Package leaflet: Information for the user

Instanyl 50 micrograms/dose nasal spray, solution, 100 micrograms/dose nasal spray, solution, 200 micrograms/dose nasal spray, solution

fentanyl
Please read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Never give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effect, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

What Instanyl is and what it is used for
What you need to know before using Instanyl
How to use Instanyl
Possible side effects
How to store Instanyl
Contents of the pack and other information

1. What Instanyl is and what it is used for

Instanyl contains the active substance fentanyl and belongs to a group of strong analgesics called opioids. Opioids work by blocking pain signals traveling to the brain. Instanyl acts rapidly and is used to relieve intense breakthrough pain in cancer patients who are already being treated with opioids for their underlying pain. Intense breakthrough pain is sudden additional pain that occurs despite the use of regular opioid medication for pain relief.

2. What you should know before using Instanyl

Do not use Instanyl

if you are allergic to fentanyl or to any of the other ingredients of this medicine (listed in section 6)
if you have not been taking, on a daily and regular basis for at least one week, an opioid medicine prescribed for persistent pain (e.g. codeine, fentanyl, hydromorphone, morphine, oxycodone, pethidine). If you are not using these medicines, you must not use Instanyl, as this could increase the risk of your breathing becoming dangerously slow and/or shallow, or even stopping
if you are taking a medicine containing sodium oxybate
if you suffer from short-term pain other than breakthrough pain caused by injuries or surgical procedures, headaches or migraines
if you have serious breathing difficulties or suffer from severe chronic obstructive pulmonary disease (COPD)
if you have previously undergone facial radiotherapy
if you suffer from recurrent episodes of nosebleeds

Warnings and precautions
Keep this medicine in a safe and secure place, out of reach of other people (see section 5 “How to store Instanyl” for more information).
Talk to your doctor or pharmacist before taking Instanyl, especially:

if you suffer from long-standing chronic obstructive pulmonary disease, as your breathing may be worsened by Instanyl;
if you have heart problems, particularly slow heart rate, low blood pressure or reduced blood volume;
if you have liver or kidney problems;
if you have brain function disorders, for example due to a brain tumour, head injury or increased intracranial pressure;
if you have previously developed adrenal insufficiency or lack of sex hormones (androgen deficiency) while using opioids;
if you are taking sedative medicines such as benzodiazepines or related drugs (also refer to section “Other medicines and Instanyl”);
if you are taking antidepressants or antipsychotics (also refer to section “Other medicines and Instanyl”);
if you are taking medicines known as partial opioid agonists/antagonists, e.g. buprenorphine, nalbuphine and pentazocine (medicines for pain treatment), as you may experience symptoms of withdrawal syndrome. Refer to section “Other medicines and Instanyl” for further information;
if you use other nasal sprays, for example for treatment of common cold or allergies.

Sleep-related breathing disorders
Instanyl may cause sleep-related breathing disorders such as sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxaemia (low blood oxygen levels during sleep). Symptoms may include pauses in breathing during sleep, night awakenings due to breathlessness, difficulty maintaining sleep or excessive daytime sleepiness. If you or someone else notices these symptoms, consult your doctor. Your doctor may consider reducing the dose.
If you feel short of breath while being treated with Instanyl, it is very important that you contact your doctor or hospital immediately.
Consult your doctor during treatment with Instanyl if:

you experience pain or increased sensitivity to pain (hyperalgesia) that does not respond to an increase in the dose of the prescribed medicine
you experience a combination of the following symptoms: nausea, vomiting, anorexia, fatigue, weakness, dizziness and low blood pressure. Together, these symptoms may indicate a potentially life-threatening condition called adrenal insufficiency, in which the adrenal glands do not produce enough hormones.

