Consumer medicine information

DBL Fentanyl Injection

Fentanyl

BRAND INFORMATION

Brand name

DBL Fentanyl Injection

Active ingredient

Fentanyl

Schedule

S8

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using DBL Fentanyl Injection.

SUMMARY CMI

DBL™ Fentanyl Injection

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

WARNING: Important safety information is provided in a boxed warning in the full CMI. Read before using this medicine.

1. Why am I being treated with DBL Fentanyl Injection?

DBL Fentanyl Injection contains the active ingredient fentanyl citrate. DBL Fentanyl Injection is a short-term pain reliever that belongs to a group of medicines called opioid analgesics. It is most commonly used to relieve severe pain. It may also be used just before, or during, an operation, to help the anaesthetic work better.

For more information, see Section 1. Why am I being treated with DBL Fentanyl Injection? in the full CMI.

2. What should I know before treatment with DBL Fentanyl Injection?

Do not use if you have ever had an allergic reaction to fentanyl or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before treatment with DBL Fentanyl Injection? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with DBL Fentanyl Injection and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How is DBL Fentanyl Injection given?

Your doctor will decide what dose of fentanyl you will receive. This depends on your age, physical condition and other factors, such as your weight.

More instructions can be found in Section 4. How is DBL Fentanyl Injection given? in the full CMI.

5. What should I know during treatment with DBL Fentanyl Injection?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are being given fentanyl.
  • If you become pregnant while you are being treated with fentanyl, tell your doctor immediately.
Things you should not do
  • Do not stop using this medicine suddenly. If you have been using fentanyl for more than two weeks, you may experience unpleasant feelings if you stop fentanyl suddenly.
Driving or using machines
  • Do not drive a car, operate machinery, or do anything else that could be dangerous until you know how fentanyl affects you. Fentanyl may cause drowsiness and impair coordination.
Drinking alcohol
  • Do not drink alcohol while you are being treated with fentanyl.
Looking after your medicine
  • If you are being given DBL Fentanyl Injection while in hospital, it will be stored in the pharmacy or on the ward. Store below 25°C.

For more information, see Section 5. What should I know during treatment with DBL Fentanyl Injection? in the full CMI.

6. Are there any side effects?

Common side effects include sweating, dizziness, faintness, nausea or vomiting. Tell your doctor immediately if you notice slow or troubled breathing, muscle stiffness, slowed heart rate, blurred vision, spasm of the larynx (voice box) or itching. If you experience serious side effects such as allergic reactions, agitation, hallucinations, twitching or loss of coordination, severe dizziness and weakness, irregular heart rate, changes in blood pressure, skin turning blue or unconsciousness, you may need urgent medical attention or hospitalisation.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

WARNING:

Limitations of use

DBL Fentanyl Injection should only be used when your doctor decides that other treatment options are not able to effectively manage your pain or you cannot tolerate them.

Hazardous and harmful use

DBL Fentanyl Injection poses risks of abuse, misuse and addiction which can lead to overdose and death. Your doctor will monitor you regularly during treatment.

Life threatening breathing problems

DBL Fentanyl Injection can cause life-threatening or fatal breathing problems (slow, shallow, unusual or no breathing) even when used as recommended. These problems can occur at any time during use, but the risk is higher when first starting fentanyl and after a dose increase, if you are older, or have an existing problem with your lungs. Your doctor will monitor you and change the dose as appropriate.

Use of other medicines while using fentanyl

Using fentanyl with other medicines that can make you feel drowsy such as sleeping tablets (e.g. benzodiazepines), other pain relievers, antihistamines, antidepressants, antipsychotics, gabapentinoids (e.g. gabapentin and pregabalin), cannabis and alcohol may result in severe drowsiness, decreased awareness, breathing problems, coma and death. Your doctor will minimise the dose and duration of use; and monitor you for signs and symptoms of breathing difficulties and sedation. You must not drink alcohol while using fentanyl.



FULL CMI

DBL™ Fentanyl Injection

Active ingredient(s): fentanyl citrate

Consumer Medicine Information (CMI)

This leaflet provides important information about using DBL Fentanyl Injection. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using DBL Fentanyl Injection.

Where to find information in this leaflet:

1. Why am I being treated with DBL Fentanyl Injection?
2. What should I know before treatment with DBL Fentanyl Injection?
3. What if I am taking other medicines?
4. How is DBL Fentanyl Injection given?
5. What should I know during treatment with DBL Fentanyl Injection?
6. Are there any side effects?
7. Product details

1. Why am I being treated with DBL Fentanyl Injection?

DBL Fentanyl Injection contains the active ingredient fentanyl citrate. DBL Fentanyl Injection is a short-term pain reliever that belongs to a group of medicines called opioid analgesics. Fentanyl acts in the brain and spinal cord. It works quickly to reduce pain and its effects wear off quickly.

Fentanyl may be used alone but is usually used in hospital with other anaesthetics or with a sedative such as droperidol before an operation to provide an anaesthetic effect and during an operation to help continue the anaesthesia.

Your doctor may have prescribed it for another reason.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

2. What should I know before treatment with DBL Fentanyl Injection?

If you are not sure whether you should be given this medicine, talk to your doctor or pharmacist.

Warnings

Do not use DBL Fentanyl Injection if you:

  • are allergic to fentanyl, or any of the ingredients listed at the end of this leaflet. Symptoms of an allergic reaction may include:
    - shortness of breath
    - wheezing or difficulty breathing
    - swelling of the face, lips, tongue or other parts of the body
    - rash, itching or hives on the skin.

Always check the ingredients to make sure you can use this medicine.

  • have bronchial asthma or severe disease relating to the lungs
  • have breathing difficulties or shallow breathing
  • are undergoing treatment with monoamine oxidase (MAO) inhibitors (e.g. phenelzine, tranylcypromine, moclobemide or selegiline) or have stopped MAO inhibitor treatment during the last fourteen days
  • have myasthenia gravis (severe muscle weakness)
  • have long-standing pain not related to cancer.

