Drugs List

Therapeutic Indications

Uses

Analgesia and suppression of respiratory activity in mechanically ventilated patients receiving intensive care.

Analgesia for painful manoeuvres.

An aid to compliance with mechanical ventilation and tolerance of the endotracheal tube.

Administration

For intravenous infusion.

Induction doses should be infused slowly over 3 minutes. An increased incidence of hypotension has been associated with rates of less than one minute.

Reconstitution

Alfentanil concentrate for solution for infusion should be diluted with sodium chloride 0.9% infusion, glucose 5% infusion, or compound sodium lactate intravenous infusion (Hartmann's solution). These dilutions are compatible with plastic bags and giving sets.

From a microbiological viewpoint, the diluted product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally be no longer than 24 hours at 2 to 8 degrees C, unless dilution was completed under aseptic conditions.

Compatibilities

Sodium chloride 0.9% infusion
Glucose 5% infusion
Compound sodium lactate intravenous infusion (Hartmann's solution)

Contraindications

Respiratory depression or obstructive airway disease unless ventilated.
Risk of paralytic ileus
Raised intracranial pressure
Head injury
Coma

Precautions and Warnings

Alfentanil should only be used by physicians experienced in the use of potent opioids when administered by continuous intravenous infusion and the management of respiratory effects of potent opioids. Resuscitation equipment, oxygen and narcotic antagonists must be readily available.

Patients receiving anaesthesia should be continuously monitored by a person not involved in the procedure. Monitor oxygen saturation and observed for signs of hypertension, apnoea, upper airway obstruction and/or oxygen desaturation. Pulse oximetry or some other means of monitoring is recommended.

Significant respiratory depression and loss of consciousness will occur following doses of alfentanil exceeding 1mg, and this effect is dose related. This effect is usually short in duration and can be reversed by specific opioid antagonists, such as naloxone. The duration of respiratory depression may last for longer than the opioid antagonist action, therefore additional doses of the antagonist may be required.

Following the discontinuation of alfentanil infusion, the patient should be closely observed for at least 6 hours. Prior use of opioid medication may enhance or prolong alfentanil respiratory effects. Respiratory depression may persist into or recur in the postoperative period. Before the patient is discharged from the recovery area, adequate spontaneous breathing must be established and maintained in the absence of stimulation. Monitoring of the patient should continue well after surgery due to the possibility of delayed respiratory depression.

Use with caution in:
Breastfeeding - see Lactation section
Pregnancy and Labour - see Pregnancy section

Hyperventilation during anaesthesia may alter the patient's response to carbon dioxide and affect respiration after the procedure.

Rapid bolus injections should be avoided in patients with compromised intracerebral compliance. A transient decrease in the mean arterial pressure, occasionally with a transient reduction of the cerebral perfusion pressure, may be experienced in these patients.

A decrease in blood pressure may occur following alfentanil administration. This effect may be exaggerated in patients with hypovolaemia or patients receiving concurrent sedatives. Measures should be taken to maintain a stable arterial blood pressure. Consider giving fluid replacement prior to induction: administration of alfentanil may produce loss of vascular tone and hypotension.

Alfentanil may cause bradycardia which can be severe with rapid onset. This can be antagonised by atropine. Care should be taken when alfentanil is administered after other drugs that can cause cardiac depression or increased vagal tone (e.g. anaesthetics or beta-blockers) as these may predispose the patient to bradycardia or hypotension. In patients who have not received atropine, cardiac arrest following bradycardia may occur. An anticholinergic drug should be available in case asystole occurs.

Heart rate and blood pressure should be monitored carefully and appropriate measures taken if hypotension or bradycardia occur, including a reduction in the rate of administration of alfentanil.

Use with caution if the patient has received monoamine oxidase inhibitors within the 2 weeks prior to administration of the alfentanil infusion.

