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AYENDI 720MICROGRAM/ACTUATION NASAL SPRAY

Active substance(s): DIAMORPHINE HYDROCHLORIDE / DIAMORPHINE HYDROCHLORIDE / DIAMORPHINE HYDROCHLORIDE

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Package leaflet: Information for the user
Ayendi 1600 microgram/actuation Nasal Spray
Ayendi 720 microgram/actuation Nasal Spray
Diamorphine hydrochloride
(referred to as Ayendi Nasal Spray
throughout this leaflet)

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
or pharmacist.
- This medicine has been prescribed only for you.
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 or
pharmacist. This includes any possible side effects
not listed in this leaflet.
What is in this leaflet:
1. What Ayendi Nasal Spray is and what it is used for
2. What you need to know before you are given Ayendi
Nasal Spray
3. How you will be given Ayendi Nasal Spray
4. Possible side effects
5. How to store Ayendi Nasal Spray
6. Contents of the pack and other information
1. What Ayendi Nasal Spray is and what it is used
for
Ayendi Nasal Spray is used in hospital emergency
departments for the relief of severe pain caused by
accidental injury in children and teenagers between
2 and 15 years of age.
2. What you need to know before you are given
Ayendi Nasal Spray
You should not be given Ayendi Nasal Spray if you:
- are allergic to diamorphine hydrochloride or any of the
other ingredients of this medicine (listed in Section 6)
- have problems with your lungs or breathing such as
‘hypoventilation’ or Chronic Obstructive Pulmonary
Disorder (COPD)
- are having an asthma attack
- have been told you have a tumour of the adrenal
gland near your kidney called phaeochromocytoma
- have severe stomach cramps caused by a condition
known as biliary colic
- have increased pressure on the brain, have just had
a head injury or if you are unconscious
- are suffering from acute alcoholism
- are at risk of a blocked intestine
- are suffering from acute diarrhoea
Warnings and precautions
Talk to your doctor before you are given Ayendi Nasal
Spray if you:
- have a history of drug abuse
- have problems with your bile duct
- suffer from asthma (your doctor may decide to give
you Ayendi Nasal Spray if your asthma is controlled)
- are suffering from mental illness brought on by an
infection
- have reduced breathing or heart rate
- have an under-active thyroid or adrenal gland
- suffer from an enlarged prostrate gland (in men) or
have difficulty passing urine
- have a bowel disease such as Crohn’s disease or
ulcerative colitis
- have low blood pressure
- are in a severe state of shock
- suffer from fits (convulsions)
- are very run down
- have a blocked nose or a cold
- have liver or kidney disease.
There is a risk of spreading infections if a new nasal tip
is not used for each patient.
Other medicines and Ayendi Nasal Spray
Tell your doctor or nurse if you are taking, have recently
taken or might take any other medicines, including
medicines obtained without a prescription.
In particular tell your doctor or nurse if you are taking
any of the following:
- medicines given before an operation to help you sleep
- mexiletine, used to control heart rhythm
- monoamine oxidase inhibitors (MAOIs) such as
moclobemide or phenelzine used in the treatment of
depression. You must tell your doctor if you have
stopped taking these or related medicines in the last
two weeks
- tricyclic antidepressants, which are used in the
treatment of depression
- ritonavir, used to treat HIV (a viral infection)
- tranquillising drugs or sleeping tablets such as
diazepam, nitrazepam and temazepam
- medicines used to treat mental illness including
schizophrenia, such as chlorpromazine and haloperidol
- medicines used to treat diarrhoea such as
loperamide and kaolin
- medicines used before operations and after heart
attacks, such as atropine
- medicines used to treat feeling and being sick, such
as metoclopramide or domperidone, used to treat
stomach ulcers and indigestion
- Entonox, a medical anaesthesia gas.
Information for Healthcare Professionals
Ayendi 1600 microgram/actuation Nasal Spray
Ayendi 720 microgram/actuation Nasal Spray
Please refer to the Summary of Product Characteristics (SmPC)
for further details of this product.
Therapeutic Indications
For the treatment of acute severe nociceptive pain in children and
adolescents 2 to 15 years of age in a hospital setting. Ayendi
Nasal Spray should be administered in the emergency setting
by practitioners experienced in the administration of opioids in
children and with appropriate monitoring.
Posology and Method of Administration
The dose should not be repeated.
Posology
Patients should be dosed according to weight.
The 720microgram/actuation Nasal Spray is only suitable for
children weighing between 12kg and less than 30kg.
The 1600microgram/actuation Nasal Spray is only suitable for
children weighing between 30kg and 50kg.
Child
Weight
(kg)