Check with your doctor if you:

  • have or have had any other medical conditions, especially the following:
    - kidney or liver problems
    - lung or breathing problems
    - slow or irregular heartbeats; heart problems
    - snoring or sleep apnoea (you temporarily stop breathing or have difficulty breathing while asleep)
    - recent head injury
    - mental health conditions (e.g. depression, anxiety or personality disorder)
  • or anyone in your family have abused or are dependent on alcohol, prescription medicine or other illegal substances (addiction)
  • are a smoker
  • take any medicines for any other condition
  • have allergies to any other medicines, foods, preservatives or dyes.

If you have not told your doctor or pharmacist about any of the above, tell them before you are given DBL Fentanyl Injection.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

As fentanyl crosses the placenta, your doctor or pharmacist will discuss the possible risks and benefits of you being given DBL Fentanyl Injection during pregnancy.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

As fentanyl may pass into breast milk, breastfeeding is not recommended for 24 hours following use of DBL Fentanyl Injection. Your doctor or pharmacist will discuss the possible risks and benefits of being given DBL Fentanyl Injection during breastfeeding.

Children

DBL Fentanyl Injection should not be given to children under the age of 2 years. There is not enough information to recommend the use of this medicine for children under the age of 2 years.

Addiction

You can become addicted to fentanyl even if you use it exactly as prescribed. Fentanyl may become habit forming causing mental and physical dependence. If abused it may become less able to reduce pain.

Dependence

As with all other opioid containing products, your body may become used to you using fentanyl. Using it for a long time (i.e. more than two weeks) may result in physical dependence (i.e. it can be habit-forming or addictive). Physical dependence means that you may experience withdrawal symptoms if you stop using fentanyl suddenly, so it is important to use it exactly as directed by your doctor.

However, it is also important to keep your pain under control. Your doctor can advise you on how to manage this.

Tolerance

Tolerance to fentanyl may develop, which means that the effect of the medicine may decrease. If this happens, more may be needed to maintain the same effect.

Withdrawal

Continue using your medicine for as long as your doctor tells you. If you stop using this medicine suddenly, your pain may worsen and you may experience some or all of the following withdrawal symptoms:

  • nervousness, restlessness, agitation, trouble sleeping or anxiety
  • body aches, weakness or stomach cramps
  • loss of appetite, nausea, vomiting or diarrhoea
  • increased heart rate, breathing rate or pupil size
  • watery eyes, runny nose, chills or yawning
  • increased sweating.

DBL Fentanyl Injection given to the mother during labour can cause breathing problems and signs of withdrawal in the newborn.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with DBL Fentanyl Injection and affect how it works. These include:

  • barbiturates
  • general and local anaesthetics (e.g. lidocaine)
  • strong pain killers (e.g. opioid analgesics)
  • sedating antipsychotics (e.g. droperidol, chlorpromazine, fluphenazine and thioridazine) and centrally-active anti-emetics (e.g. metoclopramide and promethazine)
  • benzodiazepines (and other medicines) to treat anxiety, acute stress reactions, agitation, tremor, such as diazepam, alprazolam, lorazepam or midazolam
  • other medicines which may make you drowsy such as sleeping tablets, tablets to calm your nerves, sedatives, tranquilisers, hypnotics and muscle relaxants
  • antidepressants or medicines for anxiety disorders such as:
    - selective serotonin re-uptake inhibitors (SSRIs)
    - serotonin norepinephrine reuptake inhibitors (SNRIs)
    - monoamine oxidase (MAO) inhibitors (e.g. phenelzine, tranylcypromine and moclobemide)
  • MAO inhibitor used to treat Parkinson's disease e.g. selegiline, rasagiline and safinamide.
  • medicines to treat mental disorders
  • medicines to treat seizures (gabapentinoids e.g. gabapentin, pregabalin)

Medicines that may increase the effect of DBL Fentanyl Injection include:

  • macrolide antibiotics (e.g. erythromycin)
  • azole-antifungal agents (e.g. ketoconizole)
  • protease inhibitors or medication for HIV (e.g. ritonavir)

Medicines that may reduce the effect of DBL Fentanyl Injection include:

  • rifampin (anti-tuberculosis medication)
  • carbamazepine and phenytoin, medicines used to control fits or seizures.

These medicines may be affected by DBL Fentanyl Injection or may affect how well it works. You may need different amounts of your medicine, or different medicines. Your doctor or pharmacist will advise you.

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while you are being given this medicine.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect DBL Fentanyl Injection.

4. How is DBL Fentanyl Injection given?

How much is given

  • Your doctor will decide what dose you will receive. This depends on your age, physical condition and other factors, such as your weight.

How is it given

  • Your doctor or nurse will usually give DBL Fentanyl Injection to you.
  • DBL Fentanyl Injection is given as an injection into a vein or muscle.

If you are given too much (overdose)

DBL Fentanyl Injection is administered under the care of a highly trained doctor so overdose rarely occurs.

However, if you or someone else receive too much (overdose), and experience one or more of the symptoms below, urgent medical attention is required. Keep the person awake by talking to them or gently shaking them every now and then. You should follow the above steps even if someone other than you have accidentally used DBL Fentanyl Injection that was prescribed for you.

Symptoms of an overdose may include:

  • slow, unusual or difficult breathing causing skin to turn blue
  • severe drowsiness, dizziness or unconsciousness
  • confusion, memory loss, impairment of vision or coordination
  • slow or weak heartbeat, decreases in heart rate and blood pressure
  • nausea or vomiting
  • convulsions or fits
  • severe weakness or muscle stiffness

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know during treatment with DBL Fentanyl Injection?

Things you should do

  • Tell any other doctors, dentists and pharmacists who are treating you that you are being given DBL Fentanyl Injection.
  • If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you are being given DBL Fentanyl Injection.
  • If you plan to have surgery that needs a local or general anaesthetic, tell your doctor or dentist you are being given DBL Fentanyl Injection.
  • If you become pregnant while you are being treated with DBL Fentanyl Injection, tell your doctor or pharmacist.
  • Tell your doctor, pharmacist or nurse if you have any concerns about being given DBL Fentanyl Injection.

