Consumer medicine information

Aspen Fentanyl solution for injection

Fentanyl

BRAND INFORMATION

Brand name

Aspen Fentanyl

Active ingredient

Fentanyl

Schedule

S8

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Aspen Fentanyl solution for injection.

What is in this leaflet

This leaflet answers some of the common questions people ask about ASPEN FENTANYL. It does not contain all the information that is known about ASPEN FENTANYL.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given ASPEN FENTANYL against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What ASPEN FENTANYL is used for

ASPEN FENTANYL is a powerful drug used to relieve pain and produce sleepiness.

It can be used as a premedication before an operation, or with a general anaesthetic during an operation. It can also be used after painful operations to reduce the pain that you feel.

ASPEN FENTANYL belongs to a group of medicines called opioid (narcotic) analgesics.

It works by changing the messages that are sent to the brain about pain.

Your doctor will have explained why you are being treated with ASPEN FENTANYL and told you what dose you will be given.

Follow all directions given to you by your doctor carefully. They may differ from the information contained in this leaflet.

Ask your doctor if you want more information.

Your doctor may prescribe this medicine for another use.

ASPEN FENTANYL can be addictive, but when it is used only to relieve or prevent pain it is unlikely to become habit forming.

Before you are given it

When you must not use it

You should not be given ASPEN FENTANYL if you are pregnant or breastfeeding unless your doctor says it is safe.

Ask your doctor about the risks and benefits involved.

We do not know if it is safe for you to be given ASPEN FENTANYL while you are pregnant. It may affect your baby if it is given early in pregnancy or in the last weeks before your baby is due.

We do not know if your baby can take in ASPEN FENTANYL from breast milk if you are breastfeeding.

ASPEN FENTANYL solution for injection should only be used if the solution is clear, the package is undamaged and the use by (expiry) date marked on the pack has not passed.

Before you are given it

You must tell your doctor if:

  1. you have been given ASPEN FENTANYL before and had any problems with it.
  2. you have any allergies to any ingredients listed at the end of this leaflet, other opioid analgesics (strong pain killers) e.g. morphine or pethidine, or any other substances.
If you have an allergic reaction, you may get a skin rash, hay fever or an asthma attack.
  1. you have any of these medical conditions:
  • problems with your breathing such as severe asthma, severe bronchitis or emphysema
  • a history of fits or head injuries
  • myasthenia gravis (muscle weakness)
  • heart problems
  • liver or kidney problems
  • you are taking MAO (monoamine oxidase) Inhibitors or have taken them within the last 14 days (ask your pharmacist if you are unsure)
  • safe use in children under two year of age has not been established
  • history of drug dependence.

It may not be safe for you to be given ASPEN FENTANYL if you have any of these conditions.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription at the chemist, supermarket or health food shop. These medicines may affect the way ASPEN FENTANYL works.

Your doctor or pharmacist can tell you what to do if you are taking any other medicines.

If you have not told your doctor about any of these things, tell them before you are given any ASPEN FENTANYL.

How ASPEN FENTANYL is given

ASPEN FENTANYL will be given to you by injection by an experienced doctor and you will be under constant supervision.

The injection may be given into a vein or into a muscle. It may be given before, during or after surgery.

Your doctor will prescribe the correct dose based on factors such as your age, bodyweight, physical status and medical condition.

How long to take it

Continue taking your medicine for as long as your doctor tells you. If you stop having 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.

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

If you take too much (Overdose):

The doctor or nurse giving you ASPEN FENTANYL will be experienced in its use, so it is extremely unlikely that you will be given too much.

However, the first sign of overdosage is often muscle spasm, followed by a marked slowing of your breathing, accompanied by a bluish tinge on the skin. You will probably lose consciousness.

ASPEN FENTANYL doses should be carefully worked out, so problems with overdosage are unlikely. There are other drugs, e.g. naloxone or nalorphine, which can be used if needed to reverse the effects of too much ASPEN FENTANYL.

If you or someone else receive too much (overdose), and experience one or more of the symptoms below call triple zero (000) for an ambulance. 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 Aspen Fentanyl that was prescribed for you. If someone takes an overdose they may experience one or more of the following symptoms:

  • Slow, unusual or difficult breathing
  • Drowsiness, dizziness or unconsciousness
  • Slow or weak heartbeat
  • Nausea or vomiting
  • Convulsions or fits

If you think you or someone else may have used too much Aspen Fentanyl 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.

