Instanyl 200 micrograms / dose Guard nasal spray – patient leaflet, side effects, dosage

1. What Instanyl is and what it is used for

Instanyl contains the active substance fentanyl and belongs to a group of strong painkillers called opioids. Opioids act by blocking the pain signals to the brain.

Instanyl acts rapidly and is used for relieving breakthrough pain in adult cancer patients already treated with opioids for their usual pain. Breakthrough pain is an additional sudden pain that occurs despite you having taken your usual opioid pain relieving medicines.

2. What you need to know before you use Instanyl

Do not use Instanyl

• if you are allergic to fentanyl or any of the other ingredients of this medicine (listed in section 6).
• if you are not regularly using a prescribed opioid medicine (e.g codeine, fentanyl, hydromorphone, morphine, oxycodone, pethidine), every day on a regular schedule, for at least a week, to control your persistent pain. If you have not been using these medicines you must not use Instanyl, because it may increase the risk that breathing could become dangerously slow and/or shallow, or even stop.
• If you are taking a medicine which contains sodium oxybate.
• if you suffer from short-term pain other than breakthrough pain.
• if you have serious difficulties breathing or suffer from a serious obstructive lung disease.
• if you have previously received facial radiotherapy.
• if you suffer from recurrent episodes of nose bleeding.

Warnings and precautions

Store this medicine in a safe and secure place, where other people cannot access it (see section 5. How to store Instanyl for more information).

Talk to your doctor or pharmacist before using Instanyl, especially:

• if you suffer from a long-term obstructive lung disease, your breathing may be impaired by

  Instanyl.

• if you have problems with your heart especially slow heart rate, low blood pressure or low blood volume.
• if you have problems with your liver or kidneys.
• if you have problems with your brain function, e.g. due to a brain tumour, a head injury or increased intracranial pressure.

• if you have ever developed adrenal insufficiency or lack of sex hormones (androgen deficiency)

  with opioid use.

• if you take sedative medicines such as benzodiazepines or related drugs (please also refer to the section ‘Other medicines and Instanyl’).
• if you take antidepressants or antipsychotics (please also refer to the section ‘Other medicines and Instanyl’).
• if you take medicines called partial agonist/antagonists e.g. buprenorphine, nalbuphine and pentazocine (medicines for treatment of pain) as you may experience symptoms of withdrawal syndrome. Please refer to the section ‘Other medicines and Instanyl’ for more information.
• if you use other nasal spray products, e.g. for common cold or allergy.

Sleep-related breathing disorders

Instanyl can cause sleep-related breathing disorders such as sleep apnoea (breathing pauses during sleep) and sleep related hypoxemia (low oxygen level in the blood). The symptoms can include breathing pauses during sleep, night awakening due to shortness of breath, difficulties to maintain sleep or excessive drowsiness during the day. If you or another person observe these symptoms, contact your doctor. A dose reduction may be considered by your doctor.

If you experience difficulties breathing while being treated with Instanyl, it is very important that you contact your doctor or hospital immediately.

Consult your doctor while using Instanyl, if:

Long-term use and tolerance

This medicine contains fentanyl which is an opioid medicine. Repeated use of opioid painkillers can result in the drug being less effective (you become accustomed to it, known as drug tolerance). You may also become more sensitive to pain while using Instanyl. This is known as hyperalgesia. Increasing the dose of Instanyl may help to further reduce your pain for a while, but it may also be harmful. If you notice that your medicine becomes less effective, talk to your doctor. Your doctor will decide whether it is better for you to increase the dose or to gradually decrease your use of Instanyl.

Dependence and addiction

Repeated use of Instanyl can also lead to dependence, abuse and addiction which may result in life-threatening overdose. The risk of these side effects can increase with a higher dose and longer duration of use. Dependence or addiction can make you feel that you are no longer in control of how much medicine you need to use or how often you need to use it. You might feel that you need to carry on using your medicine, even when it doesn’t help to relieve your pain.