Things you should not do:

  • Do not give DBL Fentanyl Injection to anyone else, even if they have the same condition as you.
  • Do not use DBL Fentanyl Injection to treat any other complaints unless your doctor tells you to.
  • Do not stop using DBL Fentanyl Injection, or lower the dosage, without checking with your doctor or pharmacist.
  • Do not take any other medicines, whether they are prescription or over-the-counter medicines, unless they have been prescribed or recommended by a doctor or pharmacist who knows you are being treated with DBL Fentanyl Injection.
  • Avoid smoking or taking other drugs unless your doctor tells you to.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how DBL Fentanyl Injection affects you.

DBL Fentanyl Injection may cause feelings of weakness, dizziness, drowsiness and impairment of coordination in some people. Do not drive a car, operate machinery, or do anything else that could be dangerous if you are drowsy or feeling uncoordinated.

Drinking alcohol

Tell your doctor if you drink alcohol.

Do not drink alcohol while you are undergoing treatment with fentanyl unless otherwise advised by your doctor or pharmacist as drowsiness and coordination impairment may be worse.

Looking after your medicine

If you are being given DBL Fentanyl Injection while in hospital, it will be stored in the pharmacy or on the ward.

DBL Fentanyl Injection should be stored in a cool, dry place, protected from light where the temperature stays below 25°C.

Do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

When to discard your medicine

Do not use this medicine after the expiry date.

DBL Fentanyl Injection should not be given to you if the packaging is torn or shows signs of tampering.

Getting rid of any unwanted medicine

If your doctor tells you to stop using this medicine or the expiry date as passed, take it to any pharmacy for safe disposal.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Common side effects

Common side effectsWhat to do
  • sweating
  • dizziness, faintness
  • nausea, vomiting
Speak to your doctor if you have any of these common side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • agitation, hallucinations
  • slow or troubled breathing
  • muscle stiffness, twitching or loss of coordination
  • severe dizziness and weakness
  • slow, fast or irregular heart rate
  • blurred vision
  • increase or decrease in blood pressure
  • skin turning blue and clammy
  • unconsciousness
  • spasm of the larynx (voice box)
  • allergic reactions
  • itching
The following side effects may occur when a sedating medicine (e.g. droperidol) is used with DBL Fentanyl Injection
  • chills, shivering
  • restlessness
  • drowsiness
  • short periods of depression
  • imaginary events
  • uncontrolled movement of the body or eyes
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
Tell your doctor immediately if you experience any of these symptoms. You may need urgent medical attention or hospitalisation.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Tell your doctor immediately if you have unwanted side effects which continue after your treatment has stopped.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What DBL Fentanyl Injection contains

Active ingredient
(main ingredient)		Fentanyl citrate
Other ingredients
(inactive ingredients)		Sodium hydroxide
Sodium chloride
Hydrochloric acid
Water for injections

Do not use this medicine if you are allergic to any of these ingredients.

DBL Fentanyl Injection does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

What DBL Fentanyl Injection looks like

DBL Fentanyl Injection is a sterile, aqueous, preservative-free, colourless or almost colourless solution in glass ampoules.

It is available in the following strengths and pack sizes:

  • 100 micrograms / 2 mL x 5 ampoules AUST R 107025
  • 500 micrograms / 10 mL x 5 ampoules AUST R 107027

Who distributes DBL Fentanyl Injection

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizermedicalinformation.com.au

This leaflet was prepared in January 2024.

Published by MIMS March 2024

BRAND INFORMATION

Brand name

DBL Fentanyl Injection

Active ingredient

Fentanyl

Schedule

S8

 

1 Name of Medicine

Fentanyl citrate.

2 Qualitative and Quantitative Composition

DBL Fentanyl Injection is a sterile solution of fentanyl citrate and sodium chloride in water for injections. It is presented in ampoules and containing 2 mL or 10 mL of a 50 microgram per mL solution of fentanyl present as fentanyl citrate. The solution does not contain any preservative. The pH of the solution is adjusted with sodium hydroxide or hydrochloric acid to 5.0 to 7.5, if necessary.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

DBL Fentanyl Injection is a clear, colourless solution for injection containing fentanyl citrate equivalent to fentanyl 50 microgram per mL.
Fentanyl citrate is a white or almost white powder, soluble in water, freely soluble in methanol, sparingly soluble in alcohol.

4 Clinical Particulars

4.1 Therapeutic Indications

DBL Fentanyl Injection is indicated for analgesic action of short duration during premedication, induction and maintenance of anaesthesia and in the immediate post-operative periods. It may be used as an opioid analgesic supplement in general and regional anaesthesia.
Fentanyl may be used in combination with neuroleptic agents such as droperidol as an anaesthetic premedication, for the induction of anaesthesia, and as an adjunct in the maintenance of general and regional anaesthesia. The state of neurolept analgesia may be converted to neurolept anaesthesia by the concurrent administration of 65% nitrous oxide in oxygen.

4.2 Dose and Method of Administration

Dosage.

Dosage should be individualised. Some of the factors to be considered in determining the dose are age, body weight, physical status, underlying pathological condition, use of other medicines, type of anaesthesia to be used, and the surgical procedure involved.
Vital signs should be monitored routinely.
Reduced dosage is generally indicated for high-risk patients, including geriatric or debilitated patients, or those who have received other CNS depressant drugs. When used in conjunction with other CNS depressants as low as 25 to 33% of the usual dose is recommended.

Adult dosage.

1. Premedication. (To be appropriately modified in the elderly, debilitated and those who have received other depressant drugs). 50 to 100 microgram (1 to 2 mL) fentanyl administered intramuscularly 30 to 60 minutes prior to surgery (modified for high risk patients).
2. Adjunct to general anaesthesia.

Induction.

50 to 100 microgram (1 to 2 mL) administered intravenously and repeated at 2 to 3 minute intervals, until the desired effect is achieved. A reduced dose 25 to 50 microgram (0.5 to 1 mL) is recommended for elderly or high-risk patients.

Maintenance.