A reduced dosage may be required in elderly patients - see Dosage; Elderly
A reduced dosage may be required in debilitated patients or patients with adrenocortical insufficiency - see Dosage; Additional Dosage

The dose should be titrated with care and prolonged monitoring may be required in patients with hypothyroidism, pulmonary disease, decreased respiratory reserve, alcoholism, renal impairment ( see Dosage; Renal Impairment) or hepatic impairment ( see Dosage; Hepatic Impairment).

As with all opioids, use with caution in patients with myasthenia gravis, hypotension, asthma, prostatic hypertrophy, obstructive or inflammatory bowel disease, biliary tract disorders, convulsive disorders or shock.

To avoid excessive doses, obese patients may require doses based on their lean (ideal) body mass.

Repeated administration may cause dependence and tolerance. Use with caution in patients with a history of drug dependence. Higher doses may be required in patients receiving chronic opioid therapy or those with a history of opioid abuse.

The half life of alfentanil is prolonged in neonates and accumulation is likely with prolonged use.

There is little experience with alfentanil concentrate for solution for infusion in children. It may be more appropriate to use the lower strength alfentanil 500micrograms/ml solution. Consult appropriate monograph for full information.

Muscle rigidity, may occur, potentially affecting all skeletal muscles. The incidence and severity of the muscle rigidity is dose related, sometimes occurring at does of 20microgram/kg and consistently appearing at doses in excess of 130microgram/kg. This may be helped with neuromuscular blocking drugs, slow IV injection or premedication with a benzodiazepine or a muscle relaxant.

Non-epileptic (myo)clonic movements may occur.

Avoid abrupt withdrawal after long term use.

Alfentanil infusions should be discontinued at least 10 to 15 minutes prior to the end of surgery during general anaesthesia. During administration of alfentanil during monitored anaesthesia care, infusions of alfentanil may be continued to the end of the procedure.

Advise patient to avoid alcohol.

Patients must be advised not to drive or operate machinery for 24 hours after alfentanil administration.

All patients require careful monitoring for signs of abuse and addiction.

Adrenal insufficiency has been reported with opioid use, as opioid may influence the gonadal or the hypothalamic-pituitary-adrenal axes. Changes in serum prolactin, plasma cortisol and testosterone levels have been shown with the use of opioids. If adrenal insufficiency is suspected, gradually wean patient off opioid treatment until adrenal function is recovered. Continue with corticosteroid treatment until adrenal function has recovered and opioid treatment can commence.

Neonate exposure in labour, risk of respiratory depression.

Neonate exposed in utero, monitor for neonatal withdrawal syndrome.

Advise that effects are potentiated by CNS depressants (including alcohol). Monitor at regular intervals as withdrawal symptoms & dependence may occur. Monitor patients with a history of alcoholism and drug abuse. Progressive withdrawal recommended. Consider dose reduction or alternative opioid in cases of hyperalgesia. Monitor patients on prolonged therapy. When used with SSRIs, risk of Serotonin syndrome. Neonate exposed in labour: Risk of respiratory depression. Neonate exposed in utero: Monitor for neonatal withdrawal syndrome.

Pregnancy and Lactation

Pregnancy

Use alfentanil with caution during pregnancy.

The manufacturer advises caution when prescribing alfentanil during pregnancy.

At the time of writing there is limited published information regarding the use of alfentanil during pregnancy. Alfentanil crosses the placenta, and regular use during pregnancy may result in drug dependence in the foetus and withdrawal symptoms in the neonate. Use of alfentanil during labour may result in respiratory depression in the neonate. Animal studies have not shown teratogenic or acute embryotoxic effects.

Lactation

The use of alfentanil is contraindicated during breastfeeding.

The manufacturer does not recommend the use of alfentanil during breastfeeding. Alfentanil is secreted into breast milk, and may cause respiratory depression in the breastfeed infant.

LactMed (2018) states that there is limited data regarding intravenous use thus alternative agents are preferred. If alfentanil is used during breastfeeding and the infant shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately.