Approx
Age
(years)

No of
Sprays

Dose
Diamorphine
HCl (mg)

720 microgram/actuation strength –
Children 12kg to less than 30kg
12 to <18
2-5
2
1.44
18 to <24
5-8
3
2.16
24 to <30
8-10
4
2.88
1600 microgram/actuation strength – Children 30kg up to 50kg
30 to <40
40 to 50

10-14
14-15

2
3

3.20
4.80

Method of administration
Ayendi nasal spray is intended for nasal use only.
A new tip should be used for any new patient to avoid risk of
microbial contamination and soiling of the tip.
Ensure that the dip tube remains in the solution during priming
and re-priming to avoid air entering the pump spray and affecting
dose uniformity.
The spray should be directed at the nasal side wall (lateral nasal
wall) rather than straight up the nose. It is recommended that the
patient sits in a semi-recumbent position at about 45 degrees
when the nasal spray is being administered.
Ayendi should be delivered using a total of 2 - 4 actuations of the
appropriate product strength directed into alternate nostrils and
according to the weight of the child.

Your doctor may stop you from using any other nasal
spray whilst you are being given Ayendi Nasal Spray.
Ayendi Nasal Spray with alcohol
You should not drink alcohol whilst being given Ayendi
Nasal Spray as it will increase its effects.
Pregnancy and breast-feeding
Ayendi Nasal Spray has not been tested in pregnant or
breast-feeding women. If you are given diamorphine
during labour there is a risk that you could be sick and
have breathing difficulties, or the baby could have
trouble starting breathing.
If you are pregnant or breast-feeding, or think you may
be pregnant or you are planning to have a baby, ask
your doctor for advice before being given this medicine.
Your doctor will decide if it is necessary for you to be
given Ayendi Nasal Spray. Ask your doctor for advice
before taking any medicine.
Driving and using machines
You may be drowsy and confused after being given Ayendi
Nasal Spray so you should not drive or operate machinery.
The medicine can affect your ability to drive as it may
make you sleepy or dizzy.
• Do not drive while taking this medicine until you know
how it affects you.
• It is an offence to drive if this medicine affects your
ability to drive.
• However, you would not be committing an offence if:
The medicine has been prescribed to treat a medical
° 
or dental problem and
You have taken it according to the instructions
° 
given by the prescriber or in the information provided
with the medicine and
° It was not affecting your ability to drive safely
Talk to your doctor or pharmacist if you are not sure
whether it is safe for you to drive while taking this medicine.
Important information about some of the
ingredients in Ayendi Nasal Spray
This medicine contains benzaklonium chloride which
may cause irritation of the skin inside the nose or
difficulty in breathing or wheezing.
3. How Ayendi Nasal Spray is given
The dose should not be repeated.
Ayendi is only intended for intranasal administration,
and must not be administered by any other route.
The 720microgram/actuation Nasal Spray is only suitable
for children weighing between 12kg and less than 30kg.
The 1600microgram/actuation Nasal Spray is only
suitable for children weighing between 30kg and 50kg.
The recommended dose is:
720mcg/ actuation for children 12kg to less than 30 kg
Weight of child


Approx
Age
(years)

