a Patient 
Information Card. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Instructing patients / users on the proper use of Nyxoid  
 
Nyxoid should only be made available once the suitability and competence of an individual to 
administer naloxone in the appropriate circumstances has been established.  Patients or any other 
person who might be in a position to administer Nyxoid must be instructed in its proper use and the 
importance of seeking medical assistance. 
 
Nyxoid is not a substitute for emergency medical care and may be used instead of intravenous (IV) 
injection, when IV access is not immediately available.   
 
Nyxoid is intended to be administered as a part of a resuscitation intervention in suspected overdose 
casualties, where opioid drugs may be involved or suspected, likely in a non-medical setting.  
Therefore, the prescriber should take appropriate steps to ensure that the patient and/or any other 
person who might be in a position to administer Nyxoid thoroughly understands the indications and 
use of Nyxoid.   
 
The prescriber should describe the symptoms which allow presumptive diagnosis of central nervous 
system (CNS) / respiratory depression, the indication and the instructions for use with the patient and / 
or person who might be in a position to administer this product to a patient experiencing a known or 
suspected opioid overdose event.  This should be performed in accordance with the educational 
guidance for Nyxoid. 
 
Monitoring of the patient for a response  
 
Patients who respond satisfactorily to Nyxoid must be closely monitored.  The effect of some opioids 
can be longer than the effect of naloxone, which could lead to reoccurrence of respiratory depression 
and therefore further doses of naloxone may be required. 
 
Opioid withdrawal syndrome  
 
Receiving Nyxoid can lead to a rapid reversal of the opioid effect which can cause an acute 
withdrawal syndrome (see section 4.8).  Patients who are receiving opioids for the relief of chronic 
pain may experience pain and opioid withdrawal symptoms when Nyxoid is administered. 
 
Effectiveness of naloxone 
 
Reversal of buprenorphine-induced respiratory depression may be incomplete.  If an incomplete 
response occurs, respiration should be mechanically assisted. 
 
Intranasal absorption and efficacy of naloxone can be altered in patients with damaged nasal mucosa 
and septal defects. 
 



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Paediatric population 
 
Opioid withdrawal may be life-threatening in neonates if not recognised and properly treated and may 
include the following signs and symptoms: convulsions, excessive crying and hyperactive reflexes.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Naloxone elicits a pharmacological response due to the interaction with opioids and opioid agonists.  
When administered to opioid dependent subjects, naloxone can cause acute withdrawal symptoms in 
some individuals.  Hypertension, cardiac arrhythmias, pulmonary oedema and cardiac arrest have been 
described, more typically when naloxone is used post-operatively (see sections 4.4 and 4.8). 
 
Administration of Nyxoid may decrease the analgesic effects of opioids used primarily to provide pain 
relief, due to its antagonist properties (see section 4.4). 
 
When administering naloxone to patients who have received buprenorphine as an analgesic, complete 
analgesia may be restored.  It is thought that this effect is a result of the arch-shaped dose-response 
curve of buprenorphine with decreasing analgesia in the event of high doses.  However, reversal of 
respiratory depression caused by buprenorphine is limited. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no adequate data from the use of naloxone in pregnant women.  Studies in animals have 
shown reproductive toxicity only at maternally toxic doses (see section 5.3).  The potential risk for 
humans is unknown.  Nyxoid should not be used during pregnancy unless the clinical condition of the 
woman requires treatment with naloxone. 
 
In pregnant women who have been treated with Nyxoid, the fetus should be monitored for signs of 
distress. 
 
In opioid dependent pregnant women, naloxone administration can cause withdrawal symptoms in 
newborn infants (see section 4.4). 
 
Breast-feeding 
 
It is unknown whether naloxone is excreted in human breast milk and it has not been established 
whether infants who are breast-fed are affected by naloxone.  However, as naloxone is practically not 
orally bioavailable its potential to affect a breast-fed infant is negligible.  Caution should be exercised 
when naloxone is administered to a breast-feeding mother but there is no need to discontinue 
breast-feeding.  Breast-fed babies from mothers who have been treated with Nyxoid should be 
monitored to check for sedation or irritability. 
 