Side Effects

Local pain (injection site)
Shivering
Hypersensitivity reactions
Anaphylaxis
Bronchospasm
Urticaria
Hypotension
Hypertension
Muscle rigidity
Myoclonic movements
Dizziness
Headache
Nausea
Vomiting
Drowsiness
Bradycardia
Tachycardia
Arrhythmias
Asystole
Somnolence
Disorientation
Agitation
Euphoria
Apnoea
Respiratory depression
Cough
Laryngospasm
Hiccups
Pruritus
Hyperhidrosis
Urinary retention
Sensation of cold
Respiratory arrest
Constipation
Dry mouth
Biliary spasm
Palpitations
Oedema
Postural hypotension
Hallucinations
Vertigo
Dysphoria
Mood changes
Confusion
Sleep disturbances
Sexual dysfunction
Difficulty in micturition
Ureteric spasm
Miosis
Flushing
Rash
Dependence
Elevation of liver enzymes
Hypothermia
Restlessness
Raised intracranial pressure
Coma
Circulatory failure
Hypoxia
Excitation
Visual disturbances
Movement disturbances
Sedation
Dyskinesia
Unconsciousness
Convulsions
Increased heart rate
Bradypnoea
Hypercapnia
Cardiac arrest
Epistaxis
Allergic dermatitis
Erythema
Fatigue
Pain
Fever

Presentation

Concentrate infusion of alfentanil hydrochloride.

Drugs List

Therapeutic Indications

Uses

Analgesia and suppression of respiratory activity in mechanically ventilated patients receiving intensive care.

Analgesia for painful manoeuvres.

An aid to compliance with mechanical ventilation and tolerance of the endotracheal tube.

Dosage

This monograph relates only to the specific indications of the 5mg/ml alfentanil. Different strength preparations of alfentanil are available for other specific uses and the separate monographs should be consulted for further information.

Alfentanil should be administered only in a setting fully equipped for the monitoring and support of respiratory function and by persons specifically trained in the use of anaesthetic drugs and the recognition and management of the expected adverse effects of potent opioids, including respiratory resuscitation.

Maximum duration of treatment is 4 days.

At the proposed doses, alfentanil concentrate for infusion has no sedative activity and supplementation with an appropriate hypnotic or sedative agent is recommended. Admixture is not advisable as both agents require individual titration.

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For intravenous infusion.

Induction doses should be infused slowly over 3 minutes. An increased incidence of hypotension has been associated with rates of less than one minute.

Reconstitution

Alfentanil concentrate for solution for infusion should be diluted with sodium chloride 0.9% infusion, glucose 5% infusion, or compound sodium lactate intravenous infusion (Hartmann's solution). These dilutions are compatible with plastic bags and giving sets.

From a microbiological viewpoint, the diluted product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally be no longer than 24 hours at 2 to 8 degrees C, unless dilution was completed under aseptic conditions.

Compatibilities

Sodium chloride 0.9% infusion
Glucose 5% infusion
Compound sodium lactate intravenous infusion (Hartmann's solution)

Contraindications

Respiratory depression or obstructive airway disease unless ventilated.
Risk of paralytic ileus
Raised intracranial pressure
Head injury
Coma

Precautions and Warnings

Alfentanil should only be used by physicians experienced in the use of potent opioids when administered by continuous intravenous infusion and the management of respiratory effects of potent opioids. Resuscitation equipment, oxygen and narcotic antagonists must be readily available.

Patients receiving anaesthesia should be continuously monitored by a person not involved in the procedure. Monitor oxygen saturation and observed for signs of hypertension, apnoea, upper airway obstruction and/or oxygen desaturation. Pulse oximetry or some other means of monitoring is recommended.

Significant respiratory depression and loss of consciousness will occur following doses of alfentanil exceeding 1mg, and this effect is dose related. This effect is usually short in duration and can be reversed by specific opioid antagonists, such as naloxone. The duration of respiratory depression may last for longer than the opioid antagonist action, therefore additional doses of the antagonist may be required.

Following the discontinuation of alfentanil infusion, the patient should be closely observed for at least 6 hours. Prior use of opioid medication may enhance or prolong alfentanil respiratory effects. Respiratory depression may persist into or recur in the postoperative period. Before the patient is discharged from the recovery area, adequate spontaneous breathing must be established and maintained in the absence of stimulation. Monitoring of the patient should continue well after surgery due to the possibility of delayed respiratory depression.