Number
Total
of Sprays dose
delivered

12kg to <18kg

2-5

2

1.44mg

18kg to <24kg

5-8

3

2.16mg

24kg to <30kg

8-10

4

2.88mg

1600mcg/actuation for children 30kg to 50kg
Weight of child


Approx
Age
(years)

Number
Total
of Sprays dose
delivered

30kg to <40kg

10-14

2

3.20mg

40kg to 50kg

14-15

3

4.80mg

Method of administration
The spray should be directed at the nasal side wall
(lateral nasal wall) rather than straight up the nose. It is
recommended that the patient sits in a semi-recumbent
position at about 45 degrees when the nasal spray is
being administered.
Ayendi Nasal Spray should be delivered using a total
of 2 - 4 actuations of the appropriate product strength
directed into alternate nostrils and according to the
weight of the child. The maximum total dose is
2.88mg diamorphine hydrochloride (four actuations)
of the 720microgram/actuation product and
4.8mg diamorphine hydrochloride (three actuations)
of the 1600microgram/actuation product.
The patient should then be monitored for at least
30 minutes following administration.
Ensure that the dip tube remains in the solution during
priming and re-priming to avoid air entering the pump
spray and affecting dose uniformity.
A new tip should be used for any new patient to
avoid risk of microbial contamination and soiling
of the tip.
If you are given more Ayendi Nasal Spray than you
should
Possible symptoms seen if someone has been given
more diamorphine than they should include reduced rate
of breathing, coma, and pinpoint pupils along with other
symptoms; these may include cold, clammy skin, reduced
blood pressure, slow heart rate, bluish skin or lips,
limp muscles, severe weakness, severe nervousness
or restlessness, severe drowsiness, imagining things
(hallucinations), fits (convulsions) and a breakdown of
muscle fibre that could result in kidney failure.
The maximum total dose for the 720mcg product strength
is 2.88mg diamorphine hydrochloride (four actuations).
The maximum total dose for the 1600mcg product strength
is 4.8mg diamorphine hydrochloride (three actuations).
The patient should then be monitored for at least 30 minutes
following administration.
Preparation of solution
1. Flip off the plastic protective cap from the glass bottle.
2. Tear off the aluminium seal and pull out the rubber bung.
3. Twist off the seal from the plastic tube containing the liquid
and squeeze the contents into the glass bottle. Not all of the
liquid from the tube can be squeezed from the tube. This is to
be expected and calculations have been made to allow for the
amount of liquid left in the tube.
4. Push the nasal pump with the paediatric nasal tip attached
onto the glass bottle so that it snaps into place and remove the
green safety clip. Unopened packed nasal tips should be used
to avoid microbial cross-contamination.
5. Swirl gently until all the diamorphine powder is dissolved, this
should take approximately one minute with gentle movement of
the bottle. To avoid excessive foaming, do not vigorously shake
the bottle.
6. Prime the nasal spray by holding it upright and actuating eight
times in order to achieve the optimum spray before the first use.
Following this, each time the disposable paediatric tip is changed
(e.g. for each child) the pump must be primed a further two times
to ensure the correct dose is delivered. The product should be
primed into a sink. Replace the green safety clip before applying
a new tip to prevent accidental actuation.
7. Ensure that the dip tube remains in the solution during
priming and re-priming to avoid air entering the pump
spray and affecting dose uniformity. The bottle contains an
excess volume of solution to ensure that the dip tube remains
covered during priming and administration to ensure correct
functioning of the spray.
8. Write the date of reconstitution and the date for discarding on
the label of the bottle.

Measure bar should be 150mm at 100% scale

artwork.leicester@multipkg.com

Clearly mark any amendments on one proof and return to MPS

Warning! We cannot accept responsibility for any errors
in this proof after approval. Whilst we take extreme care
at all times to ensure accuracy to our clientʼs brief,
the final responsibility must be taken by our client.
IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING
FULL APPROVAL OF DESIGN AND TEXT.