Fertility 
 
No clinical data on effects of naloxone on fertility are available, however data from rat studies (see 
section 5.3) indicate no effects.  
 
4.7 Effects on ability to drive and use machines 
 
Patients who have received naloxone to reverse the effects of opioids should be warned not to drive, to 
operate machinery or to engage in other activities demanding physical or mental exertion for at least 
24 hours, since the effect of the opioids may return. 
 



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4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most common adverse drug reaction (ADR) seen with naloxone administration is nausea 
(frequency very common).  Typical opioid withdrawal syndrome is expected with naloxone which 
may be caused by the abrupt withdrawal of opioid in persons physically dependent on them.  
 
Tabulated list of adverse reactions  
 
The following adverse reactions have been reported with Nyxoid and/or other naloxone-containing 
medicinal products during clinical studies and post marketing experience.  ADRs are listed below by 
system organ class and frequency.   
 
Frequency categories are assigned to those adverse reactions considered to be at least possibly causally 
related to naloxone and are defined as very common: (≥ 1/10); common: (≥ 1/100, < 1/10); 
uncommon: (≥ 1/1,000, < 1/100); rare: (≥ 1/10,000, < 1/1,000) very rare: (< 1/10,000); not known 
(cannot be estimated from the available data). 
 
  
Immune system disorders  
 
Very rare:  Hypersensitivity, Anaphylactic shock 
 
 
Nervous system disorders 
 
Common  Dizziness, Headache 
 
Uncommon  Tremor 
 
Cardiac disorders 
 
Common  Tachycardia 
 
Uncommon  Arrhythmia, Bradycardia 
 
Very rare  Cardiac fibrillation, Cardiac arrest 
 
Vascular disorders 
 
Common  Hypotension, Hypertension 
 
Respiratory, thoracic and mediastinal disorders 
 
Uncommon  Hyperventilation 
 
Very rare  Pulmonary oedema 
 
Gastrointestinal disorders 
 
Very common Nausea 
 
Common  Vomiting 
 
Uncommon  Diarrhoea, Dry mouth 
 



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Skin and subcutaneous tissue disorders 
 
Uncommon  Hyperhidrosis 
 
Very rare  Erythema multiforme 
 
General disorders and administration site conditions 
 
Uncommon  Drug withdrawal syndrome (in patients dependent on opioids) 
 
 
Description of selected adverse reactions 
 
Drug withdrawal syndrome 
 
Signs and symptoms of drug withdrawal syndrome include restlessness, irritability, hyperaesthesia, 
nausea, vomiting, gastrointestinal pain, muscle spasms, dysphoria, insomnia, anxiety, hyperhidrosis, 
piloerection, tachycardia, increased blood pressure, yawning, pyrexia.  Behavioural changes including 
violent behaviour, nervousness and excitement may also be observed. 
 
Vascular disorders 
 
In reports on intravenous/intramuscular naloxone: hypotension, hypertension, cardiac arrhythmia 
(including ventricular tachycardia and fibrillation) and pulmonary oedema have occurred with the 
postoperative use of naloxone.  Adverse cardiovascular effects have occurred more frequently in 
postoperative patients with a pre-existing cardiovascular disease or in those receiving other medicines 
that produce similar adverse cardiovascular effects. 
 