Use with caution in:
Breastfeeding - see Lactation section
Pregnancy and Labour - see Pregnancy section

Hyperventilation during anaesthesia may alter the patient's response to carbon dioxide and affect respiration after the procedure.

Rapid bolus injections should be avoided in patients with compromised intracerebral compliance. A transient decrease in the mean arterial pressure, occasionally with a transient reduction of the cerebral perfusion pressure, may be experienced in these patients.

A decrease in blood pressure may occur following alfentanil administration. This effect may be exaggerated in patients with hypovolaemia or patients receiving concurrent sedatives. Measures should be taken to maintain a stable arterial blood pressure. Consider giving fluid replacement prior to induction: administration of alfentanil may produce loss of vascular tone and hypotension.

Alfentanil may cause bradycardia which can be severe with rapid onset. This can be antagonised by atropine. Care should be taken when alfentanil is administered after other drugs that can cause cardiac depression or increased vagal tone (e.g. anaesthetics or beta-blockers) as these may predispose the patient to bradycardia or hypotension. In patients who have not received atropine, cardiac arrest following bradycardia may occur. An anticholinergic drug should be available in case asystole occurs.

Heart rate and blood pressure should be monitored carefully and appropriate measures taken if hypotension or bradycardia occur, including a reduction in the rate of administration of alfentanil.

Use with caution if the patient has received monoamine oxidase inhibitors within the 2 weeks prior to administration of the alfentanil infusion.

A reduced dosage may be required in elderly patients - see Dosage; Elderly
A reduced dosage may be required in debilitated patients or patients with adrenocortical insufficiency - see Dosage; Additional Dosage

The dose should be titrated with care and prolonged monitoring may be required in patients with hypothyroidism, pulmonary disease, decreased respiratory reserve, alcoholism, renal impairment ( see Dosage; Renal Impairment) or hepatic impairment ( see Dosage; Hepatic Impairment).

As with all opioids, use with caution in patients with myasthenia gravis, hypotension, asthma, prostatic hypertrophy, obstructive or inflammatory bowel disease, biliary tract disorders, convulsive disorders or shock.

To avoid excessive doses, obese patients may require doses based on their lean (ideal) body mass.

Repeated administration may cause dependence and tolerance. Use with caution in patients with a history of drug dependence. Higher doses may be required in patients receiving chronic opioid therapy or those with a history of opioid abuse.

The half life of alfentanil is prolonged in neonates and accumulation is likely with prolonged use.

There is little experience with alfentanil concentrate for solution for infusion in children. It may be more appropriate to use the lower strength alfentanil 500micrograms/ml solution. Consult appropriate monograph for full information.

Muscle rigidity, may occur, potentially affecting all skeletal muscles. The incidence and severity of the muscle rigidity is dose related, sometimes occurring at does of 20microgram/kg and consistently appearing at doses in excess of 130microgram/kg. This may be helped with neuromuscular blocking drugs, slow IV injection or premedication with a benzodiazepine or a muscle relaxant.

Non-epileptic (myo)clonic movements may occur.

Avoid abrupt withdrawal after long term use.

Alfentanil infusions should be discontinued at least 10 to 15 minutes prior to the end of surgery during general anaesthesia. During administration of alfentanil during monitored anaesthesia care, infusions of alfentanil may be continued to the end of the procedure.

Advise patient to avoid alcohol.

Patients must be advised not to drive or operate machinery for 24 hours after alfentanil administration.

All patients require careful monitoring for signs of abuse and addiction.

Adrenal insufficiency has been reported with opioid use, as opioid may influence the gonadal or the hypothalamic-pituitary-adrenal axes. Changes in serum prolactin, plasma cortisol and testosterone levels have been shown with the use of opioids. If adrenal insufficiency is suspected, gradually wean patient off opioid treatment until adrenal function is recovered. Continue with corticosteroid treatment until adrenal function has recovered and opioid treatment can commence.