When seeking medical attention, take this leaflet and remaining medicine with you to show the doctor. Also tell them about any other medicines or alcohol which have been taken.

Things to be careful of:

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

As with all other opioid containing products, your body may become used to you taking Aspen Fentanyl. Taking it may result in physical dependence. Physical dependence means that you may experience withdrawal symptoms if you stop taking Aspen Fentanyl suddenly, so it is important to take it exactly as directed by your doctor.

Tolerance to Aspen 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.

Side effects

Tell your doctor or nurse as soon as possible if you do not feel well after you have been given ASPEN FENTANYL.

This medicine helps most people suffering severe pain, but it may have unwanted side-effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your doctor, nurse or pharmacist to answer any questions you may have.

After you have been given ASPEN FENTANYL you will probably feel light-headed, dizzy, sleepy and you may feel quite strange, especially if you are not lying down.

Tell your doctor or nurse if you notice any of the following side effects and they worry you.

ASPEN FENTANYL may cause slowing down of breathing or muscle spasm.

ASPEN FENTANYL sometimes causes:

  • changes in blood pressure (higher or lower)
  • dizziness
  • nausea (feeling sick)
  • vomiting
  • blurred vision
  • itching
  • euphoria (exaggerated sense of well-being).

Tell your doctor if you notice anything else that is making you feel unwell. Some people may get other side effects after being given ASPEN FENTANYL.

After taking it

Storage

If you are storing ASPEN FENTANYL at home keep them in the original pack in a cool dry place where the temperature stays below 30°C.

Do not store it or any other medicine in the bathroom or near a sink. Heat and dampness can destroy some medicines.

Keep medicines where young children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Do not leave it in the car on hot days.

Disposal

Make sure that you return to your doctor or pharmacist any injections that have passed the use by (expiry) date marked on the pack, or if you have any left over when your doctor says you no longer need to be given ASPEN FENTANYL injections.

Product Description

ASPEN FENTANYL solution for injection is a clear, colourless solution in a glass ampoule.

Available in packs of 5 or 10 ampoules.

ASPEN FENTANYL solution for injection is available in two strengths:

  • 100 micrograms/2 mL
  • 500 micrograms/10 mL

Ingredients

Active ingredient:

Each ASPEN FENTANYL injection contains fentanyl citrate 50 microgram/mL as the active ingredient.

Inactive ingredients:

  • sodium chloride
  • water for injections.

Sponsor

Aspen Pharmacare Australia Pty Ltd
34-36 Chandos St
St Leonards NSW 2065
Australia

Australian Registration Numbers:

100 micrograms/2 mL: AUST R 170929

500 micrograms/10 mL: AUST R 170931

This leaflet was revised in November 2020.

Published by MIMS January 2021

BRAND INFORMATION

Brand name

Aspen Fentanyl

Active ingredient

Fentanyl

Schedule

S8

 

1 Name of Medicine

Fentanyl citrate.

2 Qualitative and Quantitative Composition

Aspen Fentanyl solution for injection contains fentanyl citrate 0.0785 mg/mL (equivalent to fentanyl 0.05 mg/mL) as the active ingredient. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Aspen Fentanyl solution for injection is a clear and colourless solution in a glass ampoule.

4 Clinical Particulars

4.1 Therapeutic Indications

Short duration analgesia during premedication, induction and maintenance of anaesthesia, and in the immediate postoperative period.
Opioid analgesic supplement to general and regional anaesthesia.
Combination with a neuroleptic as an anaesthetic premedication for the induction of anaesthesia, and as an adjunct in the maintenance of general and regional anaesthesia.

4.2 Dose and Method of Administration

Dosage should be individualised according to age, bodyweight, physical status, underlying pathological condition, use of other drugs, type of anaesthesia to be used and the surgical procedure involved (also see Section 4.4 Special Warnings and Precautions for Use).
Aspen Fentanyl injection contains no antimicrobial agent. It should be used only once and any residue discarded.

Adults.

Premedication.