Paediatric population 
 
Nyxoid is intended for use in adolescents 14 years and over.  Frequency, type and severity of adverse 
reactions in adolescents are expected to be the same as in adults.   
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation 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 via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
In view of the indication and the broad therapeutic margin, overdose is not to be expected.  
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antidotes, ATC code: V03AB15 
 
Mechanism of action and pharmacodynamic effects 
 
Naloxone, a semisynthetic morphine derivative (N-allyl-nor-oxymorphone), is a specific opioid 
antagonist that acts competitively at opioid receptors.  It reveals very high affinity for the opioid 
receptor sites and therefore displaces both opioid agonists and partial antagonists.  Naloxone does not 
possess the "agonistic" or morphine-like properties characteristic of other opioid antagonists.  In the 



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absence of opioids or agonistic effects of other opioid antagonists, it exhibits essentially no 
pharmacologic activity.  Naloxone has not been shown to produce tolerance or cause physical or 
mental dependence.  
 
As the duration of action of some opioid agonists may be longer than that of naloxone, the effects of 
the opioid agonist may return as the effects of naloxone disappear.  This may necessitate repeat doses 
of naloxone – though the need for repeat naloxone doses is dependent on the quantity, type and route 
of administration of the opioid agonist that is being treated.  
 
Paediatric population 
 
No data are available. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Intranasal administration of naloxone has demonstrated naloxone to be rapidly absorbed, as evidenced 
by very early appearance (as early as 1 minute after administration) of the active substance in systemic 
circulation.  
 
A study investigating intranasal naloxone at doses of 1, 2, 4 mg (MR903-1501) shows that the 
median (range) tmax associated with intranasal administration of naloxone was 15 (10, 60) minutes for 
1 mg, 30 (8, 60) minutes for 2 mg and 15 (10, 60) minutes for 4 mg intranasal doses.  Onset of action 
following intranasal administration can reasonably be expected to occur in each individual before the 
tmax is reached. 
 
The half value duration (HVD) values for intranasal administration were longer than for IM 
administration (intranasal, 2 mg, 1.27h, IM, 0.4 mg 1.09h) from which we can infer a longer duration 
of action of naloxone given by the intranasal rather than the IM route.  If the duration of action of the 
opioid agonist exceeds that of intranasal naloxone, the effects of the opioid agonist may return, 
necessitating a second intranasal naloxone administration. 
 
A study demonstrated mean absolute bioavailability of 47% and mean half-lives of 1.4 h from 
intranasal doses of 2 mg. 
 
Biotransformation 
 
Naloxone is rapidly metabolized in the liver and excreted in the urine.  It undergoes extensive hepatic 
metabolism mainly by glucuronide conjugation.  The principal metabolites are 
naloxone-3-glucuronide, 6-beta-naloxol and its glucuronide.  
 
Elimination 
 
There are no data available on the excretion of naloxone following intranasal administration, however, 
the disposition of labelled naloxone following IV administration was studied in healthy volunteers and 
opioid-dependent patients.  Following an IV dose of 125 µg, 38% of the dose was recovered in the 
urine within 6 hours in healthy volunteers compared with 25% of the dose being recovered in 
opioid-dependent patients in the same time period.  After a period of 72 hours, 65% of the injected 
dose was recovered in urine in the healthy volunteers compared with 68% of the dose in 
opiate-dependent patients.  
 
Paediatric population 
 
No data are available. 
 



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5.3 Preclinical safety data 
 
Genotoxicity and carcinogenicity 
 
Naloxone was not mutagenic in the bacterial reverse mutation assay, but was positive in mouse 
lymphoma assay and was clastogenic in vitro, however, naloxone was not clastogenic in vivo.  
Naloxone was not carcinogenic following oral administration in a rat 2-year study or in a 26-week 
study in Tg-rasH2 mice.  Overall, the weight of evidence indicates that naloxone poses minimal, if 
any, risk for human genotoxicity and carcinogenicity. 
 
Reproductive and developmental toxicity 
 
Naloxone had no effect on fertility and reproduction in the rat or on early embryonic development of 
the rat and rabbit.  In peri-post natal rat studies, naloxone produced increased pup deaths in the 
immediate post-partum period at the high doses that also caused significant maternal toxicity in rats 
(e.g. bodyweight loss, convulsions).  Naloxone did not affect development or behaviour of surviving 
pups.  Naloxone is therefore not teratogenic in rats or rabbits. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Trisodium citrate dihydrate 
Sodium chloride 
Hydrochloric acid 
Sodium hydroxide 
Purified water 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Do not freeze.  
 