If you experience recurrent nosebleeds or nasal disorders during use of Instanyl, you should contact your doctor, who will consider alternative treatments for breakthrough pain.
Long-term use and tolerance
This medicine contains fentanyl, an opioid medicine. Repeated use of opioid painkillers may make the medicine less effective (you become accustomed to it, a phenomenon known as drug tolerance). You may also become more sensitive to pain during treatment with Instanyl. This is known as hyperalgesia. Increasing the dose of Instanyl may help reduce pain for a while, but it may also be harmful. If you notice the medicine becoming less effective, talk to your doctor. Your doctor will decide whether it is better to increase the dose or gradually reduce the use of Instanyl.
Dependence and substance abuse
Repeated use of Instanyl may also lead to dependence, abuse and substance abuse, which may result in a potentially fatal overdose. The risk of these adverse effects may increase with higher doses and prolonged duration of use. Dependence or substance abuse may make you feel as if you have lost control over the amount of medicine needed or how often you need to use it. You may feel a need to continue using the medicine, even if it no longer helps relieve pain.
The risk of developing dependence or substance abuse varies from person to person. You may have a higher risk of becoming dependent on or abusing Instanyl if:

you or a family member have previously suffered from alcohol, prescription medicine or illegal substance abuse or dependence (“substance abuse”);
you are a smoker;
you have previously had mood disorders (depression, anxiety or a personality disorder) or have been treated by a psychiatrist for other mental illnesses.

The appearance of any of the following signs during use of Instanyl may be a sign of dependence or substance abuse.

You feel the need to use the medicine for a longer period than prescribed by your doctor
You feel the need to use a higher dose than recommended
You use the medicine for reasons other than those prescribed, for example “to stay calm” or “to help sleep”
You have repeatedly tried to stop or control use of this medicine without success
When you stop taking the medicine, you feel unwell (e.g. nausea, vomiting, diarrhoea, anxiety, chills, tremors and sweating) and feel better when you start taking it again (“withdrawal symptoms”)

If you notice any of these signs, talk to your doctor to discuss the best treatment approach for you, including whether it is appropriate to stop treatment and how to stop safely.
Children and adolescents
Instanyl must 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 those not requiring a prescription.
Instanyl may affect or be affected by other medicines.
You should be particularly careful if you are being treated with any of the following medicines:

Other pain medicines and some nerve pain medicines (gabapentin and pregabalin).
Medicines that normally cause drowsiness (sedative effect), such as sleeping pills, sedative medicines like benzodiazepines or related drugs, medicines for anxiety, antihistamines, tranquilisers, skeletal muscle relaxants and gabapentinoids (gabapentin and pregabalin). Concomitant use of these medicines with Instanyl may increase the risk of drowsiness, deep sedation and impaired breathing (respiratory depression), a condition that may lead to coma and be potentially fatal. For this reason, concomitant use should only be considered if no other treatment options are possible. However, if your doctor prescribes Instanyl together with sedative medicines, the dose and duration of concomitant treatment should be limited. Inform your doctor about all sedative medicines you are taking and follow your doctor’s dosage recommendations carefully. It may be helpful to inform friends or family members to watch for the appearance of the symptoms mentioned above. If you experience these symptoms, contact your doctor.
Medicines that may affect how your body metabolises Instanyl, such as:
- ritonavir, nelfinavir, amprenavir, and fosamprenavir (used to treat HIV infection)
- CYP3A4 inhibitors such as ketoconazole, itraconazole, or fluconazole (used to treat fungal infections)
troleandomycin, clarithromycin, or erythromycin (used to treat bacterial infections)
aprepitant (used to treat severe nausea)
diltiazem and verapamil (used to treat high blood pressure or heart conditions)
- Medicines called monoamine oxidase inhibitors (MAO inhibitors) (used in severe depression), taken within the last two weeks.
- The risk of adverse effects increases if you are taking medicines such as certain antidepressants or antipsychotics. Instanyl may interact with these medicines and cause changes in mental state (e.g. agitation, hallucinations, coma) and other effects such as body temperature above 38 °C, rapid heartbeat, unstable blood pressure and exaggerated reflexes, muscle rigidity, lack of coordination and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea). Your doctor will advise whether Instanyl is suitable for you.
- Medicines known as partial opioid agonists/antagonists, e.g. buprenorphine, nalbuphine and pentazocine (medicines for pain treatment). You may experience symptoms of withdrawal syndrome (nausea, vomiting, diarrhoea, anxiety, chills, tremor and sweating).
- Other medicines taken by nasal route, particularly oxymetazoline, xylometazoline and similar medicines used to relieve nasal congestion.

