INSTANYL 100 micrograms/dose NASAL SPRAY SOLUTION

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 already using a prescribed opioid medicine every day for your persistent pain (e.g. codeine, fentanyl, hydromorphone, morphine, oxycodone, meperidine), as the risk of your breathing becoming too slow and/or too shallow, and even stopping, may increase. If you have not been using these medicines, do not use Instanyl;
• if you are taking a medicine that contains sodium oxybate;
• if you have short-term pain that is not breakthrough pain;
• if you have severe breathing difficulties or severe obstructive lung disease.
• if you have had previous radiotherapy to the head;
• if you have repeated episodes of nosebleeds.

Warnings and precautions

Keep this medicine out of the sight and reach of children and in a safe place to prevent accidental use (see section 5 Storing Instanyl for further information).

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

• if you have chronic obstructive lung disease, Instanyl may affect your breathing rhythm.
• if you have heart problems, especially slow heart rate, low blood pressure or low blood volume.
• if you have liver or kidney problems.
• if you have problems with your brain function, for example due to a brain tumour, head injury or increased pressure in the skull.
• if you have ever experienced adrenal insufficiency or a lack of sex hormones (androgen deficiency) when using opioids.
• if you are taking sedatives, such as benzodiazepines or related medicines (see also section “Using Instanyl with other medicines”).
• if you are taking antidepressants or antipsychotics (see also section “Using Instanyl with other medicines”).
• if you are taking medicines called partial agonist/antagonists, e.g. buprenorphine, nalbuphine and pentazocine (painkillers), as they may cause withdrawal symptoms. See section “Using Instanyl with other medicines” for more information.
• if you are using other nasal spray products, e.g. for the common cold or for allergy.

Sleep-related breathing disorders

Instanyl may cause sleep-related breathing disorders, including sleep apnoea (pauses in breathing while sleeping) and sleep hypoxemia (low oxygen levels in the blood). Symptoms may include pauses in breathing while sleeping, waking up in the middle of the night due to lack of breath, difficulty staying asleep or excessive sleepiness during the day. If you or someone else notices these symptoms, contact your doctor to consider reducing the dose.

It is very important that you contact your doctor immediately if you experience breathing difficulties while being treated with Instanyl.

Talk to your doctor if, while using Instanyl, you:

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

If you experience repeated nosebleeds or notice nasal discomfort during treatment with Instanyl, you should talk to your doctor, who will consider an alternative treatment for your breakthrough pain.

Long-term use and tolerance

This medicine contains fentanyl, an opioid. Repeated use of opioid painkillers can make the medicine less effective (your body gets used to it, which is known as pharmacological tolerance). You may also become more sensitive to pain when using Instanyl. This is known as hyperalgesia. Increasing the dose of Instanyl may continue to reduce the pain for a while, but it can also be harmful. If you notice that the medicine is becoming less effective, talk to your doctor. Your doctor will decide whether it is best for you to increase the dose or gradually reduce your use of Instanyl.

Dependence and addiction

Repeated use of Instanyl can also lead to dependence, abuse and addiction, which can result in a potentially life-threatening overdose. The risk of these side effects may be greater with higher doses and longer use. Dependence or addiction can lead to a loss of control over the amount of medicine you use or how often you use it. You may feel a need to keep using the medicine even if it no longer helps with the pain.

The risk of dependence or addiction varies from person to person. Your risk of becoming dependent on or addicted to Instanyl may be greater if:

• you or a family member have abused alcohol, prescription medicines or illegal drugs (‘addiction’).
• you smoke.
• you have previously had problems with your mood (depression, anxiety or personality disorder) or have received treatment from a psychiatrist for other mental health diseases.

If you notice any of the following symptoms while using Instanyl, it could be a sign of dependence or addiction.

• you need to use the medicine for longer than prescribed by your doctor.
• you need to use a higher dose than recommended.
• you are using the medicine for reasons other than those prescribed, e.g. ‘to feel calm’ or ‘to help you sleep’.
• you have repeatedly tried to stop or control your use of the medicine but failed.
• you feel unwell when you stop using the medicine (e.g. nausea, vomiting, diarrhoea, anxiety, shivering, shaking and sweating), and you feel better once you start using it again (‘withdrawal symptoms’).

If you notice any of these signs, talk to your doctor to determine the best course of treatment for you, when it is appropriate to stop the medicine and how to do it safely.

Children and adolescents

Instanyl must not be used in children and adolescents under 18 years.

Using Instanyl with other medicines

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines, including those obtained without a prescription.

Instanyl may affect or be affected by other medicines.

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

• Other painkillers and medicines for nerve pain, such as gabapentin and pregabalin.
• any medicine that makes you sleepy (has a sedative effect) such as sleeping pills, sedatives (e.g. benzodiazepines or related medicines), medicines for anxiety, antihistamines or tranquillisers, muscle relaxants and gabapentinoids (gabapentin and pregabalin). Using these medicines at the same time as Instanyl may cause drowsiness, deep sedation and affect your ability to breathe (respiratory depression), which can lead to coma or even death. Therefore, concomitant use should only be considered when no other treatment options are available.