6.5 Nature and contents of container 
 
The immediate container consists of a type I glass vial with siliconised chlorobutyl stopper containing 
0.1 ml solution.  The secondary packaging (actuator) is comprised of polypropylene and stainless 
steel. 
 
Each pack contains two single-dose nasal sprays. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 



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7. MARKETING AUTHORISATION HOLDER 
 
Mundipharma Corporation (Ireland) Limited 
Millbank House 
Arkle Road 
Sandyford Industrial Estate 
Dublin 18 
Ireland  
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1238/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 10 November 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 



10 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE  
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
 



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A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
 
BARD PHARMACEUTICALS LIMITED 
UNIT 191, CAMBRIDGE SCIENCE PARK,  
MILTON ROAD,  
CAMBRIDGE, CB4 0GW,  
United Kingdom 
 
Mundipharma DC B.V. 
Leusderend 16 
3832 RC Leusden 
Netherlands 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
• Periodic safety update reports  
 
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
The MAH shall perform the required  pharmacovigilance activities and interventions detailed in the  
agreed RMP presented in Module 1.8.2 of the marketing authorisation and any agreed  subsequent 
updates of the RMP. 
 
An updated RMP should be submitted: 
 
• At the request of the European Medicines Agency; 

 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.  

 
• Additional risk minimisation measures  
 



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Prior to launch of Nyxoid in each Member State the Marketing Authorisation Holder must agree about 
the content and format of the educational materials, including communication media, distribution 
modalities, and any other aspects of the programme, with the National Competent Authority. 
 
The MAH shall ensure that in each MS where Nyxoid is marketed, all relevant health care 
professionals (HCP) who are expected to prescribe and/or supply Nyxoid are provided with: 
 

• HCP Guidance Document with training delivery instructions 
 
• The patient/carer information card 
 
• Access to a video on how to use Nyxoid 

 
The HCP Guidance Document should include: 
 

• A brief introduction on Nyxoid 
 
• A list of the educational material included in the training program 
 
• Details of what information needs to be shared when training the patient/carer 
 

o how to manage a known or suspected opioid overdosed and how to properly 
administer Nyxoid  
 

o how to minimise the occurrence and severity of the following risks associated with 
Nyxoid: reappearance of respiratory depression, precipitation of acute opioid 
withdrawal effect and lack of efficacy due to medication error 
 

• Instructions that the HCP  has to provide the patient/carer with the PIC and to make sure 
that the patients/carers will have access to the video (either through the PIC or memory 
stick) and are encouraged to read the quick starting guide (QSG) and package leaflet 
included in the medicinal product outer carton. 

 
The Patient Information Card should include: 
 

• Information about Nyxoid and the fact that it cannot replace provision of basic life 
support 
 

• Identification of signs of suspected opioid overdose, especially respiratory depression and 
information on how to check the airways and breathing 
 

• Emphasis on the need to make an immediate emergency call for an ambulance 
 

• Information on how to use the nasal spray to correctly administer Nyxoid 
 

• Information on placing the patient into recovery position and administering the second 
dose, if required, in this position 
 

• Information on how to manage and monitor the patient until the emergency medical 
assistance arrives 
 

• Awareness of possible important risks such as opioid withdrawal symptoms and 
recurrence of respiratory depression 
 

• Reference to the QSG on the back of the product immediate packaging 
 



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The Video should include: 
 

• Steps detailing management of a patient which are aligned with information in PIC and 
package leaflet 
 

• It should be available as 
 
o A link for online access in the HPD and PIC 

 
o Memory stick for HCP use to train, if WiFi not accessible 

 
• Obligation to conduct post-authorisation measures 
 
The MAH shall complete, within the stated timeframe, the below measures: 
 
Description Due date 
Post-authorisation efficacy study (PAES):  
The Effectiveness of Nyxoid (intranasal naloxone) Administration by Lay People in 
Reversing Opioid Overdose. 