The risk of becoming dependent or addicted varies from person to person. You may have a greater risk of becoming dependent or addicted on Instanyl if:

• you or anyone in your family have ever abused or been dependent on alcohol, prescription medicines or illegal drugs (“addiction”).
• you are a smoker.
• you have ever had problems with your mood (depression, anxiety or a personality disorder) or have been treated by a psychiatrist for other mental illness.

If you notice any of the following signs whilst using Instanyl, it could be a sign that you have become dependent or addicted.

• you need to use the medicine for longer than advised by your doctor
• you need to use more than the recommended dose

• you are using the medicine for reasons other than prescribed, for instance, ‘to stay calm’ or

  ‘help you sleep’

• you have made repeated, unsuccessful attempts to quit or control the use of the medicine
• when you stop taking the medicine you feel unwell (e.g. nausea, vomiting, diarrhoea, anxiety, chills, tremor, and sweating), and you feel better once using the medicine again (‘withdrawal effects’)

If you notice any of these signs, speak to your doctor to discuss the best treatment pathway for you, including when it is appropriate to stop and how to stop safely.

• you experience pain or increased sensitivity to pain (hyperalgesia) which does not respond to a higher dosage of your medicine as prescribed by your doctor.
• you experience a combination of the following symptoms: nausea, vomiting, anorexia, fatigue, weakness, dizziness and low blood pressure. Together these symptoms may be a sign of a potentially life-threatening condition called adrenal insufficiency, a condition in which the adrenal glands do not produce enough hormones.

If you experience recurrent nose bleeding or nasal discomfort whilst being treated with Instanyl, you must contact your doctor, who will consider alternative treatment for your breakthrough pain.

Children and adolescents

Instanyl should not be used in children and adolescents under 18 years of age.

Other medicines and Instanyl

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

Instanyl may affect or be affected by other medicines.

Special care should be taken if you are treated with any of the following medicines:

• other medicines for pain and some painkillers for nerve pain (such as gabapentin and pregabalin).

• any medicines which might normally make you sleepy (have a sedative effect) such as sleeping pills, sedative medicines such as benzodiazepines or related medicines, medicines to treat anxiety, antihistamines, or tranquillisers, skeletal muscle relaxants and gabapentinoids (gabapentin and pregabalin). The use of such other medicines at the same time as Instanyl, may cause risk of drowsiness, deep sedation and affect your ability to breathe (respiratory depression), which may lead to coma and may be life-threatening. Because of this, concomitant use should only be considered when other treatment options are not possible. However if your doctor does prescribe Instanyl together with sedative medicines the dose and duration of concomitant treatment should be limited by your doctor.

  Please tell your doctor about all sedative medicines you are taking, and follow your doctor’s dose recommendation closely. It could be helpful to inform friends or relatives to be aware of the signs and symptoms stated above. Contact your doctor when experiencing such symptoms.

• any medicines that might have an effect on the way in which your body breaks down Instanyl, such as:

  • ritonavir, nelfinavir, amprenavir, and fosamprenavir (medicines that help control HIV infection);
  • CYP3A4 inhibitors such as ketoconazole, itraconazole, or fluconazole (used for treatment of fungal infections);
  • troleandomycin, clarithromycin, or erythromycin (medicines for treatment of bacterial infections);
  • aprepitant (used to treat severe nausea);
  • diltiazem and verapamil (medicines for treatment of high blood pressure or heart diseases).
• medicines called Monoamine Oxidase Inhibitors (MAOI) used for severe depression, even if you have been treated with one in the past 2 weeks.
• The risk of side effects increases if you are taking medicines such as certain antidepressants or antipsychotics. Instanyl may interact with these medicines and you may experience mental status changes (e.g. agitation, hallucinations, coma), and other effects such as body temperature above 38 °C, increase in heart rate, unstable blood pressure, and exaggeration of reflexes, muscular rigidity, lack of coordination and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea). Your doctor will tell you whether Instanyl is suitable for you.