25 to 50 microgram (0.5 to 1 mL) should be administered intravenously or intramuscularly when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia.
3. Adjunct to regional anaesthesia. 50 to 100 microgram administered intramuscularly or by slow intravenous injection when analgesia is required.
4. Post-operatively (recovery room). 50 to 100 microgram (1 to 2 mL) administered intramuscularly repeated in 1 to 2 hours as needed.

Children's dosage.

Do not use DBL Fentanyl Injection in children less than 2 years of age. For children aged between 2 to 12 years, fentanyl may be used for induction and maintenance at a reduced level as low as 20 to 30 microgram (0.4 to 0.6 mL) per 10 kg bodyweight (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use).

Use in elderly patients.

Elderly patients may require lower doses of fentanyl and a varied dosage regimen as they may be more susceptible to adverse effects, such as respiratory depression and cardiovascular effects.

Dosage adjustments.

Renal impairment.

Fentanyl should be used with caution in patients with impaired renal function.

Hepatic impairment.

Fentanyl should be used with caution in patients with impaired hepatic function.

Instructions for use.

Fentanyl should be given only in an environment where the airway can be controlled and by personnel who can control the airway (see Section 4.4 Special Warnings and Precautions for Use, Respiratory depression (hypoventilation)).
DBL Fentanyl Injection is administered by intramuscular or intravenous injection only.
The dosage of fentanyl should be given in the smallest effective dose and as infrequently as possible to minimise the development of tolerance and physical dependence. Contains no antimicrobial agent. Product is for single use in one patient only. Discard any residue.

Handling instructions.

Wear gloves while opening the ampoule.
Accidental dermal exposure should be treated by rinsing the affected area with water. Avoid usage of soap, alcohol, and other cleaning materials that may cause chemical or physical abrasions to the skin.

4.3 Contraindications

Fentanyl is contraindicated in patients with a known hypersensitivity or intolerance to fentanyl or other opioid analgesics.
It should not be administered to patients who fall into the following categories:
Children less than 2 years old, because the safety of fentanyl in this age group has not been established (see Section 4.4 Special Warnings and Precautions for Use, Paediatric use).
Patients with severe respiratory disease, acute respiratory disease, respiratory depression, patients who may be particularly susceptible to respiratory depression such as comatose patients who may have head injury, brain tumour or increased intracranial pressure (see Section 4.4 Special Warnings and Precautions for Use, Respiratory depression (hypoventilation)).
Patients suffering from bronchial asthma.
Patients who have received monoamine oxidase (MAO) inhibitors within the previous 14 days (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Patients with myasthenia gravis. Fentanyl may cause thoracic muscle rigidity following intravenous administration. It should not be used in patients with a history of myasthenia gravis, as reversal of thoracic muscle rigidity with muscle relaxants is inappropriate in these patients.
Use in chronic non-cancer pain.

4.4 Special Warnings and Precautions for Use

Hazardous and harmful use.

DBL Fentanyl Injection contains the opioid fentanyl and is a potential drug of abuse, misuse and addiction. Addiction can occur in patients appropriately prescribed fentanyl at recommended doses.
The risk of addiction is increased in patients with a personal or family history of substance abuse (including alcohol and prescription and illicit drugs) or mental illness. The risk also increases the longer the drug is used and with higher doses. Patients should be assessed for their risks for opioid abuse or addiction prior to being prescribed fentanyl.
All patients receiving opioids should be routinely monitored for signs of misuse and abuse. Abuse or intentional misuse of fentanyl may result in overdose and/or death. Opioids are sought by people with addiction and may be subject to diversion. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the safe storage and proper disposal of any unused drug (see Section 6.4 Special Precautions for Storage; Section 6.6 Special Precautions for Disposal). Caution patients that abuse of oral or transdermal forms of opioids by parenteral administration can result in serious adverse events, which may be fatal.
Patients should be advised not to share fentanyl with anyone else.

Accidental ingestion/exposure.

Accidental ingestion or exposure of fentanyl, especially by children, can result in a fatal overdose of fentanyl. Patients and their caregivers should be given information on safe storage and disposal of unused fentanyl (see Section 4.2 Dose and Method of Administration, Handling instructions; Section 6.4 Special Precautions for Storage; Section 6.6 Special Precautions for Disposal).

Respiratory depression (hypoventilation).

Profound analgesia is accompanied by marked respiratory depression, which can persist or recur in the post-operative period. Hyperventilation during anaesthesia may alter the patient's responses to CO2, thus affecting respiration post-operatively. Therefore, patients should remain under appropriate surveillance.
It has been reported that diminished sensitivity to CO2 stimulation may persist longer than depression of respiratory rate. This dose related effect of respiratory depression peaks between 5 and 15 minutes after injection, but seldom lasts longer than 30 minutes.
Serious, life-threatening or fatal respiratory depression can occur with the use of opioids even when used as recommended. It can occur at any time during the use of fentanyl, but the risk is greatest during initiation of therapy or following an increase in dose. Patients should be monitored closely for respiratory depression at these times.
The risk of life-threatening respiratory depression is also higher in elderly, frail, or debilitated patients, in patients with existing impairment of respiratory function (e.g. chronic obstructive pulmonary disease, asthma) and in patients with hepatic and renal impairment (see Conditions which require dose reduction). Opioids should be used with caution and with close monitoring in these patients (see Section 4.2 Dose and Method of Administration). During anaesthesia this may be managed by assisted or controlled respiration. The use of opioids is contraindicated in patients with severe respiratory disease, acute respiratory disease and respiratory depression (see Section 4.3 Contraindications).
The risk of respiratory depression is greater with the use of high doses of opioids, especially high potency and modified release formulations, and in opioid naïve patients. Initiation of opioid treatment should be at the lower end of the dosage recommendations with careful titration of doses to achieve effective pain relief. Careful calculation of equianalgesic doses is required when changing opioids or switching from immediate release to modified release formulations, together with consideration of pharmacological differences between opioids. Consider starting the new opioid at a reduced dose to account for individual variation in response.
Respiratory depression caused by opioid analgesics is dose related and can be reversed by opioid antagonists, such as naloxone, but additional doses of naloxone may be necessary because the respiratory depression may last longer than the duration of action of the opioid antagonist. Consult individual prescribing information (for naloxone) before employing opioid antagonists. Appropriate surveillance should be maintained for the duration of opioid antagonist action. The use of an opioid antagonist will also reverse analgesia. For discussion of opioid antagonists in Section 4.9 Overdose.
Respiratory depression is more likely to occur with intravenous administration if a dose is given too rapidly and it rarely occurs with intramuscular administration.
Resuscitative equipment and an opioid antagonist should be readily available to manage apnoea.
Opioids can cause central sleep apnoea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper.
The effect on respiratory depression persists longer than the measured analgesic effect, and care should be taken, with the total opioid dose considered when fentanyl is given postoperatively. The recommended dose may be as low as quarter of that normally prescribed.