Q4 2022 

 



14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



15 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



16 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

CARTON 

1. NAME OF THE MEDICINAL PRODUCT

Nyxoid 1.8 mg nasal spray, solution in a single-dose container 
naloxone  

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each nasal spray container delivers 1.8 mg of naloxone (as hydrochloride dihydrate) 

3. LIST OF EXCIPIENTS

Excipients: Trisodium citrate dihydrate, sodium chloride, hydrochloric acid sodium hydroxide, 
purified water. 

4. PHARMACEUTICAL FORM AND CONTENTS

Nasal spray, solution in a single-dose container 

2 single-dose containers 

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use. 
Nasal use. 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY

Do not prime or test before use.  Each spray contains only one dose. 

For overdose of opioids (such as heroin) 

8. EXPIRY DATE

EXP 



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9. SPECIAL STORAGE CONDITIONS 
 
Do not freeze.  
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Mundipharma Corporation (Ireland) Limited 
Millbank House 
Arkle Road 
Sandyford Industrial Estate 
Dublin 18 
Ireland . 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1238/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Nyxoid 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 



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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nyxoid 1.8 mg nasal spray, solution in a single-dose container 
naloxone 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Mundipharma Corporation (Ireland) Limited 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Single-dose nasal spray for overdose of opioids (such as heroin)  
Do not test before use 
 

 
Call an ambulance 
 

 
Lay down. Tilt head back. 
 

 
Spray into one nostril. 
 



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Lay in recovery position. 
 
Not better? After 2-3 mins, use 2nd spray. 
 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
INTRANASAL SPRAY/DEVICE LABEL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Nyxoid 1.8 mg nasal spray, solution in a single-dose container 
naloxone 
Nasal use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1.8 mg 
 
 
6. OTHER 
 
 



21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



22 

Package leaflet: Information for the user 
 

Nyxoid 1.8 mg nasal spray, solution in a single-dose container  
Naloxone 

 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Nyxoid is and what it is used for 
2. What you need to know before you receive Nyxoid 
3. How Nyxoid is to be given 
4. Possible side effects 
5. How to store Nyxoid 
6. Contents of the pack and other information 
 
 
1. What Nyxoid is and what it is used for 
 
This medicine contains the active substance naloxone.  Naloxone temporarily reverses the effects of 
opioids such as heroin, methadone, fentanyl, oxycodone, buprenorphine and morphine. 
 
Nyxoid is a nasal spray used for the emergency treatment of opioid overdose or possible opioid 
overdose in adults and adolescents over 14 years.  Signs of overdose include:  
• breathing problems  
• severe sleepiness  
• not responding to a loud noise or touch. 
 
If you are at risk of an opioid overdose you should always carry your Nyxoid with you. Nyxoid 
works for a short time only to reverse the effects of opioids while you wait for emergency medical 
attention.  It is not a substitute for emergency medical care.  Nyxoid is intended for use by 
appropriately trained individuals.   
 
Always tell your friends and family that you carry Nyxoid with you. 
 
 
2. What you need to know before you receive Nyxoid 
 
Do not use Nyxoid  
 
If you are allergic to naloxone or any of the other ingredients of this medicine (listed in section 6).  
 
Warnings and precautions  
 
Nyxoid will be supplied to you only after you or your carer have been taught how to use it. 
 
It is to be given right away and does not take the place of emergency medical care.   
 
• Emergency services should be called if an opioid overdose is suspected. 
 



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The signs and symptoms of an opioid overdose can return after this nasal spray is given.  If this 
happens, further doses may be given after 2 to 3 minutes using a new nasal spray.  The patient should 
be monitored closely until emergency help has arrived after being given this medicine. 
 