• medicines called partial agonist/antagonists e.g. buprenorphine, nalbuphine and pentazocine

  (medicines for treatment of pain). You could experience symptoms of withdrawal syndrome (nausea, vomiting, diarrhoea, anxiety, chills, tremor, and sweating).

• Other medicines taken via the nose, especially oxymetazoline, xylometazoline and similar medicines, which are used for relief of nose congestions.

Instanyl with food, drink and alcohol

Do not drink alcohol whilst being treated with Instanyl, as it can increase the risk of experiencing dangerous side effects.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby ask your doctor or pharmacist for advice before taking any medicine.

Instanyl should not be used during pregnancy unless you have discussed this with your doctor.

Instanyl should not be used during childbirth because fentanyl may cause serious breathing problems in the new-born child.

Fentanyl can get into breast milk and may cause side effects in the breast-fed infant. Do not use Instanyl if you are breast-feeding. You should not start breast-feeding until at least 5 days after the last dose of Instanyl.

Driving and using machines

You should not drive or use machinery whilst being treated with Instanyl. Instanyl can cause dizziness, drowsiness and visual disturbances, which may affect your ability to drive or use machines.

3. How to use Instanyl

Before starting treatment and regularly during treatment, your doctor will also discuss with you what you may expect from using Instanyl, when and how long you need to take it, when to contact your doctor, and when you need to stop it (see also section 2).

Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

The dose of Instanyl is independent of your usual cancer pain treatment.

When you first start using Instanyl, your doctor will work with you to find the dose that will relieve your breakthrough pain.

The initial dose is one puff of 50 micrograms in one nostril each time you have an episode of breakthrough pain. During the determination of your right dose, your doctor may instruct you to change to a higher dose.

If your breakthrough pain is not relieved after 10 minutes, you may use only one puff more for this episode.

Generally you should wait 4 hours before treating another episode of breakthrough pain. On exceptional occasions where a new episode occurs earlier, you can use Instanyl to treat it but you must wait at least 2 hours before doing so. If you regularly have breakthrough pain episodes that are less than 4 hours apart, contact your doctor as your usual cancer pain treatment may have to be changed.

You can use Instanyl to treat up to four episodes of breakthrough pain per day.

If you experience more than four episodes of breakthrough pain per day, contact your doctor, as your usual cancer pain treatment may have to be changed.

Do not change the dose of Instanyl or your other pain medicines on your own. Change in dose must be done together with your doctor.

Instanyl incorporates an electronic dose counter, and a lock out period between doses to reduce the risk of overdose, and helps you to use it adequately. The dose counter enables you, and your doctor, to monitor and adapt your use. After two doses are taken within 60 minutes, Instanyl will lock for a period of 2 hours, from the first dose taken, until another dose can be administered.

Instanyl is for nasal use.

Please read the instructions for use on the back of this leaflet to learn how to use the nasal spray.

If you use more Instanyl than you should or if you think someone has accidentally used Instanyl

You should contact your doctor, hospital or emergency room for assessment of the risk and for advice if you have taken more Instanyl than you should.

Symptoms of overdose are:

Sleepiness, drowiness, dizziness, reduced body temperature, slow heart beat, difficulties coordinating arms and legs.

In serious cases taking too much Instanyl may cause coma, sedation, convulsions or severe breathing difficulties (very slow or shallow breathing). An overdose may also result in a brain disorder known as toxic leukoencephalopathy.

If you feel any of the above symptoms you should seek immediate medical assistance.

Note to carers

If you see the person taking Instanyl suddenly acting slowly, having difficulties breathing or if you have difficulties waking the person up:

• you should immediately call for emergency help.
• while waiting for the emergency help, you must try to keep the person awake by talking to or gently shaking the person every now and then.