Tolerance and opioid use disorder (abuse and dependence).

Neuroadaptation of the opioid receptors to repeated administration of opioids can produce tolerance and physical dependence. Tolerance is the need for increasing doses to maintain analgesia. Tolerance may occur to both the desired and undesired effects of the opioid. Patients on chronic opioid therapy or with a history of opioid abuse may require higher doses.
Repeated use of opioids may lead to opioid use disorder (OUD). Abuse or intentional misuse of opioids may result in overdose and/or death. The risk of developing OUD is increased in patients with a personal or a family history (parents or siblings) of substance use disorders (including alcohol use disorder), in current tobacco users or in patients with a personal history of other mental health disorders (e.g. major depression, anxiety and personality disorders).
Physical dependence, which can occur after several days to weeks of continued opioid usage, results in withdrawal symptoms if the opioid is ceased abruptly or the dose is significantly reduced. Withdrawal symptoms can also occur following the administration of an opioid antagonist (e.g. naloxone) or partial agonist (e.g. buprenorphine). Withdrawal can result in some or all of the following symptoms: dysphoria, restlessness/agitation, lacrimation, rhinorrhoea, yawning, sweating, chills, myalgia, mydriasis, irritability, anxiety, increasing pain, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhoea, increased blood pressure, increased respiratory rate and increased heart rate.
When discontinuing fentanyl in a person who may be physically-dependent, the drug should not be ceased abruptly but withdrawn by tapering the dose gradually (see Ceasing opioids; see Section 4.2 Dose and Method of Administration).

Ceasing opioids.

Abrupt discontinuation or rapid decreasing of the dose in a person physically dependent on an opioid may result in serious withdrawal symptoms and uncontrolled pain (see Tolerance and opioid use disorder (abuse and dependence)). Such symptoms may lead the patient to seek other sources of licit or illicit opioids. Opioids should not be ceased abruptly in a patient who is physically dependent but withdrawn by tapering the dose slowly. Factors to take into account when deciding how to discontinue or decrease therapy include the dose and duration of the opioid the patient has been taking, the type of pain being treated and the physical and psychological attributes of the patient. A multimodal approach to pain management should be in place before initiating an opioid analgesic taper. During tapering, patients require regular review and support to manage any increase in pain, psychological distress and withdrawal symptoms.
There are no standard tapering schedules suitable for all patients and an individualised plan is necessary. In general, tapering should involve a dose reduction of no more than 10 percent to 25 percent every 2 to 4 weeks (see Section 4.2 Dose and Method of Administration). If the patient is experiencing increased pain or serious withdrawal symptoms, it may be necessary to go back to the previous dose until stable before proceeding with a more gradual taper.
When ceasing opioids in a patient who has a suspected opioid use disorder, the need for medication assisted treatment and/or referral to a specialist should be considered.

Head injuries and increased intracranial pressure.

Fentanyl is contraindicated in patients who may be particularly susceptible to respiratory depression, such as comatose patients who may have a head injury or brain tumour (see Section 4.3 Contraindications). In addition, fentanyl may obscure the clinical course of patients with a head injury.
The use of rapid bolus injections of opioids should be avoided in patients with compromised intracerebral compliance; in such patients the transient decrease in the mean arterial pressure has occasionally been accompanied by a short-lasting reduction of the cerebral perfusion pressure.

Neonatal withdrawal syndrome.

There is a risk that newborn infants will experience neonatal withdrawal syndrome following prolonged use of opioids, including fentanyl, during pregnancy (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).

Hyperalgesia.

Hyperalgesia may occur with the use of opioids, particularly at high doses. Hyperalgesia may manifest as an unexplained increase in pain, increased levels of pain with increasing opioid dosages or diffuse sensitivity not associated with the original pain. Hyperalgesia should not be confused with tolerance (see Tolerance and opioid use disorder (abuse and dependence)). If opioid induced hyperalgesia is suspected, the dose should be reduced and tapered off if possible. A change to a different opioid may be required.

Severe cardiovascular depression.

Fentanyl may cause severe bradycardia, severe hypotension including orthostatic hypotension, and syncope. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g. phenothiazines or general anaesthetics) (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). In patients with circulatory shock, fentanyl may cause vasodilation that can further reduce cardiac output and blood pressure. Monitor these patients for signs of hypotension after initiating or titrating the dosage of fentanyl.

Cardiac effects.

Fentanyl should be used with caution in patients with cardiac arrhythmias, including bradyarrhythmias (due to its weak cholinergic activity). Fentanyl may produce bradycardia, and possibly asystole, if the patient has received an insufficient amount of anticholinergic or when fentanyl is combined with non-vagolytic muscle relaxants. Opioids may induce hypotension, particularly in hypovolaemic patients. Appropriate measures should be taken to maintain stable arterial pressure.

Muscle rigidity.

Intravenous administration of fentanyl may cause muscle rigidity, particularly of the muscles of respiration and alter the rate of respiration especially in patients suffering from myasthenia gravis. This effect is related to the speed of injection and its incidence can be reduced by a slow intravenous injection (ordinarily sufficient for lower doses) and the use of muscle relaxants.
Non-epileptic (myo)clonic movements can occur.