(To be appropriately modified in the elderly, debilitated and those who receive other depressant drugs.) 50 to 100 microgram (1 to 2 mL) may be administered intramuscularly 30 to 60 minutes prior to surgery.

Adjunct to general anaesthesia.

Induction.

50 to 100 microgram (1 to 2 mL) intravenously initially, repeat at two to three minute intervals until desired effect is achieved. A reduced dose of 25 to 50 microgram (0.5 to 1 mL) is recommended in elderly and poor risk patients.

Maintenance.

25 to 50 microgram (0.5 to 1 mL) intravenously or intramuscularly when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia.

Adjunct to regional anaesthesia.

50 to 100 microgram (1 to 2 mL) may be administered intramuscularly or slowly intravenously when additional analgesia is required.

Postoperatively (recovery room).

50 to 100 microgram (1 to 2 mL) may be administered intramuscularly for the control of pain, tachypnoea and emergence delirium. The dose may be repeated in one or two hours as needed.

Children.

For induction and maintenance in children 2 to 12 years of age, a reduced dose of 20 to 30 microgram (0.4 to 0.6 mL)/10 kg is recommended.

4.3 Contraindications

1. Known hypersensitivity or intolerance to fentanyl or other opioid analgesics.
2. Bronchial asthma (also see Section 4.4 Special Warnings and Precautions for Use).
3. In patients with severe respiratory disease, acute respiratory disease and respiratory depression.
4. Head injuries and increased intracranial pressure. As for any opioid analgesic, fentanyl should not be used in patients susceptible to respiratory depression, such as comatose patients who may have head injuries or a brain tumour (also see Section 4.4 Special Warnings and Precautions for Use). Fentanyl may obscure the clinical course of patients with a head injury.
5. Concomitant monoamine oxidase inhibitors. Severe and unpredictable potentiation by MAO inhibitors (monoamine oxidase inhibitors, MAOIs) has been reported with opioid analgesics and the use of fentanyl in patients who have received MAO inhibitors within 14 days is not recommended (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Monoamine oxidase inhibitors).
6. Myasthenia gravis. Fentanyl may cause muscle rigidity upon intravenous administration. Therefore, the need for reversal with muscle relaxants contraindicates its use in patients with a history of myasthenia gravis.
7. Use in chronic (long-term) non-cancer pain.
8. Use in children 2 years of age or younger. Safe conditions for use have not been established.

4.4 Special Warnings and Precautions for Use

Hazardous and harmful use.

Aspen Fentanyl contains the opioid fentanyl citrate and is a potential drug of abuse, misuse and addiction. Addiction can occur in patients appropriately prescribed Aspen 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 Aspen Fentanyl.
All patients receiving opioids should be routinely monitored for signs of misuse and abuse. 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 Aspen Fentanyl with anyone else.

Respiratory depression.

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 Aspen 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 and in patients with existing impairment of respiratory function (e.g. chronic obstructive pulmonary disease; asthma) and in patients with hepatic and renal impairment (see subheading 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. (see Section 4.2 Dose and Method of Administration).

Use of opioid antagonists for respiratory depression.

Respiratory depression caused by opioid analgesics can be reversed by opioid antagonists.
However, appropriate surveillance should be maintained because the duration of respiratory depression of doses of fentanyl employed during anaesthesia is usually longer than the duration of opioid antagonist action. Consult individual product information (nalorphine or naloxone) before employing opioid antagonists.

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 Aspen 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 Aspen Fentanyl.

Tolerance, dependence and withdrawal.

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.
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 Aspen 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; Section 4.2 Dose and Method of Administration).

Accidental ingestion/exposure.

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

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, dependence and withdrawal). 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.

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, dependence and withdrawal). 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.
Adequate facilities should be available for postoperative monitoring and ventilation.
Resuscitative equipment, oxygen and an opioid antagonist should be readily available to manage apnoea.
Fentanyl should only be used by experienced doctors and in patients who are under constant supervision.

Concomitant neuroleptics.

If fentanyl is administered with neuroleptics, the user should be familiar with the special properties of each drug, particularly with regard to durations of action. In addition, when such a combination is used, fluids and other countermeasures to manage hypotension should be available.

Total opioid dose.