• if the person has difficulty breathing, you should prompt the person to breathe in every

  5-10 seconds.

• if the person has stopped breathing, you should attempt to resuscitate her/him until emergency help arrives.

If you think someone has accidentally taken Instanyl, please seek immediate medical assistance. Try to keep the person awake until emergency help arrives.

If someone has accidentally taken Instanyl, they may have the same symptoms as described above for overdose.

If you forget to use Instanyl

If the breakthrough pain is still ongoing, you may take Instanyl as prescribed by your doctor. If the breakthrough pain has stopped, do not take Instanyl until the next episode of breakthrough pain occurs.

If you stop using Instanyl

You should discontinue Instanyl when you no longer have any breakthrough pain. You should however continue to take your usual pain relieving medicine to treat your cancer pain. Contact your doctor to confirm the correct dose of your usual medicine if you are not sure. You may experience withdrawal symptoms similar to the possible side effects of Instanyl when discontinuing Instanyl. If you experience withdrawal symptoms, you should contact your doctor. Your doctor will evaluate if you need medicine to reduce or eliminate the withdrawal symptoms.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The side effects will often stop or reduce in intensity with continued use of the product.

Discontinue the treatment and contact your doctor, hospital or emergency room immediately, if you:

• experience sudden, severe allergic reaction with breathing difficulty, swelling, lightheadedness, fast heartbeat, sweating or loss of consciousness.
• experience severe breathing difficulties.
• have a rattling sound when you breathe in.
• have convulsive pain.
• experience extreme dizziness.

These side effects can be very serious.

Other side effects reported after use of Instanyl:

Common (may affect up to 1 in 10 people):

Sleepiness, dizziness even with difficulties keeping balance, headache, irritation of the throat, nausea, vomiting, flushing, feeling very warm, excessive sweating.

Uncommon (may affect up to 1 in 100 people):

Sleeplessness, drowsiness, convulsive muscle contractions, abnormal sensation of the skin even unpleasant, change of taste, motion sickness, low blood pressure, severe breathing problems, nose bleeds, nasal ulcer, runny nose, constipation, inflammation of the mouth, dry mouth, skin pain, itching of the skin, fever.

Not known (frequency cannot be estimated from the available data):

Allergic reaction, fall, diarrhoea, convulsions (fits), loss of consciousness, swelling of arms or legs, seeing or hearing things that are not really there (hallucinations), delirium (symptoms may include a combination of agitation, restlessness, disorientation, confusion, fear, seeing or hearing things that are not really there, sleep disturbance, nightmares), drug tolerance, drug dependence (addiction), drug abuse (see section 2), fatigue, malaise, withdrawal syndrome (may manifest by the occurrence of the following side effects nausea, vomiting, diarrhoea, anxiety, chills, tremor, and sweating), shortness of breath.

There have also been reports of patients developing a hole in the septum of the nose – the structure, which separates the nostrils.

Prolonged treatment with fentanyl during pregnancy may cause withdrawal symptoms in the newborn which can be life-threatening (see section 2)

You should tell your doctor if you experience recurrent episodes of nose bleeding or nasal discomfort.

Reporting of side effects

If you get any side effects talk to your doctor. This includes any side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Instanyl

The pain-relieving medicine in Instanyl is very strong and can be life-threatening to children. Instanyl must be kept out of the sight and reach of children. Always close after use by putting the child-resistant cap back on to the nasal spray.

Store this medicine in a safe and secure place, where other people cannot access it. It can cause serious harm and be fatal to people who may take this medicine by accident, or intentionally when it has not been prescribed for them.

Do not use Instanyl after the expiry date which is stated on the nasal spray after EXP. The expiry date refers to the last day of the month.

Store below 30 °C. Keep the nasal spray stored upright. Do not freeze. If Instanyl nasal spray is frozen the spray pump may crack. If uncertain of how the pump has been stored, you should check the spray pump before use.