Conditions which require dose reduction.

Dosage reduction is desirable in patients suffering from hypothyroidism, chronic hepatic disease, pulmonary disease, decreased respiratory reserve and alcoholism. Such patients also require prolonged post-operative monitoring.

Management of complications.

Patients receiving fentanyl should be kept under close medical supervision. Resuscitative facilities and an opioid antagonist compatible with the patient's condition should be available for the management of complications.

Fentanyl as a supplement for anaesthesia.

Certain forms of conduction anaesthesia, such as spinal anaesthesia and some peridural anaesthetics can alter respiration by blocking intercostal nerves. Through other mechanisms fentanyl can also alter respiration. Therefore, when fentanyl is used to supplement these forms of anaesthesia, the anaesthetist should be familiar with the physiological alterations involved and be prepared to manage them in patients selected for these forms of anaesthesia.

Supervision during use.

Fentanyl should only be used by experienced physicians and in patients who are under constant supervision.

Serotonin syndrome.

Caution is advised when fentanyl is co-administered with drugs that affect the serotonergic neurotransmitter systems.
The development of a potentially life-threatening serotonin syndrome may occur with the concomitant use of serotonergic drugs such as Selective Serotonin Re-uptake Inhibitors (SSRIs), Serotonin Norepinephrine Re-uptake Inhibitors (SNRIs), and with drugs which impair metabolism of serotonin (including Monoamine Oxidase Inhibitors [MAOIs]). This may occur within the recommended dose.
Serotonin syndrome may include mental status changes (e.g. agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, labile blood pressure, hyperthermia, diaphoresis), neuromuscular abnormalities (e.g. hyperreflexia, incoordination, rigidity, tremor, myoclonus), and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea).
If serotonin syndrome is suspected, rapid discontinuation of fentanyl should be considered. A dose reduction or discontinuation of at least one of the other serotonergic medicines being taken should be also considered depending on the severity of symptoms.

Cytochrome P450 3A4 interactions.

Concomitant use of fentanyl with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g. erythromycin), azole-antifungal agents (e.g. ketoconazole), and protease inhibitors (e.g. ritonavir), may increase plasma concentrations of fentanyl and prolong opioid adverse reactions, which may exacerbate respiratory depression (see Section 4.4 Special Warnings and Precautions for Use), particularly when an inhibitor is added after a stable dose of fentanyl is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in fentanyl-treated patients may increase fentanyl plasma concentrations and prolong opioid adverse reactions. When using fentanyl with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in fentanyl-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of fentanyl (see Section 4.2 Dose and Method of Administration; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Concomitant use of fentanyl with CYP3A4 inducers, or discontinuation of a CYP3A4 inhibitor, could result in lower than expected fentanyl plasma concentrations and decrease efficacy. When using fentanyl with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor, monitor patients closely at frequent intervals and consider adjusting the fentanyl dosage (see Section 4.2 Dose and Method of Administration; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol.

Concomitant use of opioids and benzodiazepines or other CNS depressants, including alcohol, may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of fentanyl with CNS depressant medicines, such as other opioid analgesics, benzodiazepines, gabapentinoids, cannabis, sedatives, hypnotics, tricyclic antidepressants, antipsychotics, antihistamines, centrally-active anti-emetics, general anaesthetics, tranquilisers, or other CNS depressants, including alcohol, should be reserved for patients for whom other treatment options are not possible.
If a decision is made to prescribe fentanyl concomitantly with any of the medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response.
Patients should be followed closely for signs and symptoms of respiratory depression and sedation. Patients and their caregivers should be made aware of these symptoms. Patients and their caregivers should also be informed of the potential harms of consuming alcohol while taking fentanyl.
Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of medicine-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Combination with neuroleptics.

When fentanyl is used in conjunction with neuroleptics such as droperidol, the differing duration of action should be taken into account. Hypotension can occur which may be due to hypovolaemia so appropriate parenteral therapy should be readily available.

General.

As has been observed with all opioid analgesics, episodes suggestive of sphincter of Oddi spasm may occur with fentanyl.
Vital signs should be monitored carefully.

Obese patients.

Fentanyl should be administered with additional caution in obese patients. Obese patients should be observed carefully for signs of fentanyl toxicity.

Use in hepatic impairment.

Fentanyl should be administered with caution to patients with liver dysfunction.

Use in renal impairment.

Fentanyl should be administered with caution to patients with kidney dysfunction. They should be observed carefully for signs of fentanyl toxicity. Such patients also require prolonged post-operative monitoring.

Use in the elderly or debilitated patient.

Elderly patients may require lower doses of fentanyl and a varied dosage regimen as they may be more susceptible to adverse effects, such as respiratory depression and cardiovascular effects. They may also have age related kidney function impairment, resulting in lower clearance rates of fentanyl.

Paediatric use.

Safe use of DBL Fentanyl Injection in children younger than 2 years has not been established. It should not be administered in children younger than 2 years of age.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

CNS depressants.

Other drugs with CNS depressant activity, e.g. other opioid analgesics, benzodiazepines, gabapentinoids (gabapentin and pregabalin), cannabis, sedatives, hypnotics, tricyclic antidepressants, antipsychotics, antihistamines, centrally-active anti-emetics, general anaesthetics, tranquilisers, other CNS depressants, including alcohol; fentanyl may have additive or potentiating effects with these drugs.
Patients who have received other CNS depressant drugs will require a lower dose of fentanyl than usual. Likewise, following the administration of fentanyl, the dose of other CNS depressant drugs should also be reduced. This is particularly important after surgery, because profound analgesia is accompanied by marked respiratory depression, which can persist or recur in the postoperative period. Administration of a CNS depressant, such as benzodiazepine or related drugs, during this period may disproportionally increase the risk of respiratory depression (see Section 4.4 Special Warnings and Precautions for Use). Post-operative opioids, including fentanyl and other CNS depressant drugs should be given initially in reduced doses, as low as 1/4 to 1/3 of doses usually recommended. As with other opioids, the respiratory depressant effect of fentanyl persists longer than the measured analgesic effect. The total dose of all opioid analgesics should be taken into account before giving opioid analgesics during recovery from anaesthesia. See Table 1 and Table 2.
For etomidate, the total plasma clearance is decreased by 2.7-fold and volume of distribution is decreased by a factor 2.4 while half-life increased by 1.2 times when administered with fentanyl. Simultaneous administration of fentanyl and intravenous midazolam results in an increase in the terminal plasma half-life and a reduction in the plasma clearance of midazolam. When these drugs are co-administered with fentanyl their dose may need to be reduced.