Instanyl with food, drinks or alcohol
Do not drink alcohol during treatment with Instanyl, as this may increase the risk of dangerous adverse effects.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant or are planning to become pregnant, or if you are breastfeeding, ask your doctor or pharmacist for advice before taking any medicine.
Instanyl must not be used during pregnancy unless you have discussed it with your doctor.
Instanyl must not be used during childbirth because fentanyl may cause serious breathing problems in the newborn.
Fentanyl may pass into breast milk and may cause adverse effects in the breastfed newborn. Do not use Instanyl if you are breastfeeding. You must not start breastfeeding for at least 5 days after your last dose of Instanyl.
Driving and using machines
You must not drive or operate machinery while being treated with Instanyl. Instanyl may cause dizziness, drowsiness and vision disturbances, which may affect your ability to drive or operate machinery.

3. How to use Instanyl

Before starting treatment and regularly during treatment, your doctor will discuss with you
what to expect from using Instanyl, when and for how long it should be used, when to
contact your doctor, and when treatment should be stopped (see also section 2, Withdrawal symptoms when stopping Instanyl).
Always use this medicine exactly as your doctor has instructed. If you have any doubts, consult your
doctor or pharmacist.
The dose of Instanyl is independent of your usual treatment for cancer-related pain.
When you start using Instanyl for the first time, your doctor will help you find the dose that provides
relief from breakthrough pain.
The initial dose is one 50 microgram spray in one nostril each time you experience an episode of intense breakthrough pain. During dose titration, your doctor may instruct you on how to increase to a higher dose.
If intense breakthrough pain has not subsided after 10 minutes, use only one additional spray for this episode.
Generally, you should wait 4 hours before treating another episode of intense breakthrough pain. In exceptional cases, if a new episode of intense breakthrough pain occurs earlier, you may use Instanyl to treat it, but you must wait at least 2 hours from the last spray. If you regularly experience episodes of intense breakthrough pain less than 4 hours apart, contact your doctor, as your baseline pain treatment may need adjustment.
You may use Instanyl to treat up to four episodes of intense breakthrough pain per day.
If you experience more than four episodes of intense breakthrough pain per day, contact your doctor,
as they may consider changing your baseline cancer pain treatment.
To keep track of the number of Instanyl doses used, you should use the table provided in the patient information leaflet located on the lid of the child-resistant packaging.
Do not change the dose of Instanyl or any other pain medication on your own. Dose adjustments should always be made in consultation with your doctor.
Instanyl is for nasal use only.
To learn how to use Instanyl, read the Instructions for Use at the end of this package leaflet.
If you use more Instanyl than you should or if you think someone has accidentally taken Instanyl
Contact your doctor, hospital, or emergency department to assess the risk and receive advice if you have used more Instanyl than prescribed.
Symptoms of overdose include:
Drowsiness, lethargy, dizziness, decreased body temperature, slowed heart rate, difficulty coordinating arms and legs.
In severe cases, Instanyl overdose can cause coma, sedation, seizures, or serious breathing difficulties (very slow or shallow breathing). Overdose may also cause a brain disorder known as toxic leukoencephalopathy.
If you notice any of the symptoms described above, seek immediate medical help.
Note for caregivers
If you notice that the person taking Instanyl suddenly becomes slow, has difficulty breathing, or is difficult to wake:

You must call emergency services immediately.
While waiting for help, keep the person awake by talking to them or gently shaking them from time to time.
If the person has difficulty breathing, encourage them to breathe every 5–10 seconds.
If the person has stopped breathing, begin resuscitation attempts until emergency help arrives.