Customer

Wockhardt UK Limited

Colours Used

Description

Ayendi common leaflet

Process Black

Item Code

105742/4

Profile

n-a

Size

420 x 148mm

Min. Point Size

6pt (Main Body) / 7pt (Variables)

Market

UK

Language

English

Proof By

chris.jenney

Proof No.

1

Date

10/08/2016

Artwork No.

678658

Keyline (non-printing)
Text free area (non-printing)

Pharma
Code

42

If you have been given more Ayendi Nasal Spray than
you should, your doctor will treat you according to your
symptoms. This may include help with your breathing
or blood flow. The medicine naloxone may be given to
you to reverse the effects of diamorphine.
If you have any further questions on the use of this
medicine, ask your doctor or nurse.
4. Possible side effects
Like all medicines, Ayendi Nasal Spray can cause side
effects, although not everybody gets them.
The frequencies are defined as:
Very common (affects more than 1 patient in 10)
Common (affects 1 to 10 patients in 100)
Uncommon (affects 1 to 10 patients in 1,000)
Rare (affects 1 to 10 patients in 10,000)
Very rare (affects less than 1 patient in 10,000)
Not known (frequency cannot be estimated from the
available data).
Difficulty in breathing and physical and psychological
dependence are possible serious side effects.
Side effects that are common include:
- drowsiness
- feeling or being sick
- constipation
- sweating.
Apart from constipation, these side effects tend to
disappear with time.
The following side effects have been reported in
clinical trials where children age 2 to 16 years were
given Ayendi Nasal Spray:
Very common:
- sore nose
Common:
- dizziness
- change in the sense of taste
- sneezing
- nose bleeds
- inflammation of the larynx (laryngitis)
- feeling or being sick
- itching of the skin
- pain caused by use of the nasal pump
Uncommon:
- feeling anxious
- feeling tired or sleepy
- numbness or tingling of the inside of the mouth
- drowsiness
- feeling nervous
- headache
- itchy eyes
- inflammation of the surface of the eyes
- paleness of the skin
- a decrease in the normal level of oxygen in the blood
- hiccups
- problems with the lining of the nose
- runny nose
- pain in the abdomen
- vomiting blood
- fever
- feeling hot
- dry mouth
- shallow breathing
Other side effects of diamorphine include the
following:
Uncommon:
- dizziness
- feeling faint on standing up
- small pupils (in the eye)
- blurred vision
- double vision or other changes in vision
- mental clouding or confusion
- mood changes
- feeling extremely happy for no particular reason
- imagining things (hallucinations)
- headache
- vertigo
- facial flushing
- dry mouth
- difficulty or pain in passing urine
- passing less urine than usual
- biliary spasm (causing pain in the right side of your
abdomen, particularly after eating a meal, which may
spread towards your right shoulder)
- palpitations
- slower or faster pulse
- skin rash, wheals or itching
- reduced sexual drive or impotence after long term use
- if diamorphine is given for a long time it is possible that
you may become dependent on it and have withdrawal
symptoms if it is stopped suddenly.
Rare:
- intravenous injection (injection into a vein) may cause
a severe allergic reaction.
If you get any side effects, talk to your doctor. This includes
any possible side effects not listed in this leaflet.
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 Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard
By reporting side effects you can help provide more
information on the safety of this medicine.

5. How to store Ayendi Nasal Spray
Keep this medicine out of the sight and reach of children.
The medicine should not be used after the expiry date
which is stated on the carton and label after ‘EXP’.
The expiry date refers to the last day of that month.
Do not use this medicine if the powder, liquid or
prepared solution show signs of discolouration.
Before reconstitution: The nasal diamorphine
hydrochloride should be stored below 25°C in the
original outer carton (containing all components of the
nasal spray) to protect from light.
After reconstitution: The nasal solution should be stored
below 25°C in the original carton to protect from light
and used within two weeks or discarded.
Medicines should not be disposed of via wastewater
or household waste. Your doctor will dispose of this
medicine appropriately.
6. Contents of the pack and other information
What Ayendi Nasal Spray contains
- The active substance is diamorphine hydrochloride.
There are two strengths of spray available. One strength
gives a 50 microlitre spray containing 1600 microgram
of diamorphine. The other gives a 50 microlitre spray
containing 720 microgram of diamorphine.
- The other ingredients in the spray are benzalkonium
chloride solution (50% w/v), disodium edetate, sodium
chloride, hydrochloric acid (pH adjuster), sodium
hydroxide (pH adjuster) and Purified water.
What Ayendi Nasal Spray looks like and contents of
the pack
Nasal spray, powder for solution
Clear Type 1 neutral glass bottle (8ml or 17ml) with a
dark grey rubber (bromobutyl) stopper and an aluminium
overseal with a white (720mcg) or green (1600mcg) flip
off-tear off seal.
Diluent for Reconstitution
Squeezable, medium density polyethylene (MDPE) tube
with a high density polyethylene (HDPE) neck and a
twist-off top, containing 5ml of diluent for the 8ml product
and 10ml of diluent for the 17ml product.
Nasal Spray, solution
Clear Type 1 neutral glass bottle (8ml or 17ml) with a
nasal spray pump. Pack includes 9 disposable white
polypropylene nasal tips. The replacement tips are
provided in individual tamper evident packs. Unopened
packed nasal tips should be used to avoid microbial
cross-contamination.
Each 8ml bottle of Nasal Spray, solution, contains
68 metered dose sprays. Each 17ml bottle of Nasal
Spray, solution contains 160 metered dose sprays, plus
a residual excess to ensure the correct functioning of
the pump spray. Each metered spray is 50 microlitres.
The spray will be a clear, colourless to pale straw
coloured solution in a nasal spray.
The spray will have been prepared before it is given to you.
Marketing Authorisation Holder
Wockhardt UK Limited, Ash Road North, Wrexham
LL13 9UF, United Kingdom.
Manufacturer
CP Pharmaceuticals Limited, Ash Road North,
Wrexham LL13 9UF, United Kingdom.
Other formats:
To listen to or request a copy of this leaflet in Braille,
large print or audio please call, free of charge:
0800 198 5000 (UK Only)
Please be ready to give the following information:
Product Name
Reference Number
Ayendi 720 microgram/
PL 29831/0465
actuation Nasal Spray
Ayendi 1600 microgram/ PL 29831/0466
actuation Nasal Spray
This is a service provided by the Royal National Institute
of Blind People.
This leaflet was last revised in 08/2016.

105742/4
Special warnings and precautions for use specific to Ayendi Nasal
Spray
Ayendi contains benzalkonium chloride which may cause irritation
of the nasal mucosa.
Concomitant use of Ayendi and other medicinal products
administered via the nose has not been evaluated in the clinical
trials. It is recommended that alternative administration forms
should be considered for concomitant treatment of concurrent
diseases that can be treated via nasal administration.
No clinical data is available on the efficacy of this product in
children suffering from rhinitis or the common cold.
Pharmacodynamic properties
Diamorphine is a narcotic analgesic which acts primarily on the
central nervous system and smooth muscle. It is predominantly
a central nervous system depressant but it has stimulant actions
resulting in nausea, vomiting and miosis.
In a multicentre, randomised, single blind, parallel group,
controlled trial to compare the effectiveness of nasal diamorphine
with intramuscular morphine for analgesia in children and
teenagers aged between three and 16 years with acute pain due
to a clinical fracture, onset of pain relief was faster in the spray
group than in the intramuscular group.
Pharmacokinetic properties
Diamorphine is a potent opiate analgesic which has a more
rapid onset of activity than morphine as the first metabolite,
monoacetylmorphine, more readily crosses the blood brain barrier.
Diamorphine is essentially a pro-drug for the active metabolites
morphine and morphine-6- glucuronide (see metabolism below).
Following single dose administration of 0.06mg/kg diamorphine
intranasal in children, mean peak plasma concentrations of
morphine was estimated as 14.0 ng/ml with a median Tmax of
22.1 minutes.
Pharmaceutical Particulars
Qualitative And Quantitative Composition
Each bottle contains diamorphine 144mg as diamorphine
hydrochloride (equivalent to 720microgram in each 50microlitre
spray following reconstitution).
Each bottle contains diamorphine 320mg as diamorphine
hydrochloride (equivalent to 1600microgram in each 50microlitre
spray following reconstitution).
When reconstituted the spray contains 0.02% benzalkonium chloride.
For a full list of excipients, see List of Excipients below.
Pharmaceutical Form
Powder and diluent for reconstitution for nasal spray, solution
After reconstitution
Nasal spray, solution
A clear, colourless to pale straw coloured solution
Before reconstitution
Nasal spray, powder for solution
A white to off-white, freeze-dried powder.

Diluent for reconstitution
Clear, colourless 0.5%w/v preserved saline solution.
List of Excipients
Nasal spray, powder for solution
None
Diluent for reconstitution and Nasal spray, solution
Benzalkonium Chloride Solution (50% w/v), Disodium Edetate,
Sodium Chloride, Hydrochloric Acid (for pH adjustment),
Sodium Hydroxide (for pH adjustment), Purified water
Incompatibilities
None
Shelf life
Nasal spray, powder for solution and Diluent for reconstitution:
8ml vial - 36 months
17ml vial - 36 months
Nasal Spray, solution
2 weeks
Special precautions for storage
Nasal spray, powder for solution and Diluent for reconstitution:
Store below 25°C. Store in the original carton to protect from light.
Nasal Spray, solution
Store below 25°C. Store in the original carton to protect from light.
Nature and contents of container
Nasal spray, powder for solution
Clear Type 1 neutral glass bottle (8ml or 17ml) with a dark grey
rubber (bromobutyl) stopper and an aluminium overseal with a
white flip off-tear off seal. (720mcg) or a green flip off-tear off seal
(1600mcg).
Diluent for Reconstitution
Squeezable, medium density polyethylene (MDPE) tube with
a high density polyethylene (HDPE) neck and a twist-off top,
containing 5ml of diluent for the 8ml product and 10ml of diluent
for the 17ml product.
Nasal Spray, solution
Clear Type 1 neutral glass bottle (8ml or 17ml) with a nasal spray
pump. Pack includes 9 disposable white polypropylene nasal tips.
The replacement tips are provided in individual tamper evident
packs. Unopened packed nasal tips should be used to avoid
microbial cross-contamination. Additional replacement tips can
be ordered.
Each 8ml bottle of Nasal Spray, solution, contains 68 metered doses
and each 17ml bottle of Nasal Spray, solution, contains 160 metered
dose sprays. Each metered spray is 50 microlitres.
Special precautions for disposal
Any unused medicinal product or waste material should be disposed
of in accordance with local requirements and in a manner appropriate
for controlled drugs.

105742/4

Measure bar should be 150mm at 100% scale

artwork.leicester@multipkg.com

Clearly mark any amendments on one proof and return to MPS

Warning! We cannot accept responsibility for any errors
in this proof after approval. Whilst we take extreme care
at all times to ensure accuracy to our clientʼs brief,
the final responsibility must be taken by our client.
IF YOU SIGN THIS PROOF YOU ARE SIGNIFYING
FULL APPROVAL OF DESIGN AND TEXT.

Customer

Wockhardt UK Limited

Colours Used

Description

Ayendi common leaflet

Process Black

Item Code

105742/4

Profile

n-a

Size

420 x 148mm

Min. Point Size

6pt (Main Body) / 7pt (Variables)

Market

UK

Language

English

Proof By

chris.jenney

Proof No.

1

Date

10/08/2016

Artwork No.

678658

Keyline (non-printing)
Text free area (non-printing)

Pharma
Code

42

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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