Conduction anaesthesia.

Certain forms conduction anaesthesia, such as spinal anaesthesia and some peridural anaesthetics can alter respiration by blocking intercostal nerves. Through other mechanisms (see Section 5 Pharmacological Properties) fentanyl can also alter respiration. Therefore, when fentanyl is used to supplement these forms of anaesthesia, the anaesthetist should be familiar with the special properties of each drug (particularly with the widely differing durations of actions), the physiological alterations involved and be prepared to manage them in patients selected for these forms of anaesthesia.

Lidocaine.

Concurrent administration of lidocaine and fentanyl may lead to a reduced seizure threshold.

MAO inhibitors.

Untoward incidents resulting from concurrent administration of opioids and MAO inhibitors have occurred. Nearly all of these reports have involved pethidine, but the safety of fentanyl has not been established in this situation. Therefore, before receiving fentanyl, patients should not have taken a MAO inhibitor within the previous 14 days (see Section 4.3 Contraindications).

Serotonergic drugs.

The concomitant use of opioids including fentanyl with a serotonergic agent, such as a selective serotonin reuptake inhibitor (SSRI), a serotonin norepinephrine reuptake inhibitor (SNRI) or a monoamine oxidase inhibitor (MAOI), may increase the risk of serotonin syndrome, a potentially life threatening condition (see Section 4.4 Special Warnings and Precautions for Use; Section 4.3 Contraindications).

Neuroleptics.

The combination of fentanyl with a neuroleptic such as droperidol, may cause hypotension (see Section 4.4 Special Warnings and Precautions for Use). If this occurs, the possibility of hypovolaemia should also be considered. Care should be exercised in moving and positioning patients because of the possibility of orthostatic hypotension. If fluid therapy, together with other countermeasures, does not correct hypotension it may be necessary to administer a pressor agent other than adrenaline. Adrenaline may paradoxically decrease blood pressure in patients who have received droperidol, due to its alpha-adrenergic blocking action. Pulmonary arterial pressure may also be decreased. This should be considered when interpreting pulmonary arterial pressure measurements as it might determine the final management of the patient. The EEG pattern may return to normal slowly when droperidol is used with fentanyl. This should be taken into account if the EEG pattern is used for postoperative monitoring. Neuroleptics can induce extrapyramidal symptoms that can be controlled with anti-Parkinson agents.

Nitrous oxide.

Nitrous oxide has been reported to produce cardiovascular depression when given with high doses of fentanyl.

Amiodarone.

Profound bradycardia, sinus arrest and hypotension have occurred when patients receiving amiodarone have been given fentanyl for anaesthesia.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Impairment of fertility has been observed in female rats given fentanyl 160 microgram/kg/day subcutaneously (no effect dose not established) or 400 microgram/kg/day intravenously (no effect dose 100 microgram/kg/day). Fertility in male rats was unaffected at 400 microgram/kg/day intravenously.
(Category C)
Category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human foetus or neonate without causing malformations. These effects may be reversible.
Although no teratogenic or acute embryotoxic effects have been observed in animal experiments, insufficient data are available to evaluate any harmful effects in man. Consequently, the risks and potential benefits should be considered before this drug is administered to pregnant patients.
Opioid analgesics may cause respiratory depression in the newborn infant. Administration during childbirth (including caesarean section) is not recommended, because fentanyl crosses the placenta (foetal blood concentrations about 40% of maternal blood concentrations) and the foetal respiratory centre is particularly sensitive to opioids which may suppress spontaneous respiration in the newborn. If fentanyl is administered during childbirth, an assisted ventilation equipment must be immediately available for the mother and infant. An opioid antagonist must always be available for the baby.
Prolonged use of fentanyl during pregnancy can result in physical dependence in the neonate and neonatal withdrawal syndrome shortly after birth. Neonatal withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Advise pregnant women using opioids of neonatal withdrawal syndrome and ensure that appropriate treatment will be available.
Neonatal withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhoea, and failure to gain weight. The onset, duration, and severity of neonatal withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal withdrawal syndrome and manage accordingly.
In pregnant rats, fentanyl is embryocidal as evidenced by increased resorptions at doses of 30 microgram/kg/day intravenously or 160 microgram/kg/day or greater subcutaneously. Intravenous administration to rats at 30 microgram/kg/day during organogenesis was associated with prolonged delivery time and increased postnatal mortality of offspring. There was no effect on embryofoetal development when rats received subcutaneous fentanyl at doses up to 500 microgram/kg/day throughout gestation, and no evidence of teratogenicity in rabbits administered fentanyl at intravenous doses up to 400 microgram/kg/day during organogenesis. The potential risk for humans is unknown.
 Fentanyl is excreted into human breast milk and may cause sedation or respiratory depression in the newborn/infant. Therefore, breast-feeding or use of expressed breast milk is not recommended for 24 hours following administration of fentanyl. The risk/benefit of breast-feeding following fentanyl administration should be considered.

4.7 Effects on Ability to Drive and Use Machines

Fentanyl may cause drowsiness and general impairment of co-ordination and may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car or operating machinery. Ambulatory patients should be cautioned against driving or operating machinery. Patients should only drive or operate a machine if sufficient time has elapsed (at least 24 hours) after the administration of fentanyl.

4.8 Adverse Effects (Undesirable Effects)

Clinical data.