Conditions to look out for 
• If you are physically dependent on opioids or if you have received high doses of opioids (for 

example heroin, methadone, fentanyl, oxycodone, buprenorphine or morphine).  You may get 
strong withdrawal symptoms with this medicine (see later in section 4 of this leaflet under 
‘Conditions to look out for’) 

• If you take opioids to control pain.  The pain may increase when you receive Nyxoid. 
• If you use buprenorphine.  Nyxoid may not fully reverse breathing problems. 
 
Tell your doctor if you have damage to the inside of your nose as this could affect how Nyxoid 
works. 
 
Children and adolescents 
 
Nyxoid is not for use in children or adolescents under 14 years.  
 
Receiving Nyxoid close to giving birth 
 
Tell your midwife or doctor if you have received Nyxoid close to or during labour. 
Your baby could suffer from sudden opioid withdrawal syndrome, which could be life-threatening if 
not treated. 
Watch out for the following symptoms in your baby during the first 24 hours after the baby is born:  
• seizures (fits) 
• crying more than usual 
• increased reflexes. 
 
Other medicines and Nyxoid 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
 
Pregnancy, breastfeeding and fertility 
 
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask 
your doctor or pharmacist for advice before receiving a supply of this medicine. 
If you are given Nyxoid while you are pregnant or breast-feeding, your baby should be closely 
monitored. 
 
Driving and using machines 
 
After taking this medicine, you must not drive, operate machinery or engage in any other physically or 
mentally demanding activity for at least 24 hours, since the effects of opioids may recur.  
 
 
3. How Nyxoid is to be given 
 
Always use this medicine exactly as your doctor, pharmacist or nurse has told you.  Check with your 
doctor, pharmacist or nurse if you are not sure. 
 
Training will be provided on how to use Nyxoid before it is supplied to you.  Below is a step by step 
guide. 
 



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Instructions for giving Nyxoid nasal spray:  
 
1. Check for symptoms and response.   

- Check for a response, to see if the person is conscious.  You can shout their name, 
gently shake their shoulders, talk loudly into their ears, rub their breastbone (sternum), 
pinch their ear or the bed of their fingernail. 

- Check airways and breathing.  Clear the mouth and nose of any blockages.  For 
10 seconds check for breathing – is the chest moving?  Can you hear breathing sounds?  
Can you feel breath on the cheek? 

- Check for signs of overdose, such as: no response to touch or sounds, slow uneven 
breathing or no breathing, snoring, gasping or gulping, blue or purple fingernails or lips. 

- If an overdose is suspected Nyxoid should be given. 
 
2. Call for an ambulance.  Nyxoid is not a substitute for emergency medical care. 
 

 
 
3. Peel off the back of the blister from the corner to remove the nasal spray from the container.  

Place the nasal spray within easy reach. 
 

 
 
4. Lay the patient on their back. Support the back of the neck and allow the head to tilt back.  

Clear away anything blocking their nose. 
 

 
 
5. Hold the nasal spray with your thumb on the bottom of the plunger and your first and middle 

fingers on either side of the nozzle.  Do not prime or test the Nyxoid nasal spray before use 
as it contains only one dose of naloxone and cannot be reused. 

 

 
 



25 

6. Gently insert the device nozzle in one nostril.  Press firmly on the plunger until it clicks to 
give the dose.  Remove the nasal spray nozzle from the nostril after giving the dose. 

 

 
 
7. Place the patient into the recovery position on their side with mouth open pointing towards the 

ground and stay with the patient until the emergency services arrive.  Watch for an 
improvement in the patient’s breathing level, alertness and response to noise and touch.   

 

 
 
8. If the patient is no better within 2-3 minutes, a second dose can be given.  Be aware – even if 

they wake up, they may become unconscious again, and stop breathing.  If this happens, a 
second dose can be given immediately.  Give Nyxoid in the other nostril using a new Nyxoid 
nasal spray.  This can be done while the patient is in the recovery position.   