As with other potent opioids, the respiratory depressant effect of fentanyl persists longer than the measured analgesic effect. The total dose of all opioid analgesics should be considered before additional opioid analgesics are given during recovery from anaesthesia. It is recommended that postoperative opioids, when required, should be used initially in reduced doses, as low as one-quarter to one-third of those usually recommended.

Muscle rigidity.

Fentanyl may cause muscle rigidity, particularly involving the muscles of respiration. This effect is related to the dose and speed of injection and may be reduced by slow intravenous injection. If this effect occurs, it may be managed by the use of assisted or controlled respiration and, if necessary, by administration of a neuromuscular blocking agent compatible with the patient's condition. Nonepileptic myoclonic movements can occur.

Impaired liver and kidney function.

Fentanyl should be administered with caution to patients with liver and kidney dysfunction because of the importance of these organs in the metabolism and excretion of drugs.

Bradycardia.

Fentanyl may produce bradycardia, and possibly asystole. Bradycardia may be treated with atropine; however, fentanyl should be used with caution in patients with cardiac bradyarrhythmias.

Sphincter of Oddi spasm.

As has been observed with all opioid analgesics, episodes suggestive of sphincter of Oddi spasm may occur with fentanyl.

Adjunct to conduction 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.

Monitoring.

Vital signs should be monitored routinely.

Hypotension.

Opioids may induce hypotension, particularly in hypovolaemic patients. Appropriate measures should be taken to maintain stable arterial pressure.

Use in hepatic impairment.

Fentanyl should be used with caution.

Use in renal impairment.

Fentanyl should be used with caution.

Use in the elderly.

Elderly, debilitated patients.

The initial fentanyl dose should be reduced in elderly and debilitated patients. Elderly patients 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. Opioids should be titrated with caution in patients with any of the following conditions: uncontrolled hypothyroidism, pulmonary disease, decreased respiratory reserve, alcoholism, impaired hepatic or renal function. Such patients also require prolonged postoperative monitoring.

Paediatric use.

The safety of fentanyl in children younger than 2 years of age has not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

1. Other central nervous system depressants.

Other drugs with CNS depressant activity, e.g., other opioid analgesics, benzodiazepines, gabapentinoids, cannabis, sedatives, hypnotics, tricyclic antidepressants, antipsychotics, antihistamines, centrally-active antiemetics, general anaesthetics, tranquilisers, other CNS depressants, including alcohol; fentanyl may have additive or potentiating effects with these drugs. When patients have received such drugs, the dose of fentanyl required will be less than usual. Likewise, following the administration of fentanyl, the dose of other CNS depressant drugs should be reduced (see Section 4.4 Special Warnings and Precautions for Use).

2. Fentanyl/neuroleptic combination.

(Also see Section 4.8 Adverse Effects (Undesirable Effects)). When a neuroleptic such as droperidol is used with fentanyl, pulmonary arterial pressure may be decreased. Hypotension can occur and, possibly, hypovolaemia (which should be managed with appropriate parenteral fluids).
Repositioning of the patient to improve venous return to the heart should be considered when operative conditions permit. Care should be exercised in moving and positioning of patients because of the possibility of orthostatic hypotension. If volume expansion with fluids together with other countermeasures do not correct hypotension, the administration of pressor agents other than adrenaline should be considered. Because of the alpha-adrenergic blocking action of droperidol, adrenaline may paradoxically decrease the blood pressure in patients treated with droperidol.
When droperidol is used with fentanyl and the EEG is used for postoperative monitoring, it may be found that the EEG pattern returns to normal slowly.

3. Monoamine oxidase inhibitors.

Severe and unpredictable potentiation by MAOIs has been reported with opioid analgesics. Since the safety of fentanyl in this regard has not been established, the use of fentanyl in patients who have received MAOIs within 14 days is not recommended (see Section 4.3 Contraindications, Concomitant monoamine oxidase inhibitors).