If you suspect someone has accidentally taken Instanyl, seek immediate medical help. Try to keep the person awake until help arrives.
If someone has accidentally taken Instanyl, they may experience the same symptoms described above for overdose.
If you forget to use Instanyl
If intense breakthrough pain is still present, you may take Instanyl as prescribed by your doctor. If the episode of intense breakthrough pain has passed, do not take Instanyl until the next episode of intense breakthrough pain occurs.
If you stop using Instanyl
You should stop taking Instanyl when you no longer have any episodes of intense breakthrough pain. However, you must continue taking your usual medication for cancer-related pain. If you are unsure, contact your doctor to confirm the correct dose of your usual medication.
When stopping Instanyl, you may experience withdrawal symptoms similar to the possible side effects of Instanyl. If you experience withdrawal symptoms, contact your doctor. Your doctor will assess whether you need medication to reduce or eliminate withdrawal symptoms.
If you have any questions about the use of Instanyl, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine may cause side effects, although not everyone gets them.
The side effects usually stop or decrease in intensity with continued use of the product.
Stop treatment immediately and contact your doctor, hospital or emergency department if:

you experience a sudden, severe allergic reaction, with difficulty breathing, swelling, dizziness, rapid heartbeat, sweating or loss of consciousness
you have severe difficulty breathing
you hear a wheezing sound when inhaling
you have a cramping pain
you experience severe dizziness

These side effects can be very serious.
Other side effects reported after use of Instanyl:
Common side effects (may occur in up to 1 in 10 people):
Somnolence, dizziness including difficulty maintaining balance, headache, throat irritation, nausea, vomiting, flushing, intense sensation of warmth, excessive sweating.
Uncommon side effects (may occur in up to 1 in 100 people):
Insomnia, somnolence, convulsive muscle contractions, abnormal, sometimes unpleasant sensation on the skin, changes in taste, motion sickness, low blood pressure, serious breathing problems, nosebleeds, nasal ulcer, runny nose, constipation, inflammation of the mouth, dry mouth, skin pain, skin itching, fever.
Not known (frequency cannot be estimated from the available data):
Allergic reaction, falls, diarrhoea, seizures (fits), loss of consciousness, swelling 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 are not real, sleep disturbances, nightmares), drug tolerance, substance dependence (addiction), drug abuse (see section 2), fatigue, malaise, withdrawal syndrome (which may present with the following side effects: nausea, vomiting, diarrhoea, anxiety, chills, tremor and sweating), shortness of breath.
Cases of patients reporting a hole in the nasal septum – the structure separating the nostrils – have also been reported.
Prolonged treatment with fentanyl during pregnancy may cause withdrawal symptoms in the newborn baby, which may result in death (see section 2).
Inform your doctor if you experience recurrent episodes of nosebleeds or nasal discomfort.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system detailed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Instanyl

The pain-relieving substance contained in Instanyl is very potent and can be life-threatening
to children. Instanyl must be kept out of sight and reach of children.
After use, always return the nasal spray to its packaging with child-resistant closure.
Store this medicine in a safe and secure place, inaccessible to other people. Accidental or intentional
intake of this medicine by individuals for whom it has not been prescribed may cause severe harm or be fatal.
Do not use Instanyl after the expiry date stated on the vial after "Exp". The expiry date refers to the last day of that month.
Store below 30 °C. Keep the nasal spray in an upright position. Do not freeze. If the Instanyl nasal spray freezes, the dosing pump may break. If you are unsure how the pump has been stored, check it before use.
Expired or unused Instanyl may still contain enough medicine to be harmful to others, especially children. Do not dispose of any medicine via wastewater or household waste. Any used or unused nasal spray must be systematically disposed of according to local requirements or returned to the pharmacist in its child-resistant packaging. Ask your pharmacist how to dispose of medicines no longer in use. This will help 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 of fentanyl. One spray
(100 microlitres) contains 50 micrograms of fentanyl.
100 micrograms/dose: 1 ml contains fentanyl citrate equivalent to 1,000 micrograms of fentanyl. One spray
(100 microlitres) contains 100 micrograms of fentanyl.
200 micrograms/dose: 1 ml contains fentanyl citrate equivalent to 2,000 micrograms of fentanyl. One spray
(100 microlitres) contains 200 micrograms of fentanyl.
The other components are monobasic sodium phosphate dihydrate, dibasic sodium phosphate dihydrate, and purified water.
Description of the appearance of Instanyl and contents of the pack
Instanyl is a nasal spray solution. The solution is clear and colourless. It is contained in a brown glass bottle with a metering pump.
The nasal spray is supplied in child-resistant packaging with three different concentrations:
1.8 ml (corresponding to 10 doses), 2.9 ml (corresponding to 20 doses), and 5.0 ml (corresponding to 40 doses).
Not all pack sizes may be marketed.
The labelling of the three concentrations of Instanyl is colour-coded:
50 micrograms/dose – the label is orange
100 micrograms/dose – the label is purple
200 micrograms/dose – the label is blue-green.
Marketing Authorisation Holder
Istituto Gentili S.r.l.
Via San Giuseppe Cottolengo 15
20143 Milano
Italy
Manufacturer
Curida AS
Solbærvegen 5
NO-2409 Elverum
Norway
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