 
9. If the patient does not respond to two doses, further doses may be given (if available).  Stay 

with the patient and continue to watch for an improvement until the emergency services arrive 
who will give further treatment. 

 
In patients who are unconscious and not breathing normally additional life-saving support should be 
given if possible.  
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects although not everyone gets them.  The side 
effects below may happen with this medicine. 
 
Conditions to look out for 
 
Nyxoid can cause acute withdrawal symptoms if the patient is dependent on opioid drugs.  
Symptoms can include: 
• Fast heart rate, high blood pressure 
• Body aches and stomach cramps 
• Feeling sick, vomiting, diarrhoea 
• Sweating, fever, goose bumps, shivering or trembling 
• Changes in behaviour including violent behaviour, nervousness, anxiety, excitement, 

restlessness or irritability 
• Unpleasant or uncomfortable mood 
• Increased skin sensitivity 
• Difficulty in sleeping. 
 



26 

Acute withdrawal symptoms occur uncommonly (may affect up to 1 in 100 people).   
Tell your doctor if you experience any of these symptoms. 
 
Very common: may affect more than 1 in 10 people 
• Feeling sick 
 
Common: may affect up to 1 in 10 people 
• Dizziness, headache 
• Fast heart rate 
• High blood pressure, low blood pressure 
• Being sick (vomiting) 
 
Uncommon: may affect up to 1 in 100 people  
• Tremor 
• Slow heart rate 
• Sweating 
• Irregular heart beat 
• Diarrhoea  
• Dry mouth 
• Rapid breathing 
 
Very rare: may affect up to 1 in 10,000 people  
• Allergic reactions such as swelling of the face, mouth, lips or throat, allergic shock  
• Life-threatening irregular heartbeat, heart attack 
• Build-up of fluid in the lungs 
• Skin problems such as itching, rash, redness, swelling, severe flaking or peeling of the skin. 
 
Reporting of side effects 
 
If you get any side effects, talk to your doctor, pharmacist or nurse.  This includes any possible side 
effects not listed in this leaflet.  You can also report side effects directly via the national reporting 
system listed in Appendix V.  By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Nyxoid 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton, blister pack and the label 
after EXP.  The expiry date refers to the last day of that month.  
 
Do not freeze. 
 
Do not throw away any medicines via wastewater or household waste.  Ask your pharmacist how to 
dispose of medicines no longer required.  These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Nyxoid contains 
 
- The active substance is naloxone. Each nasal spray contains 1.8 mg of naloxone (as 

hydrochloride dihydrate). 
- The other ingredients are trisodium citrate dihydrate, sodium chloride, hydrochloric acid, 

sodium hydroxide and purified water.  



27 

 
What Nyxoid looks like and contents of the pack 
 
This medicine contains naloxone in 0.1 ml of a clear, colourless to pale yellow solution in a pre-filled 
nasal spray, solution in a single dose container.  
 
Nyxoid is packed in a carton containing 2 nasal sprays individually sealed in blisters.  Each nasal 
spray contains one single dose of naloxone.  
 
Marketing Authorisation Holder:  
Mundipharma Corporation (Ireland) Limited 
Millbank House 
Arkle Road 
Sandyford Industrial Estate 
Dublin 18 
Ireland  
 
Manufacturer: 
Bard Pharmaceuticals Limited 
Cambridge Science Park 
Milton Road 
Cambridge 
CB4 0GW 
United Kingdom 
 
Mundipharma DC B.V. 
Leusderend 16 
3832 RC Leusden 
Netherlands 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Mundipharma Comm. VA 
+32 15 45 11 80 
info@mundipharma.be 
  