4. Nitrous oxide.

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

5. Amiodarone.

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

6. Adrenergic blockers and calcium channel blockers.

The combination of calcium channel blockers and beta-adrenergic blockers during fentanyl anaesthesia should be used with caution since severe hypotension has been reported to occur.
Coadministration of the following drugs may enhance or prolong the effects of fentanyl: azole antifungals, macrolide antibiotics and protease inhibitors such as ritonavir.
Coadministration of the following drugs may decrease the plasma concentration of fentanyl: phenytoin.
Coadministration of sibutramine hydrochloride with fentanyl may increase the risk of serotonin syndrome (hypertension, hypothermia, myoclonus and mental status changes).
The concurrent administration of fentanyl and naltrexone precipitates opioid withdrawal symptoms.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Opioid analgesics may cause respiratory depression in the newborn infant. These products should only be used during labour after weighing the needs of the mother against the risk to the fetus. If fentanyl is nevertheless administered, an antidote should always be at hand for the child. The safe use of fentanyl has not been established with respect to possible adverse effects upon fetal development. Therefore, it should be used in women of childbearing potential only when in the judgment of the doctor the potential benefits outweigh the possible hazards.
Withdrawal symptoms in newborn infants have been reported with prolonged use of opioids.
 Fentanyl may enter the maternal milk. Therefore, breastfeeding is not recommended for 24 hours following the administration of this drug.

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.

4.8 Adverse Effects (Undesirable Effects)

More common reactions.

Respiratory depression, apnoea, muscular rigidity, myoclonic movements and bradycardia.
If these remain untreated, respiratory arrest, circulatory depression or cardiac arrest could occur.
Respiratory depression is more likely to occur with intravenous administration if a dose is given too rapidly; it rarely occurs with intramuscular administration. If respiratory depression occurs during anaesthesia, assisted or controlled respiration will provide adequate ventilation without reversing analgesia. Respiratory depression can be immediately reversed by opioid antagonists (e.g. nalorphine) which, it should be noted, will also reverse analgesia. Secondary rebound respiratory depression has been observed after the operation in rare instances.
Muscular rigidity may be associated with reduced pulmonary compliance and/or apnoea, laryngospasm or bronchospasm. Prompt reversal of this effect can be achieved with the intravenous administration of an appropriate single dose of a muscle relaxant such as suxamethonium. Assisted or controlled respiration is required to provide ventilation after the use of muscle relaxants.
Bradycardia and other cholinergic effects may occur and can be controlled with the appropriate dose of atropine. The inclusion of atropine or other anticholinergic agents in the preanaesthetic regimen tends to reduce the occurrence of such effects.

Less common reactions.

Hypotension, hypertension, dizziness, blurred vision, miosis, nausea, emesis, laryngospasm, diaphoresis, itching, euphoria, seizures, spasm of the sphincter of Oddi and anaphylaxis. Motor stimulation and bronchospasm may occur with high doses of fentanyl. Less frequently, cardiac arrhythmias, postoperative mental depression, paradoxical CNS excitation or delirium may occur.

Fentanyl/neuroleptic combination.

When a neuroleptic such as droperidol is used with fentanyl, the following adverse reactions can occur: chills and/or shivering, restlessness and postoperative hallucinatory episodes sometimes associated with transient periods of mental depression; extrapyramidal symptoms (dystonia, akathisia and oculogyric crisis) have been observed up to 24 hours postoperatively. When they occur, extrapyramidal symptoms can usually be controlled with antiparkinson agents.
Postoperative drowsiness is also frequently reported following the use of droperidol. 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

Symptoms.

Narcosis (which may be preceded by marked skeletal muscle rigidity), cardiorespiratory depression accompanied by cyanosis, followed by a fall in body temperature, circulatory collapse, coma and possibly death.

Treatment.