INSTRUCTIONS FOR USE OF INSTANYL NASAL SPRAY

To learn how to use Instanyl nasal spray, carefully read the instructions below:
Preparation of Instanyl nasal spray for use:

Before using the nasal spray for the first time:
- It must be primed by pressing 3 or 4 times until a fine mist appears.
During priming, medication may be released. For this reason:
- Priming must be performed in a well-ventilated area.
- Do not direct the nasal spray towards yourself or other people.
- Do not direct the nasal spray towards objects or surfaces that could come into contact with other people, especially children.
If you have not used Instanyl for more than 7 days, you must re-prime the pump by pressing the nasal spray in the air before taking the next dose.

How to use Instanyl nasal spray:

Blow your nose if it feels blocked or if you have a cold.
Sit or stand upright.
Remove the protective cap from the spray.

Schematic drawing of a bottle with a dropper and a black arrow indicating removal of the top cap

Hold the nasal spray upright.
Tilt your head slightly forward.
Close one nostril by pressing it sideways with a finger and insert the spray nozzle into the other nostril (about 1 cm). It does not matter which nostril you use. If you need a second dose after 10 minutes to achieve adequate pain relief, this dose should be administered into the other nostril.

Black and white line drawing of a person holding a syringe in one hand and pressing the plunger with the other

Press the pump quickly and completely downward once with two fingers while inhaling through your nose. It is important to ensure that the pump is fully depressed. You may not feel the dose in your nose, but if the plunger has been pressed, the dose has been delivered.
After use, clean the nasal spray actuator with a clean cloth and then dispose of the cloth.

If you need a second dose of Instanyl after 10 minutes to achieve adequate pain relief, repeat steps 1 to 8 in the other nostril.
After use, always return Instanyl to its child-resistant packaging. Keep out of sight and reach of children.

Two hands holding a medical device with black arrows indicating inward pressure

Record the number of doses used and the number of doses remaining in the nasal spray using the dose-tracking card supplied with Instanyl nasal spray. Each time you use Instanyl nasal spray, ensure that this information is recorded by you or by the person assisting you on the provided tracking card.
If Instanyl nasal spray is blocked or not delivering properly:
If it is blocked, point the nasal spray away from yourself (and others) and press firmly on the pump. This should clear any blockage.
If the nasal spray still does not work properly, contact your pharmacist. Never attempt to repair or disassemble the nasal spray yourself. This could result in the administration of an incorrect dose.

Patient Information Leaflet: Information for the user

Instanyl 50 micrograms nasal spray, solution in single-dose container, 100 micrograms nasal spray, solution in single-dose container, 200 micrograms nasal spray, solution in single-dose container

fentanyl
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Never give it to other people, even if they have the same symptoms as you, because it could be dangerous.
If you experience any side effect, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

What Instanyl is and what it is used for
What you need to know before using Instanyl
How to use Instanyl
Possible side effects
How to store Instanyl
Contents of the pack and other information

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 work by blocking pain signals traveling to the brain.
Instanyl acts rapidly and is used to relieve intense breakthrough pain in cancer patients who are already being treated with opioids for their background pain. Intense breakthrough pain is sudden additional pain that occurs despite ongoing treatment with a regular opioid medicine for pain relief.