However, if your doctor prescribes Instanyl and sedatives, you should limit both the dose and duration of concomitant treatment.

Tell your doctor about all sedatives you are taking and follow their dosing recommendations carefully. It may be helpful to inform your friends or family to be aware of the signs and symptoms mentioned above. Contact your doctor when you report such symptoms.

• any medicine that may change how your body breaks down Instanyl, such as:

• ritonavir, nelfinavir, amprenavir, and fosamprenavir (medicines that help control HIV infections);
• CYP3A4 inhibitors, such as ketoconazole, itraconazole, or fluconazole (used to treat fungal infections);
• troleandomycin, clarithromycin, or erythromycin (medicines for treating bacterial infections);
• aprepitant (used to treat severe nausea);
• diltiazem and verapamil (medicines for treating high blood pressure or heart disease).

• medicines called Monoamine Oxidase Inhibitors (MAOIs), used for severe depression, even if you have been treated with one of these in the last 2 weeks.
• the risk of side effects increases if you are taking certain antidepressants or antipsychotics. Instanyl may interact with these medicines and you may experience changes in mental status (e.g. agitation, hallucinations, coma) and other effects such as body temperature above 38°C, increased heart rate, unstable blood pressure and exaggerated reflexes, muscle stiffness, lack of coordination and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea). Your doctor will tell you if Instanyl is suitable for you.
• medicines called partial agonist/antagonists, e.g. buprenorphine, nalbuphine and pentazocine (painkillers). You may experience withdrawal symptoms (nausea, vomiting, diarrhoea, anxiety, shivering, shaking and sweating).
• other nasal spray medicines, especially oxymetazoline, xylometazoline and similar medicines, used for relieving nasal congestion.

Instanyl with food, drinks and alcohol

Do not drink alcohol while being treated with Instanyl, as it may increase the risk of serious 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 using any medicine.

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

Instanyl should not be used during labour, as fentanyl can cause serious breathing problems in the newborn.

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

Driving and using machines

You should not drive or use machines while being treated with Instanyl. Instanyl can cause dizziness, drowsiness and changes in vision, 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 explain what you can expect from using Instanyl, when and for how long you should use it, when you should contact your doctor and when you should stop using it (see also section 2).

Follow the instructions for administration of this medicine exactly as your doctor has told you. If you are unsure, ask your doctor or pharmacist.

The dose of Instanyl is separate from your background treatment for cancer pain.

When you start using Instanyl, your doctor will determine with you the dose that relieves your breakthrough pain.

The initial dose is one spray of 50 micrograms into one nostril each time you have a breakthrough pain episode. During the titration of your effective dose, your doctor may instruct you to switch to a higher dose.

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

In general, you should wait 4 hours before treating another episode of breakthrough pain. In exceptional cases, when a new episode occurs before 4 hours, you can use Instanyl to treat this episode, but you should wait at least 2 hours before doing so. If you regularly experience episodes of breakthrough pain separated by less than 4 hours, contact your doctor, as your regular cancer pain treatment may need to be changed.

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

Contact your doctor if you experience more than four episodes of breakthrough pain per day, as your background treatment for cancer pain may need to be changed.

Do not change the dose of Instanyl or your other painkillers yourself. Changes in dose should be made with your doctor.

Instanyl has a dose counter and a time lock between doses to reduce the risk of overdose and help you use it correctly. The dose counter allows you and your doctor to monitor and adjust your use. After two doses have been taken within 60 minutes, Instanyl will be locked for a period of 2 hours, starting from the first dose, until another dose can be dispensed.

Instanyl is for nasal use.

You should read the instructions on how to use the nasal spray that are on the back of this leaflet to learn how to use it.

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

If you have used more Instanyl than you should, contact your doctor, hospital or emergency service to assess the risk and advise on what to do.

The symptoms of overdose are:

Drowsiness, lethargy, dizziness, decreased body temperature, decreased heart rate, difficulties with coordination of arms and legs.

In severe cases, symptoms of overdose with Instanyl may include coma, sedation, convulsions or severe breathing difficulties (very slow or shallow breathing). An overdose can also cause a brain disorder known as toxic leucoencephalopathy.

If you notice any of these symptoms, you should seek medical help immediately.

Note for persons taking care of the patient:

If you notice that the person being treated with Instanyl becomes suddenly drowsy, has breathing difficulties or has difficulty staying awake:

• you should seek immediate emergency help.
• while waiting for help, try to keep the person awake by talking to them or gently shaking them from time to time.
• if the person has breathing difficulties, try to get them to breathe every 5-10 seconds.
• if the person stops breathing, try to resuscitate them until emergency help arrives.

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

If someone has used Instanyl accidentally, they may experience the same symptoms as described above in case of overdose.

If you forget to use Instanyl

If your breakthrough pain continues, you can use Instanyl as prescribed by your doctor. If your breakthrough pain has stopped, do not use Instanyl until your next breakthrough pain episode.

If you stop treatment with Instanyl

You should stop treatment with Instanyl when you no longer have breakthrough pain. However, you should continue to use your background painkiller to treat your cancer pain. If you are unsure, talk to your doctor to confirm the correct dose of your regular painkiller.