Lietuva 
Mundipharma Corporation (Ireland) Limited 
Airija 
Tel +353 1 206 3800 
 

България 
ТП„Мундифарма медикъл ООД“ 
Тел.: + 359 2 962 13 56 
e-mail: mundipharma@mundipharma.bg 
 

Luxembourg/Luxemburg 
Mundipharma Comm. VA 
+32 15 45 11 80 
info@mundipharma.be 
 

Česká republika 
Mundipharma GesmbH. Austria - organizační 
složka  
Tel: + 420 222 318 221 
E-Mail: office@mundipharma.cz 
 

Magyarország 
Medis Hungary Kft 
Tel: +36 23 801 028 
info@medis.hu 
 

Danmark 
Mundipharma A/S 
Tlf. 45 17 48 00 
mundipharma@mundipharma.dk 
 

Malta 
Mundipharma Corporation (Ireland) Limited 
L-Irlanda 
Tel +353 1 206 3800 



28 

Deutschland 
Mundipharma GmbH 
Gebührenfreie Info-Line: +49 69 506029-000 
info@mundipharma.de 
 

Nederland 
Mundipharma Pharmaceuticals B.V. 
Tel: + 31 (0)33 450 82 70 
info@mundipharma.nl 
 

Eesti 
Mundipharma Corporation (Ireland) Limited 
L-Irlanda 
Tel +353 1 206 3800 

Norge 
Mundipharma AS 
Tlf: + 47 67 51 89 00 
post@mundipharma.no 
 

Ελλάδα 
Mundipharma Corporation (Ireland) Limited 
Ιρλανδία 
Tel +353 1 206 3800 

Österreich 
Mundipharma Gesellschaft m.b.H. 
Tel: +43 (0)1 523 25 05-0 
info@mundipharma.at 
 

España 
Mundipharma Pharmaceuticals, S.L.  
Tel: +34 91 3821870 
infomed@mundipharma.es 
 

Polska 
Mundipharma Polska Sp. z o.o. 
Tel: + (48 22) 866 87 12 
biuro@mundipharma.pl  
 

France 
MUNDIPHARMA SAS 
+33 1 40 65 29 29 
infomed@mundipharma.fr 
 

Portugal 
Mundipharma Farmacêutica Lda 
Tel: +351 21 901 31 62 
med.info@mundipharma.pt 
 

Hrvatska 
Medis Adria d.o.o. 
Tel: + 385 (0) 1 230 34 46 
info@medisadria.hr 
 

România 
Mundipharma Gesellschaft m.b.H., Austria 
Tel: +40751 121 222 
office@mundipharma.ro 
 

Ireland 
Mundipharma Pharmaceuticals Limited 
Tel +353 1 206 3800 
 

Slovenija 
Medis, d.o.o. 
Tel: +386 158969 00 
info@medis.si 
 

Ísland 
Icepharma hf. 
Tlf: + 354 540 8000 
icepharma@icepharma.is 
 

Slovenská republika 
Mundipharma Ges.m.b.H.-o.z. 
Tel: + 4212 6381 1611 
mundipharma@mundipharma.sk 
 

Italia 
Mundipharma Pharmaceuticals Srl 
Tel: +39 02 3182881 
infomedica@mundipharma.it 
 

Suomi/Finland 
Mundipharma Oy 
Puh/Tel: + 358 (0)9 8520 2065 
info@mundipharma.fi 
 

Κύπρος 
Mundipharma Pharmaceuticals Ltd 
Τηλ.: +357 22 815656 
info@mundipharma.com.cy 

Sverige 
Mundipharma AB 
Tel: + 46 (0)31 773 75 30 
info@mundipharma.se 
 

Latvija 
SIA Inovatīvo biomedicīnas tehnoloģiju institūts  
Tel: + 37167800810 
anita@ibti.lv 
 

United Kingdom 
Napp Pharmaceuticals Limited 
Tel: +44(0) 1223 424444 
 

 



29 

This leaflet was last revised in. 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu  
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION 
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET