AYENDI 1600MICROGRAMS / ACTUATION NASAL SPRAY - patient leaflet, side effects, dosage

Patient leaflet - AYENDI 1600MICROGRAMS / ACTUATION NASAL SPRAY

- 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.

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 of Sprays	Total 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 of Sprays	Total 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.

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	10–14	2	3.20
40 to 50	14–15	3	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.

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.

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.

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:

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 informationwhat 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/ actuation Nasal Spray	PL 29831/0465
Ayendi 1600 microgram/ actuation Nasal Spray	PL 29831/0466

This is a service provided by the Royal National Institute of Blind People.

This leaflet was last revised in 08/2016.

105742/4

Twockhardt

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