Instanyl that has passed the expiry date or is no longer required, may still contain enough medicine to be harmful to other people, especially children.

This instrument is labelled in accordance with the EU Waste Electrical and Electronic Equipment Directive (WEEE). Do not throw away any medicines via wastewater or household waste. Any used or unused nasal spray should be returned to the pharmacy or disposed according to other local requirements. Ask your pharmacist how to dispose of medicines you no longer use. These measures will help to protect the environment.

6. Contents of the pack and other information

What Instanyl contains

The active substance is fentanyl. The content is:

50 micrograms/dose: 1 ml contains fentanyl citrate equivalent to 500 micrograms fentanyl. 1 puff (100 microlitres) contains 50 micrograms fentanyl.

100 micrograms/dose: 1 ml contains fentanyl citrate equivalent to 1,000 micrograms fentanyl. 1 puff (100 microlitres) contains 100 micrograms fentanyl.

200 micrograms/dose: 1 ml contains fentanyl citrate equivalent to 2,000 micrograms fentanyl. 1 puff (100 microlitres) contains 200 micrograms fentanyl.

The other ingredients are sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, and purified water.

What Instanyl looks like and contents of the pack

Instanyl DoseGuard is a nasal spray, solution. The solution is clear and colourless. It is contained in a nasal spray with a metering pump, an electronic display, a dose counter, an in-built lock-out mechanism and a child-resistant cap.

The nasal spray comes in three different pack sizes: 3.2 ml (equal to 20 doses), 4.3 ml (equal to 30 doses) and 5.3 ml (equal to 40 doses).

Not all pack sizes may be marketed.

The labelling of the three Instanyl strengths is differentiated by colour:

50 micrograms/dose labelling is orange.

100 micrograms/dose labelling is purple. 200 micrograms/dose labelling is greenish-blue.

Marketing Authorisation Holder

Istituto Gentili S.r.l.

Via San Giuseppe Cottolengo 15

20143 Milan

Italy

Manufacturer

Curida AS

Solbærvegen 5

NO-2409 Elverum

Norway

This leaflet was last revised in September 2024.

INSTRUCTIONS FOR USE OF INSTANYL

Please read the following instructions carefully to learn how to use the Instanyl nasal spray.

Important information before use:

• Do not modify the device.
• Keep liquids from entering the device.

The Instanyl nasal spray has:

• A built-in lock-out which controls how often the nasal spray can be used
• A child-resistant cap, which must be put on the nasal spray, when the nasal spray is not used

• An electronic display which:

  • shows how many times to pump (prime) your product before using
  • shows the number of doses left
  • shows whether the nasal spray is locked or ready for use

How to remove and re-attach the child-resistant cap

Remove the child-resistant cap by pressing on both sides of the cap and then turn it counter clockwise and lift it off.

To re-attach the child-resistant cap, place it on the nasal spray tip and turn the cap clockwise. The child-resistant cap will click when re-attached.

Always put the child-resistant cap back on to the nasal spray after use.

Spray Tip

Spray Tip

Base/Pump

Unlocking White Button

Child-Resistant Cap

Electronic Display

Preparing the Instanyl nasal spray

Before using the nasal spray for the first time, it must be primed until the display shows the number of doses.

Instructions for priming the device are listed below (“Priming steps”).

Note: To pump, place 2 fingers on top of either side of the spray tip base and place thumb under the device, then squeeze.

Warning: During this priming process some medicine will be expelled. Therefore:

• Priming must be performed in a well ventilated area.
• Do not point the nasal spray in the direction of yourself or other people.
• Do not point the nasal spray in the direction of surfaces and objects that could come into contact with other people, particularly children.
• Do not inhale the medicine expelled during priming.