Neonate exposure in labour, risk of respiratory depression.

Neonate exposed in utero, monitor for neonatal withdrawal syndrome.

Advise that effects are potentiated by CNS depressants (including alcohol). Monitor at regular intervals as withdrawal symptoms & dependence may occur. Monitor patients with a history of alcoholism and drug abuse. Progressive withdrawal recommended. Consider dose reduction or alternative opioid in cases of hyperalgesia. Monitor patients on prolonged therapy. When used with SSRIs, risk of Serotonin syndrome. Neonate exposed in labour: Risk of respiratory depression. Neonate exposed in utero: Monitor for neonatal withdrawal syndrome.

Pregnancy and Lactation

Pregnancy

Use alfentanil with caution during pregnancy.

The manufacturer advises caution when prescribing alfentanil during pregnancy.

At the time of writing there is limited published information regarding the use of alfentanil during pregnancy. Alfentanil crosses the placenta, and regular use during pregnancy may result in drug dependence in the foetus and withdrawal symptoms in the neonate. Use of alfentanil during labour may result in respiratory depression in the neonate. Animal studies have not shown teratogenic or acute embryotoxic effects.

Lactation

The use of alfentanil is contraindicated during breastfeeding.

The manufacturer does not recommend the use of alfentanil during breastfeeding. Alfentanil is secreted into breast milk, and may cause respiratory depression in the breastfeed infant.

LactMed (2018) states that there is limited data regarding intravenous use thus alternative agents are preferred. If alfentanil is used during breastfeeding and the infant shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately.

Effects on Ability to Drive and Operate Machinery

This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them.

Counselling

Advise patient to avoid alcohol.

Patients must be advised not to drive or operate machinery for 24 hours after alfentanil administration.

Side Effects

Local pain (injection site)
Shivering
Hypersensitivity reactions
Anaphylaxis
Bronchospasm
Urticaria
Hypotension
Hypertension
Muscle rigidity
Myoclonic movements
Dizziness
Headache
Nausea
Vomiting
Drowsiness
Bradycardia
Tachycardia
Arrhythmias
Asystole
Somnolence
Disorientation
Agitation
Euphoria
Apnoea
Respiratory depression
Cough
Laryngospasm
Hiccups
Pruritus
Hyperhidrosis
Urinary retention
Sensation of cold
Respiratory arrest
Constipation
Dry mouth
Biliary spasm
Palpitations
Oedema
Postural hypotension
Hallucinations
Vertigo
Dysphoria
Mood changes
Confusion
Sleep disturbances
Sexual dysfunction
Difficulty in micturition
Ureteric spasm
Miosis
Flushing
Rash
Dependence
Elevation of liver enzymes
Hypothermia
Restlessness
Raised intracranial pressure
Coma
Circulatory failure
Hypoxia
Excitation
Visual disturbances
Movement disturbances
Sedation
Dyskinesia
Unconsciousness
Convulsions
Increased heart rate
Bradypnoea
Hypercapnia
Cardiac arrest
Epistaxis
Allergic dermatitis
Erythema
Fatigue
Pain
Fever

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Storage requirements vary according to brand

Further Information

Last Full Review Date: August 2011

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th edition (2008) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Injectable Medicines Administration Guide, 3rd edition (2010) UCL NHS Foundation Trust. Wiley-Blackwell, Oxford.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics. Alfentanil 5mg/m solution for injectionl. Hameln Pharmaceuticals Ltd. Revised January 2014.

Summary of Product Characteristics. Rapifen Intensive Care. Piramal Critical Care Ltd. Revised August 2020.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Alfentanil Last revised: 31 October 2018
Last accessed: 20 May 2021

Gov.uk. Government departments. Department for Transport. Publications. Drug driving and medicine: advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: https://www.gov.uk Last accessed: 6 January 2015 New drug driving offence implications for medicines packaging. Medicines Regulatory News. 10 December 2013. Available at: https://www.mhra.gov.uk Last accessed: 6 January 2015

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 16 August 2017