2. What you must know before using 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 taking, on a daily and regular basis, an opioid medicine by prescription (e.g. codeine, fentanyl, hydromorphone, morphine, oxycodone, pethidine) for at least one week to control persistent pain. If you are not using these medicines, you must not use Instanyl, as this could increase the risk of your breathing becoming dangerously slow and/or shallow, or even stopping;
if you are taking a medicine containing sodium oxybate;
if you suffer from short-term pain other than breakthrough pain caused by injury or surgery, headaches or migraines;
if you have serious breathing difficulties or suffer from severe chronic obstructive pulmonary disease (COPD);
if you have previously undergone facial radiotherapy;
if you suffer from recurrent episodes of nosebleeds.

Warnings and precautions
Keep this medicine in a safe and secure place, out of reach of other people (see section 5 “How to store Instanyl” for further information).
Talk to your doctor or pharmacist before using Instanyl, especially:

if you suffer from chronic obstructive pulmonary disease (COPD), as your breathing may be impaired by Instanyl;
if you have heart problems, especially slow heart rate, low blood pressure or reduced blood volume;
if you have liver or kidney problems;
if you have brain function disorders, for example due to a brain tumour, head injury or increased intracranial pressure;
if you have previously developed adrenal insufficiency or lack of sex hormones (androgen deficiency) with opioid use;
if you are taking sedative medicines such as benzodiazepines or related drugs (also refer to section “Other medicines and Instanyl”);
if you are taking antidepressants or antipsychotics (also refer to section “Other medicines and Instanyl”);
if you are taking medicines known as partial opioid agonists/antagonists, e.g. buprenorphine, nalbuphine and pentazocine (medicines for pain treatment), as you may experience symptoms of withdrawal syndrome. Refer to section “Other medicines and Instanyl” for further information;
if you are using other nasal sprays, e.g. for treatment of common cold or allergies.

Sleep-related breathing disorders
Instanyl may cause sleep-related breathing disorders such as sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxaemia (low oxygen levels in the blood). Symptoms may include pauses in breathing during sleep, waking up at night due to breathlessness, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else notices these symptoms, contact your doctor. Your doctor may consider reducing your dose.
If you feel difficulty breathing while being treated with Instanyl, it is very important that you contact your doctor or hospital immediately.
Contact your doctor during treatment with Instanyl if:

you experience pain or increased sensitivity to pain (hyperalgesia) that does not respond to an increase in the dose of your prescribed medicine;
you experience a combination of the following symptoms: nausea, vomiting, anorexia, fatigue, weakness, dizziness and low blood pressure. Taken together, these symptoms may indicate a potentially life-threatening condition called adrenal insufficiency, in which the adrenal glands do not produce enough hormones.

If you experience recurrent nosebleeds or nasal disorders while using Instanyl, you must contact your doctor, who will consider alternative treatments for breakthrough pain.
Long-term use and tolerance
This medicine contains fentanyl, an opioid medicine. Repeated use of opioid painkillers may make the medicine less effective (you become accustomed to it, a phenomenon known as drug tolerance). You may also become more sensitive to pain during treatment with Instanyl. This is known as hyperalgesia. Increasing the dose of Instanyl may help reduce pain for a while, but it may also be harmful. If you notice the medicine becoming less effective, contact your doctor. Your doctor will decide whether it is better to increase the dose or gradually reduce the use of Instanyl.
Dependence and substance abuse
Repeated use of Instanyl may also lead to dependence, abuse and substance abuse, which may result in potentially fatal overdose. The risk of these adverse effects may increase with higher doses and prolonged duration of use. Dependence or substance abuse may make you feel that you have lost control over the amount of medicine needed or how often you need to use it. You may feel the need to continue using the medicine, even if it no longer helps relieve your pain.
The risk of developing dependence or substance abuse varies from person to person. You may have a higher risk of becoming dependent on or abusing Instanyl if:

you or a family member has previously suffered from alcohol, prescription medicine or illegal substance abuse or dependence (“substance abuse”);
you are a smoker;
you have previously had mood disorders (depression, anxiety or a personality disorder) or have been treated by a psychiatrist for other mental illnesses.