The safety of fentanyl was evaluated in 376 subjects who participated in 20 clinical trials evaluating fentanyl used as an anaesthetic. These subjects were administered at least one dose of fentanyl injection and provided safety data. Adverse drug reactions (ADRs), as identified by the investigator, reported for ≥ 1% of fentanyl injection-treated subjects in these studies are shown in Table 3.
Additional ADRs that occurred in < 1% of fentanyl injection-treated subjects in the 20 clinical trials are listed below in Table 4.

Postmarketing data.

Adverse drug reactions first identified during post-marketing experience with fentanyl injection are included in Table 5, based on spontaneous reporting rates. The frequencies are provided according to the following convention: very common: ≥ 1/10; common: ≥ 1/100 and < 1/10; uncommon: ≥ 1/1,000 and < 1/100; rare: ≥ 1/10,000, < 1/1,000; very rare: < 1/10,000, including isolated reports.
The major adverse reactions associated with fentanyl are respiratory depression, apnoea, muscle rigidity, myoclonic movements and bradycardia, which if untreated, can lead to conditions such as cardiac arrest, circulatory depression and respiratory arrest.
Respiratory depression (usually associated with intravenous use) can be immediately reversed by an opioid antagonist. The respiratory depression is more likely to occur if the intravenous injection is given too rapidly; it rarely occurs with intramuscular injection. Secondary rebound respiratory depression has been observed after the operation in rare instances.
Muscle rigidity is a common side effect, and may be associated with reduced pulmonary compliance and/or apnoea, laryngospasm or bronchospasm. It may be reversed by intravenous administration of a muscle relaxant such as suxamethonium followed by controlled or artificial respiration.
Bradycardia can be controlled by the use of atropine. Bradycardia and other cholinergic effects are less likely if atropine or other anticholinergic agents are included in the pre-anaesthetic regimen.
Other reported adverse effects of fentanyl, when used alone, include elevated blood pressure, hypotension, blurred vision, dizziness, nausea, emesis, laryngospasm, diaphoresis, itching, euphoria and spasm of the sphincter of Oddi.
Less frequently, cardiac arrhythmias, postoperative mental depression, paradoxical CNS excitation or delirium may occur. Motor stimulation and bronchospasm may occur with high doses of fentanyl. Miosis or seizures may occur.
When used in conjunction with a neuroleptic agent such as droperidol, reported adverse effects include chills and/or shivering, restlessness, postoperative hallucinations, drowsiness, mental depression and extrapyramidal symptoms (dystonia, akathisia and oculogyric crisis). These have been observed up to 24 hours postoperatively. Elevated blood pressure, with or without pre-existing hypertension, has been reported following administration of fentanyl combined with droperidol. This might be due to unexplained alterations in sympathetic activity following large doses; however, it is also frequently attributed to anaesthetic and surgical stimulation during light anaesthesia.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Signs and symptoms.

The manifestations of DBL Fentanyl Injection overdosage are an extension of its pharmacological actions. In sufficient overdosage, fentanyl would produce narcosis, which may be preceded by marked skeletal muscle rigidity. Respiratory depression, which can vary in severity from bradypnoea to apnoea, may occur. This may be accompanied by cyanosis, followed by a fall in body temperature, circulatory collapse, coma and death. Toxic leucoencephalopathy has been observed with fentanyl overdose.

Treatment.

Respiration may need to be assisted or controlled and an adequate airway be maintained. An opioid antagonist such as naloxone should be available to manage respiratory depression. However, it should be remembered that the duration of respiratory depression may be longer than the duration of action of the opioid antagonist, and other more immediate and supportive treatment should be initiated.
If respiratory depression is associated with muscle rigidity, it may be necessary to facilitate assisted or controlled respiration with the use of a neuromuscular blocking agent. If hypotension occurs and is possibly associated with hypovolaemia, appropriate fluid therapy should be used.
Bradycardia may be treated by administering atropine or a neuromuscular blocking agent with vagolytic activity such as pancuronium or gallamine.
Hypotension may be treated by administration of appropriate parenteral fluid therapy. Repositioning of the patient to improve venous return to the heart should be considered and, if necessary, a vasopressor and/or naloxone (postoperatively only) may be administered.
Other supportive measures should also be employed as needed.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Fentanyl is a synthetic opioid analgesic related to the phenylpiperidines such as morphine. As an analgesic it is estimated to be about 80 times more potent than morphine. As with morphine and pethidine in equianalgesic doses, fentanyl produces respiratory depression, but there is a quicker return to normal respiration in healthy individuals.
Fentanyl unlike other phenylpiperidines rarely produces histamine release and exhibits little hypnotic activity.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Following parenteral administration via intravenous or intramuscular injection the action of fentanyl is rapid. Peak analgesic effect occurs within several minutes and has a duration of 30 to 60 minutes following a single dose of up to 100 microgram given intravenously. Respiratory depressant effects last longer than analgesia.

Distribution.

After intravenous injection, serum concentrations of fentanyl have been shown to decrease rapidly to about 20% of peak concentrations within 5 minutes of injection, followed by a slower decrease over the next 10 to 20 minutes to stabilise at a low concentration for 2 hours after injection. The short duration of action is probably due to the redistribution with up to 70% being bound to plasma proteins.

Metabolism.

Fentanyl is metabolised, mainly in the liver, to inactive metabolites norfentanyl, 4-N-anilinopiperidine and propionic acid. In vitro data show fentanyl is metabolized to norfentanyl mainly by CYP3A4.

Excretion.

About 20% of the drug is excreted in the urine within 8 hours, with up to 90% as the metabolites and 10% as unchanged fentanyl.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Hydrochloric acid, sodium chloride, sodium hydroxide, water for injections.

6.2 Incompatibilities

Fentanyl is incompatible with thiopental sodium and methohexitone sodium.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

DBL Fentanyl Injection is available in the following presentations in 5 ampoule (clear glass) pack sizes:
100 microgram per 2 mL;
500 microgram per 10 mL.
Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

The chemical formula of fentanyl citrate is C22H28N2O.C6H8O7 and its molecular weight is 528.6. The chemical structure of fentanyl citrate is:

CAS number.

990-73-8.

7 Medicine Schedule (Poisons Standard)

Schedule 8 (Controlled Drug).

Summary Table of Changes