You may experience sudden withdrawal symptoms similar to the possible side effects of Instanyl if you stop using Instanyl. If you experience withdrawal symptoms, talk to your doctor. Your doctor will assess whether you need medicine to reduce or stop these symptoms.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Frequently, adverse effects will disappear or decrease with continued use of the medicine.

Interrupt treatment and contact your doctor, hospital, or emergency service immediately if:

• you experience a severe and sudden allergic reaction with difficulty breathing, inflammation, feeling of mild dizziness, increased heart rate, sweating, or loss of consciousness.
• you experience severe breathing difficulties.
• you have a whistling sound when inhaling.
• you have convulsive pain.
• you experience extreme dizziness.

These adverse effects can be very serious.

Other adverse effects observed after using Instanyl:

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

Drowsiness, dizziness even with difficulty maintaining balance, headache, throat irritation, nausea, vomiting, flushing, feeling of intense heat, excessive sweating.

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

Insomnia, lethargy, muscle convulsions, strange or unpleasant sensation in the skin, alteration of taste, motion-induced dizziness, low blood pressure, severe respiratory problems, nasal bleeding, nasal ulcer, runny nose, constipation, mouth inflammation, dry mouth, skin discomfort, skin itching, fever.

Unknown(frequency cannot be estimated from available data):

Allergic reaction, falls, diarrhea, seizures (epileptic crisis), loss of consciousness, inflammation of arms or legs, seeing or hearing things that are not real (hallucinations), delirium (symptoms may include a combination of agitation, restlessness, disorientation, confusion, fear, seeing or hearing things that do not exist, sleep disorders, nightmares), pharmacological tolerance, drug dependence (addiction), drug abuse (see section 2), fatigue, general malaise, withdrawal syndrome (which can manifest with the appearance of the following adverse effects: nausea, vomiting, diarrhea, anxiety, chills, tremors, and sweating), breathing difficulties.

Cases have also been observed of patients who have developed a perforation in the nasal septum – the structure that separates the nostrils.

You should inform your doctor if you suffer from repeated episodes of nasal bleeding or nose discomfort.

Prolonged treatment with fentanyl during pregnancy can cause withdrawal symptoms in the newborn, which can be potentially fatal (see section 2).

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish System of Pharmacovigilance of Medicines for Human Use: https://www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Instanyl

The analgesic contained in Instanyl is very potent and can be fatal in children. Instanyl must be kept out of sight and out of reach of children. The child-resistant safety cap on the nasal spray should always be replaced after each use.

Do not use Instanyl after the expiration date stated on the packaging after CAD or EXP. The expiration date is the last day of the indicated month.

Store below 30°C. Do not freeze. If the Instanyl nasal spray is frozen, the device may break. You should check the spray button before use if you are unsure how it has been stored.

Instanyl packages that have exceeded the expiration date or are no longer to be used may still contain enough medication to harm other people, especially children.

6. Container Content and Additional Information

Instanyl Composition

The active ingredient is fentanyl citrate. The content is:

50 micrograms/dose: 1 ml contains fentanyl citrate equivalent to 500 micrograms of fentanyl. One spray (100 microliters) contains 50 micrograms of fentanyl.

100 micrograms/dose: 1 ml contains fentanyl citrate equivalent to 1,000 micrograms of fentanyl. One spray (100 microliters) contains 100 micrograms of fentanyl.

200 micrograms/dose: 1 ml contains fentanyl citrate equivalent to 2,000 micrograms. One spray (100 microliters) contains 200 micrograms of fentanyl.

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

Appearance of Instanyl and Container Content

Instanyl DoseGuard is a nasal spray solution. The solution is clear and colorless. It contains a nasal spray with a dosing pump, an electronic indicator, a dose counter, an integrated lock mechanism, and a child-resistant closure.

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

Only some package sizes may be marketed.

The labeling of the three Instanyl concentrations differs in color:

For 50 micrograms/dose, the labeling is orange.

For 100 micrograms/dose, the labeling is purple.

For 200 micrograms/dose, the labeling is greenish-blue.

Marketing Authorization Holder

Istituto Gentili S.r.l.

Via San Giuseppe Cottolengo 15

20143 Milano

Italy

Manufacturer

Curida AS

Solbærvegen 5

NO-2409 Elverum

Norway

Date of Last Revision of this Leaflet

August 2024

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

INSTANYL USE INSTRUCTIONS

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

Important Information Before Use:

• Do not modify the medical device.
• Do not allow liquids to enter the medical device.

The Instanyl nasal spray includes:

• An integrated lock function that controls how often the nasal spray can be used.
• A child-resistant closure that must be placed when the nasal spray is not in use.

• An electronic indicator that

• shows how many times the nasal spray needs to be pressed (prepared) before using the product.
• shows the number of doses remaining.
• shows if the nasal spray is blocked or ready to be used.

How to Remove and Replace the Child-Resistant Closure

Preparing the Instanyl Nasal Spray

If you notice that the nasal spray indicator does not work as described in the “Use Instructions”, you should contact your doctor or pharmacist.