In the presence of hypoventilation or apnoea, oxygen should be administered and respiration assisted or controlled as necessary. A patent airway must be maintained.
If depressed respiration is associated with muscular rigidity, an intravenous neuromuscular blocking agent might be required to facilitate assisted or controlled respiration.
The patient should be carefully observed for 24 hours; body warmth and adequate fluid intake should be maintained.
If severe or persistent hypotension occurs, the possibility of hypovolaemia should be considered and managed with appropriate parenteral fluid therapy.
A specific opioid antagonist, such as nalorphine or naloxone, should be available for use as indicated to manage respiratory depression. This does not preclude the use of more immediate countermeasures. The duration of respiratory depression following overdosage of fentanyl is usually longer than the duration of opioid antagonist action.
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 an opioid analgesic. A dose of fentanyl 100 microgram (i.e. 0.1 mg or 2 mL of the injection) is approximately equivalent in analgesic activity to 10 mg of morphine or 75 mg of pethidine. The principal actions of therapeutic value are analgesia and sedation. Alterations in respiratory rate and alveolar ventilation associated with opioid analgesics may last longer than the analgesic effect. As the dose of opioid is increased, the decrease in pulmonary exchange becomes greater. Large doses may produce apnoea. Fentanyl appears to have less emetic activity than either morphine or pethidine. Histamine assays and skin weal testing in humans indicate that clinically significant histamine release rarely occurs with fentanyl. Recent assays in humans show no clinically significant histamine release at doses up to 50 microgram/kg (0.05 mg/kg or 1 mL/kg). Fentanyl preserves cardiac stability and blunts stress related hormonal changes at higher doses.
Fentanyl produces minimal cortical depression and may act by filling receptor sites located in the thalamus, midbrain and spinal cord. A specific morphine antagonist (e.g. nalorphine) produces reversal of respiratory, cardiovascular, miotic and motor incoordination effects and also produces reversal of analgesia, euphoria and sedation. Rigidity of the diaphragm and intercostal muscles can be eliminated by suxamethonium. Cholinergic effects such as bradycardia are reversed by atropine.
As with longer acting opioid analgesics, the duration of the respiratory depressant effect of fentanyl may be longer than the analgesic effect. The following observations have been reported concerning altered respiratory response to CO2 stimulation following administration of fentanyl to man.
1. Diminished sensitivity to CO2 stimulation may persist longer than depression of respiratory rate. Fentanyl frequently slows the respiratory rate (see Section 4.4 Special Warnings and Precautions for Use).
2. Altered sensitivity to CO2 stimulation has been demonstrated for up to four hours following a single intravenous dose of fentanyl 600 microgram (12 mL) to healthy volunteers.
3. The duration and degree of respiratory depression is dose related.
4. The peak respiratory depressant effect of a single intravenous dose of fentanyl is noted 5 to 15 minutes following injection. (See Section 4.4 Special Warnings and Precautions for Use, Respiratory depression).

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

The pharmacokinetics of fentanyl can be described by a three compartment model, with a distribution time of 1.7 minutes, redistribution of 13 minutes and a terminal elimination half-life of 219 minutes. The volume of distribution for fentanyl is 4 L/kg.

Absorption.

The onset of action is almost immediate when the drug is given intravenously; however, the maximal analgesic and respiratory depressant effect may not be noted for several minutes. The usual duration of action of the analgesic effect is 30 to 60 minutes after a single intravenous dose of up to 100 microgram. Following intramuscular administration, the onset of action is from seven to eight minutes and the duration of action is one to two hours.

Distribution.

Fentanyl plasma protein binding capacity increases with increasing ionisation of the drug. Alterations in pH may affect its distribution between plasma and the central nervous system. It accumulates in skeletal muscle and fat, and is released slowly into the blood.

Metabolism and excretion.

Fentanyl is primarily transformed in the liver and demonstrates a high first-pass clearance with approximately 75% of an intravenous dose excreted in urine, primarily as metabolites, with less than 10% representing the unchanged drug. Approximately 9% of the dose is recovered in the faeces, primarily as metabolites.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Aspen Fentanyl contains the following excipients: sodium chloride and water for injections.
Aspen Fentanyl solution for injection contains no antimicrobial agent.

6.2 Incompatibilities

Incompatibilities - Fentanyl is incompatible with thiopentone 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 30°C. Protect from light.

6.5 Nature and Contents of Container

Aspen Fentanyl solution for injection is available in glass ampoules containing 100 micrograms/2 mL, 250 micrograms/5 mL or 500 micrograms/10 mL. They are available in packs of 5 or 10 ampoules.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical name: N-Phenyl-N-[1-(2-phenylethyl) piperidin-4-yl] propanamide dihydrogen 2-hydroxypropane-1,2,3-tricarboxylate.
Molecular formula: C22H28N2O,C6H8O7.
Molecular weight: 528.61.

Chemical structure.


CAS number.

990-73-8.

7 Medicine Schedule (Poisons Standard)

S8 - Controlled Drug.

Summary Table of Changes