Priming steps:

1. 1. Press and release the white button on the side of the nasal spray. The display will now turn on and show ‘P5’.
2. 2. Hold the nasal spray upright and pump the nasal spray once in the air. The display now shows ‘P4’ and a lock symbol appears.
3. 3. When the lock symbol starts flashing, press and release the white side button again; the lock symbol will disappear in the display.
4. 4. Hold the nasal spray upright and pump the nasal spray in the air again. The display will now show ‘P3’ and the lock symbol.
5. 5. When the lock symbol starts flashing, press and release the white side button again; the lock symbol will disappear in the display.
6. 6. Hold the nasal spray upright and pump the nasal spray in the air again. The display will show ‘P2’ and lock the symbol.
7. 7. When the lock symbol starts flashing, press and release the white side button again; the lock symbol will disappear in the display.
8. 8. Hold the nasal spray upright and pump the nasal spray in the air again. The display will show ‘P1’ and lock the symbol.
9. 9. When the lock symbol starts flashing, press and release the white side button again; the lock symbol will disappear in the display.
10. 10. Hold the nasal spray upright and pump the nasal spray in the air again. The display will now changes to show the number of doses in the nasal spray (i.e. 20, 30 or 40 doses) and flashing lock symbol.

The nasal spray is now ready for use.

Note: Depending on your prescription, the starting number can be 20, 30 or 40.

Re-priming the Instanyl nasal spray (after 7 days or more)

If you have not used Instanyl for 7 days or more, the nasal spray must be primed again by pumping once before the next dose is taken. This will be indicated by a ‘P’ in the display.

Re-priming steps:

1. 1. Remove the cap.
2. 2. Press and release the white side button; the lock symbol will disappear in the display.
3. 3. The display will show a ‘P’ without the lock symbol, indicating that the device can be primed.
4. 4. Hold the nasal spray upright and pump the nasal spray once in the air.

Warning: During this priming process some medicine will be expelled. Therefore:

• Priming must be performed in a well ventilated area.
• Do not point the nasal spray in the direction of yourself or other people.
• Do not point the nasal spray in the direction of surfaces and objects that could come into contact with other people, particularly children.
• Once primed, the display shows the number of doses left and the nasal spray is ready for use again.

How to use Instanyl nasal spray

Explanation of the symbols in the electronic display

The nasal spray must be pumped 5 times (primed), before it can be used (see section ‘Preparing the Instanyl nasal spray’). The display counts downward after each pump (P5, P4, P3, P2 and P1). The nasal spray is ready, when the display shows the number of doses (i.e. 20, 30 or 40 doses).

When priming, please refer to the above safety warning instructions (see section above “Priming steps”).

The nasal spray has not been used for 7 days or more and must be primed again by pumping once in the air in a well-ventilated area before use (see below).

The ‘P’ symbol will disappear from the display when the nasal spray is primed again.

When re-priming, please refer to the above safety warning instructions (See section above “Re-priming steps”).

LOCK symbol

The nasal spray is locked and cannot be used.

When the locking period is over, the lock symbol will start flashing. The lock symbol will disappear from the display, when the white button on the side of the nasal spray is pressed; the nasal spray can now be used again when an episode of breakthrough pain occurs.

COUNTDOWN-CLOCK symbol

Shows how much time is left of the locking period.

The countdown-clock is counting downwards. Each black mark equals 10 minutes; the maximum locking period is 2 hours. It is recommended that you wait for 4 hours before treating the next episode of breakthrough pain. The COUNTDOWN-CLOCK symbol is displayed together with the LOCK-symbol.

The number of doses left in the nasal spray is shown. After each dose, the number is counting downwards on the display. Depending on the nasal spray, the starting number can be 20, 30 or 40.

BATTERY symbol

The battery life is about to run out. The number of doses in the display changes to 5. This is the approximate number of doses that can be delivered from the nasal spray, before the battery is too low and the display turns off. The battery cannot be replaced and you will need to contact your doctor or pharmacist to get a new nasal spray.

If you experience that the nasal spray does not work as described in the “Instructions for use” please contact your doctor or pharmacist.