The appearance of any of the following signs during treatment with Instanyl may indicate dependence or substance abuse:

You feel the need to use the medicine for longer than prescribed by your doctor;
You feel the need to use a higher dose than recommended;
You use the medicine for reasons other than those prescribed, for example “to stay calm” or “to help sleep”;
You have repeatedly tried to stop or control your use of this medicine without success;
When you stop taking the medicine, you feel unwell (e.g. nausea, vomiting, diarrhoea, anxiety, chills, tremors and sweating), and when you start taking it again, you feel better (“withdrawal symptoms”).

If you notice any of these signs, contact your doctor to discuss the best treatment approach for you, including when it may be appropriate to stop treatment and how to stop safely.
Children and adolescents
Instanyl must 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 those not requiring a prescription.
Instanyl may affect or be affected by other medicines.
You must be especially careful if you are taking any of the following medicines:

Other pain medicines and certain nerve pain medicines (gabapentin and pregabalin);
Medicines that normally cause drowsiness (have a sedative effect), such as sleeping pills, sedative medicines like benzodiazepines or related drugs, medicines for anxiety, antihistamines, tranquilisers, skeletal muscle relaxants and gabapentinoids (gabapentin and pregabalin). Concomitant use of these medicines with Instanyl may increase the risk of drowsiness, deep sedation and impaired breathing (respiratory depression), a condition that may lead to coma and be potentially fatal. For this reason, concomitant use should only be considered if no other treatment options are possible. However, if your doctor prescribes Instanyl together with sedative medicines, the dose and duration of concomitant treatment must be limited. Inform your doctor about all sedative medicines you are taking and follow your doctor’s dosage recommendations carefully. It may be helpful to inform friends or family members to watch for the signs and symptoms mentioned above. If you experience these symptoms, contact your doctor.
Medicines that may affect how your body metabolises Instanyl, such as:
- ritonavir, nelfinavir, amprenavir, and fosamprenavir (used to treat HIV infection);
- CYP3A4 inhibitors such as ketoconazole, itraconazole, or fluconazole (used to treat fungal infections);
- troleandomycin, clarithromycin, or erythromycin (used to treat bacterial infections);
- aprepitant (used to treat severe nausea);
- diltiazem and verapamil (used to treat high blood pressure or heart conditions);
Medicines known as monoamine oxidase inhibitors (MAOIs) (used in severe depression), taken within the last two weeks;
The risk of adverse effects increases if you are taking medicines such as certain antidepressants or antipsychotics. Instanyl may interact with these medicines and cause changes in mental status (e.g. agitation, hallucinations, coma) and other effects such as body temperature above 38°C, rapid heartbeat, unstable blood pressure, exaggerated reflexes, muscle rigidity, lack of coordination and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea). Your doctor will advise you whether Instanyl is suitable for you;
Medicines known as opioid agonists/partial antagonists, e.g. buprenorphine, nalbuphine and pentazocine (medicines for pain treatment). You may experience symptoms of withdrawal syndrome (nausea, vomiting, diarrhoea, anxiety, chills, tremors and sweating);
Other nasal medicines, particularly oxymetazoline, xylometazoline and similar medicines used to relieve nasal congestion.

Instanyl with food, drinks or alcohol
Do not drink alcohol during treatment with Instanyl, as this may increase the risk of dangerous adverse effects.
Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant or are planning to become pregnant, or if you are breastfeeding, ask your doctor or pharmacist for advice before taking any medicine.
Instanyl must not be used during pregnancy unless you have discussed it with your doctor.
Instanyl must not be used during childbirth because fentanyl may cause serious breathing problems in the newborn.
Fentanyl may pass into breast milk and may cause adverse effects in the breastfed newborn. Do not use Instanyl if you are breastfeeding. You must not start breastfeeding for at least 5 days after your last dose of Instanyl.
Driving and using machines
You must not drive or operate machinery while being treated with Instanyl. Instanyl may cause dizziness, drowsiness and visual disturbances, which may affect your ability to drive or operate machinery.